Young women who received the quadrivalent human papillomavirus (HPV) vaccine had fewer and fewer infections with high-risk HPV strains covered by the vaccine year after year, but the incidence of high-risk strains that were not covered by the vaccine increased over the same 12-year period, researchers report in a study published August 23 in JAMA Open Network.

“One of the unique contributions that this study provides is the evaluation of a real-world example of the HPV infection rates following immunization in a population of adolescent girls and young adult women at a single health center in a large U.S. city, reflecting strong evidence of vaccine effectiveness,” write Nicolas F. Schlecht, PhD, a professor of oncology at Roswell Park Comprehensive Cancer Center, Buffalo, and his colleagues. “Previous surveillance studies from the U.S. have involved older women and populations with relatively low vaccine coverage.”

In addition to supporting the value of continuing to vaccinate teens against HPV, the findings underscore the importance of continuing to screen women for cervical cancer, Dr. Schlecht said in an interview.

“HPV has not and is not going away,” he said. “We need to keep on our toes with screening and other measures to continue to prevent the development of cervix cancer,” including monitoring different high-risk HPV types and keeping a close eye on cervical precancer rates, particularly CIN3 and cervix cancer, he said. “The vaccines are definitely a good thing. Just getting rid of HPV16 is an amazing accomplishment.”

Kevin Ault, MD, a professor of ob/gyn and academic specialist director of clinical and translational research at the University of Kansas, Kansas City, told this news organization that other studies have had similar findings, but this one is larger with longer follow-up.

“The take-home message is that vaccines work, and this is especially true for the HPV vaccine,” said Dr. Ault, who was not involved in the research. “The vaccine prevents HPV infections and the consequences of these infections, such as cervical cancer. The results are consistent with other studies in different settings, so they are likely generalizable.”

The researchers collected data from October 2007, shortly after the vaccine was approved, through September 2019 on sexually active adolescent and young women aged 13 to 21 years who had received the HPV vaccine and had agreed to follow-up assessments every 6 months until they turned 26. Each follow-up included the collecting of samples of cervical and anal cells for polymerase chain reaction testing for the presence of HPV types.

More than half of the 1,453 participants were Hispanic (58.8%), and half were Black (50.4%), including 15% Hispanic and Black patients. The average age of the participants was 18 years. They were tracked for a median 2.4 years. Nearly half the participants (48%) received the HPV vaccine prior to sexual debut.

For the longitudinal study, the researchers adjusted for participants’ age, the year they received the vaccine, and the years since they were vaccinated. They also tracked breakthrough infections for the four types of HPV covered by the vaccine in participants who received the vaccine before sexual debut.

“We evaluated whether infection rates for HPV have changed since the administration of the vaccine by assessing longitudinally the probability of HPV detection over time among vaccinated participants while adjusting for changes in cohort characteristics over time,” the researchers write. In their statistical analysis, they made adjustments for the number of vaccine doses participants received before their first study visit, age at sexual debut, age at first vaccine dose, number of sexual partners in the preceding 6 months, consistency of condom use during sex, history of a positive chlamydia test, and, for anal HPV analyses, whether the participants had had anal sex in the previous 6 months.

The average age at first intercourse remained steady at 15 years throughout the study, but the average age of vaccination dropped from 18 years in 2008 to 12 years in 2019 (P < .001). More than half the participants (64%) had had at least three lifetime sexual partners at baseline.

After adjustment for age, the researchers found that the incidence of the four HPV types covered by the vaccine – HPV-6, HPV-11, HPV-16, and HPV-18 – dropped more each year, shifting from 9.1% from 2008-2010 to 4.7% from 2017-2019. The effect was even greater among those vaccinated prior to sexual debut; for those patients, the incidence of the four vaccine types dropped from 8.8% to 1.7% over the course of the study. Declines over time also occurred for anal types HPV-31 (adjusted odds ratio [aOR] = 0.76) and HPV-45 (aOR = 0.77). Those vaccinated prior to any sexual intercourse had 19% lower odds of infection per year with a vaccine-covered HPV type.

“We were really excited to see that the types targeted by the vaccines were considerably lower over time in our population,” Dr. Schlecht told this news organization. “This is an important observation, since most of these types are the most worrisome for cervical cancer.”

They were surprised, however, to see overall HPV prevalence increase over time, particularly with the high-risk HPV types that were not covered by the quadrivalent vaccine.

Prevalence of cervical high-risk types not in the vaccine increased from 25.1% from 2008-2010 to 30.5% from 2017-2019. Odds of detection of high-risk HPV types not covered by the vaccine increased 8% each year, particularly for HPV-56 and HPV-68; anal HPV types increased 11% each year. Neither age nor recent number of sexual partners affected the findings.

“The underlying mechanisms for the observed increased detection of specific non-vaccine HPV types over time are not yet clear.”

“We hope this doesn’t translate into some increase in cervical neoplasia that is unanticipated,” Dr. Schlecht said. He noted that the attributable risks for cancer associated with nonvaccine high-risk HPV types remain low. “Theoretical concerns are one thing; actual data is what drives the show,” he said.

The research was funded by the National Institutes of Health and the Icahn School of Medicine at Mount Sinai, New York. Dr. Schlecht has served on advisory boards for Merck, GlaxoSmithKline (GSK), and PDS Biotechnology. One author previously served on a GSK advisory board, and another worked with Merck on an early vaccine trial. Dr. Ault has disclosed no relevant financial relationships.

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

Young women who received the quadrivalent human papillomavirus (HPV) vaccine had fewer and fewer infections with high-risk HPV strains covered by the vaccine year after year, but the incidence of high-risk strains that were not covered by the vaccine increased over the same 12-year period, researchers report in a study published August 23 in JAMA Open Network.

“One of the unique contributions that this study provides is the evaluation of a real-world example of the HPV infection rates following immunization in a population of adolescent girls and young adult women at a single health center in a large U.S. city, reflecting strong evidence of vaccine effectiveness,” write Nicolas F. Schlecht, PhD, a professor of oncology at Roswell Park Comprehensive Cancer Center, Buffalo, and his colleagues. “Previous surveillance studies from the U.S. have involved older women and populations with relatively low vaccine coverage.”

In addition to supporting the value of continuing to vaccinate teens against HPV, the findings underscore the importance of continuing to screen women for cervical cancer, Dr. Schlecht said in an interview.

“HPV has not and is not going away,” he said. “We need to keep on our toes with screening and other measures to continue to prevent the development of cervix cancer,” including monitoring different high-risk HPV types and keeping a close eye on cervical precancer rates, particularly CIN3 and cervix cancer, he said. “The vaccines are definitely a good thing. Just getting rid of HPV16 is an amazing accomplishment.”

Kevin Ault, MD, a professor of ob/gyn and academic specialist director of clinical and translational research at the University of Kansas, Kansas City, told this news organization that other studies have had similar findings, but this one is larger with longer follow-up.

“The take-home message is that vaccines work, and this is especially true for the HPV vaccine,” said Dr. Ault, who was not involved in the research. “The vaccine prevents HPV infections and the consequences of these infections, such as cervical cancer. The results are consistent with other studies in different settings, so they are likely generalizable.”

The researchers collected data from October 2007, shortly after the vaccine was approved, through September 2019 on sexually active adolescent and young women aged 13 to 21 years who had received the HPV vaccine and had agreed to follow-up assessments every 6 months until they turned 26. Each follow-up included the collecting of samples of cervical and anal cells for polymerase chain reaction testing for the presence of HPV types.

More than half of the 1,453 participants were Hispanic (58.8%), and half were Black (50.4%), including 15% Hispanic and Black patients. The average age of the participants was 18 years. They were tracked for a median 2.4 years. Nearly half the participants (48%) received the HPV vaccine prior to sexual debut.

For the longitudinal study, the researchers adjusted for participants’ age, the year they received the vaccine, and the years since they were vaccinated. They also tracked breakthrough infections for the four types of HPV covered by the vaccine in participants who received the vaccine before sexual debut.

“We evaluated whether infection rates for HPV have changed since the administration of the vaccine by assessing longitudinally the probability of HPV detection over time among vaccinated participants while adjusting for changes in cohort characteristics over time,” the researchers write. In their statistical analysis, they made adjustments for the number of vaccine doses participants received before their first study visit, age at sexual debut, age at first vaccine dose, number of sexual partners in the preceding 6 months, consistency of condom use during sex, history of a positive chlamydia test, and, for anal HPV analyses, whether the participants had had anal sex in the previous 6 months.

The average age at first intercourse remained steady at 15 years throughout the study, but the average age of vaccination dropped from 18 years in 2008 to 12 years in 2019 (P < .001). More than half the participants (64%) had had at least three lifetime sexual partners at baseline.

After adjustment for age, the researchers found that the incidence of the four HPV types covered by the vaccine – HPV-6, HPV-11, HPV-16, and HPV-18 – dropped more each year, shifting from 9.1% from 2008-2010 to 4.7% from 2017-2019. The effect was even greater among those vaccinated prior to sexual debut; for those patients, the incidence of the four vaccine types dropped from 8.8% to 1.7% over the course of the study. Declines over time also occurred for anal types HPV-31 (adjusted odds ratio [aOR] = 0.76) and HPV-45 (aOR = 0.77). Those vaccinated prior to any sexual intercourse had 19% lower odds of infection per year with a vaccine-covered HPV type.

“We were really excited to see that the types targeted by the vaccines were considerably lower over time in our population,” Dr. Schlecht told this news organization. “This is an important observation, since most of these types are the most worrisome for cervical cancer.”

They were surprised, however, to see overall HPV prevalence increase over time, particularly with the high-risk HPV types that were not covered by the quadrivalent vaccine.

Prevalence of cervical high-risk types not in the vaccine increased from 25.1% from 2008-2010 to 30.5% from 2017-2019. Odds of detection of high-risk HPV types not covered by the vaccine increased 8% each year, particularly for HPV-56 and HPV-68; anal HPV types increased 11% each year. Neither age nor recent number of sexual partners affected the findings.

“The underlying mechanisms for the observed increased detection of specific non-vaccine HPV types over time are not yet clear.”

“We hope this doesn’t translate into some increase in cervical neoplasia that is unanticipated,” Dr. Schlecht said. He noted that the attributable risks for cancer associated with nonvaccine high-risk HPV types remain low. “Theoretical concerns are one thing; actual data is what drives the show,” he said.

The research was funded by the National Institutes of Health and the Icahn School of Medicine at Mount Sinai, New York. Dr. Schlecht has served on advisory boards for Merck, GlaxoSmithKline (GSK), and PDS Biotechnology. One author previously served on a GSK advisory board, and another worked with Merck on an early vaccine trial. Dr. Ault has disclosed no relevant financial relationships.

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

Young women who received the quadrivalent human papillomavirus (HPV) vaccine had fewer and fewer infections with high-risk HPV strains covered by the vaccine year after year, but the incidence of high-risk strains that were not covered by the vaccine increased over the same 12-year period, researchers report in a study published August 23 in JAMA Open Network.

“One of the unique contributions that this study provides is the evaluation of a real-world example of the HPV infection rates following immunization in a population of adolescent girls and young adult women at a single health center in a large U.S. city, reflecting strong evidence of vaccine effectiveness,” write Nicolas F. Schlecht, PhD, a professor of oncology at Roswell Park Comprehensive Cancer Center, Buffalo, and his colleagues. “Previous surveillance studies from the U.S. have involved older women and populations with relatively low vaccine coverage.”

In addition to supporting the value of continuing to vaccinate teens against HPV, the findings underscore the importance of continuing to screen women for cervical cancer, Dr. Schlecht said in an interview.

“HPV has not and is not going away,” he said. “We need to keep on our toes with screening and other measures to continue to prevent the development of cervix cancer,” including monitoring different high-risk HPV types and keeping a close eye on cervical precancer rates, particularly CIN3 and cervix cancer, he said. “The vaccines are definitely a good thing. Just getting rid of HPV16 is an amazing accomplishment.”

Kevin Ault, MD, a professor of ob/gyn and academic specialist director of clinical and translational research at the University of Kansas, Kansas City, told this news organization that other studies have had similar findings, but this one is larger with longer follow-up.

“The take-home message is that vaccines work, and this is especially true for the HPV vaccine,” said Dr. Ault, who was not involved in the research. “The vaccine prevents HPV infections and the consequences of these infections, such as cervical cancer. The results are consistent with other studies in different settings, so they are likely generalizable.”

The researchers collected data from October 2007, shortly after the vaccine was approved, through September 2019 on sexually active adolescent and young women aged 13 to 21 years who had received the HPV vaccine and had agreed to follow-up assessments every 6 months until they turned 26. Each follow-up included the collecting of samples of cervical and anal cells for polymerase chain reaction testing for the presence of HPV types.

More than half of the 1,453 participants were Hispanic (58.8%), and half were Black (50.4%), including 15% Hispanic and Black patients. The average age of the participants was 18 years. They were tracked for a median 2.4 years. Nearly half the participants (48%) received the HPV vaccine prior to sexual debut.

For the longitudinal study, the researchers adjusted for participants’ age, the year they received the vaccine, and the years since they were vaccinated. They also tracked breakthrough infections for the four types of HPV covered by the vaccine in participants who received the vaccine before sexual debut.

“We evaluated whether infection rates for HPV have changed since the administration of the vaccine by assessing longitudinally the probability of HPV detection over time among vaccinated participants while adjusting for changes in cohort characteristics over time,” the researchers write. In their statistical analysis, they made adjustments for the number of vaccine doses participants received before their first study visit, age at sexual debut, age at first vaccine dose, number of sexual partners in the preceding 6 months, consistency of condom use during sex, history of a positive chlamydia test, and, for anal HPV analyses, whether the participants had had anal sex in the previous 6 months.

The average age at first intercourse remained steady at 15 years throughout the study, but the average age of vaccination dropped from 18 years in 2008 to 12 years in 2019 (P < .001). More than half the participants (64%) had had at least three lifetime sexual partners at baseline.

After adjustment for age, the researchers found that the incidence of the four HPV types covered by the vaccine – HPV-6, HPV-11, HPV-16, and HPV-18 – dropped more each year, shifting from 9.1% from 2008-2010 to 4.7% from 2017-2019. The effect was even greater among those vaccinated prior to sexual debut; for those patients, the incidence of the four vaccine types dropped from 8.8% to 1.7% over the course of the study. Declines over time also occurred for anal types HPV-31 (adjusted odds ratio [aOR] = 0.76) and HPV-45 (aOR = 0.77). Those vaccinated prior to any sexual intercourse had 19% lower odds of infection per year with a vaccine-covered HPV type.

“We were really excited to see that the types targeted by the vaccines were considerably lower over time in our population,” Dr. Schlecht told this news organization. “This is an important observation, since most of these types are the most worrisome for cervical cancer.”

They were surprised, however, to see overall HPV prevalence increase over time, particularly with the high-risk HPV types that were not covered by the quadrivalent vaccine.

Prevalence of cervical high-risk types not in the vaccine increased from 25.1% from 2008-2010 to 30.5% from 2017-2019. Odds of detection of high-risk HPV types not covered by the vaccine increased 8% each year, particularly for HPV-56 and HPV-68; anal HPV types increased 11% each year. Neither age nor recent number of sexual partners affected the findings.

“The underlying mechanisms for the observed increased detection of specific non-vaccine HPV types over time are not yet clear.”

“We hope this doesn’t translate into some increase in cervical neoplasia that is unanticipated,” Dr. Schlecht said. He noted that the attributable risks for cancer associated with nonvaccine high-risk HPV types remain low. “Theoretical concerns are one thing; actual data is what drives the show,” he said.

The research was funded by the National Institutes of Health and the Icahn School of Medicine at Mount Sinai, New York. Dr. Schlecht has served on advisory boards for Merck, GlaxoSmithKline (GSK), and PDS Biotechnology. One author previously served on a GSK advisory board, and another worked with Merck on an early vaccine trial. Dr. Ault has disclosed no relevant financial relationships.

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

A higher intake of flavonoid-rich foods such as berries, apples, tea, and red wine is associated with a clinically relevant reduction in blood pressure levels, an association that is partially explained by bacteria in an individual’s gut microbiome, new research suggests.

In a population-based study of more than 900 individuals, those with the highest intake of flavonoid-containing foods had significantly lower systolic blood pressure and pulse pressure, as well as greater gut microbial diversity, compared with those with the lowest intakes.

Up to 15% of this observed association was explained by the gut microbiome, suggesting that these microbes play a key role in metabolizing flavonoids to enhance their cardioprotective effects, according to the researchers.

The study was published online in the journal Hypertension.

“We know what we eat plays a critical role in shaping our gut microbiome, but little is known about the relative importance of plant foods and specific constituents called flavonoids,” lead researcher Aedin Cassidy, PhD, chair and professor of nutrition and medicine at the Institute for Global Food Security, Queen’s University, Belfast, Northern Ireland, said in an interview.

“Unlike many other food constituents, flavonoids are predominantly metabolized in the gut, suggesting that the gut microbiome may be more important in enhancing their biological activity than for other things we eat,” Dr. Cassidy said.

“There is mounting evidence from population-based studies and clinical trials that a higher intake of flavonoids and flavonoid-rich foods can improve heart health, but for the first time, we provide data highlighting the key role of the gut microbiome in explaining the association between such foods and blood pressure,” she noted. “This is one of the first studies to address this.”

For this analysis, Dr. Cassidy and her group sought to assess to what extent the composition of the gut microbiome might explain the association of habitual flavonoid and flavonoid-rich food intake with systolic and diastolic blood pressure in a community-based sample of 904 individuals aged 25-82 years from Germany’s PopGen biobank.

The researchers evaluated participants’ food intake, gut microbiome, and blood pressure levels together with other clinical and molecular phenotyping at regular follow-up examinations.

Participants’ intake of flavonoid-rich foods during the previous year was calculated from a self-reported food questionnaire detailing the frequency and quantity eaten of 112 foods, and flavonoid values were assigned to foods according to United States Department of Agriculture data on flavonoid content in food.

Participants’ gut microbiome was assessed by fecal bacterial DNA extracted from stool samples.

After an overnight fast, participants’ blood pressure levels were measured three times in 3-minute intervals after an initial 5-minute rest period. Researchers also collected participants’ diet and lifestyle information.

Analysis of the data showed the following:

• Eating 1.5 servings of berries per day (about 1 cup) was associated with a 4.1–mm Hg reduction in systolic BP; 12% of this association was explained by gut microbiome factors.
• Drinking three glasses of red wine per week was associated with a 3.7–mm Hg reduction in systolic BP; 15% of this association was explained by the gut microbiome.

“These blood pressure–lowering effects are achievable with simple changes to the daily diet,” Dr. Cassidy said.

“Incorporating flavonoid-rich foods into the diet can have clinically relevant reductions in systolic blood pressure and pulse pressure, and a healthy gut microbiome is important to break down flavonoids to a more cardioprotective form,” she said.

“Our findings indicate future trials should look at participants according to metabolic profile in order to more accurately study the roles of metabolism and the gut microbiome in regulating the effects of flavonoids on blood pressure,” said Dr. Cassidy.

“A better understanding of the highly individual variability of flavonoid metabolism could very well explain why some people have greater cardiovascular protection benefits from flavonoid-rich foods than others.”
 

‘Interesting’ data

“The data are interesting,” David Jenkins, MD, PhD, DSc, professor of medicine and nutrition at the University of Toronto, said in an interview.

“Berries and red wine appear to be associated with lower systolic blood pressures. Lower blood pressures have been found in general in people who consume more plant-based diets, especially those high in fruits and vegetables,” noted Dr. Jenkins, who was not involved with this study.

“Berries and grapes high in polyphenols may have many health benefits as antioxidants, and in a recent study have been shown to reduce cardiovascular mortality. The change in chronic microflora is also of interest as this will change with increased fruit and vegetable consumption,” he said.

Perhaps one word of caveat, Dr. Jenkins added: “Alcohol has been found to increase blood pressure and the risk of stroke. Presumably the beneficial effects as seen here were when wine is consumed in moderation.”
 

