Clinical Endocrinology News

The concept that there is a male equivalent of polycystic ovary syndrome (PCOS) was first described more than 15 years ago; a new study has further validated the principle using a polygenic risk score.

By demonstrating a high rates of cardiometabolic dysfunction and androgenic conditions in men with a high PCOS risk score, “we have shown that these genetic risk factors can act independently of ovarian function,” reported Jia Zhu, MD, a clinical endocrinology fellow at Boston Children’s Hospital.

The characterization of a male equivalent of PCOS has implications for both men and women, according to Dr. Zhu. For men, better definition of a phenotype has potential to accelerate the recognition and treatment of an inherited metabolic disorder. For women, this direction of study might help to unravel the relationship between the metabolic pathology and symptoms involving the reproductive system.

Affecting up to 10% of women, PCOS is characterized by ovulatory dysfunction and hyperandrogenism commonly associated with insulin resistance, obesity, and elevation in cardiovascular risk factors. Familial clustering implies an important genetic component, but the relationship between metabolic and ovulatory dysfunction remains incompletely understood.

“Both ovarian-related and ovarian-independent factors have been implicated in the pathogenesis of PCOS, but it remains to be determined which are the inciting events and which are the secondary consequences,” Dr. Zhu explained during his presentation of the study at the annual meeting of the Endocrine Society.
 

Polygenic risk score applied to men

In this study, a polygenic risk score algorithm developed to predict PCOS in women was applied to men. The risk score was developed through genetic testing in 206,851 unrelated women in the UK Biobank. This algorithm was then applied to stratify risk in 176,360 men from the same biobank. For males, several adjustments were made, including those for age and genetic components relevant to ancestry.

When stratified into quintiles, those at highest risk, relative to those at lower risk, had numerically modest but highly significant increased odds ratio for obesity defined by a body mass index (BMI) of at least 30 kg/m² (OR, 1.17; P < .13 x 10^–29) and type 2 diabetes (OR, 1.15; P = .53 x 10^–7). Those in the highest risk group were also more likely to have coronary artery disease (HR, 1.05; P = .01) as well as androgenic alopecia (OR, 1.05; P = .03).

When stratified into deciles of risk, a stepwise increase was observed for the prevalence of several cardiovascular risk factors. These included hemoglobin A1c, triglycerides, BMI, and free androgen, reported Dr. Zhu.

The relationship between the risk score and both coronary artery disease and several dyslipidemias appeared to be mediated by BMI, but the relationship between the PCOS polygenic risk score and type 2 diabetes persisted after adjusting for BMI.

For women, the implication of this analysis is that the reproductive dysfunction associated with PCOS might arise in at least some cases “secondarily from the genetically determined disruption of biological pathways common to both men and women,” Dr. Zhu said. She suggested that efforts to dissect these biological pathways might provide a path to under-standing the underlying mechanism of the ovarian complications, such as irregular menstrual periods, infertility, and ovarian cysts.
 

Family history of PCOS central to male risk

For men, a family history of PCOS might be relevant to predicting increased risk of type 2 diabetes, obesity and cardiovascular disease, Dr. Zhu indicated. In addition, this syndrome is also likely relevant to such signs of hyperandrogenism as hair loss and low testosterone levels in males with the PCOS-equivalent syndrome.

Other investigators have also suggested that male-equivalent PCOS exists and might be clinically relevant. According to Frederica Di Guardio, MD, a gynecologist in the department of medical surgical specialties, University of Catania (Italy), there is enough evidence for a PCOS-equivalent syndrome in men to consider asking males with obesity or other evidence of the metabolic abnormalities about a family history of PCOS.

“These patients have a high risk of developing cardiovascular disease, metabolic syndrome, and carotid atherosclerotic plaques,” she advised on the basis of her own and previous studies. By asking about a family history of PCOS in males, it can raise clinical suspicion and permit early intervention.

Not least important, identifying males at risk can allow them “to adopt a healthy lifestyle, preventing the risk of metabolic and cardiovascular events,” Dr. Di Guardio said.

In a recent review article on the male PCOS syndrome, Dr. Di Guardio traced the male PCOS-equivalent syndrome to a 2004 article. She reported that more than 30 articles have been published subsequently.

There is no formal clinical definition of male equivalent PCOS. According to her review of published studies, Dr. Di Guardio acknowledged that there has been considerable heterogeneity in the prevalence of the associated features, but the unifying factor is the presence of a set of genes associated with PCOS. In men, as well as in women, these appear to drive an increased risk of metabolic abnormalities and cardiovascular disease.

Dr. Zhu and Dr. Di Guardio reported no relevant conflicts of interest.

The concept that there is a male equivalent of polycystic ovary syndrome (PCOS) was first described more than 15 years ago; a new study has further validated the principle using a polygenic risk score.

By demonstrating a high rates of cardiometabolic dysfunction and androgenic conditions in men with a high PCOS risk score, “we have shown that these genetic risk factors can act independently of ovarian function,” reported Jia Zhu, MD, a clinical endocrinology fellow at Boston Children’s Hospital.

The characterization of a male equivalent of PCOS has implications for both men and women, according to Dr. Zhu. For men, better definition of a phenotype has potential to accelerate the recognition and treatment of an inherited metabolic disorder. For women, this direction of study might help to unravel the relationship between the metabolic pathology and symptoms involving the reproductive system.

Affecting up to 10% of women, PCOS is characterized by ovulatory dysfunction and hyperandrogenism commonly associated with insulin resistance, obesity, and elevation in cardiovascular risk factors. Familial clustering implies an important genetic component, but the relationship between metabolic and ovulatory dysfunction remains incompletely understood.

“Both ovarian-related and ovarian-independent factors have been implicated in the pathogenesis of PCOS, but it remains to be determined which are the inciting events and which are the secondary consequences,” Dr. Zhu explained during his presentation of the study at the annual meeting of the Endocrine Society.
 

Polygenic risk score applied to men

In this study, a polygenic risk score algorithm developed to predict PCOS in women was applied to men. The risk score was developed through genetic testing in 206,851 unrelated women in the UK Biobank. This algorithm was then applied to stratify risk in 176,360 men from the same biobank. For males, several adjustments were made, including those for age and genetic components relevant to ancestry.

When stratified into quintiles, those at highest risk, relative to those at lower risk, had numerically modest but highly significant increased odds ratio for obesity defined by a body mass index (BMI) of at least 30 kg/m² (OR, 1.17; P < .13 x 10^–29) and type 2 diabetes (OR, 1.15; P = .53 x 10^–7). Those in the highest risk group were also more likely to have coronary artery disease (HR, 1.05; P = .01) as well as androgenic alopecia (OR, 1.05; P = .03).

When stratified into deciles of risk, a stepwise increase was observed for the prevalence of several cardiovascular risk factors. These included hemoglobin A1c, triglycerides, BMI, and free androgen, reported Dr. Zhu.

The relationship between the risk score and both coronary artery disease and several dyslipidemias appeared to be mediated by BMI, but the relationship between the PCOS polygenic risk score and type 2 diabetes persisted after adjusting for BMI.

For women, the implication of this analysis is that the reproductive dysfunction associated with PCOS might arise in at least some cases “secondarily from the genetically determined disruption of biological pathways common to both men and women,” Dr. Zhu said. She suggested that efforts to dissect these biological pathways might provide a path to under-standing the underlying mechanism of the ovarian complications, such as irregular menstrual periods, infertility, and ovarian cysts.
 

Family history of PCOS central to male risk

For men, a family history of PCOS might be relevant to predicting increased risk of type 2 diabetes, obesity and cardiovascular disease, Dr. Zhu indicated. In addition, this syndrome is also likely relevant to such signs of hyperandrogenism as hair loss and low testosterone levels in males with the PCOS-equivalent syndrome.

Other investigators have also suggested that male-equivalent PCOS exists and might be clinically relevant. According to Frederica Di Guardio, MD, a gynecologist in the department of medical surgical specialties, University of Catania (Italy), there is enough evidence for a PCOS-equivalent syndrome in men to consider asking males with obesity or other evidence of the metabolic abnormalities about a family history of PCOS.

“These patients have a high risk of developing cardiovascular disease, metabolic syndrome, and carotid atherosclerotic plaques,” she advised on the basis of her own and previous studies. By asking about a family history of PCOS in males, it can raise clinical suspicion and permit early intervention.

Not least important, identifying males at risk can allow them “to adopt a healthy lifestyle, preventing the risk of metabolic and cardiovascular events,” Dr. Di Guardio said.

In a recent review article on the male PCOS syndrome, Dr. Di Guardio traced the male PCOS-equivalent syndrome to a 2004 article. She reported that more than 30 articles have been published subsequently.

There is no formal clinical definition of male equivalent PCOS. According to her review of published studies, Dr. Di Guardio acknowledged that there has been considerable heterogeneity in the prevalence of the associated features, but the unifying factor is the presence of a set of genes associated with PCOS. In men, as well as in women, these appear to drive an increased risk of metabolic abnormalities and cardiovascular disease.

Dr. Zhu and Dr. Di Guardio reported no relevant conflicts of interest.

The concept that there is a male equivalent of polycystic ovary syndrome (PCOS) was first described more than 15 years ago; a new study has further validated the principle using a polygenic risk score.

By demonstrating a high rates of cardiometabolic dysfunction and androgenic conditions in men with a high PCOS risk score, “we have shown that these genetic risk factors can act independently of ovarian function,” reported Jia Zhu, MD, a clinical endocrinology fellow at Boston Children’s Hospital.

The characterization of a male equivalent of PCOS has implications for both men and women, according to Dr. Zhu. For men, better definition of a phenotype has potential to accelerate the recognition and treatment of an inherited metabolic disorder. For women, this direction of study might help to unravel the relationship between the metabolic pathology and symptoms involving the reproductive system.

Affecting up to 10% of women, PCOS is characterized by ovulatory dysfunction and hyperandrogenism commonly associated with insulin resistance, obesity, and elevation in cardiovascular risk factors. Familial clustering implies an important genetic component, but the relationship between metabolic and ovulatory dysfunction remains incompletely understood.

“Both ovarian-related and ovarian-independent factors have been implicated in the pathogenesis of PCOS, but it remains to be determined which are the inciting events and which are the secondary consequences,” Dr. Zhu explained during his presentation of the study at the annual meeting of the Endocrine Society.
 

Polygenic risk score applied to men

In this study, a polygenic risk score algorithm developed to predict PCOS in women was applied to men. The risk score was developed through genetic testing in 206,851 unrelated women in the UK Biobank. This algorithm was then applied to stratify risk in 176,360 men from the same biobank. For males, several adjustments were made, including those for age and genetic components relevant to ancestry.

When stratified into quintiles, those at highest risk, relative to those at lower risk, had numerically modest but highly significant increased odds ratio for obesity defined by a body mass index (BMI) of at least 30 kg/m² (OR, 1.17; P < .13 x 10^–29) and type 2 diabetes (OR, 1.15; P = .53 x 10^–7). Those in the highest risk group were also more likely to have coronary artery disease (HR, 1.05; P = .01) as well as androgenic alopecia (OR, 1.05; P = .03).

When stratified into deciles of risk, a stepwise increase was observed for the prevalence of several cardiovascular risk factors. These included hemoglobin A1c, triglycerides, BMI, and free androgen, reported Dr. Zhu.

The relationship between the risk score and both coronary artery disease and several dyslipidemias appeared to be mediated by BMI, but the relationship between the PCOS polygenic risk score and type 2 diabetes persisted after adjusting for BMI.

For women, the implication of this analysis is that the reproductive dysfunction associated with PCOS might arise in at least some cases “secondarily from the genetically determined disruption of biological pathways common to both men and women,” Dr. Zhu said. She suggested that efforts to dissect these biological pathways might provide a path to under-standing the underlying mechanism of the ovarian complications, such as irregular menstrual periods, infertility, and ovarian cysts.
 

Family history of PCOS central to male risk

For men, a family history of PCOS might be relevant to predicting increased risk of type 2 diabetes, obesity and cardiovascular disease, Dr. Zhu indicated. In addition, this syndrome is also likely relevant to such signs of hyperandrogenism as hair loss and low testosterone levels in males with the PCOS-equivalent syndrome.

Other investigators have also suggested that male-equivalent PCOS exists and might be clinically relevant. According to Frederica Di Guardio, MD, a gynecologist in the department of medical surgical specialties, University of Catania (Italy), there is enough evidence for a PCOS-equivalent syndrome in men to consider asking males with obesity or other evidence of the metabolic abnormalities about a family history of PCOS.

“These patients have a high risk of developing cardiovascular disease, metabolic syndrome, and carotid atherosclerotic plaques,” she advised on the basis of her own and previous studies. By asking about a family history of PCOS in males, it can raise clinical suspicion and permit early intervention.

Not least important, identifying males at risk can allow them “to adopt a healthy lifestyle, preventing the risk of metabolic and cardiovascular events,” Dr. Di Guardio said.

In a recent review article on the male PCOS syndrome, Dr. Di Guardio traced the male PCOS-equivalent syndrome to a 2004 article. She reported that more than 30 articles have been published subsequently.

There is no formal clinical definition of male equivalent PCOS. According to her review of published studies, Dr. Di Guardio acknowledged that there has been considerable heterogeneity in the prevalence of the associated features, but the unifying factor is the presence of a set of genes associated with PCOS. In men, as well as in women, these appear to drive an increased risk of metabolic abnormalities and cardiovascular disease.

Dr. Zhu and Dr. Di Guardio reported no relevant conflicts of interest.