Supports recommendations

The study by Cassidy and colleagues supports the dietary recommendations from the American Heart Association (AHA) for heart health, Penny M. Kris-Etherton, PhD, RDN, professor of nutritional sciences, Penn State University, University Park, Pa., and chair, AHA Council on Lifestyle and Cardiometabolic Health, said in an interview.

“The AHA recommends a healthy dietary pattern that emphasizes a variety of plant foods including fruits, vegetables, whole grains, legumes, nuts, and seeds and is low in sodium, saturated fat, and added sugars. Lean protein foods, including plant protein foods, are recommended, and red meat should be limited. If alcohol is consumed it should be done in moderation,” Dr. Kris-Etherton said.

“Based on these AHA dietary recommendations, a wide variety of plant foods will promote consumption of many flavonoids that have demonstrated CVD benefits, such as lowering systolic blood pressure as reported by the authors, as well as promoting healthy endothelial function and having antithrombotic, anti-inflammatory and antioxidant effects,” she said in email.

“This recommended dietary pattern will have other cardiovascular health benefits, such as decreasing LDL cholesterol, due to its very healthy nutrient profile. The exciting new finding reported by Cassidy et al. is that the effects of dietary flavonoids on lowering systolic blood pressure are modulated by the gut microbiome,” Dr. Kris-Etherton said.

“Further research needs to be done to confirm these findings and to identify how different foods affect specific gut bacteria that benefit cardiovascular health.”

The research was funded by grants from the German Research Foundation and the German Federal Ministry of Education and Research. Dr. Cassidy and Dr. Jenkins have disclosed no relevant financial relationships. Dr. Kris-Etherton is a spokesperson for the AHA.

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

A higher intake of flavonoid-rich foods such as berries, apples, tea, and red wine is associated with a clinically relevant reduction in blood pressure levels, an association that is partially explained by bacteria in an individual’s gut microbiome, new research suggests.

In a population-based study of more than 900 individuals, those with the highest intake of flavonoid-containing foods had significantly lower systolic blood pressure and pulse pressure, as well as greater gut microbial diversity, compared with those with the lowest intakes.

Up to 15% of this observed association was explained by the gut microbiome, suggesting that these microbes play a key role in metabolizing flavonoids to enhance their cardioprotective effects, according to the researchers.

The study was published online in the journal Hypertension.

“We know what we eat plays a critical role in shaping our gut microbiome, but little is known about the relative importance of plant foods and specific constituents called flavonoids,” lead researcher Aedin Cassidy, PhD, chair and professor of nutrition and medicine at the Institute for Global Food Security, Queen’s University, Belfast, Northern Ireland, said in an interview.

“Unlike many other food constituents, flavonoids are predominantly metabolized in the gut, suggesting that the gut microbiome may be more important in enhancing their biological activity than for other things we eat,” Dr. Cassidy said.

“There is mounting evidence from population-based studies and clinical trials that a higher intake of flavonoids and flavonoid-rich foods can improve heart health, but for the first time, we provide data highlighting the key role of the gut microbiome in explaining the association between such foods and blood pressure,” she noted. “This is one of the first studies to address this.”

For this analysis, Dr. Cassidy and her group sought to assess to what extent the composition of the gut microbiome might explain the association of habitual flavonoid and flavonoid-rich food intake with systolic and diastolic blood pressure in a community-based sample of 904 individuals aged 25-82 years from Germany’s PopGen biobank.

The researchers evaluated participants’ food intake, gut microbiome, and blood pressure levels together with other clinical and molecular phenotyping at regular follow-up examinations.

Participants’ intake of flavonoid-rich foods during the previous year was calculated from a self-reported food questionnaire detailing the frequency and quantity eaten of 112 foods, and flavonoid values were assigned to foods according to United States Department of Agriculture data on flavonoid content in food.

Participants’ gut microbiome was assessed by fecal bacterial DNA extracted from stool samples.

After an overnight fast, participants’ blood pressure levels were measured three times in 3-minute intervals after an initial 5-minute rest period. Researchers also collected participants’ diet and lifestyle information.

Analysis of the data showed the following:

• Eating 1.5 servings of berries per day (about 1 cup) was associated with a 4.1–mm Hg reduction in systolic BP; 12% of this association was explained by gut microbiome factors.
• Drinking three glasses of red wine per week was associated with a 3.7–mm Hg reduction in systolic BP; 15% of this association was explained by the gut microbiome.

“These blood pressure–lowering effects are achievable with simple changes to the daily diet,” Dr. Cassidy said.

“Incorporating flavonoid-rich foods into the diet can have clinically relevant reductions in systolic blood pressure and pulse pressure, and a healthy gut microbiome is important to break down flavonoids to a more cardioprotective form,” she said.

“Our findings indicate future trials should look at participants according to metabolic profile in order to more accurately study the roles of metabolism and the gut microbiome in regulating the effects of flavonoids on blood pressure,” said Dr. Cassidy.

“A better understanding of the highly individual variability of flavonoid metabolism could very well explain why some people have greater cardiovascular protection benefits from flavonoid-rich foods than others.”
 

‘Interesting’ data

“The data are interesting,” David Jenkins, MD, PhD, DSc, professor of medicine and nutrition at the University of Toronto, said in an interview.

“Berries and red wine appear to be associated with lower systolic blood pressures. Lower blood pressures have been found in general in people who consume more plant-based diets, especially those high in fruits and vegetables,” noted Dr. Jenkins, who was not involved with this study.

“Berries and grapes high in polyphenols may have many health benefits as antioxidants, and in a recent study have been shown to reduce cardiovascular mortality. The change in chronic microflora is also of interest as this will change with increased fruit and vegetable consumption,” he said.

Perhaps one word of caveat, Dr. Jenkins added: “Alcohol has been found to increase blood pressure and the risk of stroke. Presumably the beneficial effects as seen here were when wine is consumed in moderation.”
 

Supports recommendations

The study by Cassidy and colleagues supports the dietary recommendations from the American Heart Association (AHA) for heart health, Penny M. Kris-Etherton, PhD, RDN, professor of nutritional sciences, Penn State University, University Park, Pa., and chair, AHA Council on Lifestyle and Cardiometabolic Health, said in an interview.

“The AHA recommends a healthy dietary pattern that emphasizes a variety of plant foods including fruits, vegetables, whole grains, legumes, nuts, and seeds and is low in sodium, saturated fat, and added sugars. Lean protein foods, including plant protein foods, are recommended, and red meat should be limited. If alcohol is consumed it should be done in moderation,” Dr. Kris-Etherton said.

“Based on these AHA dietary recommendations, a wide variety of plant foods will promote consumption of many flavonoids that have demonstrated CVD benefits, such as lowering systolic blood pressure as reported by the authors, as well as promoting healthy endothelial function and having antithrombotic, anti-inflammatory and antioxidant effects,” she said in email.

“This recommended dietary pattern will have other cardiovascular health benefits, such as decreasing LDL cholesterol, due to its very healthy nutrient profile. The exciting new finding reported by Cassidy et al. is that the effects of dietary flavonoids on lowering systolic blood pressure are modulated by the gut microbiome,” Dr. Kris-Etherton said.

“Further research needs to be done to confirm these findings and to identify how different foods affect specific gut bacteria that benefit cardiovascular health.”

The research was funded by grants from the German Research Foundation and the German Federal Ministry of Education and Research. Dr. Cassidy and Dr. Jenkins have disclosed no relevant financial relationships. Dr. Kris-Etherton is a spokesperson for the AHA.

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

A higher intake of flavonoid-rich foods such as berries, apples, tea, and red wine is associated with a clinically relevant reduction in blood pressure levels, an association that is partially explained by bacteria in an individual’s gut microbiome, new research suggests.

In a population-based study of more than 900 individuals, those with the highest intake of flavonoid-containing foods had significantly lower systolic blood pressure and pulse pressure, as well as greater gut microbial diversity, compared with those with the lowest intakes.

Up to 15% of this observed association was explained by the gut microbiome, suggesting that these microbes play a key role in metabolizing flavonoids to enhance their cardioprotective effects, according to the researchers.

The study was published online in the journal Hypertension.

“We know what we eat plays a critical role in shaping our gut microbiome, but little is known about the relative importance of plant foods and specific constituents called flavonoids,” lead researcher Aedin Cassidy, PhD, chair and professor of nutrition and medicine at the Institute for Global Food Security, Queen’s University, Belfast, Northern Ireland, said in an interview.

“Unlike many other food constituents, flavonoids are predominantly metabolized in the gut, suggesting that the gut microbiome may be more important in enhancing their biological activity than for other things we eat,” Dr. Cassidy said.

“There is mounting evidence from population-based studies and clinical trials that a higher intake of flavonoids and flavonoid-rich foods can improve heart health, but for the first time, we provide data highlighting the key role of the gut microbiome in explaining the association between such foods and blood pressure,” she noted. “This is one of the first studies to address this.”

For this analysis, Dr. Cassidy and her group sought to assess to what extent the composition of the gut microbiome might explain the association of habitual flavonoid and flavonoid-rich food intake with systolic and diastolic blood pressure in a community-based sample of 904 individuals aged 25-82 years from Germany’s PopGen biobank.

The researchers evaluated participants’ food intake, gut microbiome, and blood pressure levels together with other clinical and molecular phenotyping at regular follow-up examinations.

Participants’ intake of flavonoid-rich foods during the previous year was calculated from a self-reported food questionnaire detailing the frequency and quantity eaten of 112 foods, and flavonoid values were assigned to foods according to United States Department of Agriculture data on flavonoid content in food.

Participants’ gut microbiome was assessed by fecal bacterial DNA extracted from stool samples.

After an overnight fast, participants’ blood pressure levels were measured three times in 3-minute intervals after an initial 5-minute rest period. Researchers also collected participants’ diet and lifestyle information.

Analysis of the data showed the following:

• Eating 1.5 servings of berries per day (about 1 cup) was associated with a 4.1–mm Hg reduction in systolic BP; 12% of this association was explained by gut microbiome factors.
• Drinking three glasses of red wine per week was associated with a 3.7–mm Hg reduction in systolic BP; 15% of this association was explained by the gut microbiome.

“These blood pressure–lowering effects are achievable with simple changes to the daily diet,” Dr. Cassidy said.

“Incorporating flavonoid-rich foods into the diet can have clinically relevant reductions in systolic blood pressure and pulse pressure, and a healthy gut microbiome is important to break down flavonoids to a more cardioprotective form,” she said.

“Our findings indicate future trials should look at participants according to metabolic profile in order to more accurately study the roles of metabolism and the gut microbiome in regulating the effects of flavonoids on blood pressure,” said Dr. Cassidy.

“A better understanding of the highly individual variability of flavonoid metabolism could very well explain why some people have greater cardiovascular protection benefits from flavonoid-rich foods than others.”
 

‘Interesting’ data

“The data are interesting,” David Jenkins, MD, PhD, DSc, professor of medicine and nutrition at the University of Toronto, said in an interview.

“Berries and red wine appear to be associated with lower systolic blood pressures. Lower blood pressures have been found in general in people who consume more plant-based diets, especially those high in fruits and vegetables,” noted Dr. Jenkins, who was not involved with this study.

“Berries and grapes high in polyphenols may have many health benefits as antioxidants, and in a recent study have been shown to reduce cardiovascular mortality. The change in chronic microflora is also of interest as this will change with increased fruit and vegetable consumption,” he said.

Perhaps one word of caveat, Dr. Jenkins added: “Alcohol has been found to increase blood pressure and the risk of stroke. Presumably the beneficial effects as seen here were when wine is consumed in moderation.”
 

Supports recommendations

The study by Cassidy and colleagues supports the dietary recommendations from the American Heart Association (AHA) for heart health, Penny M. Kris-Etherton, PhD, RDN, professor of nutritional sciences, Penn State University, University Park, Pa., and chair, AHA Council on Lifestyle and Cardiometabolic Health, said in an interview.

“The AHA recommends a healthy dietary pattern that emphasizes a variety of plant foods including fruits, vegetables, whole grains, legumes, nuts, and seeds and is low in sodium, saturated fat, and added sugars. Lean protein foods, including plant protein foods, are recommended, and red meat should be limited. If alcohol is consumed it should be done in moderation,” Dr. Kris-Etherton said.

“Based on these AHA dietary recommendations, a wide variety of plant foods will promote consumption of many flavonoids that have demonstrated CVD benefits, such as lowering systolic blood pressure as reported by the authors, as well as promoting healthy endothelial function and having antithrombotic, anti-inflammatory and antioxidant effects,” she said in email.

“This recommended dietary pattern will have other cardiovascular health benefits, such as decreasing LDL cholesterol, due to its very healthy nutrient profile. The exciting new finding reported by Cassidy et al. is that the effects of dietary flavonoids on lowering systolic blood pressure are modulated by the gut microbiome,” Dr. Kris-Etherton said.

“Further research needs to be done to confirm these findings and to identify how different foods affect specific gut bacteria that benefit cardiovascular health.”

The research was funded by grants from the German Research Foundation and the German Federal Ministry of Education and Research. Dr. Cassidy and Dr. Jenkins have disclosed no relevant financial relationships. Dr. Kris-Etherton is a spokesperson for the AHA.

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

Individuals with cognitively stimulating jobs are at a lower risk of developing dementia than their peers with less challenging employment, new research suggests.

Results from a large, multicohort study also showed an association between cognitive stimulation and lower levels of certain plasma proteins, providing possible clues on a protective biological mechanism.

“These new findings support the hypothesis that mental stimulation in adulthood may postpone the onset of dementia,” Mika Kivimäki, PhD, professor and director of the Whitehall II Study, department of epidemiology, University College London, said in an interview.

The results were published online Aug. 19, 2021, in the BMJ.
 

‘Work fast and hard’

Researchers assessed the association between workplace cognitive stimulation and dementia incidence in seven cohorts that included almost 108,000 men and women (mean age, 44.6 years). All were free of dementia at baseline.

Participants included civil servants, public sector employees, forestry workers, and others from the general working population.

Investigators separated the participants into three categories of workplace cognitive stimulation: “high,” which referred to both high job demand and high job control; “low,” which referred to low demands and low control; and “medium,” which referred to all other combinations of job demand and job control.

“Highly cognitively stimulating jobs require you to work fast and hard, learn new things, be creative, and have a high level of skill,” said Dr. Kivimäki.

The researchers controlled for low education, hypertension, smoking, obesity, depression, physical inactivity, diabetes, low social contact, excessive alcohol consumption, and traumatic brain injury. These represent 10 of the 12 dementia risk factors named by the 2020 Lancet Commission on Dementia Prevention as having convincing evidence, Dr. Kivimäki noted.

Although the investigators had no data on the other two risk factors of hearing loss and air pollution, these are unlikely to be confounding factors, he said.

Follow-up for incident dementia varied from 13.7 to 30.1 years, depending on the cohort, and was 16.7 years in the total patient population. The mean age at dementia onset was 71.2 years.
 

Benefits across the life course

Results showed that incident dementia per 10,000 person years was 7.3 in the low–cognitive stimulation group and 4.8 in the high-stimulation group, for a difference of 2.5.

“These differences were relatively small because the incidence of dementia in this relatively young population was low,” Dr. Kivimäki said.

Compared with those with low stimulation, the adjusted hazard ratio for dementia for this with high stimulation was 0.77 (95% CI, 0.65-0.92).

The results were similar for men and women, and for those younger and older than 60 years. However, the link between workplace cognitive stimulation appeared stronger for Alzheimer’s disease than for other dementias.

There also appeared to be additive effects of higher cognitive stimulation in both childhood, as indicated by higher educational attainment, and adulthood, based on work characteristics, said Dr. Kivimäki.

“These findings support the benefits of cognitive stimulation across the life course, with education leading to higher peak cognitive performance and cognitive stimulation at work lowering age-related cognitive decline,” he added.

The findings don’t seem to be the result of workers with cognitive impairment remaining in unchallenging jobs, he noted. Separate analyses showed lower dementia incidence even when 10 years or more separated the assessment of cognitive stimulation and the dementia diagnosis.

“This suggests that the findings are unlikely to be biased due to reverse causation,” Dr. Kivimäki said.
 

Possible mechanism

Findings were similar when the researchers assessed effect from job changes. “This is probably because people in highly stimulating jobs are more likely to change to another highly stimulating job than to a low-stimulating job,” said Dr. Kivimäki. “Similarly, people with less stimulating jobs are seldom able to change to a substantially more stimulating job.”

As a dementia risk factor, low workplace stimulation is comparable with high alcohol intake and physical inactivity, but is weaker than education, diabetes, smoking, hypertension, and obesity, Dr. Kivimäki noted.

When asked about individuals with less cognitively stimulating jobs who are enormously stimulated outside work, he said that “previous large-scale studies have failed to find evidence that leisure time cognitive activity would significantly reduce risk of dementia.”

To explore potential underlying mechanisms, the investigators examined almost 5,000 plasma proteins in more than 2,200 individuals from one cohort in the Whitehall II study. They found six proteins were significantly lower among participants with high versus low cognitive stimulation.

In another analysis that included more than 13,500 participants from the Whitehall and another cohort, higher levels of three of these plasma proteins were associated with increased dementia risk – or conversely, lower protein levels with lower dementia risk.

The findings suggest a “novel plausible explanation” for the link between workplace cognitive stimulation and dementia risk, said Dr. Kivimäki.

He noted that higher levels of certain proteins prevent brain cells from forming new connections.
 

‘Some of the most compelling evidence to date’

In an accompanying editorial, Serhiy Dekhtyar, PhD, assistant professor (Docent), Aging Research Center, Karolinska Institute, Stockholm, noted that the study is “an important piece of work” and “some of the most compelling evidence to date” on the role of occupational cognitive stimulation in dementia risk.

The large-scale investigation in multiple cohorts and contexts has “advanced the field” and could help “explain previously mixed findings in the literature,” Dekhtyar said in an interview.

Importantly, the researchers provide “an indication of biological mechanisms potentially connecting work mental stimulation and dementia,” he added.

However, Dr. Dekhtyar noted that the difference of 2.5 incident cases of dementia per 10,000 person years of follow-up between the low and high mental-stimulation groups “is not especially large” – although it is comparable with other established risk factors for dementia.

He suspects the effect size would have been larger had the follow-up for dementia been longer.

Dr. Dekhtyar also raised the possibility that “innate cognition” might affect both educational and occupational attainment, and the subsequent dementia risk.

“Without taking this into account, we may inadvertently conclude that education or occupational stimulation help differentially preserve cognition into late life – when in reality, it may be initial differences in cognitive ability that are preserved throughout life,” he concluded.

Funding sources for the study included Nordic Research Programme on Health and Welfare (NordForsk), Medical Research Council, Wellcome Trust, Academy of Finland, and Helsinki Institute of Life Science. Dr. Kivimäki has received support from NordForsk, the UK Medical Research Council, the Wellcome Trust, the Academy of Finland, and the Helsinki Institute of Life Science. Dr. Dekhtyar disclosed no relevant financial relationships.

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

Individuals with cognitively stimulating jobs are at a lower risk of developing dementia than their peers with less challenging employment, new research suggests.

Results from a large, multicohort study also showed an association between cognitive stimulation and lower levels of certain plasma proteins, providing possible clues on a protective biological mechanism.

“These new findings support the hypothesis that mental stimulation in adulthood may postpone the onset of dementia,” Mika Kivimäki, PhD, professor and director of the Whitehall II Study, department of epidemiology, University College London, said in an interview.

The results were published online Aug. 19, 2021, in the BMJ.
 

‘Work fast and hard’

Researchers assessed the association between workplace cognitive stimulation and dementia incidence in seven cohorts that included almost 108,000 men and women (mean age, 44.6 years). All were free of dementia at baseline.

Participants included civil servants, public sector employees, forestry workers, and others from the general working population.

Investigators separated the participants into three categories of workplace cognitive stimulation: “high,” which referred to both high job demand and high job control; “low,” which referred to low demands and low control; and “medium,” which referred to all other combinations of job demand and job control.

“Highly cognitively stimulating jobs require you to work fast and hard, learn new things, be creative, and have a high level of skill,” said Dr. Kivimäki.

The researchers controlled for low education, hypertension, smoking, obesity, depression, physical inactivity, diabetes, low social contact, excessive alcohol consumption, and traumatic brain injury. These represent 10 of the 12 dementia risk factors named by the 2020 Lancet Commission on Dementia Prevention as having convincing evidence, Dr. Kivimäki noted.

Although the investigators had no data on the other two risk factors of hearing loss and air pollution, these are unlikely to be confounding factors, he said.

Follow-up for incident dementia varied from 13.7 to 30.1 years, depending on the cohort, and was 16.7 years in the total patient population. The mean age at dementia onset was 71.2 years.
 

Benefits across the life course

Results showed that incident dementia per 10,000 person years was 7.3 in the low–cognitive stimulation group and 4.8 in the high-stimulation group, for a difference of 2.5.

“These differences were relatively small because the incidence of dementia in this relatively young population was low,” Dr. Kivimäki said.

Compared with those with low stimulation, the adjusted hazard ratio for dementia for this with high stimulation was 0.77 (95% CI, 0.65-0.92).

The results were similar for men and women, and for those younger and older than 60 years. However, the link between workplace cognitive stimulation appeared stronger for Alzheimer’s disease than for other dementias.

There also appeared to be additive effects of higher cognitive stimulation in both childhood, as indicated by higher educational attainment, and adulthood, based on work characteristics, said Dr. Kivimäki.

“These findings support the benefits of cognitive stimulation across the life course, with education leading to higher peak cognitive performance and cognitive stimulation at work lowering age-related cognitive decline,” he added.

The findings don’t seem to be the result of workers with cognitive impairment remaining in unchallenging jobs, he noted. Separate analyses showed lower dementia incidence even when 10 years or more separated the assessment of cognitive stimulation and the dementia diagnosis.

“This suggests that the findings are unlikely to be biased due to reverse causation,” Dr. Kivimäki said.
 

Possible mechanism

Findings were similar when the researchers assessed effect from job changes. “This is probably because people in highly stimulating jobs are more likely to change to another highly stimulating job than to a low-stimulating job,” said Dr. Kivimäki. “Similarly, people with less stimulating jobs are seldom able to change to a substantially more stimulating job.”

As a dementia risk factor, low workplace stimulation is comparable with high alcohol intake and physical inactivity, but is weaker than education, diabetes, smoking, hypertension, and obesity, Dr. Kivimäki noted.

When asked about individuals with less cognitively stimulating jobs who are enormously stimulated outside work, he said that “previous large-scale studies have failed to find evidence that leisure time cognitive activity would significantly reduce risk of dementia.”

To explore potential underlying mechanisms, the investigators examined almost 5,000 plasma proteins in more than 2,200 individuals from one cohort in the Whitehall II study. They found six proteins were significantly lower among participants with high versus low cognitive stimulation.

In another analysis that included more than 13,500 participants from the Whitehall and another cohort, higher levels of three of these plasma proteins were associated with increased dementia risk – or conversely, lower protein levels with lower dementia risk.

The findings suggest a “novel plausible explanation” for the link between workplace cognitive stimulation and dementia risk, said Dr. Kivimäki.

He noted that higher levels of certain proteins prevent brain cells from forming new connections.
 

‘Some of the most compelling evidence to date’

In an accompanying editorial, Serhiy Dekhtyar, PhD, assistant professor (Docent), Aging Research Center, Karolinska Institute, Stockholm, noted that the study is “an important piece of work” and “some of the most compelling evidence to date” on the role of occupational cognitive stimulation in dementia risk.

The large-scale investigation in multiple cohorts and contexts has “advanced the field” and could help “explain previously mixed findings in the literature,” Dekhtyar said in an interview.

Importantly, the researchers provide “an indication of biological mechanisms potentially connecting work mental stimulation and dementia,” he added.

However, Dr. Dekhtyar noted that the difference of 2.5 incident cases of dementia per 10,000 person years of follow-up between the low and high mental-stimulation groups “is not especially large” – although it is comparable with other established risk factors for dementia.

He suspects the effect size would have been larger had the follow-up for dementia been longer.

Dr. Dekhtyar also raised the possibility that “innate cognition” might affect both educational and occupational attainment, and the subsequent dementia risk.

“Without taking this into account, we may inadvertently conclude that education or occupational stimulation help differentially preserve cognition into late life – when in reality, it may be initial differences in cognitive ability that are preserved throughout life,” he concluded.

Funding sources for the study included Nordic Research Programme on Health and Welfare (NordForsk), Medical Research Council, Wellcome Trust, Academy of Finland, and Helsinki Institute of Life Science. Dr. Kivimäki has received support from NordForsk, the UK Medical Research Council, the Wellcome Trust, the Academy of Finland, and the Helsinki Institute of Life Science. Dr. Dekhtyar disclosed no relevant financial relationships.

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

Individuals with cognitively stimulating jobs are at a lower risk of developing dementia than their peers with less challenging employment, new research suggests.

Results from a large, multicohort study also showed an association between cognitive stimulation and lower levels of certain plasma proteins, providing possible clues on a protective biological mechanism.

“These new findings support the hypothesis that mental stimulation in adulthood may postpone the onset of dementia,” Mika Kivimäki, PhD, professor and director of the Whitehall II Study, department of epidemiology, University College London, said in an interview.

The results were published online Aug. 19, 2021, in the BMJ.
 

‘Work fast and hard’

Researchers assessed the association between workplace cognitive stimulation and dementia incidence in seven cohorts that included almost 108,000 men and women (mean age, 44.6 years). All were free of dementia at baseline.

Participants included civil servants, public sector employees, forestry workers, and others from the general working population.

Investigators separated the participants into three categories of workplace cognitive stimulation: “high,” which referred to both high job demand and high job control; “low,” which referred to low demands and low control; and “medium,” which referred to all other combinations of job demand and job control.

“Highly cognitively stimulating jobs require you to work fast and hard, learn new things, be creative, and have a high level of skill,” said Dr. Kivimäki.

The researchers controlled for low education, hypertension, smoking, obesity, depression, physical inactivity, diabetes, low social contact, excessive alcohol consumption, and traumatic brain injury. These represent 10 of the 12 dementia risk factors named by the 2020 Lancet Commission on Dementia Prevention as having convincing evidence, Dr. Kivimäki noted.

Although the investigators had no data on the other two risk factors of hearing loss and air pollution, these are unlikely to be confounding factors, he said.

Follow-up for incident dementia varied from 13.7 to 30.1 years, depending on the cohort, and was 16.7 years in the total patient population. The mean age at dementia onset was 71.2 years.
 

Benefits across the life course

Results showed that incident dementia per 10,000 person years was 7.3 in the low–cognitive stimulation group and 4.8 in the high-stimulation group, for a difference of 2.5.

“These differences were relatively small because the incidence of dementia in this relatively young population was low,” Dr. Kivimäki said.

Compared with those with low stimulation, the adjusted hazard ratio for dementia for this with high stimulation was 0.77 (95% CI, 0.65-0.92).

The results were similar for men and women, and for those younger and older than 60 years. However, the link between workplace cognitive stimulation appeared stronger for Alzheimer’s disease than for other dementias.

There also appeared to be additive effects of higher cognitive stimulation in both childhood, as indicated by higher educational attainment, and adulthood, based on work characteristics, said Dr. Kivimäki.

“These findings support the benefits of cognitive stimulation across the life course, with education leading to higher peak cognitive performance and cognitive stimulation at work lowering age-related cognitive decline,” he added.

The findings don’t seem to be the result of workers with cognitive impairment remaining in unchallenging jobs, he noted. Separate analyses showed lower dementia incidence even when 10 years or more separated the assessment of cognitive stimulation and the dementia diagnosis.

“This suggests that the findings are unlikely to be biased due to reverse causation,” Dr. Kivimäki said.
 

Possible mechanism

Findings were similar when the researchers assessed effect from job changes. “This is probably because people in highly stimulating jobs are more likely to change to another highly stimulating job than to a low-stimulating job,” said Dr. Kivimäki. “Similarly, people with less stimulating jobs are seldom able to change to a substantially more stimulating job.”

As a dementia risk factor, low workplace stimulation is comparable with high alcohol intake and physical inactivity, but is weaker than education, diabetes, smoking, hypertension, and obesity, Dr. Kivimäki noted.

When asked about individuals with less cognitively stimulating jobs who are enormously stimulated outside work, he said that “previous large-scale studies have failed to find evidence that leisure time cognitive activity would significantly reduce risk of dementia.”

To explore potential underlying mechanisms, the investigators examined almost 5,000 plasma proteins in more than 2,200 individuals from one cohort in the Whitehall II study. They found six proteins were significantly lower among participants with high versus low cognitive stimulation.

In another analysis that included more than 13,500 participants from the Whitehall and another cohort, higher levels of three of these plasma proteins were associated with increased dementia risk – or conversely, lower protein levels with lower dementia risk.

The findings suggest a “novel plausible explanation” for the link between workplace cognitive stimulation and dementia risk, said Dr. Kivimäki.

He noted that higher levels of certain proteins prevent brain cells from forming new connections.
 

‘Some of the most compelling evidence to date’

In an accompanying editorial, Serhiy Dekhtyar, PhD, assistant professor (Docent), Aging Research Center, Karolinska Institute, Stockholm, noted that the study is “an important piece of work” and “some of the most compelling evidence to date” on the role of occupational cognitive stimulation in dementia risk.

The large-scale investigation in multiple cohorts and contexts has “advanced the field” and could help “explain previously mixed findings in the literature,” Dekhtyar said in an interview.

Importantly, the researchers provide “an indication of biological mechanisms potentially connecting work mental stimulation and dementia,” he added.

However, Dr. Dekhtyar noted that the difference of 2.5 incident cases of dementia per 10,000 person years of follow-up between the low and high mental-stimulation groups “is not especially large” – although it is comparable with other established risk factors for dementia.

He suspects the effect size would have been larger had the follow-up for dementia been longer.

Dr. Dekhtyar also raised the possibility that “innate cognition” might affect both educational and occupational attainment, and the subsequent dementia risk.

“Without taking this into account, we may inadvertently conclude that education or occupational stimulation help differentially preserve cognition into late life – when in reality, it may be initial differences in cognitive ability that are preserved throughout life,” he concluded.

Funding sources for the study included Nordic Research Programme on Health and Welfare (NordForsk), Medical Research Council, Wellcome Trust, Academy of Finland, and Helsinki Institute of Life Science. Dr. Kivimäki has received support from NordForsk, the UK Medical Research Council, the Wellcome Trust, the Academy of Finland, and the Helsinki Institute of Life Science. Dr. Dekhtyar disclosed no relevant financial relationships.

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

Background: In the United States, CAP was responsible for nearly 50,000 deaths in 2017. Prompt and accurate diagnosis promotes early treatment and avoids unnecessary antibiotic treatment for nonpneumonia lower respiratory tract infection patients. Diagnosis is based on signs and symptoms, as well as available imaging. Inflammatory markers such as CRP, white blood cell count, and procalcitonin are readily available in the ED and outpatient settings.

The study had a some of limitations. The blinding of the person performing the index test to the reference standard and vice versa was not clear. Further, it was unclear if the person interpreting the reference standard was blinded to the index test in five studies and absent in one. Other limitations were inconsistent reporting of abnormal post hoc cutoffs and only two biomarkers being reported in a single study.

Combining a biomarker with signs and symptoms has the potential to improve diagnostic accuracy in the outpatient setting further. CRP was found to be most accurate regardless of the cutoff used; however, further studies without threshold effect will prove beneficial.

Bottom line: CRP is a more accurate and useful biomarker for outpatient CAP diagnosis than procalcitonin or leukocytosis.

Citation: Ebell MH et al. Accuracy of biomarkers for the diagnosis of adult community-acquired pneumonia: A meta-analysis. Acad Emerg Med. 2020;27(3):195-206.

Dr. Castellanos is a hospitalist and assistant professor of medicine at UK HealthCare, Lexington, Ky.

Background: In the United States, CAP was responsible for nearly 50,000 deaths in 2017. Prompt and accurate diagnosis promotes early treatment and avoids unnecessary antibiotic treatment for nonpneumonia lower respiratory tract infection patients. Diagnosis is based on signs and symptoms, as well as available imaging. Inflammatory markers such as CRP, white blood cell count, and procalcitonin are readily available in the ED and outpatient settings.

The study had a some of limitations. The blinding of the person performing the index test to the reference standard and vice versa was not clear. Further, it was unclear if the person interpreting the reference standard was blinded to the index test in five studies and absent in one. Other limitations were inconsistent reporting of abnormal post hoc cutoffs and only two biomarkers being reported in a single study.

Combining a biomarker with signs and symptoms has the potential to improve diagnostic accuracy in the outpatient setting further. CRP was found to be most accurate regardless of the cutoff used; however, further studies without threshold effect will prove beneficial.

Bottom line: CRP is a more accurate and useful biomarker for outpatient CAP diagnosis than procalcitonin or leukocytosis.

Citation: Ebell MH et al. Accuracy of biomarkers for the diagnosis of adult community-acquired pneumonia: A meta-analysis. Acad Emerg Med. 2020;27(3):195-206.

Dr. Castellanos is a hospitalist and assistant professor of medicine at UK HealthCare, Lexington, Ky.

Background: In the United States, CAP was responsible for nearly 50,000 deaths in 2017. Prompt and accurate diagnosis promotes early treatment and avoids unnecessary antibiotic treatment for nonpneumonia lower respiratory tract infection patients. Diagnosis is based on signs and symptoms, as well as available imaging. Inflammatory markers such as CRP, white blood cell count, and procalcitonin are readily available in the ED and outpatient settings.

The study had a some of limitations. The blinding of the person performing the index test to the reference standard and vice versa was not clear. Further, it was unclear if the person interpreting the reference standard was blinded to the index test in five studies and absent in one. Other limitations were inconsistent reporting of abnormal post hoc cutoffs and only two biomarkers being reported in a single study.

Combining a biomarker with signs and symptoms has the potential to improve diagnostic accuracy in the outpatient setting further. CRP was found to be most accurate regardless of the cutoff used; however, further studies without threshold effect will prove beneficial.

Bottom line: CRP is a more accurate and useful biomarker for outpatient CAP diagnosis than procalcitonin or leukocytosis.

Citation: Ebell MH et al. Accuracy of biomarkers for the diagnosis of adult community-acquired pneumonia: A meta-analysis. Acad Emerg Med. 2020;27(3):195-206.

Dr. Castellanos is a hospitalist and assistant professor of medicine at UK HealthCare, Lexington, Ky.

Paronychia and periungual pyogenic granulomas are the most common nail unit toxicities related to targeted cancer therapies and immunotherapies, while damage to other nail unit anatomic areas can be wide-ranging.

Those are key findings from an evidence-based literature review published on July 21, 2021, in the Journal of the American Academy of Dermatology, as a letter to the editor. “Dermatologic toxicities are often the earliest-presenting and highest-incidence adverse events due to targeted anticancer therapies and immunotherapies,” corresponding author Anisha B. Patel, MD, of the department of dermatology at the University of Texas MD Anderson Cancer Center, Houston, and colleagues wrote. “Nail unit toxicities due to immunotherapy are caused by nonspecific immune activation. Targeted therapies, particularly mitogen-activated protein kinase pathway inhibitors, lead to epidermal thinning of the nail folds and periungual tissue, increasing susceptibility to trauma and penetration by nail plate fragments. Although cutaneous toxicities have been well described, further characterization of nail unit toxicities is needed.”

The researchers searched the PubMed database using the terms nail, nail toxicity, nail dystrophy, paronychia, onycholysis, pyogenic granuloma, onychopathy, targeted therapy, and immunotherapy, and reviewed relevant articles for clinical presentation, diagnosis, incidence, outcomes, and references. They also proposed treatment algorithms for this patient population based on the existing literature and the authors’ collective clinical experience.

Dr. Patel and colleagues found that paronychia and periungual pyogenic granulomas were the most common nail unit toxicities caused by targeted therapy. “Damage to other nail unit anatomic areas includes drug induced or exacerbated lichen planus and psoriasis as well as pigmentary and neoplastic changes,” they wrote. “Onycholysis, onychoschizia, paronychia, psoriasis, lichen planus, and dermatomyositis have been reported with immune checkpoint inhibitors,” with the time of onset during the first week of treatment to several months after treatment has started.

According to National Cancer Institute criteria, nail adverse events associated with medical treatment include nail changes, discoloration, ridging, paronychia, and infection. The severity of nail loss, paronychia, and infection can be graded up to 3 (defined as “severe or medically significant but not life threatening”), while the remainder of nail toxicities may be categorized only as grade 1 (defined as “mild,” with “intervention not indicated”). “High-grade toxicities have been reported, especially with pan-fibroblast growth factor receptor inhibitors,” the authors wrote, referring to a previous study.

The review includes treatment algorithms for paronychia, periungual pyogenic granuloma, nail lichen planus, and psoriasis. “Long-acting and nonselective immunosuppressants are reserved for dose-limiting toxicities, given their unknown effects on already-immunosuppressed patients with cancer and on cancer therapy,” the authors wrote. “A discussion with the oncology department is essential before starting an immunomodulator or immunosuppressant.”

To manage onycholysis, Dr. Patel and colleagues recommended trimming the onycholytic nail plate to its attachment point. “Partial avulsion is used to treat a refractory abscess or painful hemorrhage,” they wrote. “A Pseudomonas superinfection is treated twice daily with a topical antibiotic solution. Brittle nail syndrome is managed with emollients or the application of polyureaurethane, a 16% nail solution, or a hydrosoluble nail lacquer,” they wrote, adding that biotin supplementation is not recommended.

Courtesy Dr. Jonathan Leventhal

Jonathan Leventhal, MD, who was asked to comment on the study, said that nail toxicity from targeted cancer therapy is one of the most common reasons for consultation in his role as director of the Yale University oncodermatology program at Smilow Cancer Hospital, New Haven, Conn. “When severe, these reactions frequently impact patients’ quality of life,” he said.

“This study is helpful for all dermatologists caring for cancer patients,” with strengths that include “succinctly summarizing the most prevalent conditions and providing a clear and practical algorithm for approaching these nail toxicities,” he said. In addition to targeted agents and immunotherapy, “we commonly see nail toxicities from cytotoxic chemotherapy, which was not reviewed in this paper. Multidisciplinary evaluation and dermatologic involvement is certainly beneficial to make accurate diagnoses and promptly manage these conditions, helping patients stay on their oncologic therapies.”

The researchers reported no financial disclosures. Dr. Leventhal disclosed that he is a member of the advisory board for Regeneron, Sanofi, Bristol-Myers Squibb, and La Roche–Posay. He has also received research funding from Azitra and OnQuality.
 

[email protected]

Paronychia and periungual pyogenic granulomas are the most common nail unit toxicities related to targeted cancer therapies and immunotherapies, while damage to other nail unit anatomic areas can be wide-ranging.

Those are key findings from an evidence-based literature review published on July 21, 2021, in the Journal of the American Academy of Dermatology, as a letter to the editor. “Dermatologic toxicities are often the earliest-presenting and highest-incidence adverse events due to targeted anticancer therapies and immunotherapies,” corresponding author Anisha B. Patel, MD, of the department of dermatology at the University of Texas MD Anderson Cancer Center, Houston, and colleagues wrote. “Nail unit toxicities due to immunotherapy are caused by nonspecific immune activation. Targeted therapies, particularly mitogen-activated protein kinase pathway inhibitors, lead to epidermal thinning of the nail folds and periungual tissue, increasing susceptibility to trauma and penetration by nail plate fragments. Although cutaneous toxicities have been well described, further characterization of nail unit toxicities is needed.”

The researchers searched the PubMed database using the terms nail, nail toxicity, nail dystrophy, paronychia, onycholysis, pyogenic granuloma, onychopathy, targeted therapy, and immunotherapy, and reviewed relevant articles for clinical presentation, diagnosis, incidence, outcomes, and references. They also proposed treatment algorithms for this patient population based on the existing literature and the authors’ collective clinical experience.