High-intensity interval training (HIIT) was better than moderate-intensity continuous training (MICT) for improving several measures of cardiometabolic health in women with polycystic ovary syndrome (PCOS) in a prospective, randomized, single-center study with 27 women.

yacobchuk/Getty Images

After 12 weeks on a supervised exercise regimen, the women with PCOS who followed the HIIT program had significantly better improvements in aerobic capacity, insulin sensitivity, and level of sex hormone–binding globulin, Rhiannon K. Patten, MSc, said at the annual meeting of the Endocrine Society.

“HIIT can offer superior improvements in health outcomes, and should be considered as an effective tool to reduce cardiometabolic risk in women with PCOS,” concluded Ms. Patten, a researcher in the Institute for Health and Sport at Victoria University in Melbourne in her presentation (Abstract OR10-1).

“The changes we see [after 12 weeks on the HIIT regimen] seem to occur despite no change in body mass index, so rather than focus on weight loss we encourage participants to focus on the health improvements that seem to be greater with HIIT. We actively encourage the HIIT protocol right now,” she said.

Both regimens use a stationary cycle ergometer. In the HIIT protocol patients twice weekly pedal through 12 1-minute intervals at a heart rate of 90%-100% maximum, interspersed with 1 minute rest intervals. On a third day per week, patients pedal to a heart rate of 90%-95% maximum for 6-8 intervals maintained for 2 minutes and interspersed with rest intervals of 2 minutes. The MICT regimen used as a comparator has participants pedal to 60%-70% of their maximum heart rate continuously for 50 minutes 3 days weekly.



HIIT saves time

“These findings are relevant to clinical practice, because they demonstrate that HIIT is effective in women with PCOS. Reducing the time devoted to exercise to achieve fitness goals is attractive to patients. The reduced time to achieve training benefits with HIIT should improve patient compliance,” commented Andrea Dunaif, MD, professor and chief of the division of endocrinology, diabetes, and bone disease of the Mount Sinai Health System in New York, who was not involved with the study.

The overall weekly exercise time on the MICT regimen, 150 minutes, halves down to 75 minutes a week in the HIIT program. Guideline recommendations released in 2018 by the International PCOS Network recommended these as acceptable alternative exercise strategies. Ms. Patten and her associates sought to determine whether one strategy surpassed the other, the first time this has been examined in women with PCOS, she said.

They randomized 27 sedentary women 18-45 years old with a body mass index (BMI) above 25 kg/m² and diagnosed with PCOS by the Rotterdam criteria to a 12-week supervised exercise program on either the HIIT or MICT protocol. Their average BMI at entry was 36-37 kg/m². The study excluded women who smoked, were pregnant, had an illness or injury that would prevent exercise, or were on an oral contraceptive or insulin-sensitizing medication.

At the end of 12 weeks, neither group had a significant change in average weight or BMI, and waist circumference dropped by an average of just over 2 cm in both treatment groups. Lean mass increased by a mean 1 kg in the HIIT group, a significant change, compared with a nonsignificant 0.3 kg average increase in the MICT group.
 

Increased aerobic capacity ‘partially explains’ improved insulin sensitivity

Aerobic capacity, measured as peak oxygen consumption (VO₂peak), increased by an average 5.7 mL/kg per min among the HIIT patients, significantly more than the mean 3.2 mL/kg per min increase among those in the MICT program.

The insulin sensitivity index rose by a significant, relative 35% among the HIIT patients, but barely budged in the MICT group. Fasting glucose fell significantly and the glucose infusion rate increased significantly among the women who performed HIIT, but again showed little change among those doing MICT.

Analysis showed a significant link between the increase in VO₂peak and the increase in insulin sensitivity among the women engaged in HIIT, Ms. Patten reported. The improvement in the insulin sensitivity index was “partially explained” by the increase in VO₂peak, she said.

Assessment of hormone levels showed a significant increase in sex hormone–binding globulin in the HIIT patients while those in the MICT group showed a small decline in this level. The free androgen index fell by a relative 39% on average in the HIIT group, a significant drop, but decreased by a much smaller and not significant amount among the women who did MICT. The women who performed HIIT also showed a significant drop in their free testosterone level, a change not seen with MICT.

Women who performed the HIIT protocol also had a significant improvement in their menstrual cyclicity, and significant improvements in depression, stress, and anxiety, Ms Patten reported. She next plans to do longer follow-up on study participants, out to 6 and 12 months after the end of the exercise protocol.

“Overall, the findings suggest that HIIT is superior to MICT for improving fitness and insulin sensitivity in the short term. Results from a number of studies in individuals without PCOS suggest that HIIT is superior to MICT for improving fitness short term,” commented Dr. Dunaif. “This study makes an important contribution by directly investigating the impact of training intensity in women with PCOS. Larger studies will be needed before the superiority of HIIT is established for women with PCOS, and study durations of at least several months will be needed to assess the impact on reproductive outcomes such as ovulation,” she said in an interview. She also called for assessing the effects of HIIT in more diverse populations of women with PCOS.

Ms. Patten had no disclosures. Dr. Dunaif has been a consultant to Equator Therapeutics, Fractyl Laboratories, and Globe Life Sciences.

mzoler@mdedge.com
 

High-intensity interval training (HIIT) was better than moderate-intensity continuous training (MICT) for improving several measures of cardiometabolic health in women with polycystic ovary syndrome (PCOS) in a prospective, randomized, single-center study with 27 women.

yacobchuk/Getty Images

After 12 weeks on a supervised exercise regimen, the women with PCOS who followed the HIIT program had significantly better improvements in aerobic capacity, insulin sensitivity, and level of sex hormone–binding globulin, Rhiannon K. Patten, MSc, said at the annual meeting of the Endocrine Society.

“HIIT can offer superior improvements in health outcomes, and should be considered as an effective tool to reduce cardiometabolic risk in women with PCOS,” concluded Ms. Patten, a researcher in the Institute for Health and Sport at Victoria University in Melbourne in her presentation (Abstract OR10-1).

“The changes we see [after 12 weeks on the HIIT regimen] seem to occur despite no change in body mass index, so rather than focus on weight loss we encourage participants to focus on the health improvements that seem to be greater with HIIT. We actively encourage the HIIT protocol right now,” she said.

Both regimens use a stationary cycle ergometer. In the HIIT protocol patients twice weekly pedal through 12 1-minute intervals at a heart rate of 90%-100% maximum, interspersed with 1 minute rest intervals. On a third day per week, patients pedal to a heart rate of 90%-95% maximum for 6-8 intervals maintained for 2 minutes and interspersed with rest intervals of 2 minutes. The MICT regimen used as a comparator has participants pedal to 60%-70% of their maximum heart rate continuously for 50 minutes 3 days weekly.



HIIT saves time

“These findings are relevant to clinical practice, because they demonstrate that HIIT is effective in women with PCOS. Reducing the time devoted to exercise to achieve fitness goals is attractive to patients. The reduced time to achieve training benefits with HIIT should improve patient compliance,” commented Andrea Dunaif, MD, professor and chief of the division of endocrinology, diabetes, and bone disease of the Mount Sinai Health System in New York, who was not involved with the study.

The overall weekly exercise time on the MICT regimen, 150 minutes, halves down to 75 minutes a week in the HIIT program. Guideline recommendations released in 2018 by the International PCOS Network recommended these as acceptable alternative exercise strategies. Ms. Patten and her associates sought to determine whether one strategy surpassed the other, the first time this has been examined in women with PCOS, she said.

They randomized 27 sedentary women 18-45 years old with a body mass index (BMI) above 25 kg/m² and diagnosed with PCOS by the Rotterdam criteria to a 12-week supervised exercise program on either the HIIT or MICT protocol. Their average BMI at entry was 36-37 kg/m². The study excluded women who smoked, were pregnant, had an illness or injury that would prevent exercise, or were on an oral contraceptive or insulin-sensitizing medication.

At the end of 12 weeks, neither group had a significant change in average weight or BMI, and waist circumference dropped by an average of just over 2 cm in both treatment groups. Lean mass increased by a mean 1 kg in the HIIT group, a significant change, compared with a nonsignificant 0.3 kg average increase in the MICT group.
 

Increased aerobic capacity ‘partially explains’ improved insulin sensitivity

Aerobic capacity, measured as peak oxygen consumption (VO₂peak), increased by an average 5.7 mL/kg per min among the HIIT patients, significantly more than the mean 3.2 mL/kg per min increase among those in the MICT program.

The insulin sensitivity index rose by a significant, relative 35% among the HIIT patients, but barely budged in the MICT group. Fasting glucose fell significantly and the glucose infusion rate increased significantly among the women who performed HIIT, but again showed little change among those doing MICT.

Analysis showed a significant link between the increase in VO₂peak and the increase in insulin sensitivity among the women engaged in HIIT, Ms. Patten reported. The improvement in the insulin sensitivity index was “partially explained” by the increase in VO₂peak, she said.

Assessment of hormone levels showed a significant increase in sex hormone–binding globulin in the HIIT patients while those in the MICT group showed a small decline in this level. The free androgen index fell by a relative 39% on average in the HIIT group, a significant drop, but decreased by a much smaller and not significant amount among the women who did MICT. The women who performed HIIT also showed a significant drop in their free testosterone level, a change not seen with MICT.

Women who performed the HIIT protocol also had a significant improvement in their menstrual cyclicity, and significant improvements in depression, stress, and anxiety, Ms Patten reported. She next plans to do longer follow-up on study participants, out to 6 and 12 months after the end of the exercise protocol.

“Overall, the findings suggest that HIIT is superior to MICT for improving fitness and insulin sensitivity in the short term. Results from a number of studies in individuals without PCOS suggest that HIIT is superior to MICT for improving fitness short term,” commented Dr. Dunaif. “This study makes an important contribution by directly investigating the impact of training intensity in women with PCOS. Larger studies will be needed before the superiority of HIIT is established for women with PCOS, and study durations of at least several months will be needed to assess the impact on reproductive outcomes such as ovulation,” she said in an interview. She also called for assessing the effects of HIIT in more diverse populations of women with PCOS.

Ms. Patten had no disclosures. Dr. Dunaif has been a consultant to Equator Therapeutics, Fractyl Laboratories, and Globe Life Sciences.

mzoler@mdedge.com
 

High-intensity interval training (HIIT) was better than moderate-intensity continuous training (MICT) for improving several measures of cardiometabolic health in women with polycystic ovary syndrome (PCOS) in a prospective, randomized, single-center study with 27 women.

yacobchuk/Getty Images

After 12 weeks on a supervised exercise regimen, the women with PCOS who followed the HIIT program had significantly better improvements in aerobic capacity, insulin sensitivity, and level of sex hormone–binding globulin, Rhiannon K. Patten, MSc, said at the annual meeting of the Endocrine Society.

“HIIT can offer superior improvements in health outcomes, and should be considered as an effective tool to reduce cardiometabolic risk in women with PCOS,” concluded Ms. Patten, a researcher in the Institute for Health and Sport at Victoria University in Melbourne in her presentation (Abstract OR10-1).

“The changes we see [after 12 weeks on the HIIT regimen] seem to occur despite no change in body mass index, so rather than focus on weight loss we encourage participants to focus on the health improvements that seem to be greater with HIIT. We actively encourage the HIIT protocol right now,” she said.

Both regimens use a stationary cycle ergometer. In the HIIT protocol patients twice weekly pedal through 12 1-minute intervals at a heart rate of 90%-100% maximum, interspersed with 1 minute rest intervals. On a third day per week, patients pedal to a heart rate of 90%-95% maximum for 6-8 intervals maintained for 2 minutes and interspersed with rest intervals of 2 minutes. The MICT regimen used as a comparator has participants pedal to 60%-70% of their maximum heart rate continuously for 50 minutes 3 days weekly.



HIIT saves time

“These findings are relevant to clinical practice, because they demonstrate that HIIT is effective in women with PCOS. Reducing the time devoted to exercise to achieve fitness goals is attractive to patients. The reduced time to achieve training benefits with HIIT should improve patient compliance,” commented Andrea Dunaif, MD, professor and chief of the division of endocrinology, diabetes, and bone disease of the Mount Sinai Health System in New York, who was not involved with the study.

The overall weekly exercise time on the MICT regimen, 150 minutes, halves down to 75 minutes a week in the HIIT program. Guideline recommendations released in 2018 by the International PCOS Network recommended these as acceptable alternative exercise strategies. Ms. Patten and her associates sought to determine whether one strategy surpassed the other, the first time this has been examined in women with PCOS, she said.

They randomized 27 sedentary women 18-45 years old with a body mass index (BMI) above 25 kg/m² and diagnosed with PCOS by the Rotterdam criteria to a 12-week supervised exercise program on either the HIIT or MICT protocol. Their average BMI at entry was 36-37 kg/m². The study excluded women who smoked, were pregnant, had an illness or injury that would prevent exercise, or were on an oral contraceptive or insulin-sensitizing medication.

At the end of 12 weeks, neither group had a significant change in average weight or BMI, and waist circumference dropped by an average of just over 2 cm in both treatment groups. Lean mass increased by a mean 1 kg in the HIIT group, a significant change, compared with a nonsignificant 0.3 kg average increase in the MICT group.
 

Increased aerobic capacity ‘partially explains’ improved insulin sensitivity

Aerobic capacity, measured as peak oxygen consumption (VO₂peak), increased by an average 5.7 mL/kg per min among the HIIT patients, significantly more than the mean 3.2 mL/kg per min increase among those in the MICT program.

The insulin sensitivity index rose by a significant, relative 35% among the HIIT patients, but barely budged in the MICT group. Fasting glucose fell significantly and the glucose infusion rate increased significantly among the women who performed HIIT, but again showed little change among those doing MICT.

Analysis showed a significant link between the increase in VO₂peak and the increase in insulin sensitivity among the women engaged in HIIT, Ms. Patten reported. The improvement in the insulin sensitivity index was “partially explained” by the increase in VO₂peak, she said.