Dr. Patel and colleagues found that paronychia and periungual pyogenic granulomas were the most common nail unit toxicities caused by targeted therapy. “Damage to other nail unit anatomic areas includes drug induced or exacerbated lichen planus and psoriasis as well as pigmentary and neoplastic changes,” they wrote. “Onycholysis, onychoschizia, paronychia, psoriasis, lichen planus, and dermatomyositis have been reported with immune checkpoint inhibitors,” with the time of onset during the first week of treatment to several months after treatment has started.

According to National Cancer Institute criteria, nail adverse events associated with medical treatment include nail changes, discoloration, ridging, paronychia, and infection. The severity of nail loss, paronychia, and infection can be graded up to 3 (defined as “severe or medically significant but not life threatening”), while the remainder of nail toxicities may be categorized only as grade 1 (defined as “mild,” with “intervention not indicated”). “High-grade toxicities have been reported, especially with pan-fibroblast growth factor receptor inhibitors,” the authors wrote, referring to a previous study.

The review includes treatment algorithms for paronychia, periungual pyogenic granuloma, nail lichen planus, and psoriasis. “Long-acting and nonselective immunosuppressants are reserved for dose-limiting toxicities, given their unknown effects on already-immunosuppressed patients with cancer and on cancer therapy,” the authors wrote. “A discussion with the oncology department is essential before starting an immunomodulator or immunosuppressant.”

To manage onycholysis, Dr. Patel and colleagues recommended trimming the onycholytic nail plate to its attachment point. “Partial avulsion is used to treat a refractory abscess or painful hemorrhage,” they wrote. “A Pseudomonas superinfection is treated twice daily with a topical antibiotic solution. Brittle nail syndrome is managed with emollients or the application of polyureaurethane, a 16% nail solution, or a hydrosoluble nail lacquer,” they wrote, adding that biotin supplementation is not recommended.

Courtesy Dr. Jonathan Leventhal

Jonathan Leventhal, MD, who was asked to comment on the study, said that nail toxicity from targeted cancer therapy is one of the most common reasons for consultation in his role as director of the Yale University oncodermatology program at Smilow Cancer Hospital, New Haven, Conn. “When severe, these reactions frequently impact patients’ quality of life,” he said.

“This study is helpful for all dermatologists caring for cancer patients,” with strengths that include “succinctly summarizing the most prevalent conditions and providing a clear and practical algorithm for approaching these nail toxicities,” he said. In addition to targeted agents and immunotherapy, “we commonly see nail toxicities from cytotoxic chemotherapy, which was not reviewed in this paper. Multidisciplinary evaluation and dermatologic involvement is certainly beneficial to make accurate diagnoses and promptly manage these conditions, helping patients stay on their oncologic therapies.”

The researchers reported no financial disclosures. Dr. Leventhal disclosed that he is a member of the advisory board for Regeneron, Sanofi, Bristol-Myers Squibb, and La Roche–Posay. He has also received research funding from Azitra and OnQuality.
 

[email protected]

Paronychia and periungual pyogenic granulomas are the most common nail unit toxicities related to targeted cancer therapies and immunotherapies, while damage to other nail unit anatomic areas can be wide-ranging.

Those are key findings from an evidence-based literature review published on July 21, 2021, in the Journal of the American Academy of Dermatology, as a letter to the editor. “Dermatologic toxicities are often the earliest-presenting and highest-incidence adverse events due to targeted anticancer therapies and immunotherapies,” corresponding author Anisha B. Patel, MD, of the department of dermatology at the University of Texas MD Anderson Cancer Center, Houston, and colleagues wrote. “Nail unit toxicities due to immunotherapy are caused by nonspecific immune activation. Targeted therapies, particularly mitogen-activated protein kinase pathway inhibitors, lead to epidermal thinning of the nail folds and periungual tissue, increasing susceptibility to trauma and penetration by nail plate fragments. Although cutaneous toxicities have been well described, further characterization of nail unit toxicities is needed.”

The researchers searched the PubMed database using the terms nail, nail toxicity, nail dystrophy, paronychia, onycholysis, pyogenic granuloma, onychopathy, targeted therapy, and immunotherapy, and reviewed relevant articles for clinical presentation, diagnosis, incidence, outcomes, and references. They also proposed treatment algorithms for this patient population based on the existing literature and the authors’ collective clinical experience.

Dr. Patel and colleagues found that paronychia and periungual pyogenic granulomas were the most common nail unit toxicities caused by targeted therapy. “Damage to other nail unit anatomic areas includes drug induced or exacerbated lichen planus and psoriasis as well as pigmentary and neoplastic changes,” they wrote. “Onycholysis, onychoschizia, paronychia, psoriasis, lichen planus, and dermatomyositis have been reported with immune checkpoint inhibitors,” with the time of onset during the first week of treatment to several months after treatment has started.

According to National Cancer Institute criteria, nail adverse events associated with medical treatment include nail changes, discoloration, ridging, paronychia, and infection. The severity of nail loss, paronychia, and infection can be graded up to 3 (defined as “severe or medically significant but not life threatening”), while the remainder of nail toxicities may be categorized only as grade 1 (defined as “mild,” with “intervention not indicated”). “High-grade toxicities have been reported, especially with pan-fibroblast growth factor receptor inhibitors,” the authors wrote, referring to a previous study.

The review includes treatment algorithms for paronychia, periungual pyogenic granuloma, nail lichen planus, and psoriasis. “Long-acting and nonselective immunosuppressants are reserved for dose-limiting toxicities, given their unknown effects on already-immunosuppressed patients with cancer and on cancer therapy,” the authors wrote. “A discussion with the oncology department is essential before starting an immunomodulator or immunosuppressant.”

To manage onycholysis, Dr. Patel and colleagues recommended trimming the onycholytic nail plate to its attachment point. “Partial avulsion is used to treat a refractory abscess or painful hemorrhage,” they wrote. “A Pseudomonas superinfection is treated twice daily with a topical antibiotic solution. Brittle nail syndrome is managed with emollients or the application of polyureaurethane, a 16% nail solution, or a hydrosoluble nail lacquer,” they wrote, adding that biotin supplementation is not recommended.

Courtesy Dr. Jonathan Leventhal

Jonathan Leventhal, MD, who was asked to comment on the study, said that nail toxicity from targeted cancer therapy is one of the most common reasons for consultation in his role as director of the Yale University oncodermatology program at Smilow Cancer Hospital, New Haven, Conn. “When severe, these reactions frequently impact patients’ quality of life,” he said.

“This study is helpful for all dermatologists caring for cancer patients,” with strengths that include “succinctly summarizing the most prevalent conditions and providing a clear and practical algorithm for approaching these nail toxicities,” he said. In addition to targeted agents and immunotherapy, “we commonly see nail toxicities from cytotoxic chemotherapy, which was not reviewed in this paper. Multidisciplinary evaluation and dermatologic involvement is certainly beneficial to make accurate diagnoses and promptly manage these conditions, helping patients stay on their oncologic therapies.”

The researchers reported no financial disclosures. Dr. Leventhal disclosed that he is a member of the advisory board for Regeneron, Sanofi, Bristol-Myers Squibb, and La Roche–Posay. He has also received research funding from Azitra and OnQuality.
 

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The United States Preventive Services Task Force has updated its recommendation on the age of screening for prediabetes and type 2 diabetes in the primary care setting – lowering the age from 40 to 35 years for asymptomatic patients who are overweight or obese and encouraging greater interventions when patients do show a risk.

KatarzynaBialasiewicz/Thinkstock

“The USPSTF concludes with moderate certainty that screening for prediabetes and type 2 diabetes and offering or referring patients with prediabetes to effective preventive interventions has a moderate net benefit,” the task force concludes in its recommendation, published Aug. 24 in JAMA.

“Clinicians should offer or refer patients with prediabetes to effective preventive interventions,” they write.

Experts commenting on the issue strongly emphasize that it’s not just the screening, but the subsequent intervention that is needed to make a difference.

“If young adults newly identified with abnormal glucose metabolism do not receive the needed intensive behavioral change support, screening may provide no benefit,” write Richard W. Grant, MD, MPH, and colleagues in an editorial published with the recommendation.

“Given the role of our obesogenic and physically inactive society in the shift toward earlier onset of diabetes, efforts to increase screening and recognition of abnormal glucose metabolism must be coupled with robust public health measures to address the underlying contributors.”
 

BMI cutoff lower for at-risk ethnic populations

The recommendation, which updates the task force’s 2015 guideline, carries a “B” classification, meaning the USPSTF has high certainty that the net benefit is moderate. It now specifies screening from age 35to 70 for persons classified as overweight (body mass index at least 25) or obese (BMI at least 30) and recommends referral to preventive interventions when patients are found to have prediabetes.

In addition to recommendations of lifestyle changes, such as diet and physical activity, the task force also endorses the diabetes drug metformin as a beneficial intervention in the prevention or delay of diabetes, while noting fewer overall health benefits from metformin than from the lifestyle changes.

A lower BMI cutoff of at least 23 is recommended for diabetes screening of Asian Americans, and, importantly, screening for prediabetes and diabetes should be considered at an even earlier age if the patient is from a population with a disproportionately high prevalence of diabetes, including American Indian/Alaska Native, Black, Hawaiian/Pacific Islander, Hispanic/Latino, the task force recommends.

Screening tests should include fasting plasma glucose, hemoglobin A1c, or an oral glucose tolerance test. Although screening every 3 years “may be a reasonable approach for adults with normal blood glucose levels,” the task force adds that “the optimal screening interval for adults with an initial normal glucose test result is uncertain.”
 

Data review: Few with prediabetes know they have it

The need for the update was prompted by troubling data showing increasing diabetes rates despite early signs that can and should be identified and acted upon in the primary care setting to prevent disease progression.

Data from the Centers for Disease Control and Prevention, for instance, show that while 13% of all U.S. adults 18 years or older have diabetes and 35% meet criteria for prediabetes, as many as 21% of those with diabetes were not aware of or did not report having the disease. Furthermore, only a small fraction – 15% of those with prediabetes – said they had been told by a health professional that they had this condition, the task force notes.

The task force’s final recommendation was based on a systematic review of evidence regarding the screening of asymptomatic, nonpregnant adults and the harms and benefits of interventions, such as physical activity, behavioral counseling, or pharmacotherapy.

Among key evidence supporting the lower age was a 2014 study showing that the number of people necessary to obtain one positive test for diabetes with screening sharply drops from 80 among those aged 30-34 years to just 31 among those aged 36-39.

Opportunistic universal screening of eligible people aged 35 and older would yield a ratio of 1 out of just 15 to spot a positive test, the authors of that study reported.

In addition, a large cohort study in more than 77,000 people with prediabetes strongly links the risk of developing diabetes with increases in A1c level and with increasing BMI.
 

ADA recommendations differ

The new recommendations differ from American Diabetes Association guidelines, which call for diabetes screening at all ages for people who are overweight or obese and who have one or more risk factors, such as physical inactivity or a first-degree relative with diabetes. If results are normal, repeat screening at least every 3 years is recommended.

The ADA further recommends universal screening for all adults 45 years and older, regardless of their risk factors.

For the screening of adults over 45, the ADA recommends using a fasting plasma glucose level, 2-hour plasma glucose level during a 75-g oral glucose tolerance test, or A1c level, regardless of risk factors.

The American Association of Clinical Endocrinology also recommends universal screening for prediabetes and diabetes for all adults 45 years or older, regardless of risk factors, and also advises screening those who have risk factors for diabetes regardless of age.
 

Screening of little benefit without behavior change support

In an interview, Dr. Grant added that broad efforts are essential as those at the practice level have clearly not succeeded.

“The medical model of individual counseling and referral has not really been effective, and so we really need to think in terms of large-scale public health action,” said Dr. Grant, of the division of research, Kaiser Permanente Northern California, Oakland.

His editorial details the sweeping, multifactorial efforts that are needed.

“To turn this recommendation into action – that is, to translate screening activities into improved clinical outcomes – change is needed at the patient-clinician level (recognizing and encouraging eligible individuals to be screened), health care system level (reducing screening barriers and ensuring access to robust lifestyle programs), and societal level (applying effective public health interventions to reduce obesity and increase exercise),” they write.

A top priority has to be a focus on individuals of diverse backgrounds and issues such as access to healthy programs in minority communities, Dr. Grant noted.

“Newly diagnosed adults are more likely to be African-American and Latinx,” he said.

“We really need to invest in healthier communities for low-income, non-White communities to reverse the persistent health care disparities in these communities.”

While the challenges may appear daunting, history shows they are not necessarily insurmountable – as evidenced in the campaign to discourage tobacco smoking.

“National smoking cessation efforts are one example of a mostly successful public health campaign that has made a difference in health behaviors,” Grant noted.

The recommendation is also posted on the USPSTF web site .

Dr. Grant reports receiving grants from the National Institutes of Health and the Patient-Centered Outcomes Research Institute.

The United States Preventive Services Task Force has updated its recommendation on the age of screening for prediabetes and type 2 diabetes in the primary care setting – lowering the age from 40 to 35 years for asymptomatic patients who are overweight or obese and encouraging greater interventions when patients do show a risk.

KatarzynaBialasiewicz/Thinkstock

“The USPSTF concludes with moderate certainty that screening for prediabetes and type 2 diabetes and offering or referring patients with prediabetes to effective preventive interventions has a moderate net benefit,” the task force concludes in its recommendation, published Aug. 24 in JAMA.

“Clinicians should offer or refer patients with prediabetes to effective preventive interventions,” they write.

Experts commenting on the issue strongly emphasize that it’s not just the screening, but the subsequent intervention that is needed to make a difference.

“If young adults newly identified with abnormal glucose metabolism do not receive the needed intensive behavioral change support, screening may provide no benefit,” write Richard W. Grant, MD, MPH, and colleagues in an editorial published with the recommendation.

“Given the role of our obesogenic and physically inactive society in the shift toward earlier onset of diabetes, efforts to increase screening and recognition of abnormal glucose metabolism must be coupled with robust public health measures to address the underlying contributors.”
 

BMI cutoff lower for at-risk ethnic populations

The recommendation, which updates the task force’s 2015 guideline, carries a “B” classification, meaning the USPSTF has high certainty that the net benefit is moderate. It now specifies screening from age 35to 70 for persons classified as overweight (body mass index at least 25) or obese (BMI at least 30) and recommends referral to preventive interventions when patients are found to have prediabetes.

In addition to recommendations of lifestyle changes, such as diet and physical activity, the task force also endorses the diabetes drug metformin as a beneficial intervention in the prevention or delay of diabetes, while noting fewer overall health benefits from metformin than from the lifestyle changes.

A lower BMI cutoff of at least 23 is recommended for diabetes screening of Asian Americans, and, importantly, screening for prediabetes and diabetes should be considered at an even earlier age if the patient is from a population with a disproportionately high prevalence of diabetes, including American Indian/Alaska Native, Black, Hawaiian/Pacific Islander, Hispanic/Latino, the task force recommends.

Screening tests should include fasting plasma glucose, hemoglobin A1c, or an oral glucose tolerance test. Although screening every 3 years “may be a reasonable approach for adults with normal blood glucose levels,” the task force adds that “the optimal screening interval for adults with an initial normal glucose test result is uncertain.”
 

Data review: Few with prediabetes know they have it

The need for the update was prompted by troubling data showing increasing diabetes rates despite early signs that can and should be identified and acted upon in the primary care setting to prevent disease progression.

Data from the Centers for Disease Control and Prevention, for instance, show that while 13% of all U.S. adults 18 years or older have diabetes and 35% meet criteria for prediabetes, as many as 21% of those with diabetes were not aware of or did not report having the disease. Furthermore, only a small fraction – 15% of those with prediabetes – said they had been told by a health professional that they had this condition, the task force notes.

The task force’s final recommendation was based on a systematic review of evidence regarding the screening of asymptomatic, nonpregnant adults and the harms and benefits of interventions, such as physical activity, behavioral counseling, or pharmacotherapy.

Among key evidence supporting the lower age was a 2014 study showing that the number of people necessary to obtain one positive test for diabetes with screening sharply drops from 80 among those aged 30-34 years to just 31 among those aged 36-39.

Opportunistic universal screening of eligible people aged 35 and older would yield a ratio of 1 out of just 15 to spot a positive test, the authors of that study reported.

In addition, a large cohort study in more than 77,000 people with prediabetes strongly links the risk of developing diabetes with increases in A1c level and with increasing BMI.
 

ADA recommendations differ

The new recommendations differ from American Diabetes Association guidelines, which call for diabetes screening at all ages for people who are overweight or obese and who have one or more risk factors, such as physical inactivity or a first-degree relative with diabetes. If results are normal, repeat screening at least every 3 years is recommended.

The ADA further recommends universal screening for all adults 45 years and older, regardless of their risk factors.

For the screening of adults over 45, the ADA recommends using a fasting plasma glucose level, 2-hour plasma glucose level during a 75-g oral glucose tolerance test, or A1c level, regardless of risk factors.

The American Association of Clinical Endocrinology also recommends universal screening for prediabetes and diabetes for all adults 45 years or older, regardless of risk factors, and also advises screening those who have risk factors for diabetes regardless of age.
 

Screening of little benefit without behavior change support

In an interview, Dr. Grant added that broad efforts are essential as those at the practice level have clearly not succeeded.

“The medical model of individual counseling and referral has not really been effective, and so we really need to think in terms of large-scale public health action,” said Dr. Grant, of the division of research, Kaiser Permanente Northern California, Oakland.

His editorial details the sweeping, multifactorial efforts that are needed.

“To turn this recommendation into action – that is, to translate screening activities into improved clinical outcomes – change is needed at the patient-clinician level (recognizing and encouraging eligible individuals to be screened), health care system level (reducing screening barriers and ensuring access to robust lifestyle programs), and societal level (applying effective public health interventions to reduce obesity and increase exercise),” they write.

A top priority has to be a focus on individuals of diverse backgrounds and issues such as access to healthy programs in minority communities, Dr. Grant noted.

“Newly diagnosed adults are more likely to be African-American and Latinx,” he said.

“We really need to invest in healthier communities for low-income, non-White communities to reverse the persistent health care disparities in these communities.”

While the challenges may appear daunting, history shows they are not necessarily insurmountable – as evidenced in the campaign to discourage tobacco smoking.

“National smoking cessation efforts are one example of a mostly successful public health campaign that has made a difference in health behaviors,” Grant noted.

The recommendation is also posted on the USPSTF web site .

Dr. Grant reports receiving grants from the National Institutes of Health and the Patient-Centered Outcomes Research Institute.

The United States Preventive Services Task Force has updated its recommendation on the age of screening for prediabetes and type 2 diabetes in the primary care setting – lowering the age from 40 to 35 years for asymptomatic patients who are overweight or obese and encouraging greater interventions when patients do show a risk.

KatarzynaBialasiewicz/Thinkstock

“The USPSTF concludes with moderate certainty that screening for prediabetes and type 2 diabetes and offering or referring patients with prediabetes to effective preventive interventions has a moderate net benefit,” the task force concludes in its recommendation, published Aug. 24 in JAMA.

“Clinicians should offer or refer patients with prediabetes to effective preventive interventions,” they write.

Experts commenting on the issue strongly emphasize that it’s not just the screening, but the subsequent intervention that is needed to make a difference.

“If young adults newly identified with abnormal glucose metabolism do not receive the needed intensive behavioral change support, screening may provide no benefit,” write Richard W. Grant, MD, MPH, and colleagues in an editorial published with the recommendation.

“Given the role of our obesogenic and physically inactive society in the shift toward earlier onset of diabetes, efforts to increase screening and recognition of abnormal glucose metabolism must be coupled with robust public health measures to address the underlying contributors.”
 

BMI cutoff lower for at-risk ethnic populations

The recommendation, which updates the task force’s 2015 guideline, carries a “B” classification, meaning the USPSTF has high certainty that the net benefit is moderate. It now specifies screening from age 35to 70 for persons classified as overweight (body mass index at least 25) or obese (BMI at least 30) and recommends referral to preventive interventions when patients are found to have prediabetes.

In addition to recommendations of lifestyle changes, such as diet and physical activity, the task force also endorses the diabetes drug metformin as a beneficial intervention in the prevention or delay of diabetes, while noting fewer overall health benefits from metformin than from the lifestyle changes.

A lower BMI cutoff of at least 23 is recommended for diabetes screening of Asian Americans, and, importantly, screening for prediabetes and diabetes should be considered at an even earlier age if the patient is from a population with a disproportionately high prevalence of diabetes, including American Indian/Alaska Native, Black, Hawaiian/Pacific Islander, Hispanic/Latino, the task force recommends.

Screening tests should include fasting plasma glucose, hemoglobin A1c, or an oral glucose tolerance test. Although screening every 3 years “may be a reasonable approach for adults with normal blood glucose levels,” the task force adds that “the optimal screening interval for adults with an initial normal glucose test result is uncertain.”
 

Data review: Few with prediabetes know they have it

The need for the update was prompted by troubling data showing increasing diabetes rates despite early signs that can and should be identified and acted upon in the primary care setting to prevent disease progression.

Data from the Centers for Disease Control and Prevention, for instance, show that while 13% of all U.S. adults 18 years or older have diabetes and 35% meet criteria for prediabetes, as many as 21% of those with diabetes were not aware of or did not report having the disease. Furthermore, only a small fraction – 15% of those with prediabetes – said they had been told by a health professional that they had this condition, the task force notes.

The task force’s final recommendation was based on a systematic review of evidence regarding the screening of asymptomatic, nonpregnant adults and the harms and benefits of interventions, such as physical activity, behavioral counseling, or pharmacotherapy.

Among key evidence supporting the lower age was a 2014 study showing that the number of people necessary to obtain one positive test for diabetes with screening sharply drops from 80 among those aged 30-34 years to just 31 among those aged 36-39.

Opportunistic universal screening of eligible people aged 35 and older would yield a ratio of 1 out of just 15 to spot a positive test, the authors of that study reported.

In addition, a large cohort study in more than 77,000 people with prediabetes strongly links the risk of developing diabetes with increases in A1c level and with increasing BMI.
 

ADA recommendations differ

The new recommendations differ from American Diabetes Association guidelines, which call for diabetes screening at all ages for people who are overweight or obese and who have one or more risk factors, such as physical inactivity or a first-degree relative with diabetes. If results are normal, repeat screening at least every 3 years is recommended.

The ADA further recommends universal screening for all adults 45 years and older, regardless of their risk factors.

For the screening of adults over 45, the ADA recommends using a fasting plasma glucose level, 2-hour plasma glucose level during a 75-g oral glucose tolerance test, or A1c level, regardless of risk factors.

The American Association of Clinical Endocrinology also recommends universal screening for prediabetes and diabetes for all adults 45 years or older, regardless of risk factors, and also advises screening those who have risk factors for diabetes regardless of age.
 

Screening of little benefit without behavior change support

In an interview, Dr. Grant added that broad efforts are essential as those at the practice level have clearly not succeeded.

“The medical model of individual counseling and referral has not really been effective, and so we really need to think in terms of large-scale public health action,” said Dr. Grant, of the division of research, Kaiser Permanente Northern California, Oakland.

His editorial details the sweeping, multifactorial efforts that are needed.

“To turn this recommendation into action – that is, to translate screening activities into improved clinical outcomes – change is needed at the patient-clinician level (recognizing and encouraging eligible individuals to be screened), health care system level (reducing screening barriers and ensuring access to robust lifestyle programs), and societal level (applying effective public health interventions to reduce obesity and increase exercise),” they write.

A top priority has to be a focus on individuals of diverse backgrounds and issues such as access to healthy programs in minority communities, Dr. Grant noted.

“Newly diagnosed adults are more likely to be African-American and Latinx,” he said.

“We really need to invest in healthier communities for low-income, non-White communities to reverse the persistent health care disparities in these communities.”

While the challenges may appear daunting, history shows they are not necessarily insurmountable – as evidenced in the campaign to discourage tobacco smoking.

“National smoking cessation efforts are one example of a mostly successful public health campaign that has made a difference in health behaviors,” Grant noted.

The recommendation is also posted on the USPSTF web site .

Dr. Grant reports receiving grants from the National Institutes of Health and the Patient-Centered Outcomes Research Institute.

The Diagnosis: Generalized Bullous Fixed Drug Eruption

A punch biopsy from the left thigh revealed a vacuolar interface dermatitis with full-thickness necrosis of the epidermis and a patchy lichenoid inflammatory cell infiltrate in the superficial dermis consistent with a generalized bullous fixed drug eruption (GBFDE). The patient received supportive care and methylprednisolone with improvement of symptoms.

Generalized bullous fixed drug eruption is a rare, potentially life-threatening form of a fixed drug eruption (FDE), a cutaneous drug reaction that occurs in response to a causative medication. It typically presents with welldemarcated, dusky, erythematous patches or plaques that recur in the same sites with repeat exposure.¹ The pathogenesis of FDE has been hypothesized to involve epidermal CD8+ T cells, which are activated by drug exposure and release cytotoxic molecules including Fas, Fas ligand, perforin, and granzyme B, resulting in lysis of the surrounding keratinocytes.^1-3 Common eliciting drugs include nonsteroidal anti-inflammatory drugs, antibacterial agents (particularly trimethoprim-sulfamethoxazole), barbiturates, acetaminophen, and antimalarials.1 In addition to the findings seen in FDE, GBFDE is characterized by widespread bullous skin lesions.^1-4 Typical histologic patterns seen in GBFDE are dispersed epidermal apoptotic keratinocytes, prominent dermal eosinophilic and lymphocytic infiltrates, and dermal melanophages.³ Discontinuing the causative agent and diligent prevention of re-exposure are the most important steps in management, as additional exposures can increase the number of lesions and overall severity. Symptoms typically resolve 7 to 14 days after drug discontinuation, often with postinflammatory hyperpigmentation.³

Generalized bullous fixed drug eruption presents a diagnostic challenge, as it sometimes involves the oral mucosa and can exhibit the Nikolsky sign. Thus, it often is confused with Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN).^1,4 Stevens-Johnson syndrome and TEN are severe cutaneous drug eruptions that also can present with diffuse bullous skin lesions. Stevens-Johnson syndrome and TEN are thought to be a spectrum of the same disease that initially presents with dusky red macules that can coalesce, develop central blistering, and lead to skin detachment.⁵ Stevens-Johnson syndrome is defined as skin detachment of less than 10% body surface area (BSA); TEN is defined as skin detachment of more than 30% BSA. Stevens-Johnson syndrome/TEN overlap syndrome includes skin detachment of 10% to 30% BSA.⁵

Causative medications overlap substantially with GBFDE and include anticonvulsants, sulfa-containing drugs, antibiotics, nonsteroidal anti-inflammatory drugs, and uric acid–lowering agents. The histology of SJS/TEN also is quite similar to GBFDE, and these entities may be indistinguishable without clinical information.⁵ Lee et al¹ found that absence of grouped necrotic keratinocytes (fire flag sign), deep inflammatory infiltrates, notable pigment incontinence, and higher eosinophil counts appear to be more common in GBFDE than SJS/TEN. Constitutional symptoms and mucosal involvement also were more frequent in SJS/TEN.

The timing of clinical presentation and medical history can be useful in differentiating between SJS/TEN and GBFDE. In SJS/TEN, drug exposure typically occurs 1 to 3 weeks before onset of symptoms vs 30 minutes to 24 hours in GBFDE.³ Additionally, a history of similar eruption in the same location is pathognomonic for GBFDE. Although GBFDE has been thought to have a better prognosis than SJS/TEN, more recent data suggest mortality rates may be similar.³ A case-control study found a mortality rate of 22% (13/58) in patients with GBFDE compared to 28% (n=170) in SJS/TEN patients.⁴

Erythema multiforme (EM) is an uncommon immunemediated disorder that typically presents as targetoid lesions with central epidermal necrosis in an acral distribution. Erythema multiforme can arise from a variety of factors, but up to 90% of cases are due to infection, most commonly herpes simplex virus; medications account for less than 10% of cases.⁶ Previously, EM has been thought to be on the same disease spectrum as SJS and TEN. It is now clear that EM is a separate entity with similar mucosal erosions but different cutaneous findings,⁶ mainly typical target lesions that differ from the atypical targets seen in SJS.

Staphylococcal scalded skin syndrome is a blistering skin disorder associated with local Staphylococcus aureus infection. It most commonly is seen in children and rarely occurs in adults who are not on dialysis. Some Staphylococcus strains produce exfoliative toxins A and B, which are serine proteases that target and cleave desmoglein 1, a mediator of keratinocyte adhesion. Staphylococcal scalded skin syndrome initially presents with erythema accentuated in the skin folds that becomes generalized. The disruption of keratinocyte adhesion leads to bullae formation in areas of erythema and diffuse sheetlike desquamation. Pathology reveals subcorneal rather than subepidermal blistering, which is seen in GBFDE and SJS/TEN. Treatment involves antistaphylococcal antibiotics and supportive care. With proper treatment, most cases resolve within 2 to 3 weeks.⁷

Mycoplasma pneumoniae–induced rash and mucositis presents with prominent mucositis and can have cutaneous findings of sparse vesiculobullous or targetoid eruption.⁸Mycoplasma pneumoniae typically infects the lungs and is a leading cause of community-acquired pneumonia. However, a subset of patients can have extrapulmonary disease presenting as mucocutaneous eruptions, which is preceded by an approximately weeklong prodrome of fever, cough, and malaise.⁷Mycoplasma pneumoniae–induced rash and mucositis also affect children and young patients and is more common in males.⁸

The Diagnosis: Generalized Bullous Fixed Drug Eruption

A punch biopsy from the left thigh revealed a vacuolar interface dermatitis with full-thickness necrosis of the epidermis and a patchy lichenoid inflammatory cell infiltrate in the superficial dermis consistent with a generalized bullous fixed drug eruption (GBFDE). The patient received supportive care and methylprednisolone with improvement of symptoms.

Generalized bullous fixed drug eruption is a rare, potentially life-threatening form of a fixed drug eruption (FDE), a cutaneous drug reaction that occurs in response to a causative medication. It typically presents with welldemarcated, dusky, erythematous patches or plaques that recur in the same sites with repeat exposure.¹ The pathogenesis of FDE has been hypothesized to involve epidermal CD8+ T cells, which are activated by drug exposure and release cytotoxic molecules including Fas, Fas ligand, perforin, and granzyme B, resulting in lysis of the surrounding keratinocytes.^1-3 Common eliciting drugs include nonsteroidal anti-inflammatory drugs, antibacterial agents (particularly trimethoprim-sulfamethoxazole), barbiturates, acetaminophen, and antimalarials.1 In addition to the findings seen in FDE, GBFDE is characterized by widespread bullous skin lesions.^1-4 Typical histologic patterns seen in GBFDE are dispersed epidermal apoptotic keratinocytes, prominent dermal eosinophilic and lymphocytic infiltrates, and dermal melanophages.³ Discontinuing the causative agent and diligent prevention of re-exposure are the most important steps in management, as additional exposures can increase the number of lesions and overall severity. Symptoms typically resolve 7 to 14 days after drug discontinuation, often with postinflammatory hyperpigmentation.³

Generalized bullous fixed drug eruption presents a diagnostic challenge, as it sometimes involves the oral mucosa and can exhibit the Nikolsky sign. Thus, it often is confused with Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN).^1,4 Stevens-Johnson syndrome and TEN are severe cutaneous drug eruptions that also can present with diffuse bullous skin lesions. Stevens-Johnson syndrome and TEN are thought to be a spectrum of the same disease that initially presents with dusky red macules that can coalesce, develop central blistering, and lead to skin detachment.⁵ Stevens-Johnson syndrome is defined as skin detachment of less than 10% body surface area (BSA); TEN is defined as skin detachment of more than 30% BSA. Stevens-Johnson syndrome/TEN overlap syndrome includes skin detachment of 10% to 30% BSA.⁵

Causative medications overlap substantially with GBFDE and include anticonvulsants, sulfa-containing drugs, antibiotics, nonsteroidal anti-inflammatory drugs, and uric acid–lowering agents. The histology of SJS/TEN also is quite similar to GBFDE, and these entities may be indistinguishable without clinical information.⁵ Lee et al¹ found that absence of grouped necrotic keratinocytes (fire flag sign), deep inflammatory infiltrates, notable pigment incontinence, and higher eosinophil counts appear to be more common in GBFDE than SJS/TEN. Constitutional symptoms and mucosal involvement also were more frequent in SJS/TEN.

The timing of clinical presentation and medical history can be useful in differentiating between SJS/TEN and GBFDE. In SJS/TEN, drug exposure typically occurs 1 to 3 weeks before onset of symptoms vs 30 minutes to 24 hours in GBFDE.³ Additionally, a history of similar eruption in the same location is pathognomonic for GBFDE. Although GBFDE has been thought to have a better prognosis than SJS/TEN, more recent data suggest mortality rates may be similar.³ A case-control study found a mortality rate of 22% (13/58) in patients with GBFDE compared to 28% (n=170) in SJS/TEN patients.⁴

Erythema multiforme (EM) is an uncommon immunemediated disorder that typically presents as targetoid lesions with central epidermal necrosis in an acral distribution. Erythema multiforme can arise from a variety of factors, but up to 90% of cases are due to infection, most commonly herpes simplex virus; medications account for less than 10% of cases.⁶ Previously, EM has been thought to be on the same disease spectrum as SJS and TEN. It is now clear that EM is a separate entity with similar mucosal erosions but different cutaneous findings,⁶ mainly typical target lesions that differ from the atypical targets seen in SJS.

Staphylococcal scalded skin syndrome is a blistering skin disorder associated with local Staphylococcus aureus infection. It most commonly is seen in children and rarely occurs in adults who are not on dialysis. Some Staphylococcus strains produce exfoliative toxins A and B, which are serine proteases that target and cleave desmoglein 1, a mediator of keratinocyte adhesion. Staphylococcal scalded skin syndrome initially presents with erythema accentuated in the skin folds that becomes generalized. The disruption of keratinocyte adhesion leads to bullae formation in areas of erythema and diffuse sheetlike desquamation. Pathology reveals subcorneal rather than subepidermal blistering, which is seen in GBFDE and SJS/TEN. Treatment involves antistaphylococcal antibiotics and supportive care. With proper treatment, most cases resolve within 2 to 3 weeks.⁷

Mycoplasma pneumoniae–induced rash and mucositis presents with prominent mucositis and can have cutaneous findings of sparse vesiculobullous or targetoid eruption.⁸Mycoplasma pneumoniae typically infects the lungs and is a leading cause of community-acquired pneumonia. However, a subset of patients can have extrapulmonary disease presenting as mucocutaneous eruptions, which is preceded by an approximately weeklong prodrome of fever, cough, and malaise.⁷Mycoplasma pneumoniae–induced rash and mucositis also affect children and young patients and is more common in males.⁸

The Diagnosis: Generalized Bullous Fixed Drug Eruption

A punch biopsy from the left thigh revealed a vacuolar interface dermatitis with full-thickness necrosis of the epidermis and a patchy lichenoid inflammatory cell infiltrate in the superficial dermis consistent with a generalized bullous fixed drug eruption (GBFDE). The patient received supportive care and methylprednisolone with improvement of symptoms.

Generalized bullous fixed drug eruption is a rare, potentially life-threatening form of a fixed drug eruption (FDE), a cutaneous drug reaction that occurs in response to a causative medication. It typically presents with welldemarcated, dusky, erythematous patches or plaques that recur in the same sites with repeat exposure.¹ The pathogenesis of FDE has been hypothesized to involve epidermal CD8+ T cells, which are activated by drug exposure and release cytotoxic molecules including Fas, Fas ligand, perforin, and granzyme B, resulting in lysis of the surrounding keratinocytes.^1-3 Common eliciting drugs include nonsteroidal anti-inflammatory drugs, antibacterial agents (particularly trimethoprim-sulfamethoxazole), barbiturates, acetaminophen, and antimalarials.1 In addition to the findings seen in FDE, GBFDE is characterized by widespread bullous skin lesions.^1-4 Typical histologic patterns seen in GBFDE are dispersed epidermal apoptotic keratinocytes, prominent dermal eosinophilic and lymphocytic infiltrates, and dermal melanophages.³ Discontinuing the causative agent and diligent prevention of re-exposure are the most important steps in management, as additional exposures can increase the number of lesions and overall severity. Symptoms typically resolve 7 to 14 days after drug discontinuation, often with postinflammatory hyperpigmentation.³

Generalized bullous fixed drug eruption presents a diagnostic challenge, as it sometimes involves the oral mucosa and can exhibit the Nikolsky sign. Thus, it often is confused with Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN).^1,4 Stevens-Johnson syndrome and TEN are severe cutaneous drug eruptions that also can present with diffuse bullous skin lesions. Stevens-Johnson syndrome and TEN are thought to be a spectrum of the same disease that initially presents with dusky red macules that can coalesce, develop central blistering, and lead to skin detachment.⁵ Stevens-Johnson syndrome is defined as skin detachment of less than 10% body surface area (BSA); TEN is defined as skin detachment of more than 30% BSA. Stevens-Johnson syndrome/TEN overlap syndrome includes skin detachment of 10% to 30% BSA.⁵

Causative medications overlap substantially with GBFDE and include anticonvulsants, sulfa-containing drugs, antibiotics, nonsteroidal anti-inflammatory drugs, and uric acid–lowering agents. The histology of SJS/TEN also is quite similar to GBFDE, and these entities may be indistinguishable without clinical information.⁵ Lee et al¹ found that absence of grouped necrotic keratinocytes (fire flag sign), deep inflammatory infiltrates, notable pigment incontinence, and higher eosinophil counts appear to be more common in GBFDE than SJS/TEN. Constitutional symptoms and mucosal involvement also were more frequent in SJS/TEN.

The timing of clinical presentation and medical history can be useful in differentiating between SJS/TEN and GBFDE. In SJS/TEN, drug exposure typically occurs 1 to 3 weeks before onset of symptoms vs 30 minutes to 24 hours in GBFDE.³ Additionally, a history of similar eruption in the same location is pathognomonic for GBFDE. Although GBFDE has been thought to have a better prognosis than SJS/TEN, more recent data suggest mortality rates may be similar.³ A case-control study found a mortality rate of 22% (13/58) in patients with GBFDE compared to 28% (n=170) in SJS/TEN patients.⁴

Erythema multiforme (EM) is an uncommon immunemediated disorder that typically presents as targetoid lesions with central epidermal necrosis in an acral distribution. Erythema multiforme can arise from a variety of factors, but up to 90% of cases are due to infection, most commonly herpes simplex virus; medications account for less than 10% of cases.⁶ Previously, EM has been thought to be on the same disease spectrum as SJS and TEN. It is now clear that EM is a separate entity with similar mucosal erosions but different cutaneous findings,⁶ mainly typical target lesions that differ from the atypical targets seen in SJS.

Staphylococcal scalded skin syndrome is a blistering skin disorder associated with local Staphylococcus aureus infection. It most commonly is seen in children and rarely occurs in adults who are not on dialysis. Some Staphylococcus strains produce exfoliative toxins A and B, which are serine proteases that target and cleave desmoglein 1, a mediator of keratinocyte adhesion. Staphylococcal scalded skin syndrome initially presents with erythema accentuated in the skin folds that becomes generalized. The disruption of keratinocyte adhesion leads to bullae formation in areas of erythema and diffuse sheetlike desquamation. Pathology reveals subcorneal rather than subepidermal blistering, which is seen in GBFDE and SJS/TEN. Treatment involves antistaphylococcal antibiotics and supportive care. With proper treatment, most cases resolve within 2 to 3 weeks.⁷

Mycoplasma pneumoniae–induced rash and mucositis presents with prominent mucositis and can have cutaneous findings of sparse vesiculobullous or targetoid eruption.⁸Mycoplasma pneumoniae typically infects the lungs and is a leading cause of community-acquired pneumonia. However, a subset of patients can have extrapulmonary disease presenting as mucocutaneous eruptions, which is preceded by an approximately weeklong prodrome of fever, cough, and malaise.⁷Mycoplasma pneumoniae–induced rash and mucositis also affect children and young patients and is more common in males.⁸

Pregnant women who experience migraine with aura – and also the far more common tension-type headache – are at increased risk for giving birth to small-for-gestational-age babies, according to results from an observational study.