Assessment of hormone levels showed a significant increase in sex hormone–binding globulin in the HIIT patients while those in the MICT group showed a small decline in this level. The free androgen index fell by a relative 39% on average in the HIIT group, a significant drop, but decreased by a much smaller and not significant amount among the women who did MICT. The women who performed HIIT also showed a significant drop in their free testosterone level, a change not seen with MICT.

Women who performed the HIIT protocol also had a significant improvement in their menstrual cyclicity, and significant improvements in depression, stress, and anxiety, Ms Patten reported. She next plans to do longer follow-up on study participants, out to 6 and 12 months after the end of the exercise protocol.

“Overall, the findings suggest that HIIT is superior to MICT for improving fitness and insulin sensitivity in the short term. Results from a number of studies in individuals without PCOS suggest that HIIT is superior to MICT for improving fitness short term,” commented Dr. Dunaif. “This study makes an important contribution by directly investigating the impact of training intensity in women with PCOS. Larger studies will be needed before the superiority of HIIT is established for women with PCOS, and study durations of at least several months will be needed to assess the impact on reproductive outcomes such as ovulation,” she said in an interview. She also called for assessing the effects of HIIT in more diverse populations of women with PCOS.

Ms. Patten had no disclosures. Dr. Dunaif has been a consultant to Equator Therapeutics, Fractyl Laboratories, and Globe Life Sciences.

mzoler@mdedge.com
 

Overcoming the challenges in managing type 1 diabetes can sometimes feel like an unappreciated “superpower.” That was part of the thinking behind the creation of a comic book trilogy that aims to educate people of all ages – including health care providers – about the realities of living with this condition.

The series was initially launched by a team from Portsmouth (England) Hospitals University National Health Service Trust and University Hospital Southampton NHS Foundation Trust. It is now officially backed by the NHS. The first book in the trilogy, published in 2016, visually illustrates the challenges faced by a teenage boy who had recently been diagnosed with type 1 diabetes. The second volume, released in 2018, follows a young girl who is hospitalized with diabetic ketoacidosis. The third, published in December 2020, explores the stigma associated with diabetes and delves into hypoglycemia.

Available for free online, the three comic books are meant for adults, children, health care professionals, and laypeople. This news organization spoke with series cocreator Partha Kar, MBBS, MD, national specialty adviser, Diabetes for NHS England, about the series. This interview has been edited for length and clarity.
 

How did the idea for a comic book series about type 1 diabetes come about?Dr. Kar: My Southampton colleague Mayank Patel, BM, DM, FRCP, and I were discussing ways of reaching different audiences to raise awareness about type 1 diabetes, and we had the idea of comic books. After all, comic book movies are among the biggest blockbusters if one looks at popular culture, because it’s not just kids watching them.

One of our patients made an interesting observation that really resonated. He said having type 1 diabetes was like the Marvel Comics superhero Hulk.

Several scenes in the first publication, Type 1: Origins, were based on the Hulk, a scientist who gets a radioactive dose by accident. He doesn’t like turning green when he’s angry, even though he also becomes very strong. He basically spends the rest of his life trying to find the cure for himself, but he eventually makes the best of his two worlds – Professor and Hulk – rather than constantly fighting his situation.

The story line was primarily written by a group of patients with type 1 diabetes based on their own experiences. Mayank and I were mostly just supervising and financing the project. The graphics and layout were done by Revolve Comics, a publisher specializing in health education via the comic book medium.

Our aim was to bring awareness of type 1 diabetes to people who don’t have diabetes, including teachers, family members, and friends. At the end of Origins, we provide a list of online resources for more information and for social connection.

Since it launched in October 2016, Origins has been downloaded nearly 10,000 times. Lots of local charities and schools have picked it up. Parents and kids have come to us asking for more and giving us ideas. That’s what prompted the next one.

 

The second volume, Type 1: Attack of the Ketones, is more technical and somewhat surprising in that it portrays some hospital staff members as not well-informed about type 1 diabetes. Are they part of the intended audience?

Yes, this one was directed a little bit more towards professionals, hospitals, and staff. It’s also informed by patient feedback, and dovetails with my efforts to improve hospital care for people with type 1 diabetes. But of course, patients and interested laypeople can also learn from it.

A theme in volume 2 comes from another Marvel Comics superhero, Iron Man. In the movie, when Tony Stark’s heart is severely damaged with shrapnel, he acquires an arc reactor that keeps him alive and also powers the suit that gives him superpowers. After the reactor is taken away, he devises a way to replace the missing part and reassemble the suit.

Similarly, in type 1 diabetes, the ability to produce insulin has been taken away without permission. But what is missing can thankfully be replaced, albeit imperfectly. As we illustrate, things don’t always go to plan despite best efforts to administer insulin in the right dose at the right time.

At the end of Attack of the Ketones, we provide two pages of text about recognizing and managing hyperglycemia and preventing diabetic ketoacidosis. This volume was funded by NHS England and then backed by JDRF and Diabetes UK, and many hospitals picked it up. It has had about 8,000 downloads.

 

In Volume 3, you explore stigma and the issue of language regarding type 1 diabetes. How did those topics come about?

Kar: Type 1 Mission 3: S.T.I.G.M.A. was also based on patient feedback, with input from some Indian diabetes groups I’ve worked with. Here, the protagonist is a young man with type 1 diabetes who goes on holiday to India, where diabetes stigma is widespread. The characters address language problems such as use of the word “diabetic” to label a person, and they counter misconceptions such as that diabetes is contagious. There’s an Indian comic book version of this volume out now.

The main character of this volume experiences severe hypoglycemia and is saved by a glucagon injection from a colleague, one of several presented as superheroes who help in the fight to end diabetes stigma. They are referred to as Guardians of the Glucose, a take on yet another Marvel franchise, Guardians of the Galaxy.

At the end of this volume, we provide two pages of text about recognizing, managing, and preventing hypoglycemia. Again, we hope to educate as wide an audience as possible.
 

At the end of volume 3, you also briefly mention the COVID-19 pandemic. Will there be a fourth volume dealing with that, or other topics, such as diabetes technology?

We’ve left it open. We want to see how volume 3 lands. Depending on that, we might take it forward. There are certainly plenty of topics to tackle. We’ve also discussed moving into gaming or virtual reality. Overall, we hope to educate people by engaging them in different ways.

Dr. Kar has been a consultant diabetologist/endocrinologist within the NHS since 2008. He disclosed no relevant financial relationships.

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

Overcoming the challenges in managing type 1 diabetes can sometimes feel like an unappreciated “superpower.” That was part of the thinking behind the creation of a comic book trilogy that aims to educate people of all ages – including health care providers – about the realities of living with this condition.

The series was initially launched by a team from Portsmouth (England) Hospitals University National Health Service Trust and University Hospital Southampton NHS Foundation Trust. It is now officially backed by the NHS. The first book in the trilogy, published in 2016, visually illustrates the challenges faced by a teenage boy who had recently been diagnosed with type 1 diabetes. The second volume, released in 2018, follows a young girl who is hospitalized with diabetic ketoacidosis. The third, published in December 2020, explores the stigma associated with diabetes and delves into hypoglycemia.

Available for free online, the three comic books are meant for adults, children, health care professionals, and laypeople. This news organization spoke with series cocreator Partha Kar, MBBS, MD, national specialty adviser, Diabetes for NHS England, about the series. This interview has been edited for length and clarity.
 

How did the idea for a comic book series about type 1 diabetes come about?Dr. Kar: My Southampton colleague Mayank Patel, BM, DM, FRCP, and I were discussing ways of reaching different audiences to raise awareness about type 1 diabetes, and we had the idea of comic books. After all, comic book movies are among the biggest blockbusters if one looks at popular culture, because it’s not just kids watching them.

One of our patients made an interesting observation that really resonated. He said having type 1 diabetes was like the Marvel Comics superhero Hulk.

Several scenes in the first publication, Type 1: Origins, were based on the Hulk, a scientist who gets a radioactive dose by accident. He doesn’t like turning green when he’s angry, even though he also becomes very strong. He basically spends the rest of his life trying to find the cure for himself, but he eventually makes the best of his two worlds – Professor and Hulk – rather than constantly fighting his situation.

The story line was primarily written by a group of patients with type 1 diabetes based on their own experiences. Mayank and I were mostly just supervising and financing the project. The graphics and layout were done by Revolve Comics, a publisher specializing in health education via the comic book medium.

Our aim was to bring awareness of type 1 diabetes to people who don’t have diabetes, including teachers, family members, and friends. At the end of Origins, we provide a list of online resources for more information and for social connection.

Since it launched in October 2016, Origins has been downloaded nearly 10,000 times. Lots of local charities and schools have picked it up. Parents and kids have come to us asking for more and giving us ideas. That’s what prompted the next one.

 

The second volume, Type 1: Attack of the Ketones, is more technical and somewhat surprising in that it portrays some hospital staff members as not well-informed about type 1 diabetes. Are they part of the intended audience?

Yes, this one was directed a little bit more towards professionals, hospitals, and staff. It’s also informed by patient feedback, and dovetails with my efforts to improve hospital care for people with type 1 diabetes. But of course, patients and interested laypeople can also learn from it.

A theme in volume 2 comes from another Marvel Comics superhero, Iron Man. In the movie, when Tony Stark’s heart is severely damaged with shrapnel, he acquires an arc reactor that keeps him alive and also powers the suit that gives him superpowers. After the reactor is taken away, he devises a way to replace the missing part and reassemble the suit.

Similarly, in type 1 diabetes, the ability to produce insulin has been taken away without permission. But what is missing can thankfully be replaced, albeit imperfectly. As we illustrate, things don’t always go to plan despite best efforts to administer insulin in the right dose at the right time.

At the end of Attack of the Ketones, we provide two pages of text about recognizing and managing hyperglycemia and preventing diabetic ketoacidosis. This volume was funded by NHS England and then backed by JDRF and Diabetes UK, and many hospitals picked it up. It has had about 8,000 downloads.

 

In Volume 3, you explore stigma and the issue of language regarding type 1 diabetes. How did those topics come about?

Kar: Type 1 Mission 3: S.T.I.G.M.A. was also based on patient feedback, with input from some Indian diabetes groups I’ve worked with. Here, the protagonist is a young man with type 1 diabetes who goes on holiday to India, where diabetes stigma is widespread. The characters address language problems such as use of the word “diabetic” to label a person, and they counter misconceptions such as that diabetes is contagious. There’s an Indian comic book version of this volume out now.

The main character of this volume experiences severe hypoglycemia and is saved by a glucagon injection from a colleague, one of several presented as superheroes who help in the fight to end diabetes stigma. They are referred to as Guardians of the Glucose, a take on yet another Marvel franchise, Guardians of the Galaxy.

At the end of this volume, we provide two pages of text about recognizing, managing, and preventing hypoglycemia. Again, we hope to educate as wide an audience as possible.
 

At the end of volume 3, you also briefly mention the COVID-19 pandemic. Will there be a fourth volume dealing with that, or other topics, such as diabetes technology?

We’ve left it open. We want to see how volume 3 lands. Depending on that, we might take it forward. There are certainly plenty of topics to tackle. We’ve also discussed moving into gaming or virtual reality. Overall, we hope to educate people by engaging them in different ways.

Dr. Kar has been a consultant diabetologist/endocrinologist within the NHS since 2008. He disclosed no relevant financial relationships.

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

Overcoming the challenges in managing type 1 diabetes can sometimes feel like an unappreciated “superpower.” That was part of the thinking behind the creation of a comic book trilogy that aims to educate people of all ages – including health care providers – about the realities of living with this condition.

The series was initially launched by a team from Portsmouth (England) Hospitals University National Health Service Trust and University Hospital Southampton NHS Foundation Trust. It is now officially backed by the NHS. The first book in the trilogy, published in 2016, visually illustrates the challenges faced by a teenage boy who had recently been diagnosed with type 1 diabetes. The second volume, released in 2018, follows a young girl who is hospitalized with diabetic ketoacidosis. The third, published in December 2020, explores the stigma associated with diabetes and delves into hypoglycemia.

Available for free online, the three comic books are meant for adults, children, health care professionals, and laypeople. This news organization spoke with series cocreator Partha Kar, MBBS, MD, national specialty adviser, Diabetes for NHS England, about the series. This interview has been edited for length and clarity.
 

How did the idea for a comic book series about type 1 diabetes come about?Dr. Kar: My Southampton colleague Mayank Patel, BM, DM, FRCP, and I were discussing ways of reaching different audiences to raise awareness about type 1 diabetes, and we had the idea of comic books. After all, comic book movies are among the biggest blockbusters if one looks at popular culture, because it’s not just kids watching them.

One of our patients made an interesting observation that really resonated. He said having type 1 diabetes was like the Marvel Comics superhero Hulk.

Several scenes in the first publication, Type 1: Origins, were based on the Hulk, a scientist who gets a radioactive dose by accident. He doesn’t like turning green when he’s angry, even though he also becomes very strong. He basically spends the rest of his life trying to find the cure for himself, but he eventually makes the best of his two worlds – Professor and Hulk – rather than constantly fighting his situation.

The story line was primarily written by a group of patients with type 1 diabetes based on their own experiences. Mayank and I were mostly just supervising and financing the project. The graphics and layout were done by Revolve Comics, a publisher specializing in health education via the comic book medium.

Our aim was to bring awareness of type 1 diabetes to people who don’t have diabetes, including teachers, family members, and friends. At the end of Origins, we provide a list of online resources for more information and for social connection.

Since it launched in October 2016, Origins has been downloaded nearly 10,000 times. Lots of local charities and schools have picked it up. Parents and kids have come to us asking for more and giving us ideas. That’s what prompted the next one.

 

The second volume, Type 1: Attack of the Ketones, is more technical and somewhat surprising in that it portrays some hospital staff members as not well-informed about type 1 diabetes. Are they part of the intended audience?

Yes, this one was directed a little bit more towards professionals, hospitals, and staff. It’s also informed by patient feedback, and dovetails with my efforts to improve hospital care for people with type 1 diabetes. But of course, patients and interested laypeople can also learn from it.

A theme in volume 2 comes from another Marvel Comics superhero, Iron Man. In the movie, when Tony Stark’s heart is severely damaged with shrapnel, he acquires an arc reactor that keeps him alive and also powers the suit that gives him superpowers. After the reactor is taken away, he devises a way to replace the missing part and reassemble the suit.

Similarly, in type 1 diabetes, the ability to produce insulin has been taken away without permission. But what is missing can thankfully be replaced, albeit imperfectly. As we illustrate, things don’t always go to plan despite best efforts to administer insulin in the right dose at the right time.

At the end of Attack of the Ketones, we provide two pages of text about recognizing and managing hyperglycemia and preventing diabetic ketoacidosis. This volume was funded by NHS England and then backed by JDRF and Diabetes UK, and many hospitals picked it up. It has had about 8,000 downloads.

 

In Volume 3, you explore stigma and the issue of language regarding type 1 diabetes. How did those topics come about?

Kar: Type 1 Mission 3: S.T.I.G.M.A. was also based on patient feedback, with input from some Indian diabetes groups I’ve worked with. Here, the protagonist is a young man with type 1 diabetes who goes on holiday to India, where diabetes stigma is widespread. The characters address language problems such as use of the word “diabetic” to label a person, and they counter misconceptions such as that diabetes is contagious. There’s an Indian comic book version of this volume out now.

The main character of this volume experiences severe hypoglycemia and is saved by a glucagon injection from a colleague, one of several presented as superheroes who help in the fight to end diabetes stigma. They are referred to as Guardians of the Glucose, a take on yet another Marvel franchise, Guardians of the Galaxy.

At the end of this volume, we provide two pages of text about recognizing, managing, and preventing hypoglycemia. Again, we hope to educate as wide an audience as possible.
 

At the end of volume 3, you also briefly mention the COVID-19 pandemic. Will there be a fourth volume dealing with that, or other topics, such as diabetes technology?

We’ve left it open. We want to see how volume 3 lands. Depending on that, we might take it forward. There are certainly plenty of topics to tackle. We’ve also discussed moving into gaming or virtual reality. Overall, we hope to educate people by engaging them in different ways.

Dr. Kar has been a consultant diabetologist/endocrinologist within the NHS since 2008. He disclosed no relevant financial relationships.

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

Women with polycystic ovary syndrome (PCOS) face an almost 30% increased risk for COVID-19 compared with unaffected women, even after adjusting for cardiometabolic and other related factors, suggests an analysis of United Kingdom primary care data.

“Our research has highlighted that women with PCOS are an often overlooked and potentially high-risk population for contracting COVID-19,” said joint senior author Wiebke Arlt, MD, PhD, director of the Institute of Metabolism and Systems Research at the University of Birmingham (England), in a press release.

“Before the onset of the COVID-19 pandemic, women with PCOS consistently report fragmented care, delayed diagnosis and a perception of poor clinician understanding of their condition,” added co-author Michael W. O’Reilly, MD, PhD, University of Medicine and Health Sciences, Dublin.

“Women suffering from this condition may fear, with some degree of justification, that an enhanced risk of COVID-19 infection will further compromise timely access to health care and serve to increase the sense of disenfranchisement currently experienced by many patients,” he added.

Consequently, “these findings need to be considered when designing public health policy and advice as our understanding of COVID-19 evolves,” noted first author Anuradhaa Subramanian, PhD Student, Institute of Applied Health Research, University of Birmingham.

The research was published by the European Journal of Endocrinology on March 9.
 

Women with PCOS: A distinct subgroup?

PCOS, which is thought to affect up to 16% of women, is associated with a significantly increased risk for type 2 diabetes, non-alcoholic fatty liver disease, and cardiovascular disease, all which have been linked to more severe COVID-19.

The condition is more prevalent in Black and South Asian women, who also appear to have an increased risk for severe COVID-19 vs. their White counterparts.

However, women and younger people in general have a lower overall risk for severe COVID-19 and mortality compared with older people and men.

Women with PCOS may therefore “represent a distinct subgroup of women at higher than average [on the basis of their sex and age] risk of adverse COVID-19–related outcomes,” the researchers note.

To investigate further, they collated data from The Health Improvement Network primary care database, which includes information from 365 active general practices in the U.K. for the period Jan. 31, 2020, to July 22, 2020.

They identified women with PCOS or a coded diagnosis of polycystic ovaries (PCO), and then for each woman randomly selected four unaffected controls matched for age and general practice location.

They included 21,292 women with PCOS/PCO and 78,310 controls, who had a mean age at study entry of 39.3 years and 39.5 years, respectively. The mean age at diagnosis of PCOS was 27 years, and the mean duration of the condition was 12.4 years.

The crude incidence of COVID-19 was 18.1 per 1000 person-years among women with PCOS vs. 11.9 per 1000 person-years in those without.

Cox regression analysis adjusted for age indicated that women with PCOS faced a significantly increased risk for COVID-19 than those without, at a hazard ratio of 1.51 (P < .001).

Further adjustment for body mass index (BMI) and age reduced the hazard ratio to 1.36 (P = .001).

In the fully adjusted model, which also took into account impaired glucose regulation, androgen excess, anovulation, hypertension, and other PCOS-related factors, the hazard ratio remained significant, at 1.28 (P = .015).
 

For shielding, balance benefits with impact on mental health

Joint senior author Krishnarajah Nirantharakumar, MD, PhD, also of the University of Birmingham, commented that, despite the increased risks, shielding strategies for COVID-19 need to take into account the impact of PCOS on women’s mental health.

“The risk of mental health problems, including low self-esteem, anxiety, and depression, is significantly higher in women with PCOS,” he said, “and advice on strict adherence to social distancing needs to be tempered by the associated risk of exacerbating these underlying problems.”

Arlt also pointed out that the study only looked at the incidence of COVID-19 infection, rather than outcomes.

“Our study does not provide information on the risk of a severe course of the COVID-19 infection or on the risk of COVID-19–related long-term complications [in women with PCOS], and further research is required,” she concluded.

The study was funded by Health Data Research UK and supported by the Wellcome Trust, the Health Research Board, and the National Institute for Health Research Birmingham Biomedical Research Centre based at the University of Birmingham and University Hospitals Birmingham NHS Foundation Trust. The study authors have disclosed no relevant financial relationships.

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

Women with polycystic ovary syndrome (PCOS) face an almost 30% increased risk for COVID-19 compared with unaffected women, even after adjusting for cardiometabolic and other related factors, suggests an analysis of United Kingdom primary care data.

“Our research has highlighted that women with PCOS are an often overlooked and potentially high-risk population for contracting COVID-19,” said joint senior author Wiebke Arlt, MD, PhD, director of the Institute of Metabolism and Systems Research at the University of Birmingham (England), in a press release.

“Before the onset of the COVID-19 pandemic, women with PCOS consistently report fragmented care, delayed diagnosis and a perception of poor clinician understanding of their condition,” added co-author Michael W. O’Reilly, MD, PhD, University of Medicine and Health Sciences, Dublin.

“Women suffering from this condition may fear, with some degree of justification, that an enhanced risk of COVID-19 infection will further compromise timely access to health care and serve to increase the sense of disenfranchisement currently experienced by many patients,” he added.

Consequently, “these findings need to be considered when designing public health policy and advice as our understanding of COVID-19 evolves,” noted first author Anuradhaa Subramanian, PhD Student, Institute of Applied Health Research, University of Birmingham.

The research was published by the European Journal of Endocrinology on March 9.
 

Women with PCOS: A distinct subgroup?

PCOS, which is thought to affect up to 16% of women, is associated with a significantly increased risk for type 2 diabetes, non-alcoholic fatty liver disease, and cardiovascular disease, all which have been linked to more severe COVID-19.

The condition is more prevalent in Black and South Asian women, who also appear to have an increased risk for severe COVID-19 vs. their White counterparts.

However, women and younger people in general have a lower overall risk for severe COVID-19 and mortality compared with older people and men.

Women with PCOS may therefore “represent a distinct subgroup of women at higher than average [on the basis of their sex and age] risk of adverse COVID-19–related outcomes,” the researchers note.

To investigate further, they collated data from The Health Improvement Network primary care database, which includes information from 365 active general practices in the U.K. for the period Jan. 31, 2020, to July 22, 2020.

They identified women with PCOS or a coded diagnosis of polycystic ovaries (PCO), and then for each woman randomly selected four unaffected controls matched for age and general practice location.

They included 21,292 women with PCOS/PCO and 78,310 controls, who had a mean age at study entry of 39.3 years and 39.5 years, respectively. The mean age at diagnosis of PCOS was 27 years, and the mean duration of the condition was 12.4 years.

The crude incidence of COVID-19 was 18.1 per 1000 person-years among women with PCOS vs. 11.9 per 1000 person-years in those without.

Cox regression analysis adjusted for age indicated that women with PCOS faced a significantly increased risk for COVID-19 than those without, at a hazard ratio of 1.51 (P < .001).

Further adjustment for body mass index (BMI) and age reduced the hazard ratio to 1.36 (P = .001).

In the fully adjusted model, which also took into account impaired glucose regulation, androgen excess, anovulation, hypertension, and other PCOS-related factors, the hazard ratio remained significant, at 1.28 (P = .015).
 

For shielding, balance benefits with impact on mental health

Joint senior author Krishnarajah Nirantharakumar, MD, PhD, also of the University of Birmingham, commented that, despite the increased risks, shielding strategies for COVID-19 need to take into account the impact of PCOS on women’s mental health.

“The risk of mental health problems, including low self-esteem, anxiety, and depression, is significantly higher in women with PCOS,” he said, “and advice on strict adherence to social distancing needs to be tempered by the associated risk of exacerbating these underlying problems.”

Arlt also pointed out that the study only looked at the incidence of COVID-19 infection, rather than outcomes.

“Our study does not provide information on the risk of a severe course of the COVID-19 infection or on the risk of COVID-19–related long-term complications [in women with PCOS], and further research is required,” she concluded.

The study was funded by Health Data Research UK and supported by the Wellcome Trust, the Health Research Board, and the National Institute for Health Research Birmingham Biomedical Research Centre based at the University of Birmingham and University Hospitals Birmingham NHS Foundation Trust. The study authors have disclosed no relevant financial relationships.

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

Women with polycystic ovary syndrome (PCOS) face an almost 30% increased risk for COVID-19 compared with unaffected women, even after adjusting for cardiometabolic and other related factors, suggests an analysis of United Kingdom primary care data.

“Our research has highlighted that women with PCOS are an often overlooked and potentially high-risk population for contracting COVID-19,” said joint senior author Wiebke Arlt, MD, PhD, director of the Institute of Metabolism and Systems Research at the University of Birmingham (England), in a press release.

“Before the onset of the COVID-19 pandemic, women with PCOS consistently report fragmented care, delayed diagnosis and a perception of poor clinician understanding of their condition,” added co-author Michael W. O’Reilly, MD, PhD, University of Medicine and Health Sciences, Dublin.

“Women suffering from this condition may fear, with some degree of justification, that an enhanced risk of COVID-19 infection will further compromise timely access to health care and serve to increase the sense of disenfranchisement currently experienced by many patients,” he added.

Consequently, “these findings need to be considered when designing public health policy and advice as our understanding of COVID-19 evolves,” noted first author Anuradhaa Subramanian, PhD Student, Institute of Applied Health Research, University of Birmingham.

The research was published by the European Journal of Endocrinology on March 9.
 

Women with PCOS: A distinct subgroup?

PCOS, which is thought to affect up to 16% of women, is associated with a significantly increased risk for type 2 diabetes, non-alcoholic fatty liver disease, and cardiovascular disease, all which have been linked to more severe COVID-19.

The condition is more prevalent in Black and South Asian women, who also appear to have an increased risk for severe COVID-19 vs. their White counterparts.

However, women and younger people in general have a lower overall risk for severe COVID-19 and mortality compared with older people and men.

Women with PCOS may therefore “represent a distinct subgroup of women at higher than average [on the basis of their sex and age] risk of adverse COVID-19–related outcomes,” the researchers note.

To investigate further, they collated data from The Health Improvement Network primary care database, which includes information from 365 active general practices in the U.K. for the period Jan. 31, 2020, to July 22, 2020.

They identified women with PCOS or a coded diagnosis of polycystic ovaries (PCO), and then for each woman randomly selected four unaffected controls matched for age and general practice location.

They included 21,292 women with PCOS/PCO and 78,310 controls, who had a mean age at study entry of 39.3 years and 39.5 years, respectively. The mean age at diagnosis of PCOS was 27 years, and the mean duration of the condition was 12.4 years.

The crude incidence of COVID-19 was 18.1 per 1000 person-years among women with PCOS vs. 11.9 per 1000 person-years in those without.

Cox regression analysis adjusted for age indicated that women with PCOS faced a significantly increased risk for COVID-19 than those without, at a hazard ratio of 1.51 (P < .001).

Further adjustment for body mass index (BMI) and age reduced the hazard ratio to 1.36 (P = .001).

In the fully adjusted model, which also took into account impaired glucose regulation, androgen excess, anovulation, hypertension, and other PCOS-related factors, the hazard ratio remained significant, at 1.28 (P = .015).
 

For shielding, balance benefits with impact on mental health

Joint senior author Krishnarajah Nirantharakumar, MD, PhD, also of the University of Birmingham, commented that, despite the increased risks, shielding strategies for COVID-19 need to take into account the impact of PCOS on women’s mental health.