Migraine during pregnancy has been associated in previous studies with hypertensive pregnancy complications including preeclampsia; however, little is known about other headache types and their effects on pregnancy and birth outcomes.

For their research, published online July 20 in Cephalalgia, Isabella Neri, MD, PhD, and colleagues at Hospital Policlinico of Modena, Italy, looked at headache status for 515 consecutive pregnant women evaluated during their first trimester and followed through childbirth. 

Altogether 224 women, or 43.5% of the cohort, were diagnosed with migraine without aura (n = 72), migraine with aura (n = 27), or tension-type headache (n = 125). The authors did not report on the severity or frequency of headaches.

Women with migraine with aura and tension-type headache saw higher rates of small-for-gestational-age infants (25.9% and 10.4% of births, respectively) compared with 5.5% for women without headache. Women presenting with tension-type headache saw elevated risk for small-for-gestational-age infants (odds ratio [OR] 4.19, P = .004) as did women with migraine with aura (OR 5.37, P = .02).

Admission to neonatal intensive care was significantly higher in all the headache groups. However, the authors found no statistically significant associations between headaches and any other perinatal outcome investigated in the study, including gestational diabetes, placental abruption, gestational hypertension, and preterm delivery.

A previous study conducted by the same research group had reported a relationship between migraine and gestational hypertension. The authors cited the small sample size of the migraine groups in the current study, “the diverse features of the population,” and the popularity of low-dose aspirin administration as potentially affecting that outcome.
 

Interpret findings with caution

Asked by this news organization to comment on the research, two headache neurologists praised Dr. Neri and colleagues’ research for focusing on an understudied topic – but also said that the results would not change their practice unless replicated in larger studies.

Elizabeth W. Loder, MD, MPH, chief emeritus of the division of headache at Brigham and Women’s Faulkner Hospital in Boston, urged caution in interpreting the findings, particularly with regard to tension-type headache. “This study adds to information suggesting that pregnancy complications probably are higher in women who have migraine with aura, and there’s biological plausibility for that,” Dr. Loder said. “Having aura means you may have some vascular abnormalities and things that logically might be associated with an increased risk of small-for-gestational age infants.” But the small size of the migraine-with-aura group in this study – 27 women – and the fact that other perinatal outcomes measured in the study did not reach significance, allows for the possibility that the small-for-gestational-age findings were due to chance, Dr. Loder noted.

With tension-type headache, a biological rationale for small-for-gestational-age risk is more elusive, Dr. Loder said. “I would want to see that association replicated in another study before I thought that I needed to warn women with tension-type headache about this potential outcome. There’s lot of uncertainty here about the magnitude of the risk.”

While Dr. Neri and colleagues described the instruments used in their study to diagnose migraine and migraine with aura, they did not explain how tension-type headache was diagnosed. 

Tension-type headache, while common, is still not well characterized, Dr. Loder noted, and may represent a heterogeneous condition or the milder end of a biological continuum that includes migraine with aura. Also, the group in the study had a higher prevalence of smoking, and though the authors made statistical adjustments for smoking status, “smokers are systematically different than people who aren’t in other ways that could be associated with these outcomes,” Dr. Loder said.

While the authors of the study suggested that interventions might be indicated for women with tension-type headache in pregnancy, “showing an association doesn’t necessarily mean that intervening would make a difference” on pregnancy outcomes, Dr. Loder said.

Amaal J. Starling, MD, of the Mayo Clinic in Phoenix, Ariz., said in an interview that she, too, appreciated that this study looked at pregnancy outcomes in the setting of headache disorders. “Unfortunately even though headache disorders and especially migraine affect women so much, we still know very little about migraine in pregnancy,” she said.

Dr. Starling noted that many women with migraine are discouraged by their health care providers from becoming pregnant, because of the false belief that migraine cannot be managed in pregnancy. In her own practice, she said, she treats many patients with severe headache who become pregnant and who require pharmacological intervention during pregnancy.

This does not mean she regards headache in pregnancy as innocent. “I want patients to be on high alert for changes in headache symptoms in pregnancy. If someone has worsening of headache or migraine or aura in the setting of pregnancy, we consider that a red flag,” potentially indicating complications such as high blood pressure, gestational hypertension, or a blood clot.

Like Dr. Loder, Dr. Starling said she was not surprised by Dr. Neri and colleagues’ finding that migraine with aura might impact pregnancy outcomes. “We know that migraine with aura has a lot of vascular abnormalities that underlie the pathogenesis,” she said.

Dr. Starling found the findings related to tension-type headache less convincing, not least because the diagnostic criteria for tension-type headache was not made clear in the study. “I view this as an exploratory study that says maybe there’s a signal here. A larger epidemiological study would need to be done to confirm or refute this data,” Dr. Starling said. Until the findings can be replicated, “this study would not affect my clinical practice in any way.”

Dr. Neri and colleagues described no outside funding for their research or financial conflicts of interest. Dr. Starling has received consulting fees from pharmaceutical manufacturers but reported no disclosures relevant to the study discussed. Dr. Loder reported no financial conflicts of interest.

Pregnant women who experience migraine with aura – and also the far more common tension-type headache – are at increased risk for giving birth to small-for-gestational-age babies, according to results from an observational study.

Migraine during pregnancy has been associated in previous studies with hypertensive pregnancy complications including preeclampsia; however, little is known about other headache types and their effects on pregnancy and birth outcomes.

For their research, published online July 20 in Cephalalgia, Isabella Neri, MD, PhD, and colleagues at Hospital Policlinico of Modena, Italy, looked at headache status for 515 consecutive pregnant women evaluated during their first trimester and followed through childbirth. 

Altogether 224 women, or 43.5% of the cohort, were diagnosed with migraine without aura (n = 72), migraine with aura (n = 27), or tension-type headache (n = 125). The authors did not report on the severity or frequency of headaches.

Women with migraine with aura and tension-type headache saw higher rates of small-for-gestational-age infants (25.9% and 10.4% of births, respectively) compared with 5.5% for women without headache. Women presenting with tension-type headache saw elevated risk for small-for-gestational-age infants (odds ratio [OR] 4.19, P = .004) as did women with migraine with aura (OR 5.37, P = .02).

Admission to neonatal intensive care was significantly higher in all the headache groups. However, the authors found no statistically significant associations between headaches and any other perinatal outcome investigated in the study, including gestational diabetes, placental abruption, gestational hypertension, and preterm delivery.

A previous study conducted by the same research group had reported a relationship between migraine and gestational hypertension. The authors cited the small sample size of the migraine groups in the current study, “the diverse features of the population,” and the popularity of low-dose aspirin administration as potentially affecting that outcome.
 

Interpret findings with caution

Asked by this news organization to comment on the research, two headache neurologists praised Dr. Neri and colleagues’ research for focusing on an understudied topic – but also said that the results would not change their practice unless replicated in larger studies.

Elizabeth W. Loder, MD, MPH, chief emeritus of the division of headache at Brigham and Women’s Faulkner Hospital in Boston, urged caution in interpreting the findings, particularly with regard to tension-type headache. “This study adds to information suggesting that pregnancy complications probably are higher in women who have migraine with aura, and there’s biological plausibility for that,” Dr. Loder said. “Having aura means you may have some vascular abnormalities and things that logically might be associated with an increased risk of small-for-gestational age infants.” But the small size of the migraine-with-aura group in this study – 27 women – and the fact that other perinatal outcomes measured in the study did not reach significance, allows for the possibility that the small-for-gestational-age findings were due to chance, Dr. Loder noted.

With tension-type headache, a biological rationale for small-for-gestational-age risk is more elusive, Dr. Loder said. “I would want to see that association replicated in another study before I thought that I needed to warn women with tension-type headache about this potential outcome. There’s lot of uncertainty here about the magnitude of the risk.”

While Dr. Neri and colleagues described the instruments used in their study to diagnose migraine and migraine with aura, they did not explain how tension-type headache was diagnosed. 

Tension-type headache, while common, is still not well characterized, Dr. Loder noted, and may represent a heterogeneous condition or the milder end of a biological continuum that includes migraine with aura. Also, the group in the study had a higher prevalence of smoking, and though the authors made statistical adjustments for smoking status, “smokers are systematically different than people who aren’t in other ways that could be associated with these outcomes,” Dr. Loder said.

While the authors of the study suggested that interventions might be indicated for women with tension-type headache in pregnancy, “showing an association doesn’t necessarily mean that intervening would make a difference” on pregnancy outcomes, Dr. Loder said.

Amaal J. Starling, MD, of the Mayo Clinic in Phoenix, Ariz., said in an interview that she, too, appreciated that this study looked at pregnancy outcomes in the setting of headache disorders. “Unfortunately even though headache disorders and especially migraine affect women so much, we still know very little about migraine in pregnancy,” she said.

Dr. Starling noted that many women with migraine are discouraged by their health care providers from becoming pregnant, because of the false belief that migraine cannot be managed in pregnancy. In her own practice, she said, she treats many patients with severe headache who become pregnant and who require pharmacological intervention during pregnancy.

This does not mean she regards headache in pregnancy as innocent. “I want patients to be on high alert for changes in headache symptoms in pregnancy. If someone has worsening of headache or migraine or aura in the setting of pregnancy, we consider that a red flag,” potentially indicating complications such as high blood pressure, gestational hypertension, or a blood clot.

Like Dr. Loder, Dr. Starling said she was not surprised by Dr. Neri and colleagues’ finding that migraine with aura might impact pregnancy outcomes. “We know that migraine with aura has a lot of vascular abnormalities that underlie the pathogenesis,” she said.

Dr. Starling found the findings related to tension-type headache less convincing, not least because the diagnostic criteria for tension-type headache was not made clear in the study. “I view this as an exploratory study that says maybe there’s a signal here. A larger epidemiological study would need to be done to confirm or refute this data,” Dr. Starling said. Until the findings can be replicated, “this study would not affect my clinical practice in any way.”

Dr. Neri and colleagues described no outside funding for their research or financial conflicts of interest. Dr. Starling has received consulting fees from pharmaceutical manufacturers but reported no disclosures relevant to the study discussed. Dr. Loder reported no financial conflicts of interest.

Pregnant women who experience migraine with aura – and also the far more common tension-type headache – are at increased risk for giving birth to small-for-gestational-age babies, according to results from an observational study.

Migraine during pregnancy has been associated in previous studies with hypertensive pregnancy complications including preeclampsia; however, little is known about other headache types and their effects on pregnancy and birth outcomes.

For their research, published online July 20 in Cephalalgia, Isabella Neri, MD, PhD, and colleagues at Hospital Policlinico of Modena, Italy, looked at headache status for 515 consecutive pregnant women evaluated during their first trimester and followed through childbirth. 

Altogether 224 women, or 43.5% of the cohort, were diagnosed with migraine without aura (n = 72), migraine with aura (n = 27), or tension-type headache (n = 125). The authors did not report on the severity or frequency of headaches.

Women with migraine with aura and tension-type headache saw higher rates of small-for-gestational-age infants (25.9% and 10.4% of births, respectively) compared with 5.5% for women without headache. Women presenting with tension-type headache saw elevated risk for small-for-gestational-age infants (odds ratio [OR] 4.19, P = .004) as did women with migraine with aura (OR 5.37, P = .02).

Admission to neonatal intensive care was significantly higher in all the headache groups. However, the authors found no statistically significant associations between headaches and any other perinatal outcome investigated in the study, including gestational diabetes, placental abruption, gestational hypertension, and preterm delivery.

A previous study conducted by the same research group had reported a relationship between migraine and gestational hypertension. The authors cited the small sample size of the migraine groups in the current study, “the diverse features of the population,” and the popularity of low-dose aspirin administration as potentially affecting that outcome.
 

Interpret findings with caution

Asked by this news organization to comment on the research, two headache neurologists praised Dr. Neri and colleagues’ research for focusing on an understudied topic – but also said that the results would not change their practice unless replicated in larger studies.

Elizabeth W. Loder, MD, MPH, chief emeritus of the division of headache at Brigham and Women’s Faulkner Hospital in Boston, urged caution in interpreting the findings, particularly with regard to tension-type headache. “This study adds to information suggesting that pregnancy complications probably are higher in women who have migraine with aura, and there’s biological plausibility for that,” Dr. Loder said. “Having aura means you may have some vascular abnormalities and things that logically might be associated with an increased risk of small-for-gestational age infants.” But the small size of the migraine-with-aura group in this study – 27 women – and the fact that other perinatal outcomes measured in the study did not reach significance, allows for the possibility that the small-for-gestational-age findings were due to chance, Dr. Loder noted.

With tension-type headache, a biological rationale for small-for-gestational-age risk is more elusive, Dr. Loder said. “I would want to see that association replicated in another study before I thought that I needed to warn women with tension-type headache about this potential outcome. There’s lot of uncertainty here about the magnitude of the risk.”

While Dr. Neri and colleagues described the instruments used in their study to diagnose migraine and migraine with aura, they did not explain how tension-type headache was diagnosed. 

Tension-type headache, while common, is still not well characterized, Dr. Loder noted, and may represent a heterogeneous condition or the milder end of a biological continuum that includes migraine with aura. Also, the group in the study had a higher prevalence of smoking, and though the authors made statistical adjustments for smoking status, “smokers are systematically different than people who aren’t in other ways that could be associated with these outcomes,” Dr. Loder said.

While the authors of the study suggested that interventions might be indicated for women with tension-type headache in pregnancy, “showing an association doesn’t necessarily mean that intervening would make a difference” on pregnancy outcomes, Dr. Loder said.

Amaal J. Starling, MD, of the Mayo Clinic in Phoenix, Ariz., said in an interview that she, too, appreciated that this study looked at pregnancy outcomes in the setting of headache disorders. “Unfortunately even though headache disorders and especially migraine affect women so much, we still know very little about migraine in pregnancy,” she said.

Dr. Starling noted that many women with migraine are discouraged by their health care providers from becoming pregnant, because of the false belief that migraine cannot be managed in pregnancy. In her own practice, she said, she treats many patients with severe headache who become pregnant and who require pharmacological intervention during pregnancy.

This does not mean she regards headache in pregnancy as innocent. “I want patients to be on high alert for changes in headache symptoms in pregnancy. If someone has worsening of headache or migraine or aura in the setting of pregnancy, we consider that a red flag,” potentially indicating complications such as high blood pressure, gestational hypertension, or a blood clot.

Like Dr. Loder, Dr. Starling said she was not surprised by Dr. Neri and colleagues’ finding that migraine with aura might impact pregnancy outcomes. “We know that migraine with aura has a lot of vascular abnormalities that underlie the pathogenesis,” she said.

Dr. Starling found the findings related to tension-type headache less convincing, not least because the diagnostic criteria for tension-type headache was not made clear in the study. “I view this as an exploratory study that says maybe there’s a signal here. A larger epidemiological study would need to be done to confirm or refute this data,” Dr. Starling said. Until the findings can be replicated, “this study would not affect my clinical practice in any way.”

Dr. Neri and colleagues described no outside funding for their research or financial conflicts of interest. Dr. Starling has received consulting fees from pharmaceutical manufacturers but reported no disclosures relevant to the study discussed. Dr. Loder reported no financial conflicts of interest.

Joseph E. Scherger, MD, MPH, is a family physician of 40 years and an avid runner who has carried over his passion for fitness and nutrition into treating patients.

He achieved this through moving to practicing functional medicine a decade ago.

According to Dr. Scherger, functional medicine “shifts the whole approach [to family medicine], recognizing that people’s chronic diseases, like hypertension and diabetes, are completely reversible, and the reason why is because they’re caused by what we eat and how we live.”

Practicing functional medicine continues to make working exciting for Dr. Scherger, he says.

“Now that I’ve shifted into nutrition and lifestyle, I feel like I’m a healer, you know? I’m not just refilling prescriptions anymore,” he said.

The burden of disease brought about by bad nutrition and our profit-hungry food industry is staggering, explained Dr. Scherger, As such, he encourages his patients to adopt lifestyle and nutritional changes that allow the body to become healthy again.

Dr. Scherger’s shift into lifestyle-oriented medicine reflects his own experiences with healthy living, and how it has impacted his life.

“I’m 70 years old, and I’m still running, and I feel the same as when I was 40 or 50.” He has completed 40 marathons, ten 50K and five 50-mile ultramarathon trail runs, and, although retired from long-distance running, he is currently training for an upcoming 5K Thanksgiving turkey trot with his 6-year-old grandson. “He loves it. He’s faster than I am, I have trouble keeping up with him,” he confessed.

Earlier days of career

“I’ve been very blessed to have a career that kept changing every 5-10 years,” he said. “I’ve been able to evolve in a way of shifting my interests from one area to another,” he said.

Dr. Scherger has held many positions in the medical field, from serving in the National Health Service Corps in Dixon, Calif., as a migrant health physician during 1978-1980, to being chair of graduate medical education at Eisenhower Medical Center in Rancho Mirage, Calif., from 2009 to 2015. In between, he taught at the University of California, Davis, and served as founding dean of the Florida State University College of Medicine.

Originally from Ohio, Dr. Scherger was born in 1950 in the small town of Delphos. He graduated from the University of Dayton in 1971 before attending medical school at University of California, Los Angeles, for 4 years. He then completed a family medicine residency and a masters in public health at the University of Washington, Seattle, in 1978.

A resident of the Golden State for 50 years now, Dr. Scherger describes himself as a “true Californian.” Currently, he is in practice at Eisenhower Health in La Quinta, Calif., where he is a core faculty member in the family medicine residency program. He is also a physician under the health center’s Primary Care 365 program, which offers patients regular communication with and increased access to their physicians, emphasizing on telemedicine. He also founded Restore Health – Disease Reversal, a wellness center in Indian Wells, Calif., that focuses on improving patients’ health through changes in nutrition and lifestyle.

Within his medical practice, Dr. Scherger is seen by colleagues as a doctor who not only advocates for his patients, but also goes above and beyond to solve their problems.

“He’s a leader, an advocate, and he inspires others to do what they do,” said Julia L. Martin, MD, a fellow family medicine practitioner who has been working with Dr. Scherger at the Eisenhower Medical Center for the past 5 years. “Being a physician is a very challenging role. You need to be patient and understanding in trying to investigate what the patient wants and work through that to try to find the solution. Dr. Scherger is really good at that.”
 

Inspiration for writing

Apart from his roles as a physician and faculty member, Dr. Scherger is also an author of two books: “40 Years in Family Medicine” (Scotts Valley, Calif.: CreateSpace, 2014) and “Lean and Fit: A Doctor’s Journey to Healthy Nutrition and Greater Wellness” (Scotts Valley, Calif.: CreateSpace, 2015). He admits to not being a naturally gifted writer, and is more intrinsically skilled at speaking. When he was in medical school, however, a mentor told him that the written word is eternal, and this left a deep impression on him.

“When I think of something that’s worth writing about, that I think will be a contribution to my field, I don’t hesitate to begin to write and develop,” said Dr. Scherger. “ I’ve done some research that I’m proud of, but most of [my writings] are hopefully thoughtful essays to help move my field along, and it’s enormously satisfying to make these contributions.”
 

Awards and other contributions to family medicine

Dr. Scherger’s contributions to the field of family medicine have been recognized continuously over his career.

He has served on the board of directors of the American Academy of Family Physicians and the American Board of Family Medicine. He is also the recipient of numerous awards, such as being chosen as Family Physician of the Year by the American Academy of Family Physicians and the California Academy of Family Physicians in 1989. From 1988 to 1991, he was a fellow in the Kellogg National Fellowship Program.

While he has managed to reinvent his own practice and medical focus, Dr. Scherger is also concerned with the need to remodel the current state of primary care and family medicine. Regarding challenges facing the field, he mentions the burnout faced by many doctors.