“The risk of mental health problems, including low self-esteem, anxiety, and depression, is significantly higher in women with PCOS,” he said, “and advice on strict adherence to social distancing needs to be tempered by the associated risk of exacerbating these underlying problems.”

Arlt also pointed out that the study only looked at the incidence of COVID-19 infection, rather than outcomes.

“Our study does not provide information on the risk of a severe course of the COVID-19 infection or on the risk of COVID-19–related long-term complications [in women with PCOS], and further research is required,” she concluded.

The study was funded by Health Data Research UK and supported by the Wellcome Trust, the Health Research Board, and the National Institute for Health Research Birmingham Biomedical Research Centre based at the University of Birmingham and University Hospitals Birmingham NHS Foundation Trust. The study authors have disclosed no relevant financial relationships.

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

Federal regulators on March 23 said they were “concerned” that drug maker AstraZeneca included “outdated information” in its announcement the previous day that the company’s COVID-19 vaccine was effective.

The federal Data and Safety Monitoring Board shared those concerns with the company as well as with the National Institute of Allergy and Infectious Diseases, and the U.S. Biomedical Advanced Research and Development Authority, according to a statement from NIAID issued early March 23.

“We urge the company to work with the DSMB to review the efficacy data and ensure the most accurate, up-to-date efficacy data be made public as quickly as possible,” the agency said.

The NIAID statement does not say what data may have been outdated or how it may have changed the results. The company said March 22 it plans to see U.S. authorization for the vaccine in April.

The statement from NIAID comes a day after AstraZeneca said the interim results of their phase III U.S. study found it was 79% effective against symptomatic COVID-19, 80% effective in people 65 years and older, and 100% effective against severe or critical disease and hospitalization.

Company officials and clinical trial investigators on March 22 also addressed the recent concerns about blood clots, how well the vaccine will perform against variants, and provided a timeline for seeking regulatory approval.

“There are many countries in Europe and throughout the world that have already authorized this. The fact that a United States-run study has confirmed the efficacy and safety of this vaccine, I think is an important contribution to global health in general,” Anthony Fauci, MD, chief medical advisor to President Joe Biden, said during a White House press briefing March 22.

Andy Slavitt, White House senior advisor for the COVID-19 Response Team, had a more tempered reaction.

“It’s important to remind everyone we cannot and will not get ahead of the FDA,” he said. “While we would certainly call today’s news encouraging, it’s the kind of thing we like to see, we have a rigorous process that will come once an EUA is submitted and that will give us more information.”

With 30 million doses at the ready, the company plans to file for FDA emergency use authorization “within weeks,” Menelas Pangalos, executive vice president of biopharmaceuticals research and development at AstraZeneca, said during a media briefing March 22.
 

Risk of thrombosis addressed

Regarding highly publicized reports of problems with blood clots from the AstraZeneca vaccine, the World Health Organization found the vaccine creates no greater risks, as did the European Medicines Agency

“We’ve had absolute confidence in the efficacy of the vaccine. Seeing this data now I hope gives others increased confidence that this is a very safe and effective vaccine,” Mr. Pangalos said.

“We’re glad this is being investigated really thoroughly,” Magda Sobieszczyk, MD, an infectious disease specialist at Columbia University In New York City, said. “It’s incredibly reassuring that the regulatory agencies have looked at the data thoroughly and there is no enhanced signal above what is seen in the population.”

“There were no concerning signals noted in the U.S. data,” she added.

Regarding the risk of blood clots, “These data are therefore timely in further addressing any safety concerns that could undermine vaccine uptake.” Andrew Garrett, PhD, executive vice president of scientific operations at ICON Clinical Research, agreed.

The vaccine was well-tolerated, the company reported, with no serious adverse events. Temporary pain and tenderness at the injection site, mild-to-moderate headaches, fatigue, chills, fever, muscle aches. and malaise were among the reported reactions.

The phase III interim results show 141 cases of symptomatic COVID-19 in the study of 32,449 adults. “We don’t have the whole breakdown yet . . . these are the high-level results we just got this week,” Mr. Pangalos said. Further information on rates of mild to moderate COVID-19 illness between groups is not yet available, for example.

The company explained that participants were randomly assigned to vaccine or placebo, with twice as many receiving the actual vaccine.

The trial is ongoing, so the FDA will receive information on more than the 141 COVID-19 symptomatic cases when the company submits a full primary analysis to the agency, Mr. Pangalos said.

In the phase III study, patients received two doses 4 weeks apart.

Beyond the U.S. study, the company has additional information, including real-world data from the United Kingdom, that it intends to submit to the FDA. Part of this evidence suggests increased efficacy when a second dose is administered at 3 months
 

‘Robust’ findings

“This is a large study, so these results can be expected to be robust. They could be expected to be even more so if there were more cases to compare between the groups, but 141 is still a substantial number of cases,” said Peter English, MD, of Horsham, United Kingdom, who is immediate past chair of the British Medical Association Public Health Medicine Committee.

Experts welcomed the 80% efficacy in people 65 and older in particular. “Importantly, the trial provides further support for efficacy in the elderly where previous clinical trial data, other than immunologic data, had been lacking,” Dr. Garrett said.

“It is clear this vaccine has very good efficacy. Remember that 60% was, prior to any trials being started, regarded as a good target,” said Stephen Evans, professor of pharmacoepidemiology at the London School of Hygiene & Tropical Medicine. “This efficacy does not show a notable decline at older ages. This was expected and the speculation that it was ineffective or quasi-ineffective at older ages was totally unjustified.

“This is good news for the global community and one hopes that any political statements around this good news are avoided,” he added.
 

Efficacy against variants?

Regarding virus variants, Mr. Pangalos noted the study was conducted when several variants of concern were in circulation.

“What I can say is given this study was conducted much later in terms of timing, it’s very encouraging that we’ve got such high efficacy numbers when undoubtedly there are variants of concern in circulation in this study,” Mr. Pangalos said.

“It also highlights why we believe that against severe disease, our vaccine will be effective against all variants of concern,” he added.

Once the company submits its EUA to the FDA, the company is ready to immediately distribute 30 million doses of the vaccine and expects to ship 50 million total within the first month, Ruud Dobber, PhD, AstraZeneca executive vice president and president of the AZ Biopharmaceuticals Business Unit, said during the briefing.

The vaccine can be stored at 2 to 8 degrees Celsius for at least 6 months. Like other COVID-19 vaccines already authorized for emergency use, the duration of protection with the AstraZeneca product remains unknown.

This article was updated March 23, 2021.

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

Federal regulators on March 23 said they were “concerned” that drug maker AstraZeneca included “outdated information” in its announcement the previous day that the company’s COVID-19 vaccine was effective.

The federal Data and Safety Monitoring Board shared those concerns with the company as well as with the National Institute of Allergy and Infectious Diseases, and the U.S. Biomedical Advanced Research and Development Authority, according to a statement from NIAID issued early March 23.

“We urge the company to work with the DSMB to review the efficacy data and ensure the most accurate, up-to-date efficacy data be made public as quickly as possible,” the agency said.

The NIAID statement does not say what data may have been outdated or how it may have changed the results. The company said March 22 it plans to see U.S. authorization for the vaccine in April.

The statement from NIAID comes a day after AstraZeneca said the interim results of their phase III U.S. study found it was 79% effective against symptomatic COVID-19, 80% effective in people 65 years and older, and 100% effective against severe or critical disease and hospitalization.

Company officials and clinical trial investigators on March 22 also addressed the recent concerns about blood clots, how well the vaccine will perform against variants, and provided a timeline for seeking regulatory approval.

“There are many countries in Europe and throughout the world that have already authorized this. The fact that a United States-run study has confirmed the efficacy and safety of this vaccine, I think is an important contribution to global health in general,” Anthony Fauci, MD, chief medical advisor to President Joe Biden, said during a White House press briefing March 22.

Andy Slavitt, White House senior advisor for the COVID-19 Response Team, had a more tempered reaction.

“It’s important to remind everyone we cannot and will not get ahead of the FDA,” he said. “While we would certainly call today’s news encouraging, it’s the kind of thing we like to see, we have a rigorous process that will come once an EUA is submitted and that will give us more information.”

With 30 million doses at the ready, the company plans to file for FDA emergency use authorization “within weeks,” Menelas Pangalos, executive vice president of biopharmaceuticals research and development at AstraZeneca, said during a media briefing March 22.
 

Risk of thrombosis addressed

Regarding highly publicized reports of problems with blood clots from the AstraZeneca vaccine, the World Health Organization found the vaccine creates no greater risks, as did the European Medicines Agency

“We’ve had absolute confidence in the efficacy of the vaccine. Seeing this data now I hope gives others increased confidence that this is a very safe and effective vaccine,” Mr. Pangalos said.

“We’re glad this is being investigated really thoroughly,” Magda Sobieszczyk, MD, an infectious disease specialist at Columbia University In New York City, said. “It’s incredibly reassuring that the regulatory agencies have looked at the data thoroughly and there is no enhanced signal above what is seen in the population.”

“There were no concerning signals noted in the U.S. data,” she added.

Regarding the risk of blood clots, “These data are therefore timely in further addressing any safety concerns that could undermine vaccine uptake.” Andrew Garrett, PhD, executive vice president of scientific operations at ICON Clinical Research, agreed.

The vaccine was well-tolerated, the company reported, with no serious adverse events. Temporary pain and tenderness at the injection site, mild-to-moderate headaches, fatigue, chills, fever, muscle aches. and malaise were among the reported reactions.

The phase III interim results show 141 cases of symptomatic COVID-19 in the study of 32,449 adults. “We don’t have the whole breakdown yet . . . these are the high-level results we just got this week,” Mr. Pangalos said. Further information on rates of mild to moderate COVID-19 illness between groups is not yet available, for example.

The company explained that participants were randomly assigned to vaccine or placebo, with twice as many receiving the actual vaccine.

The trial is ongoing, so the FDA will receive information on more than the 141 COVID-19 symptomatic cases when the company submits a full primary analysis to the agency, Mr. Pangalos said.

In the phase III study, patients received two doses 4 weeks apart.

Beyond the U.S. study, the company has additional information, including real-world data from the United Kingdom, that it intends to submit to the FDA. Part of this evidence suggests increased efficacy when a second dose is administered at 3 months
 

‘Robust’ findings

“This is a large study, so these results can be expected to be robust. They could be expected to be even more so if there were more cases to compare between the groups, but 141 is still a substantial number of cases,” said Peter English, MD, of Horsham, United Kingdom, who is immediate past chair of the British Medical Association Public Health Medicine Committee.

Experts welcomed the 80% efficacy in people 65 and older in particular. “Importantly, the trial provides further support for efficacy in the elderly where previous clinical trial data, other than immunologic data, had been lacking,” Dr. Garrett said.

“It is clear this vaccine has very good efficacy. Remember that 60% was, prior to any trials being started, regarded as a good target,” said Stephen Evans, professor of pharmacoepidemiology at the London School of Hygiene & Tropical Medicine. “This efficacy does not show a notable decline at older ages. This was expected and the speculation that it was ineffective or quasi-ineffective at older ages was totally unjustified.

“This is good news for the global community and one hopes that any political statements around this good news are avoided,” he added.
 

Efficacy against variants?

Regarding virus variants, Mr. Pangalos noted the study was conducted when several variants of concern were in circulation.

“What I can say is given this study was conducted much later in terms of timing, it’s very encouraging that we’ve got such high efficacy numbers when undoubtedly there are variants of concern in circulation in this study,” Mr. Pangalos said.

“It also highlights why we believe that against severe disease, our vaccine will be effective against all variants of concern,” he added.

Once the company submits its EUA to the FDA, the company is ready to immediately distribute 30 million doses of the vaccine and expects to ship 50 million total within the first month, Ruud Dobber, PhD, AstraZeneca executive vice president and president of the AZ Biopharmaceuticals Business Unit, said during the briefing.

The vaccine can be stored at 2 to 8 degrees Celsius for at least 6 months. Like other COVID-19 vaccines already authorized for emergency use, the duration of protection with the AstraZeneca product remains unknown.

This article was updated March 23, 2021.

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

Federal regulators on March 23 said they were “concerned” that drug maker AstraZeneca included “outdated information” in its announcement the previous day that the company’s COVID-19 vaccine was effective.

The federal Data and Safety Monitoring Board shared those concerns with the company as well as with the National Institute of Allergy and Infectious Diseases, and the U.S. Biomedical Advanced Research and Development Authority, according to a statement from NIAID issued early March 23.

“We urge the company to work with the DSMB to review the efficacy data and ensure the most accurate, up-to-date efficacy data be made public as quickly as possible,” the agency said.

The NIAID statement does not say what data may have been outdated or how it may have changed the results. The company said March 22 it plans to see U.S. authorization for the vaccine in April.

The statement from NIAID comes a day after AstraZeneca said the interim results of their phase III U.S. study found it was 79% effective against symptomatic COVID-19, 80% effective in people 65 years and older, and 100% effective against severe or critical disease and hospitalization.

Company officials and clinical trial investigators on March 22 also addressed the recent concerns about blood clots, how well the vaccine will perform against variants, and provided a timeline for seeking regulatory approval.

“There are many countries in Europe and throughout the world that have already authorized this. The fact that a United States-run study has confirmed the efficacy and safety of this vaccine, I think is an important contribution to global health in general,” Anthony Fauci, MD, chief medical advisor to President Joe Biden, said during a White House press briefing March 22.

Andy Slavitt, White House senior advisor for the COVID-19 Response Team, had a more tempered reaction.

“It’s important to remind everyone we cannot and will not get ahead of the FDA,” he said. “While we would certainly call today’s news encouraging, it’s the kind of thing we like to see, we have a rigorous process that will come once an EUA is submitted and that will give us more information.”