Nowadays, the work of family medicine includes much more than those common acute illnesses – it includes preventive medicine, chronic illness management and mental health counseling. “Yet, somehow, the whole economic and schedule model is based on brief visits,” said Dr. Scherger. “I think the most common reason that a lot of family doctors are burned out is that they’re expected to see so many people a day, and they know they don’t have enough time to do a really good job.”

He elaborated: “The real challenge now for family practice is to be re-engineered to be for the modern age, and not be still stuck in a ‘make an appointment, come and get it’ model of care, which is outdated. So I’ve been working a long time in trying to reinvent primary care. And, you know, it’s hard to make those changes, and it’s still a work in progress.”

One of the ways Dr. Scherger has been working on the primary care model is to help redesign it for the computer age. He started doing telemedicine and online care in 1997, even though other doctors gave him pushback for doing so at the time. Today, in his practice, half of his patients are remote, and under Eisenhower’s Primary Care 365 service, he uses telemedicine to its fullest potential.

Dr. Martin calls Dr. Scherger an “innovator,” adding: “He really tries to find what works for a solution, in different ways – not just one cookie cutter way.”

Despite nearly 50 years of being a doctor, the profession has not gotten any less rewarding for Dr. Scherger, who says he does not intend to retire as long as he is any good at it.

“My mother always said, ‘Joe, your life should be dedicated to making the world a better place.’ I really took that to heart and realized that my greatest joy is to help other people.”

Joseph E. Scherger, MD, MPH, is a family physician of 40 years and an avid runner who has carried over his passion for fitness and nutrition into treating patients.

He achieved this through moving to practicing functional medicine a decade ago.

According to Dr. Scherger, functional medicine “shifts the whole approach [to family medicine], recognizing that people’s chronic diseases, like hypertension and diabetes, are completely reversible, and the reason why is because they’re caused by what we eat and how we live.”

Practicing functional medicine continues to make working exciting for Dr. Scherger, he says.

“Now that I’ve shifted into nutrition and lifestyle, I feel like I’m a healer, you know? I’m not just refilling prescriptions anymore,” he said.

The burden of disease brought about by bad nutrition and our profit-hungry food industry is staggering, explained Dr. Scherger, As such, he encourages his patients to adopt lifestyle and nutritional changes that allow the body to become healthy again.

Dr. Scherger’s shift into lifestyle-oriented medicine reflects his own experiences with healthy living, and how it has impacted his life.

“I’m 70 years old, and I’m still running, and I feel the same as when I was 40 or 50.” He has completed 40 marathons, ten 50K and five 50-mile ultramarathon trail runs, and, although retired from long-distance running, he is currently training for an upcoming 5K Thanksgiving turkey trot with his 6-year-old grandson. “He loves it. He’s faster than I am, I have trouble keeping up with him,” he confessed.

Earlier days of career

“I’ve been very blessed to have a career that kept changing every 5-10 years,” he said. “I’ve been able to evolve in a way of shifting my interests from one area to another,” he said.

Dr. Scherger has held many positions in the medical field, from serving in the National Health Service Corps in Dixon, Calif., as a migrant health physician during 1978-1980, to being chair of graduate medical education at Eisenhower Medical Center in Rancho Mirage, Calif., from 2009 to 2015. In between, he taught at the University of California, Davis, and served as founding dean of the Florida State University College of Medicine.

Originally from Ohio, Dr. Scherger was born in 1950 in the small town of Delphos. He graduated from the University of Dayton in 1971 before attending medical school at University of California, Los Angeles, for 4 years. He then completed a family medicine residency and a masters in public health at the University of Washington, Seattle, in 1978.

A resident of the Golden State for 50 years now, Dr. Scherger describes himself as a “true Californian.” Currently, he is in practice at Eisenhower Health in La Quinta, Calif., where he is a core faculty member in the family medicine residency program. He is also a physician under the health center’s Primary Care 365 program, which offers patients regular communication with and increased access to their physicians, emphasizing on telemedicine. He also founded Restore Health – Disease Reversal, a wellness center in Indian Wells, Calif., that focuses on improving patients’ health through changes in nutrition and lifestyle.

Within his medical practice, Dr. Scherger is seen by colleagues as a doctor who not only advocates for his patients, but also goes above and beyond to solve their problems.

“He’s a leader, an advocate, and he inspires others to do what they do,” said Julia L. Martin, MD, a fellow family medicine practitioner who has been working with Dr. Scherger at the Eisenhower Medical Center for the past 5 years. “Being a physician is a very challenging role. You need to be patient and understanding in trying to investigate what the patient wants and work through that to try to find the solution. Dr. Scherger is really good at that.”
 

Inspiration for writing

Apart from his roles as a physician and faculty member, Dr. Scherger is also an author of two books: “40 Years in Family Medicine” (Scotts Valley, Calif.: CreateSpace, 2014) and “Lean and Fit: A Doctor’s Journey to Healthy Nutrition and Greater Wellness” (Scotts Valley, Calif.: CreateSpace, 2015). He admits to not being a naturally gifted writer, and is more intrinsically skilled at speaking. When he was in medical school, however, a mentor told him that the written word is eternal, and this left a deep impression on him.

“When I think of something that’s worth writing about, that I think will be a contribution to my field, I don’t hesitate to begin to write and develop,” said Dr. Scherger. “ I’ve done some research that I’m proud of, but most of [my writings] are hopefully thoughtful essays to help move my field along, and it’s enormously satisfying to make these contributions.”
 

Awards and other contributions to family medicine

Dr. Scherger’s contributions to the field of family medicine have been recognized continuously over his career.

He has served on the board of directors of the American Academy of Family Physicians and the American Board of Family Medicine. He is also the recipient of numerous awards, such as being chosen as Family Physician of the Year by the American Academy of Family Physicians and the California Academy of Family Physicians in 1989. From 1988 to 1991, he was a fellow in the Kellogg National Fellowship Program.

While he has managed to reinvent his own practice and medical focus, Dr. Scherger is also concerned with the need to remodel the current state of primary care and family medicine. Regarding challenges facing the field, he mentions the burnout faced by many doctors.

Nowadays, the work of family medicine includes much more than those common acute illnesses – it includes preventive medicine, chronic illness management and mental health counseling. “Yet, somehow, the whole economic and schedule model is based on brief visits,” said Dr. Scherger. “I think the most common reason that a lot of family doctors are burned out is that they’re expected to see so many people a day, and they know they don’t have enough time to do a really good job.”

He elaborated: “The real challenge now for family practice is to be re-engineered to be for the modern age, and not be still stuck in a ‘make an appointment, come and get it’ model of care, which is outdated. So I’ve been working a long time in trying to reinvent primary care. And, you know, it’s hard to make those changes, and it’s still a work in progress.”

One of the ways Dr. Scherger has been working on the primary care model is to help redesign it for the computer age. He started doing telemedicine and online care in 1997, even though other doctors gave him pushback for doing so at the time. Today, in his practice, half of his patients are remote, and under Eisenhower’s Primary Care 365 service, he uses telemedicine to its fullest potential.

Dr. Martin calls Dr. Scherger an “innovator,” adding: “He really tries to find what works for a solution, in different ways – not just one cookie cutter way.”

Despite nearly 50 years of being a doctor, the profession has not gotten any less rewarding for Dr. Scherger, who says he does not intend to retire as long as he is any good at it.

“My mother always said, ‘Joe, your life should be dedicated to making the world a better place.’ I really took that to heart and realized that my greatest joy is to help other people.”

Joseph E. Scherger, MD, MPH, is a family physician of 40 years and an avid runner who has carried over his passion for fitness and nutrition into treating patients.

He achieved this through moving to practicing functional medicine a decade ago.

According to Dr. Scherger, functional medicine “shifts the whole approach [to family medicine], recognizing that people’s chronic diseases, like hypertension and diabetes, are completely reversible, and the reason why is because they’re caused by what we eat and how we live.”

Practicing functional medicine continues to make working exciting for Dr. Scherger, he says.

“Now that I’ve shifted into nutrition and lifestyle, I feel like I’m a healer, you know? I’m not just refilling prescriptions anymore,” he said.

The burden of disease brought about by bad nutrition and our profit-hungry food industry is staggering, explained Dr. Scherger, As such, he encourages his patients to adopt lifestyle and nutritional changes that allow the body to become healthy again.

Dr. Scherger’s shift into lifestyle-oriented medicine reflects his own experiences with healthy living, and how it has impacted his life.

“I’m 70 years old, and I’m still running, and I feel the same as when I was 40 or 50.” He has completed 40 marathons, ten 50K and five 50-mile ultramarathon trail runs, and, although retired from long-distance running, he is currently training for an upcoming 5K Thanksgiving turkey trot with his 6-year-old grandson. “He loves it. He’s faster than I am, I have trouble keeping up with him,” he confessed.

Earlier days of career

“I’ve been very blessed to have a career that kept changing every 5-10 years,” he said. “I’ve been able to evolve in a way of shifting my interests from one area to another,” he said.

Dr. Scherger has held many positions in the medical field, from serving in the National Health Service Corps in Dixon, Calif., as a migrant health physician during 1978-1980, to being chair of graduate medical education at Eisenhower Medical Center in Rancho Mirage, Calif., from 2009 to 2015. In between, he taught at the University of California, Davis, and served as founding dean of the Florida State University College of Medicine.

Originally from Ohio, Dr. Scherger was born in 1950 in the small town of Delphos. He graduated from the University of Dayton in 1971 before attending medical school at University of California, Los Angeles, for 4 years. He then completed a family medicine residency and a masters in public health at the University of Washington, Seattle, in 1978.

A resident of the Golden State for 50 years now, Dr. Scherger describes himself as a “true Californian.” Currently, he is in practice at Eisenhower Health in La Quinta, Calif., where he is a core faculty member in the family medicine residency program. He is also a physician under the health center’s Primary Care 365 program, which offers patients regular communication with and increased access to their physicians, emphasizing on telemedicine. He also founded Restore Health – Disease Reversal, a wellness center in Indian Wells, Calif., that focuses on improving patients’ health through changes in nutrition and lifestyle.

Within his medical practice, Dr. Scherger is seen by colleagues as a doctor who not only advocates for his patients, but also goes above and beyond to solve their problems.

“He’s a leader, an advocate, and he inspires others to do what they do,” said Julia L. Martin, MD, a fellow family medicine practitioner who has been working with Dr. Scherger at the Eisenhower Medical Center for the past 5 years. “Being a physician is a very challenging role. You need to be patient and understanding in trying to investigate what the patient wants and work through that to try to find the solution. Dr. Scherger is really good at that.”
 

Inspiration for writing

Apart from his roles as a physician and faculty member, Dr. Scherger is also an author of two books: “40 Years in Family Medicine” (Scotts Valley, Calif.: CreateSpace, 2014) and “Lean and Fit: A Doctor’s Journey to Healthy Nutrition and Greater Wellness” (Scotts Valley, Calif.: CreateSpace, 2015). He admits to not being a naturally gifted writer, and is more intrinsically skilled at speaking. When he was in medical school, however, a mentor told him that the written word is eternal, and this left a deep impression on him.

“When I think of something that’s worth writing about, that I think will be a contribution to my field, I don’t hesitate to begin to write and develop,” said Dr. Scherger. “ I’ve done some research that I’m proud of, but most of [my writings] are hopefully thoughtful essays to help move my field along, and it’s enormously satisfying to make these contributions.”
 

Awards and other contributions to family medicine

Dr. Scherger’s contributions to the field of family medicine have been recognized continuously over his career.

He has served on the board of directors of the American Academy of Family Physicians and the American Board of Family Medicine. He is also the recipient of numerous awards, such as being chosen as Family Physician of the Year by the American Academy of Family Physicians and the California Academy of Family Physicians in 1989. From 1988 to 1991, he was a fellow in the Kellogg National Fellowship Program.

While he has managed to reinvent his own practice and medical focus, Dr. Scherger is also concerned with the need to remodel the current state of primary care and family medicine. Regarding challenges facing the field, he mentions the burnout faced by many doctors.

Nowadays, the work of family medicine includes much more than those common acute illnesses – it includes preventive medicine, chronic illness management and mental health counseling. “Yet, somehow, the whole economic and schedule model is based on brief visits,” said Dr. Scherger. “I think the most common reason that a lot of family doctors are burned out is that they’re expected to see so many people a day, and they know they don’t have enough time to do a really good job.”

He elaborated: “The real challenge now for family practice is to be re-engineered to be for the modern age, and not be still stuck in a ‘make an appointment, come and get it’ model of care, which is outdated. So I’ve been working a long time in trying to reinvent primary care. And, you know, it’s hard to make those changes, and it’s still a work in progress.”

One of the ways Dr. Scherger has been working on the primary care model is to help redesign it for the computer age. He started doing telemedicine and online care in 1997, even though other doctors gave him pushback for doing so at the time. Today, in his practice, half of his patients are remote, and under Eisenhower’s Primary Care 365 service, he uses telemedicine to its fullest potential.

Dr. Martin calls Dr. Scherger an “innovator,” adding: “He really tries to find what works for a solution, in different ways – not just one cookie cutter way.”

Despite nearly 50 years of being a doctor, the profession has not gotten any less rewarding for Dr. Scherger, who says he does not intend to retire as long as he is any good at it.

“My mother always said, ‘Joe, your life should be dedicated to making the world a better place.’ I really took that to heart and realized that my greatest joy is to help other people.”

The potential of polygenic risk scores (PRSs) to become key components in the assessment of individual risk for disease in the clinical setting is inching closer to fruition; however, the technology is plagued by one glaring omission of most existing PRSs – the lack of applicability to those of non-European ancestry.

Polygenic risk scores predict an individual’s risk of disease based on common genetic variants identified in large genomewide association studies (GWASs). They have gained ground in research, as well as in the unregulated realm of the direct-to-consumer market where they are sold as add-ons to DNA ancestry kits such as 23andMe and MyHeritage.com.

While the risk scores show strong validation in estimating risk among people of European descent, their striking caveat is the lack of applicability to other ancestries, particularly African, and their use in practice outside of clinical trials is discouraged in National Comprehensive Cancer Network guidelines.

Study underscores need for ethnically diverse datasets

In a recent study published in JAMA Network Open, researchers evaluated the use of polygenic risk scores’ models in a clinical setting. Researchers tested 7 PRSs models for breast cancer risk against the medical records data of 39,591 women of European, African, and Latinx ancestry.

The PRSs models – all used only for research purposes – included three models involving European ancestry cohorts, two from Latinx cohorts, and two from women African descent.

After adjusting for factors including age, breast cancer family history, and ancestry, the PRSs from women with European ancestry highly corresponded to breast cancer risk, with a mean odds ratio of 1.46 per standard deviation increase in the score.

PRSs were also generalized relatively well among women of Latinx ancestry with a mean OR of 1.31. The authors noted that association is likely caused by Latinx individuals in the United States having a greater proportion of European ancestry than individuals with African ancestry. Importantly, however, the effect size was lower for women of African ancestry with a highest OR of 1.19 per standard deviation.

In the highest percentiles of breast cancer risk, women of European descent had odds ratio as high as 2.19-2.48, suggesting a statistically significant association with overall breast cancer risk. No statistically significant associations were found among women of Latinx and African-ancestry.

The PRSs models were smaller for women of non-European ancestry and included fewer genetic variants for women of non-European ancestry were notably smaller and hence reflected fewer genetic variants. Of the two risk scores involving African ancestry, the Women’s Health Initiative for Women with African ancestry risk score had just 75 variants, while the African diaspora study (ROOT) had 34 variants, compared with 3,820 and 5,218 in the two largest European ancestry PRSs, the Breast Cancer Association Consortium and the UK Biobank, respectively.

“These results highlight the need to improve representation of diverse population groups, particularly women with African ancestry, in genomic research cohorts,” the authors wrote.

First author, Cong Liu, PhD, of Columbia University Irving Medical Center, New York, said that efforts are underway to improve the inclusivity in the Electronic Medical Records and Genomics network data set used in this study.

“Until well-developed and validated PRSs for women with non-European ancestry become available, the current PRSs based on cohorts with European ancestry could be adapted for Latinx women, but not women with African ancestry until additional data sets become available in this important and high-risk group,” Dr. Liu and colleagues wrote.

In a commentary published with the study, Payal D. Shah, MD, of the Basser Center for BRCA at the University of Pennsylvania, Philadelphia, said that PRSs are “disproportionately applicable to patients with European ancestry and are insufficiently vetted and developed in other populations. If an instrument exists that has clinical utility in informing effective cancer risk mitigation strategies, then we must strive to ensure that it is available and applicable to all.”

Higher morality among African American women

While American Cancer Society data shows women with African ancestry generally have incidence rates of breast cancer similar to White women, they have significantly higher mortality from the disease in part because of later-stage diagnosis and health care barriers.

Anne Marie McCarthy, PhD, of the University of Pennsylvania, and Katrina Armstrong, MD, of Harvard Medical School, Boston, wrote in the Journal of the National Cancer Institute that African American women “have 42% higher breast cancer mortality than white women, despite having lower disease incidence, and are more likely to be diagnosed with triple-negative breast cancer, which has poorer prognosis than other molecular subtypes.”

Dr. McCarthy and Dr. Armstrong wrote that African American women are chronically underrepresented in breast cancer studies. And as such, it is impossible to know the extent of the prevalence of mutations and risk.

Failing to address the lack of diversity in genomic studies may worsen health disparities for women with African ancestry, Dr. Liu and colleagues wrote. The higher mortality “underscores the urgent need to increase diversity in genomic studies so that future clinical applications of the PRS do not exacerbate existing health disparities. These results highlight the need to improve representation of diverse population groups, particularly women with African ancestry, in genomic research cohorts.”
 

Potential PRS benefits underscore need to eliminate bias

The potentially important benefits of PRSs as risk prediction tools used in combination with family history, reproductive history and other factors, should provide strong incentive to push for improvement, Dr. Shah wrote.

For instance, if an individual is estrogen receptor positive and shows elevations in breast cancer risk on a reliable PRS, “this may inform antiestrogen chemoprevention strategies,” she wrote.

A risk score could furthermore influence the age at which breast cancer screening should begin or factor into whether a patient should also receive surveillance breast MRI.

Importantly, PRSs could also add to other risk factors to provide more precise risk estimates and inform management of women with a pathogenic variant in a breast cancer risk predisposition gene, Dr. Shah wrote.

Confluence project

Among the most promising developments in research is the National Cancer Institute’s Confluence Project, a large research resource aiming to include approximately 300,000 breast cancer cases and 300,000 controls of different races/ethnicities, utilizing the confluence of existing GWAS and new genomewide genotyping data.

Having started enrollment in 2018, the project is approaching implementation, said Montserrat García-Closas, MD, MPH, DrPH, deputy director of cancer epidemiology and genetics with the National Cancer Institute.

“We expect genotyping to be completed by the end of 2022 and for the data to be made available to the research community soon after that,” she said.

Among the project’s key objectives are the development of PRSs to be integrated with known risk factors to provide a personalized risk assessment for breast cancer, overall and by ancestral subtype.

“We plan to apply novel methods to derive multiancestry PRS that will account for differences and similarities in genetic architecture across ethnic/racial groups to develop breast cancer PRSs that can be applied in multiethnic/racial populations,” she said.

NCI is working with investigators in Africa, Central and South America, and Asia, and reaching out to non-European organizations such as AORTIC for studies of African populations.

Direct-to-consumer global PRS

In the commercial PRS market, efforts to address diversity shortcomings are also gaining momentum, with Myriad Genetics touting a first-of-its kind “global PRS.”

The PRS, a recalibrated version the company’s riskScore PRS, sold as part of its Myriad myRisk Hereditary Cancer test, will reportedly apply to all ethnicities in estimating an individual’s 5-year and lifetime risk of breast cancer.

A study presented in June at the American Society of Clinical Oncology meeting, describes the development of the model with the use of three large ancestry-specific PRSs based on African American, Asian, and European cohorts, with the system including a total of 149 single-nucleotide polymorphisms, including 93 well established for breast cancer and 56 that are ancestry specific.

In validation of the data in an independent cohort of 62,707 individuals, the global PRS was strongly associated with breast cancer in the full combined validation cohort as well as in all three of the ancestry subcohorts.

However, the effect size among women with African ancestry was still the lowest of all of the groups, with a mean OR of 1.24 per standard deviation, versus the highest rate of mixed ancestry (OR, 1.59).

According to senior author Holly Pederson, MD, director of medical breast services at the Cleveland Clinic, the applicability of the PRS to women with African ancestry is expected to further improve as additional data become available.

“The discriminatory power in women of African descent was significantly improved but still suboptimal,” she said. “The need for more data, particularly in Black women, is challenging not only because there is likely more diversity in the genomic landscape of women of African descent, but also because the barriers created by historical, cultural, institutional and interpersonal dynamics result in the paucity of this data.”

“We must be committed to ending bias resulting in health care disparities,” Dr. Pederson said. She noted that the global PRS is nevertheless “still clinically useful in Black women,” and recommended that clinicians be up front with patients on the status of the research challenges.

“As with any clinical shared decision-making conversation between a patient and her provider, it is important for Black women to know that data is limited in the African American population, particularly given the vast genomic diversity of the African continent,” she said. “This model, as models that have gone before it, will improve with additional data, particularly in this population.”

Commercial PRSs may benefit research

While the commercial marketing of PRSs in a direct-to-consumer fashion have raised some concerns, such as how individuals respond to their risk scores, there could be important benefits as well, commented Megan C. Roberts, PhD.

“There may be an opportunity to learn from these companies about how to engage diverse communities in genomic testing,” said Dr. Roberts, an assistant professor and director of implementation science in precision health and society at the University of North Carolina at Chapel Hill. “Moreover, the data they collect from their customers often can be used for research purposes as well.”

In a recent perspective, Dr. Roberts and colleagues addressed the role of health disparities in PRSs. She’ll be joining international precision public health researchers in October in hosting a free virtual conference at UNC on the topic.

“There is a huge need to improve racial and ethnic diversity in our genomic datasets,” Dr. Roberts said. “Without this, we will not be able to return on the promise of precision medicine and prevention for improving the health of our whole population.”

Dr. Pederson disclosed that she is a consultant for Myriad Genetics.

The potential of polygenic risk scores (PRSs) to become key components in the assessment of individual risk for disease in the clinical setting is inching closer to fruition; however, the technology is plagued by one glaring omission of most existing PRSs – the lack of applicability to those of non-European ancestry.

Polygenic risk scores predict an individual’s risk of disease based on common genetic variants identified in large genomewide association studies (GWASs). They have gained ground in research, as well as in the unregulated realm of the direct-to-consumer market where they are sold as add-ons to DNA ancestry kits such as 23andMe and MyHeritage.com.

While the risk scores show strong validation in estimating risk among people of European descent, their striking caveat is the lack of applicability to other ancestries, particularly African, and their use in practice outside of clinical trials is discouraged in National Comprehensive Cancer Network guidelines.

Study underscores need for ethnically diverse datasets

In a recent study published in JAMA Network Open, researchers evaluated the use of polygenic risk scores’ models in a clinical setting. Researchers tested 7 PRSs models for breast cancer risk against the medical records data of 39,591 women of European, African, and Latinx ancestry.

The PRSs models – all used only for research purposes – included three models involving European ancestry cohorts, two from Latinx cohorts, and two from women African descent.

After adjusting for factors including age, breast cancer family history, and ancestry, the PRSs from women with European ancestry highly corresponded to breast cancer risk, with a mean odds ratio of 1.46 per standard deviation increase in the score.

PRSs were also generalized relatively well among women of Latinx ancestry with a mean OR of 1.31. The authors noted that association is likely caused by Latinx individuals in the United States having a greater proportion of European ancestry than individuals with African ancestry. Importantly, however, the effect size was lower for women of African ancestry with a highest OR of 1.19 per standard deviation.

In the highest percentiles of breast cancer risk, women of European descent had odds ratio as high as 2.19-2.48, suggesting a statistically significant association with overall breast cancer risk. No statistically significant associations were found among women of Latinx and African-ancestry.

The PRSs models were smaller for women of non-European ancestry and included fewer genetic variants for women of non-European ancestry were notably smaller and hence reflected fewer genetic variants. Of the two risk scores involving African ancestry, the Women’s Health Initiative for Women with African ancestry risk score had just 75 variants, while the African diaspora study (ROOT) had 34 variants, compared with 3,820 and 5,218 in the two largest European ancestry PRSs, the Breast Cancer Association Consortium and the UK Biobank, respectively.

“These results highlight the need to improve representation of diverse population groups, particularly women with African ancestry, in genomic research cohorts,” the authors wrote.

First author, Cong Liu, PhD, of Columbia University Irving Medical Center, New York, said that efforts are underway to improve the inclusivity in the Electronic Medical Records and Genomics network data set used in this study.

“Until well-developed and validated PRSs for women with non-European ancestry become available, the current PRSs based on cohorts with European ancestry could be adapted for Latinx women, but not women with African ancestry until additional data sets become available in this important and high-risk group,” Dr. Liu and colleagues wrote.

In a commentary published with the study, Payal D. Shah, MD, of the Basser Center for BRCA at the University of Pennsylvania, Philadelphia, said that PRSs are “disproportionately applicable to patients with European ancestry and are insufficiently vetted and developed in other populations. If an instrument exists that has clinical utility in informing effective cancer risk mitigation strategies, then we must strive to ensure that it is available and applicable to all.”

Higher morality among African American women

While American Cancer Society data shows women with African ancestry generally have incidence rates of breast cancer similar to White women, they have significantly higher mortality from the disease in part because of later-stage diagnosis and health care barriers.

Anne Marie McCarthy, PhD, of the University of Pennsylvania, and Katrina Armstrong, MD, of Harvard Medical School, Boston, wrote in the Journal of the National Cancer Institute that African American women “have 42% higher breast cancer mortality than white women, despite having lower disease incidence, and are more likely to be diagnosed with triple-negative breast cancer, which has poorer prognosis than other molecular subtypes.”

Dr. McCarthy and Dr. Armstrong wrote that African American women are chronically underrepresented in breast cancer studies. And as such, it is impossible to know the extent of the prevalence of mutations and risk.

Failing to address the lack of diversity in genomic studies may worsen health disparities for women with African ancestry, Dr. Liu and colleagues wrote. The higher mortality “underscores the urgent need to increase diversity in genomic studies so that future clinical applications of the PRS do not exacerbate existing health disparities. These results highlight the need to improve representation of diverse population groups, particularly women with African ancestry, in genomic research cohorts.”
 

Potential PRS benefits underscore need to eliminate bias

The potentially important benefits of PRSs as risk prediction tools used in combination with family history, reproductive history and other factors, should provide strong incentive to push for improvement, Dr. Shah wrote.

For instance, if an individual is estrogen receptor positive and shows elevations in breast cancer risk on a reliable PRS, “this may inform antiestrogen chemoprevention strategies,” she wrote.

A risk score could furthermore influence the age at which breast cancer screening should begin or factor into whether a patient should also receive surveillance breast MRI.

Importantly, PRSs could also add to other risk factors to provide more precise risk estimates and inform management of women with a pathogenic variant in a breast cancer risk predisposition gene, Dr. Shah wrote.

Confluence project

Among the most promising developments in research is the National Cancer Institute’s Confluence Project, a large research resource aiming to include approximately 300,000 breast cancer cases and 300,000 controls of different races/ethnicities, utilizing the confluence of existing GWAS and new genomewide genotyping data.

Having started enrollment in 2018, the project is approaching implementation, said Montserrat García-Closas, MD, MPH, DrPH, deputy director of cancer epidemiology and genetics with the National Cancer Institute.

“We expect genotyping to be completed by the end of 2022 and for the data to be made available to the research community soon after that,” she said.

Among the project’s key objectives are the development of PRSs to be integrated with known risk factors to provide a personalized risk assessment for breast cancer, overall and by ancestral subtype.

“We plan to apply novel methods to derive multiancestry PRS that will account for differences and similarities in genetic architecture across ethnic/racial groups to develop breast cancer PRSs that can be applied in multiethnic/racial populations,” she said.

NCI is working with investigators in Africa, Central and South America, and Asia, and reaching out to non-European organizations such as AORTIC for studies of African populations.

Direct-to-consumer global PRS

In the commercial PRS market, efforts to address diversity shortcomings are also gaining momentum, with Myriad Genetics touting a first-of-its kind “global PRS.”

The PRS, a recalibrated version the company’s riskScore PRS, sold as part of its Myriad myRisk Hereditary Cancer test, will reportedly apply to all ethnicities in estimating an individual’s 5-year and lifetime risk of breast cancer.

A study presented in June at the American Society of Clinical Oncology meeting, describes the development of the model with the use of three large ancestry-specific PRSs based on African American, Asian, and European cohorts, with the system including a total of 149 single-nucleotide polymorphisms, including 93 well established for breast cancer and 56 that are ancestry specific.

In validation of the data in an independent cohort of 62,707 individuals, the global PRS was strongly associated with breast cancer in the full combined validation cohort as well as in all three of the ancestry subcohorts.

However, the effect size among women with African ancestry was still the lowest of all of the groups, with a mean OR of 1.24 per standard deviation, versus the highest rate of mixed ancestry (OR, 1.59).

According to senior author Holly Pederson, MD, director of medical breast services at the Cleveland Clinic, the applicability of the PRS to women with African ancestry is expected to further improve as additional data become available.

“The discriminatory power in women of African descent was significantly improved but still suboptimal,” she said. “The need for more data, particularly in Black women, is challenging not only because there is likely more diversity in the genomic landscape of women of African descent, but also because the barriers created by historical, cultural, institutional and interpersonal dynamics result in the paucity of this data.”

“We must be committed to ending bias resulting in health care disparities,” Dr. Pederson said. She noted that the global PRS is nevertheless “still clinically useful in Black women,” and recommended that clinicians be up front with patients on the status of the research challenges.

“As with any clinical shared decision-making conversation between a patient and her provider, it is important for Black women to know that data is limited in the African American population, particularly given the vast genomic diversity of the African continent,” she said. “This model, as models that have gone before it, will improve with additional data, particularly in this population.”

Commercial PRSs may benefit research

While the commercial marketing of PRSs in a direct-to-consumer fashion have raised some concerns, such as how individuals respond to their risk scores, there could be important benefits as well, commented Megan C. Roberts, PhD.

“There may be an opportunity to learn from these companies about how to engage diverse communities in genomic testing,” said Dr. Roberts, an assistant professor and director of implementation science in precision health and society at the University of North Carolina at Chapel Hill. “Moreover, the data they collect from their customers often can be used for research purposes as well.”

In a recent perspective, Dr. Roberts and colleagues addressed the role of health disparities in PRSs. She’ll be joining international precision public health researchers in October in hosting a free virtual conference at UNC on the topic.

“There is a huge need to improve racial and ethnic diversity in our genomic datasets,” Dr. Roberts said. “Without this, we will not be able to return on the promise of precision medicine and prevention for improving the health of our whole population.”

Dr. Pederson disclosed that she is a consultant for Myriad Genetics.

The potential of polygenic risk scores (PRSs) to become key components in the assessment of individual risk for disease in the clinical setting is inching closer to fruition; however, the technology is plagued by one glaring omission of most existing PRSs – the lack of applicability to those of non-European ancestry.

Polygenic risk scores predict an individual’s risk of disease based on common genetic variants identified in large genomewide association studies (GWASs). They have gained ground in research, as well as in the unregulated realm of the direct-to-consumer market where they are sold as add-ons to DNA ancestry kits such as 23andMe and MyHeritage.com.

While the risk scores show strong validation in estimating risk among people of European descent, their striking caveat is the lack of applicability to other ancestries, particularly African, and their use in practice outside of clinical trials is discouraged in National Comprehensive Cancer Network guidelines.

Study underscores need for ethnically diverse datasets

In a recent study published in JAMA Network Open, researchers evaluated the use of polygenic risk scores’ models in a clinical setting. Researchers tested 7 PRSs models for breast cancer risk against the medical records data of 39,591 women of European, African, and Latinx ancestry.

The PRSs models – all used only for research purposes – included three models involving European ancestry cohorts, two from Latinx cohorts, and two from women African descent.

After adjusting for factors including age, breast cancer family history, and ancestry, the PRSs from women with European ancestry highly corresponded to breast cancer risk, with a mean odds ratio of 1.46 per standard deviation increase in the score.

PRSs were also generalized relatively well among women of Latinx ancestry with a mean OR of 1.31. The authors noted that association is likely caused by Latinx individuals in the United States having a greater proportion of European ancestry than individuals with African ancestry. Importantly, however, the effect size was lower for women of African ancestry with a highest OR of 1.19 per standard deviation.

In the highest percentiles of breast cancer risk, women of European descent had odds ratio as high as 2.19-2.48, suggesting a statistically significant association with overall breast cancer risk. No statistically significant associations were found among women of Latinx and African-ancestry.

The PRSs models were smaller for women of non-European ancestry and included fewer genetic variants for women of non-European ancestry were notably smaller and hence reflected fewer genetic variants. Of the two risk scores involving African ancestry, the Women’s Health Initiative for Women with African ancestry risk score had just 75 variants, while the African diaspora study (ROOT) had 34 variants, compared with 3,820 and 5,218 in the two largest European ancestry PRSs, the Breast Cancer Association Consortium and the UK Biobank, respectively.

“These results highlight the need to improve representation of diverse population groups, particularly women with African ancestry, in genomic research cohorts,” the authors wrote.

First author, Cong Liu, PhD, of Columbia University Irving Medical Center, New York, said that efforts are underway to improve the inclusivity in the Electronic Medical Records and Genomics network data set used in this study.

“Until well-developed and validated PRSs for women with non-European ancestry become available, the current PRSs based on cohorts with European ancestry could be adapted for Latinx women, but not women with African ancestry until additional data sets become available in this important and high-risk group,” Dr. Liu and colleagues wrote.

In a commentary published with the study, Payal D. Shah, MD, of the Basser Center for BRCA at the University of Pennsylvania, Philadelphia, said that PRSs are “disproportionately applicable to patients with European ancestry and are insufficiently vetted and developed in other populations. If an instrument exists that has clinical utility in informing effective cancer risk mitigation strategies, then we must strive to ensure that it is available and applicable to all.”

Higher morality among African American women

While American Cancer Society data shows women with African ancestry generally have incidence rates of breast cancer similar to White women, they have significantly higher mortality from the disease in part because of later-stage diagnosis and health care barriers.

Anne Marie McCarthy, PhD, of the University of Pennsylvania, and Katrina Armstrong, MD, of Harvard Medical School, Boston, wrote in the Journal of the National Cancer Institute that African American women “have 42% higher breast cancer mortality than white women, despite having lower disease incidence, and are more likely to be diagnosed with triple-negative breast cancer, which has poorer prognosis than other molecular subtypes.”

Dr. McCarthy and Dr. Armstrong wrote that African American women are chronically underrepresented in breast cancer studies. And as such, it is impossible to know the extent of the prevalence of mutations and risk.

Failing to address the lack of diversity in genomic studies may worsen health disparities for women with African ancestry, Dr. Liu and colleagues wrote. The higher mortality “underscores the urgent need to increase diversity in genomic studies so that future clinical applications of the PRS do not exacerbate existing health disparities. These results highlight the need to improve representation of diverse population groups, particularly women with African ancestry, in genomic research cohorts.”
 

Potential PRS benefits underscore need to eliminate bias

The potentially important benefits of PRSs as risk prediction tools used in combination with family history, reproductive history and other factors, should provide strong incentive to push for improvement, Dr. Shah wrote.

For instance, if an individual is estrogen receptor positive and shows elevations in breast cancer risk on a reliable PRS, “this may inform antiestrogen chemoprevention strategies,” she wrote.

A risk score could furthermore influence the age at which breast cancer screening should begin or factor into whether a patient should also receive surveillance breast MRI.

Importantly, PRSs could also add to other risk factors to provide more precise risk estimates and inform management of women with a pathogenic variant in a breast cancer risk predisposition gene, Dr. Shah wrote.

Confluence project

Among the most promising developments in research is the National Cancer Institute’s Confluence Project, a large research resource aiming to include approximately 300,000 breast cancer cases and 300,000 controls of different races/ethnicities, utilizing the confluence of existing GWAS and new genomewide genotyping data.

Having started enrollment in 2018, the project is approaching implementation, said Montserrat García-Closas, MD, MPH, DrPH, deputy director of cancer epidemiology and genetics with the National Cancer Institute.

“We expect genotyping to be completed by the end of 2022 and for the data to be made available to the research community soon after that,” she said.

Among the project’s key objectives are the development of PRSs to be integrated with known risk factors to provide a personalized risk assessment for breast cancer, overall and by ancestral subtype.

“We plan to apply novel methods to derive multiancestry PRS that will account for differences and similarities in genetic architecture across ethnic/racial groups to develop breast cancer PRSs that can be applied in multiethnic/racial populations,” she said.

NCI is working with investigators in Africa, Central and South America, and Asia, and reaching out to non-European organizations such as AORTIC for studies of African populations.

Direct-to-consumer global PRS

In the commercial PRS market, efforts to address diversity shortcomings are also gaining momentum, with Myriad Genetics touting a first-of-its kind “global PRS.”

The PRS, a recalibrated version the company’s riskScore PRS, sold as part of its Myriad myRisk Hereditary Cancer test, will reportedly apply to all ethnicities in estimating an individual’s 5-year and lifetime risk of breast cancer.

A study presented in June at the American Society of Clinical Oncology meeting, describes the development of the model with the use of three large ancestry-specific PRSs based on African American, Asian, and European cohorts, with the system including a total of 149 single-nucleotide polymorphisms, including 93 well established for breast cancer and 56 that are ancestry specific.

In validation of the data in an independent cohort of 62,707 individuals, the global PRS was strongly associated with breast cancer in the full combined validation cohort as well as in all three of the ancestry subcohorts.

However, the effect size among women with African ancestry was still the lowest of all of the groups, with a mean OR of 1.24 per standard deviation, versus the highest rate of mixed ancestry (OR, 1.59).

According to senior author Holly Pederson, MD, director of medical breast services at the Cleveland Clinic, the applicability of the PRS to women with African ancestry is expected to further improve as additional data become available.

“The discriminatory power in women of African descent was significantly improved but still suboptimal,” she said. “The need for more data, particularly in Black women, is challenging not only because there is likely more diversity in the genomic landscape of women of African descent, but also because the barriers created by historical, cultural, institutional and interpersonal dynamics result in the paucity of this data.”

“We must be committed to ending bias resulting in health care disparities,” Dr. Pederson said. She noted that the global PRS is nevertheless “still clinically useful in Black women,” and recommended that clinicians be up front with patients on the status of the research challenges.

“As with any clinical shared decision-making conversation between a patient and her provider, it is important for Black women to know that data is limited in the African American population, particularly given the vast genomic diversity of the African continent,” she said. “This model, as models that have gone before it, will improve with additional data, particularly in this population.”

Commercial PRSs may benefit research

While the commercial marketing of PRSs in a direct-to-consumer fashion have raised some concerns, such as how individuals respond to their risk scores, there could be important benefits as well, commented Megan C. Roberts, PhD.

“There may be an opportunity to learn from these companies about how to engage diverse communities in genomic testing,” said Dr. Roberts, an assistant professor and director of implementation science in precision health and society at the University of North Carolina at Chapel Hill. “Moreover, the data they collect from their customers often can be used for research purposes as well.”

In a recent perspective, Dr. Roberts and colleagues addressed the role of health disparities in PRSs. She’ll be joining international precision public health researchers in October in hosting a free virtual conference at UNC on the topic.

“There is a huge need to improve racial and ethnic diversity in our genomic datasets,” Dr. Roberts said. “Without this, we will not be able to return on the promise of precision medicine and prevention for improving the health of our whole population.”

Dr. Pederson disclosed that she is a consultant for Myriad Genetics.