With 30 million doses at the ready, the company plans to file for FDA emergency use authorization “within weeks,” Menelas Pangalos, executive vice president of biopharmaceuticals research and development at AstraZeneca, said during a media briefing March 22.
 

Risk of thrombosis addressed

Regarding highly publicized reports of problems with blood clots from the AstraZeneca vaccine, the World Health Organization found the vaccine creates no greater risks, as did the European Medicines Agency

“We’ve had absolute confidence in the efficacy of the vaccine. Seeing this data now I hope gives others increased confidence that this is a very safe and effective vaccine,” Mr. Pangalos said.

“We’re glad this is being investigated really thoroughly,” Magda Sobieszczyk, MD, an infectious disease specialist at Columbia University In New York City, said. “It’s incredibly reassuring that the regulatory agencies have looked at the data thoroughly and there is no enhanced signal above what is seen in the population.”

“There were no concerning signals noted in the U.S. data,” she added.

Regarding the risk of blood clots, “These data are therefore timely in further addressing any safety concerns that could undermine vaccine uptake.” Andrew Garrett, PhD, executive vice president of scientific operations at ICON Clinical Research, agreed.

The vaccine was well-tolerated, the company reported, with no serious adverse events. Temporary pain and tenderness at the injection site, mild-to-moderate headaches, fatigue, chills, fever, muscle aches. and malaise were among the reported reactions.

The phase III interim results show 141 cases of symptomatic COVID-19 in the study of 32,449 adults. “We don’t have the whole breakdown yet . . . these are the high-level results we just got this week,” Mr. Pangalos said. Further information on rates of mild to moderate COVID-19 illness between groups is not yet available, for example.

The company explained that participants were randomly assigned to vaccine or placebo, with twice as many receiving the actual vaccine.

The trial is ongoing, so the FDA will receive information on more than the 141 COVID-19 symptomatic cases when the company submits a full primary analysis to the agency, Mr. Pangalos said.

In the phase III study, patients received two doses 4 weeks apart.

Beyond the U.S. study, the company has additional information, including real-world data from the United Kingdom, that it intends to submit to the FDA. Part of this evidence suggests increased efficacy when a second dose is administered at 3 months
 

‘Robust’ findings

“This is a large study, so these results can be expected to be robust. They could be expected to be even more so if there were more cases to compare between the groups, but 141 is still a substantial number of cases,” said Peter English, MD, of Horsham, United Kingdom, who is immediate past chair of the British Medical Association Public Health Medicine Committee.

Experts welcomed the 80% efficacy in people 65 and older in particular. “Importantly, the trial provides further support for efficacy in the elderly where previous clinical trial data, other than immunologic data, had been lacking,” Dr. Garrett said.

“It is clear this vaccine has very good efficacy. Remember that 60% was, prior to any trials being started, regarded as a good target,” said Stephen Evans, professor of pharmacoepidemiology at the London School of Hygiene & Tropical Medicine. “This efficacy does not show a notable decline at older ages. This was expected and the speculation that it was ineffective or quasi-ineffective at older ages was totally unjustified.

“This is good news for the global community and one hopes that any political statements around this good news are avoided,” he added.
 

Efficacy against variants?

Regarding virus variants, Mr. Pangalos noted the study was conducted when several variants of concern were in circulation.

“What I can say is given this study was conducted much later in terms of timing, it’s very encouraging that we’ve got such high efficacy numbers when undoubtedly there are variants of concern in circulation in this study,” Mr. Pangalos said.

“It also highlights why we believe that against severe disease, our vaccine will be effective against all variants of concern,” he added.

Once the company submits its EUA to the FDA, the company is ready to immediately distribute 30 million doses of the vaccine and expects to ship 50 million total within the first month, Ruud Dobber, PhD, AstraZeneca executive vice president and president of the AZ Biopharmaceuticals Business Unit, said during the briefing.

The vaccine can be stored at 2 to 8 degrees Celsius for at least 6 months. Like other COVID-19 vaccines already authorized for emergency use, the duration of protection with the AstraZeneca product remains unknown.

This article was updated March 23, 2021.

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

Two newly published studies highlight recent success toward delaying the onset of type 1 diabetes in people at high risk and slowing progression in those with recent onset of the condition.

Both studies were initially presented in June 2020 at the annual scientific sessions of the American Diabetes Association and reported by this news organization at the time.  

As yet, neither of the two strategies – preserving insulin-producing pancreatic beta-cell function soon after diagnosis or delaying type 1 diabetes onset in those at high risk – represent a cure or certain disease prevention.

However, both can potentially lead to better long-term glycemic control with less hypoglycemia and a lower risk for diabetes-related complications.
 

Combination treatment prolongs beta-cell function in new-onset disease

The first study, entitled, “Anti–interleukin-21 antibody and liraglutide for the preservation of beta-cell function in adults with recent-onset type 1 diabetes,” was published online March 1, 2021, in The Lancet Diabetes & Endocrinology by Matthias von Herrath, MD, of Novo Nordisk, Søborg, Denmark, and colleagues.

The randomized, placebo-controlled, double-blind, phase 2 combination treatment trial involved 308 individuals aged 18-45 years who had been diagnosed with type 1 diabetes in the previous 20 weeks and still had residual beta-cell function.

Patients were randomized with 77 per group to receive monoclonal anti-IL-21 plus liraglutide, anti-IL-21 alone, liraglutide alone, or placebo. The antibody was given intravenously every 6 weeks and liraglutide or matching placebo were self-administered by daily injections.

Compared with placebo (ratio to baseline, 0.61; 39% decrease), the decrease in mixed meal tolerance test stimulated C-peptide concentration from baseline to week 54 – the primary outcome – was significantly smaller with combination treatment (0.90, 10% decrease; estimated treatment ratio, 1.48; P = .0017), but not with anti-IL-21 alone (1.23; P = .093) or liraglutide alone (1.12; P = .38).

Despite greater insulin use in the placebo group, the decrease in hemoglobin A1c (a key secondary outcome) at week 54 was greater with all active treatments (–0.50 percentage points) than with placebo (–0.10 percentage points), although the differences versus placebo were not significant.

“The combination of anti-IL-21 and liraglutide could preserve beta-cell function in recently diagnosed type 1 diabetes,” the researchers said.

“These results suggest that this combination has the potential to offer a novel and valuable disease-modifying therapy for patients with recently diagnosed type 1 diabetes. However, the efficacy and safety need to be further investigated in a phase 3 program,” Dr. von Herrath and colleagues concluded.
 

Teplizumab: 3-year data continue to show benefit

The other study looked at delaying the onset of type 1 diabetes. Entitled, “Teplizumab improves and stabilizes beta cell function in antibody-positive high-risk individuals,” the article was published online March 3, 2021, in Science Translational Medicine by Emily K. Sims, MD, of the department of pediatrics, Indiana University, Indianapolis, and colleagues.

This trial of the anti-CD3 monoclonal antibody adds an additional year of follow-up to the “game-changer” 2-year data reported in 2019.

Among the 76 individuals aged 8-49 years who were positive for two or more type 1 diabetes–related autoantibodies, 50% of those randomized to a single 14-day infusion course of teplizumab remained diabetes free at a median follow-up of 923 days, compared with only 22% of those who received placebo infusions (hazard ratio, 0.457; P = .01).

The teplizumab group had a greater average C-peptide area under the curve, compared with placebo, reflecting improved beta-cell function (1.96 vs 1.68 pmol/mL; P = .006).

C-peptide levels declined over time in the placebo group but stabilized in those receiving teplizumab (P = .0015).

“It is very encouraging to see that a single course of teplizumab delayed insulin dependence in this high-risk population for approximately 3 years versus placebo,” said Frank Martin, PhD, JDRF director of research at Provention Bio, which is developing teplizumab.

“These exciting results have been made possible by the unwavering efforts of TrialNet and Provention Bio. Teplizumab, if approved by the FDA, could positively change the course of disease development for people at risk of developing T1D and their standard of care,” he concluded.

The teplizumab study was funded by TrialNet. Dr. von Herrath is an employee of Novo Nordisk, which funded the study involving its drug liraglutide. Dr. Sims reported no relevant financial relationships.

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

Two newly published studies highlight recent success toward delaying the onset of type 1 diabetes in people at high risk and slowing progression in those with recent onset of the condition.

Both studies were initially presented in June 2020 at the annual scientific sessions of the American Diabetes Association and reported by this news organization at the time.  

As yet, neither of the two strategies – preserving insulin-producing pancreatic beta-cell function soon after diagnosis or delaying type 1 diabetes onset in those at high risk – represent a cure or certain disease prevention.

However, both can potentially lead to better long-term glycemic control with less hypoglycemia and a lower risk for diabetes-related complications.
 

Combination treatment prolongs beta-cell function in new-onset disease

The first study, entitled, “Anti–interleukin-21 antibody and liraglutide for the preservation of beta-cell function in adults with recent-onset type 1 diabetes,” was published online March 1, 2021, in The Lancet Diabetes & Endocrinology by Matthias von Herrath, MD, of Novo Nordisk, Søborg, Denmark, and colleagues.

The randomized, placebo-controlled, double-blind, phase 2 combination treatment trial involved 308 individuals aged 18-45 years who had been diagnosed with type 1 diabetes in the previous 20 weeks and still had residual beta-cell function.

Patients were randomized with 77 per group to receive monoclonal anti-IL-21 plus liraglutide, anti-IL-21 alone, liraglutide alone, or placebo. The antibody was given intravenously every 6 weeks and liraglutide or matching placebo were self-administered by daily injections.

Compared with placebo (ratio to baseline, 0.61; 39% decrease), the decrease in mixed meal tolerance test stimulated C-peptide concentration from baseline to week 54 – the primary outcome – was significantly smaller with combination treatment (0.90, 10% decrease; estimated treatment ratio, 1.48; P = .0017), but not with anti-IL-21 alone (1.23; P = .093) or liraglutide alone (1.12; P = .38).

Despite greater insulin use in the placebo group, the decrease in hemoglobin A1c (a key secondary outcome) at week 54 was greater with all active treatments (–0.50 percentage points) than with placebo (–0.10 percentage points), although the differences versus placebo were not significant.

“The combination of anti-IL-21 and liraglutide could preserve beta-cell function in recently diagnosed type 1 diabetes,” the researchers said.

“These results suggest that this combination has the potential to offer a novel and valuable disease-modifying therapy for patients with recently diagnosed type 1 diabetes. However, the efficacy and safety need to be further investigated in a phase 3 program,” Dr. von Herrath and colleagues concluded.
 

Teplizumab: 3-year data continue to show benefit

The other study looked at delaying the onset of type 1 diabetes. Entitled, “Teplizumab improves and stabilizes beta cell function in antibody-positive high-risk individuals,” the article was published online March 3, 2021, in Science Translational Medicine by Emily K. Sims, MD, of the department of pediatrics, Indiana University, Indianapolis, and colleagues.

This trial of the anti-CD3 monoclonal antibody adds an additional year of follow-up to the “game-changer” 2-year data reported in 2019.

Among the 76 individuals aged 8-49 years who were positive for two or more type 1 diabetes–related autoantibodies, 50% of those randomized to a single 14-day infusion course of teplizumab remained diabetes free at a median follow-up of 923 days, compared with only 22% of those who received placebo infusions (hazard ratio, 0.457; P = .01).

The teplizumab group had a greater average C-peptide area under the curve, compared with placebo, reflecting improved beta-cell function (1.96 vs 1.68 pmol/mL; P = .006).

C-peptide levels declined over time in the placebo group but stabilized in those receiving teplizumab (P = .0015).

“It is very encouraging to see that a single course of teplizumab delayed insulin dependence in this high-risk population for approximately 3 years versus placebo,” said Frank Martin, PhD, JDRF director of research at Provention Bio, which is developing teplizumab.

“These exciting results have been made possible by the unwavering efforts of TrialNet and Provention Bio. Teplizumab, if approved by the FDA, could positively change the course of disease development for people at risk of developing T1D and their standard of care,” he concluded.

The teplizumab study was funded by TrialNet. Dr. von Herrath is an employee of Novo Nordisk, which funded the study involving its drug liraglutide. Dr. Sims reported no relevant financial relationships.

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

Two newly published studies highlight recent success toward delaying the onset of type 1 diabetes in people at high risk and slowing progression in those with recent onset of the condition.

Both studies were initially presented in June 2020 at the annual scientific sessions of the American Diabetes Association and reported by this news organization at the time.  

As yet, neither of the two strategies – preserving insulin-producing pancreatic beta-cell function soon after diagnosis or delaying type 1 diabetes onset in those at high risk – represent a cure or certain disease prevention.

However, both can potentially lead to better long-term glycemic control with less hypoglycemia and a lower risk for diabetes-related complications.
 

Combination treatment prolongs beta-cell function in new-onset disease

The first study, entitled, “Anti–interleukin-21 antibody and liraglutide for the preservation of beta-cell function in adults with recent-onset type 1 diabetes,” was published online March 1, 2021, in The Lancet Diabetes & Endocrinology by Matthias von Herrath, MD, of Novo Nordisk, Søborg, Denmark, and colleagues.

The randomized, placebo-controlled, double-blind, phase 2 combination treatment trial involved 308 individuals aged 18-45 years who had been diagnosed with type 1 diabetes in the previous 20 weeks and still had residual beta-cell function.

Patients were randomized with 77 per group to receive monoclonal anti-IL-21 plus liraglutide, anti-IL-21 alone, liraglutide alone, or placebo. The antibody was given intravenously every 6 weeks and liraglutide or matching placebo were self-administered by daily injections.

Compared with placebo (ratio to baseline, 0.61; 39% decrease), the decrease in mixed meal tolerance test stimulated C-peptide concentration from baseline to week 54 – the primary outcome – was significantly smaller with combination treatment (0.90, 10% decrease; estimated treatment ratio, 1.48; P = .0017), but not with anti-IL-21 alone (1.23; P = .093) or liraglutide alone (1.12; P = .38).

Despite greater insulin use in the placebo group, the decrease in hemoglobin A1c (a key secondary outcome) at week 54 was greater with all active treatments (–0.50 percentage points) than with placebo (–0.10 percentage points), although the differences versus placebo were not significant.

“The combination of anti-IL-21 and liraglutide could preserve beta-cell function in recently diagnosed type 1 diabetes,” the researchers said.

“These results suggest that this combination has the potential to offer a novel and valuable disease-modifying therapy for patients with recently diagnosed type 1 diabetes. However, the efficacy and safety need to be further investigated in a phase 3 program,” Dr. von Herrath and colleagues concluded.
 

Teplizumab: 3-year data continue to show benefit

The other study looked at delaying the onset of type 1 diabetes. Entitled, “Teplizumab improves and stabilizes beta cell function in antibody-positive high-risk individuals,” the article was published online March 3, 2021, in Science Translational Medicine by Emily K. Sims, MD, of the department of pediatrics, Indiana University, Indianapolis, and colleagues.

This trial of the anti-CD3 monoclonal antibody adds an additional year of follow-up to the “game-changer” 2-year data reported in 2019.

Among the 76 individuals aged 8-49 years who were positive for two or more type 1 diabetes–related autoantibodies, 50% of those randomized to a single 14-day infusion course of teplizumab remained diabetes free at a median follow-up of 923 days, compared with only 22% of those who received placebo infusions (hazard ratio, 0.457; P = .01).

The teplizumab group had a greater average C-peptide area under the curve, compared with placebo, reflecting improved beta-cell function (1.96 vs 1.68 pmol/mL; P = .006).

C-peptide levels declined over time in the placebo group but stabilized in those receiving teplizumab (P = .0015).

“It is very encouraging to see that a single course of teplizumab delayed insulin dependence in this high-risk population for approximately 3 years versus placebo,” said Frank Martin, PhD, JDRF director of research at Provention Bio, which is developing teplizumab.

“These exciting results have been made possible by the unwavering efforts of TrialNet and Provention Bio. Teplizumab, if approved by the FDA, could positively change the course of disease development for people at risk of developing T1D and their standard of care,” he concluded.

The teplizumab study was funded by TrialNet. Dr. von Herrath is an employee of Novo Nordisk, which funded the study involving its drug liraglutide. Dr. Sims reported no relevant financial relationships.

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

Eating ultraprocessed foods poses a significant risk to cardiovascular and coronary heart health, according to prospective data from about 3,000 people in the Framingham Offspring Cohort, the second generation of participants in the Framingham Heart Study.

©Ingram Publishing/Thinkstock.com

Each regular, daily serving of ultraprocessed food was linked with significant elevations of 5%-9% in the relative rates of “hard” cardiovascular disease (CVD) events, hard coronary heart disease (CHD) events, overall CVD events, and CVD death, after adjustments for numerous potential confounders including energy intake, body mass index, waist circumference, and blood pressure, Filippa Juul, PhD, and associates wrote in a report published in the Journal of the American College of Cardiology.

“Consumption of ultraprocessed foods makes up over half of the daily calories in the average American diet and are increasingly consumed worldwide. As poor diet is a major modifiable risk factor for heart disease, it represents a critical target in prevention efforts,” said Dr. Juul, a nutritional epidemiologist at New York University, in a statement released by the American College of Cardiology.

“Our findings add to a growing body of evidence suggesting cardiovascular benefits of limiting ultraprocessed foods. Ultraprocessed foods are ubiquitous and include many foods that are marketed as healthy, such as protein bars, breakfast cereals, and most industrially produced breads,” she added. Other commonplace members of the ultraprocessed food group include carbonated soft drinks, packaged snacks, candies, sausages, margarines, and energy drinks. The concept of ultraprocessed foods as a distinct, wide-ranging, and dangerous food category first appeared in 2010, and then received an update from a United Nations panel in 2019 as what’s now called the NOVA classification system.
 

Ultraprocessed foods fly under the radar

“Although cardiovascular guidelines emphasize consuming minimally processed foods, such as fruits, vegetables, whole grains, and nuts, they give less attention to the importance of minimizing ultraprocessed food,” wrote Robert J. Ostfeld, MD, and Kathleen E. Allen, MS, in an editorial that accompanied the new report. This reduced attention may be because of a “paucity of studies examining the association cardiovascular outcomes and ultraprocessed foods.”

The new evidence demands new policies, educational efforts, and labeling changes, suggested Dr. Ostfeld, director of preventive cardiology at Montefiore Health System in New York, and Ms. Allen, a dietitian at the Geisel School of Medicine at Dartmouth, Hanover, N.H. “The goal should be to make the unhealthy choice the hard choice and the healthy choice the easy choice.”

The new analysis used data collected from people enrolled the Framingham Offspring Cohort, with their clinical metrics and diet information collected during 1991-1995 serving as their baseline. After excluding participants with prevalent CVD at baseline and those with incomplete follow-up of CVD events, the researchers had a cohort of 3,003 adults with an average follow-up of 18 years. At baseline, the cohort averaged 54 years of age; 55% were women, their average body mass index was 27.3 kg/m², and about 6% had diabetes. They reported eating, on average, 7.5 servings of ultraprocessed food daily.

During follow-up, the cohort tallied 648 incident CVD events, including 251 hard CVD events (coronary death, MI, or stroke) and 163 hard CHD events (coronary death or MI), and 713 total deaths including 108 CVD deaths. Other CVD events recorded but not considered hard included heart failure, intermittent claudication, and transient ischemic attack.

In a multivariate-adjusted analysis, each average daily portion of ultraprocessed food was linked with an significant 7% relative increase in the incidence of a hard CVD event, compared with participants who ate fewer ultraprocessed food portions, and a 9% relative increase in the rate of hard CHD events, the study’s two prespecified primary outcomes. The researchers also found that each ultraprocessed serving significantly was associated with a 5% relative increased rate of total CVD events, and a 9% relative rise in CVD deaths. The analysis showed no significant association between total mortality and ultraprocessed food intake. (Average follow-up for the mortality analyses was 20 years.)

The authors also reported endpoint associations with intake of specific types of ultraprocessed foods, and found significantly increased associations specifically for portions of bread, ultraprocessed meat, salty snacks, and low-calorie soft drinks.

Convenient, omnipresent, and affordable

The authors acknowledged that the associations they found need examination in ethnically diverse populations, but nonetheless the findings “suggest the need for increased efforts to implement population-wide strategies” to lower consumption of ultraprocessed foods. “Given the convenience, omnipresence, and affordability of ultraprocessed foods, careful nutrition counseling is needed to design individualized, patient-centered, heart-healthy diets,” they concluded.

“Population-wide strategies such as taxation on sugar-sweetened beverages and other ultraprocessed foods and recommendations regarding processing levels in national dietary guidelines are needed to reduce the intake of ultraprocessed foods,” added Dr. Juul in her statement. “Of course, we must also implement policies that increase the availability, accessibility, and affordability of nutritious, minimally processed foods, especially in disadvantaged populations. At the clinical level, there is a need for increased commitment to individualized nutrition counseling for adopting sustainable heart-healthy diets.”

The study had no commercial funding. Dr. Juul and coauthors, Dr. Ostfeld, and Ms. Allen had no disclosures.

mzoler@mdedge.com

Eating ultraprocessed foods poses a significant risk to cardiovascular and coronary heart health, according to prospective data from about 3,000 people in the Framingham Offspring Cohort, the second generation of participants in the Framingham Heart Study.

©Ingram Publishing/Thinkstock.com

Each regular, daily serving of ultraprocessed food was linked with significant elevations of 5%-9% in the relative rates of “hard” cardiovascular disease (CVD) events, hard coronary heart disease (CHD) events, overall CVD events, and CVD death, after adjustments for numerous potential confounders including energy intake, body mass index, waist circumference, and blood pressure, Filippa Juul, PhD, and associates wrote in a report published in the Journal of the American College of Cardiology.

“Consumption of ultraprocessed foods makes up over half of the daily calories in the average American diet and are increasingly consumed worldwide. As poor diet is a major modifiable risk factor for heart disease, it represents a critical target in prevention efforts,” said Dr. Juul, a nutritional epidemiologist at New York University, in a statement released by the American College of Cardiology.

“Our findings add to a growing body of evidence suggesting cardiovascular benefits of limiting ultraprocessed foods. Ultraprocessed foods are ubiquitous and include many foods that are marketed as healthy, such as protein bars, breakfast cereals, and most industrially produced breads,” she added. Other commonplace members of the ultraprocessed food group include carbonated soft drinks, packaged snacks, candies, sausages, margarines, and energy drinks. The concept of ultraprocessed foods as a distinct, wide-ranging, and dangerous food category first appeared in 2010, and then received an update from a United Nations panel in 2019 as what’s now called the NOVA classification system.
 

Ultraprocessed foods fly under the radar

“Although cardiovascular guidelines emphasize consuming minimally processed foods, such as fruits, vegetables, whole grains, and nuts, they give less attention to the importance of minimizing ultraprocessed food,” wrote Robert J. Ostfeld, MD, and Kathleen E. Allen, MS, in an editorial that accompanied the new report. This reduced attention may be because of a “paucity of studies examining the association cardiovascular outcomes and ultraprocessed foods.”

The new evidence demands new policies, educational efforts, and labeling changes, suggested Dr. Ostfeld, director of preventive cardiology at Montefiore Health System in New York, and Ms. Allen, a dietitian at the Geisel School of Medicine at Dartmouth, Hanover, N.H. “The goal should be to make the unhealthy choice the hard choice and the healthy choice the easy choice.”

The new analysis used data collected from people enrolled the Framingham Offspring Cohort, with their clinical metrics and diet information collected during 1991-1995 serving as their baseline. After excluding participants with prevalent CVD at baseline and those with incomplete follow-up of CVD events, the researchers had a cohort of 3,003 adults with an average follow-up of 18 years. At baseline, the cohort averaged 54 years of age; 55% were women, their average body mass index was 27.3 kg/m², and about 6% had diabetes. They reported eating, on average, 7.5 servings of ultraprocessed food daily.

During follow-up, the cohort tallied 648 incident CVD events, including 251 hard CVD events (coronary death, MI, or stroke) and 163 hard CHD events (coronary death or MI), and 713 total deaths including 108 CVD deaths. Other CVD events recorded but not considered hard included heart failure, intermittent claudication, and transient ischemic attack.

In a multivariate-adjusted analysis, each average daily portion of ultraprocessed food was linked with an significant 7% relative increase in the incidence of a hard CVD event, compared with participants who ate fewer ultraprocessed food portions, and a 9% relative increase in the rate of hard CHD events, the study’s two prespecified primary outcomes. The researchers also found that each ultraprocessed serving significantly was associated with a 5% relative increased rate of total CVD events, and a 9% relative rise in CVD deaths. The analysis showed no significant association between total mortality and ultraprocessed food intake. (Average follow-up for the mortality analyses was 20 years.)

The authors also reported endpoint associations with intake of specific types of ultraprocessed foods, and found significantly increased associations specifically for portions of bread, ultraprocessed meat, salty snacks, and low-calorie soft drinks.

Convenient, omnipresent, and affordable

The authors acknowledged that the associations they found need examination in ethnically diverse populations, but nonetheless the findings “suggest the need for increased efforts to implement population-wide strategies” to lower consumption of ultraprocessed foods. “Given the convenience, omnipresence, and affordability of ultraprocessed foods, careful nutrition counseling is needed to design individualized, patient-centered, heart-healthy diets,” they concluded.

“Population-wide strategies such as taxation on sugar-sweetened beverages and other ultraprocessed foods and recommendations regarding processing levels in national dietary guidelines are needed to reduce the intake of ultraprocessed foods,” added Dr. Juul in her statement. “Of course, we must also implement policies that increase the availability, accessibility, and affordability of nutritious, minimally processed foods, especially in disadvantaged populations. At the clinical level, there is a need for increased commitment to individualized nutrition counseling for adopting sustainable heart-healthy diets.”

The study had no commercial funding. Dr. Juul and coauthors, Dr. Ostfeld, and Ms. Allen had no disclosures.

mzoler@mdedge.com

Eating ultraprocessed foods poses a significant risk to cardiovascular and coronary heart health, according to prospective data from about 3,000 people in the Framingham Offspring Cohort, the second generation of participants in the Framingham Heart Study.

©Ingram Publishing/Thinkstock.com

Each regular, daily serving of ultraprocessed food was linked with significant elevations of 5%-9% in the relative rates of “hard” cardiovascular disease (CVD) events, hard coronary heart disease (CHD) events, overall CVD events, and CVD death, after adjustments for numerous potential confounders including energy intake, body mass index, waist circumference, and blood pressure, Filippa Juul, PhD, and associates wrote in a report published in the Journal of the American College of Cardiology.

“Consumption of ultraprocessed foods makes up over half of the daily calories in the average American diet and are increasingly consumed worldwide. As poor diet is a major modifiable risk factor for heart disease, it represents a critical target in prevention efforts,” said Dr. Juul, a nutritional epidemiologist at New York University, in a statement released by the American College of Cardiology.

“Our findings add to a growing body of evidence suggesting cardiovascular benefits of limiting ultraprocessed foods. Ultraprocessed foods are ubiquitous and include many foods that are marketed as healthy, such as protein bars, breakfast cereals, and most industrially produced breads,” she added. Other commonplace members of the ultraprocessed food group include carbonated soft drinks, packaged snacks, candies, sausages, margarines, and energy drinks. The concept of ultraprocessed foods as a distinct, wide-ranging, and dangerous food category first appeared in 2010, and then received an update from a United Nations panel in 2019 as what’s now called the NOVA classification system.
 

Ultraprocessed foods fly under the radar

“Although cardiovascular guidelines emphasize consuming minimally processed foods, such as fruits, vegetables, whole grains, and nuts, they give less attention to the importance of minimizing ultraprocessed food,” wrote Robert J. Ostfeld, MD, and Kathleen E. Allen, MS, in an editorial that accompanied the new report. This reduced attention may be because of a “paucity of studies examining the association cardiovascular outcomes and ultraprocessed foods.”

The new evidence demands new policies, educational efforts, and labeling changes, suggested Dr. Ostfeld, director of preventive cardiology at Montefiore Health System in New York, and Ms. Allen, a dietitian at the Geisel School of Medicine at Dartmouth, Hanover, N.H. “The goal should be to make the unhealthy choice the hard choice and the healthy choice the easy choice.”

The new analysis used data collected from people enrolled the Framingham Offspring Cohort, with their clinical metrics and diet information collected during 1991-1995 serving as their baseline. After excluding participants with prevalent CVD at baseline and those with incomplete follow-up of CVD events, the researchers had a cohort of 3,003 adults with an average follow-up of 18 years. At baseline, the cohort averaged 54 years of age; 55% were women, their average body mass index was 27.3 kg/m², and about 6% had diabetes. They reported eating, on average, 7.5 servings of ultraprocessed food daily.

During follow-up, the cohort tallied 648 incident CVD events, including 251 hard CVD events (coronary death, MI, or stroke) and 163 hard CHD events (coronary death or MI), and 713 total deaths including 108 CVD deaths. Other CVD events recorded but not considered hard included heart failure, intermittent claudication, and transient ischemic attack.

In a multivariate-adjusted analysis, each average daily portion of ultraprocessed food was linked with an significant 7% relative increase in the incidence of a hard CVD event, compared with participants who ate fewer ultraprocessed food portions, and a 9% relative increase in the rate of hard CHD events, the study’s two prespecified primary outcomes. The researchers also found that each ultraprocessed serving significantly was associated with a 5% relative increased rate of total CVD events, and a 9% relative rise in CVD deaths. The analysis showed no significant association between total mortality and ultraprocessed food intake. (Average follow-up for the mortality analyses was 20 years.)

The authors also reported endpoint associations with intake of specific types of ultraprocessed foods, and found significantly increased associations specifically for portions of bread, ultraprocessed meat, salty snacks, and low-calorie soft drinks.

Convenient, omnipresent, and affordable

The authors acknowledged that the associations they found need examination in ethnically diverse populations, but nonetheless the findings “suggest the need for increased efforts to implement population-wide strategies” to lower consumption of ultraprocessed foods. “Given the convenience, omnipresence, and affordability of ultraprocessed foods, careful nutrition counseling is needed to design individualized, patient-centered, heart-healthy diets,” they concluded.

“Population-wide strategies such as taxation on sugar-sweetened beverages and other ultraprocessed foods and recommendations regarding processing levels in national dietary guidelines are needed to reduce the intake of ultraprocessed foods,” added Dr. Juul in her statement. “Of course, we must also implement policies that increase the availability, accessibility, and affordability of nutritious, minimally processed foods, especially in disadvantaged populations. At the clinical level, there is a need for increased commitment to individualized nutrition counseling for adopting sustainable heart-healthy diets.”

The study had no commercial funding. Dr. Juul and coauthors, Dr. Ostfeld, and Ms. Allen had no disclosures.

mzoler@mdedge.com

A new study has found that older men with high levels of abdominal aortic calcification (AAC) and a prevalent vertebral fracture – both of which can be assessed via lateral spine radiographs – are at increased risk of hip, clinical vertebral, and major osteoporotic fractures.

“The results of this study and others suggest that it may be appropriate to expand lateral spine imaging to include those with a significant pre-test probability of higher AAC being present,” wrote John T. Schousboe, MD, of the Park Nicollet Clinic and HealthPartners Institute in Bloomington, Minn. The study was published in the Journal of Bone and Mineral Research.

To determine the impact of prevalent vertebral fractures and AAC on fracture risk, the researchers assessed the lateral spine radiographs of 5,365 men who were enrolled in the Osteoporotic Fractures in Men (MrOS) study. All participants were 65 years or older, community dwelling, able to walk without assistance, and without bilateral hip arthroplasties. They split patients’ 24-point AAC (ACC-24) scores at the baseline visit into four levels: 0-1, 2-4, 5-8, and greater than 9. Self-reports of fractures were solicited from the cohort every 4 months.

Of all participants, 7.6% (n = 407) had a prevalent vertebral fracture at baseline. They were, on average, 1.5 years older than participants without a fracture; they were also more likely to be white and to have a prior nonspine fracture, along with having a lower femoral neck BMD (0.718 g/cm², compared with 0.787 g/cm²; P < .001). In addition, significantly more men with a prevalent vertebral fracture had an AAC score greater than 9 (27% vs. 21.2%).

After an average follow-up period of 12.4 years (standard deviation, 5.2), 634 men had a major osteoporotic fracture, 283 had a hip fracture, 206 had a clinical vertebral fracture, and 2,626 died without having any of the three. After adjustment for risk factors such as age, prior nonspine fracture, and prevalent vertebral fracture, men with higher AAC-24 scores had a higher risk of major osteoporotic fracture, compared with men who had scores of 0-1: a hazard ratio of 1.38 (95% confidence interval, 1.10-1.73; P < .001) for scores 2-4, a HR of 1.45 (95% CI, 1.14-1.84; P < .001) for scores 5-8, and a HR of 1.65 (95% CI, 1.29-2.10; P < .001) for scores greater than 9.

Similar findings were reported regarding risk of hip fractures: a HR of 1.54 (95% CI, 1.07-2.20; P < .001) for men with AAC-24 scores 2-4, a HR of 1.40 (95% CI, 0.96-2.06; P < .001) for scores 5-8, and a HR of 2.17 (95% CI, 1.50-3.13; P < .001) for scores greater than 9. AAC-24 score severity was not associated with a higher risk of clinical vertebral fractures.

After adjustment for risk factors and AAC-24 score, men with prevalent vertebral fractures had an increased risk of all three fracture outcomes, compared with men without any fractures at baseline: a HR of 1.56 (95% CI, 1.12-2.16; P < .001) for hip fracture, a HR of 1.85 (95% CI, 1.48-2.31; P < .001) for major osteoporotic fracture, and a HR of 2.76 (95% CI, 1.94-3.91; P < .001) for clinical vertebral fracture.

Adjusting for competing mortality produced similar results: men with higher levels of AAC had increased risk of major osteoporotic fracture and hip fracture, although AAC-24 score was not associated with higher risk of clinical vertebral fractures. Prevalent vertebral fractures were also still associated with higher risk of hip (subdistribution HR, 1.42; 95% CI, 1.01-2.00; P = .004), major osteoporotic fracture (SHR, 1.71; 95% CI, 1.36-2.14; P < .001), and clinical vertebral fracture (SHR, 2.46; 95% CI, 1.72-3.52; P < .001).

Fracture risk assessment proves to be “a nice proof of concept”

“It’s well known that prevalent fractures predict future fractures,” said Thomas M. Link, MD, PhD, chief of the musculoskeletal imaging section in the department of radiology and biomedical imaging at the University of California, San Francisco, in an interview. “The new finding is that aortic calcifications combined with prevalent fractures perform better in predicting major osteoporotic fractures. Traditionally on radiographs, we note that patients who have more calcifications in vessels have less density or calcium in the bone, so this is a nice proof of concept.”

“While the study shows excellent reproducibility, it is not clear how the AAC-24 score was validated,” he added. “Theoretically, abdominal CT could be used for this.”

Along with validation of the AAC-24 score on lateral spine radiographs, he expressed a desire that future research would be “clearer regarding how this would potentially impact patient management. Prevalent fractures already are an indication to treat patients with osteoporosis-specific drugs. How would the results of this study impact management beyond that?”

The authors acknowledged their study’s other potential limitations, including limits in their ability to estimate absolute and relative hip fracture risk in men with low AAC scores but a prevalent vertebral fracture. In addition, they noted that their cohort was “mostly white, healthy, community-dwelling older men” and therefore may not be generalizable to other populations.

The study was supported by the National Institutes of Health, including grants from the National Institute on Aging, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the National Center for Advancing Translational Sciences, and the NIH Roadmap for Medical Research. One author reported being supported by a National Heart Foundation of Australia Future Leader Fellowship. The others disclosed no potential conflicts of interest.

A new study has found that older men with high levels of abdominal aortic calcification (AAC) and a prevalent vertebral fracture – both of which can be assessed via lateral spine radiographs – are at increased risk of hip, clinical vertebral, and major osteoporotic fractures.

“The results of this study and others suggest that it may be appropriate to expand lateral spine imaging to include those with a significant pre-test probability of higher AAC being present,” wrote John T. Schousboe, MD, of the Park Nicollet Clinic and HealthPartners Institute in Bloomington, Minn. The study was published in the Journal of Bone and Mineral Research.

To determine the impact of prevalent vertebral fractures and AAC on fracture risk, the researchers assessed the lateral spine radiographs of 5,365 men who were enrolled in the Osteoporotic Fractures in Men (MrOS) study. All participants were 65 years or older, community dwelling, able to walk without assistance, and without bilateral hip arthroplasties. They split patients’ 24-point AAC (ACC-24) scores at the baseline visit into four levels: 0-1, 2-4, 5-8, and greater than 9. Self-reports of fractures were solicited from the cohort every 4 months.

Of all participants, 7.6% (n = 407) had a prevalent vertebral fracture at baseline. They were, on average, 1.5 years older than participants without a fracture; they were also more likely to be white and to have a prior nonspine fracture, along with having a lower femoral neck BMD (0.718 g/cm², compared with 0.787 g/cm²; P < .001). In addition, significantly more men with a prevalent vertebral fracture had an AAC score greater than 9 (27% vs. 21.2%).

After an average follow-up period of 12.4 years (standard deviation, 5.2), 634 men had a major osteoporotic fracture, 283 had a hip fracture, 206 had a clinical vertebral fracture, and 2,626 died without having any of the three. After adjustment for risk factors such as age, prior nonspine fracture, and prevalent vertebral fracture, men with higher AAC-24 scores had a higher risk of major osteoporotic fracture, compared with men who had scores of 0-1: a hazard ratio of 1.38 (95% confidence interval, 1.10-1.73; P < .001) for scores 2-4, a HR of 1.45 (95% CI, 1.14-1.84; P < .001) for scores 5-8, and a HR of 1.65 (95% CI, 1.29-2.10; P < .001) for scores greater than 9.

Similar findings were reported regarding risk of hip fractures: a HR of 1.54 (95% CI, 1.07-2.20; P < .001) for men with AAC-24 scores 2-4, a HR of 1.40 (95% CI, 0.96-2.06; P < .001) for scores 5-8, and a HR of 2.17 (95% CI, 1.50-3.13; P < .001) for scores greater than 9. AAC-24 score severity was not associated with a higher risk of clinical vertebral fractures.

After adjustment for risk factors and AAC-24 score, men with prevalent vertebral fractures had an increased risk of all three fracture outcomes, compared with men without any fractures at baseline: a HR of 1.56 (95% CI, 1.12-2.16; P < .001) for hip fracture, a HR of 1.85 (95% CI, 1.48-2.31; P < .001) for major osteoporotic fracture, and a HR of 2.76 (95% CI, 1.94-3.91; P < .001) for clinical vertebral fracture.

Adjusting for competing mortality produced similar results: men with higher levels of AAC had increased risk of major osteoporotic fracture and hip fracture, although AAC-24 score was not associated with higher risk of clinical vertebral fractures. Prevalent vertebral fractures were also still associated with higher risk of hip (subdistribution HR, 1.42; 95% CI, 1.01-2.00; P = .004), major osteoporotic fracture (SHR, 1.71; 95% CI, 1.36-2.14; P < .001), and clinical vertebral fracture (SHR, 2.46; 95% CI, 1.72-3.52; P < .001).

Fracture risk assessment proves to be “a nice proof of concept”

“It’s well known that prevalent fractures predict future fractures,” said Thomas M. Link, MD, PhD, chief of the musculoskeletal imaging section in the department of radiology and biomedical imaging at the University of California, San Francisco, in an interview. “The new finding is that aortic calcifications combined with prevalent fractures perform better in predicting major osteoporotic fractures. Traditionally on radiographs, we note that patients who have more calcifications in vessels have less density or calcium in the bone, so this is a nice proof of concept.”

“While the study shows excellent reproducibility, it is not clear how the AAC-24 score was validated,” he added. “Theoretically, abdominal CT could be used for this.”

Along with validation of the AAC-24 score on lateral spine radiographs, he expressed a desire that future research would be “clearer regarding how this would potentially impact patient management. Prevalent fractures already are an indication to treat patients with osteoporosis-specific drugs. How would the results of this study impact management beyond that?”

The authors acknowledged their study’s other potential limitations, including limits in their ability to estimate absolute and relative hip fracture risk in men with low AAC scores but a prevalent vertebral fracture. In addition, they noted that their cohort was “mostly white, healthy, community-dwelling older men” and therefore may not be generalizable to other populations.

The study was supported by the National Institutes of Health, including grants from the National Institute on Aging, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the National Center for Advancing Translational Sciences, and the NIH Roadmap for Medical Research. One author reported being supported by a National Heart Foundation of Australia Future Leader Fellowship. The others disclosed no potential conflicts of interest.

A new study has found that older men with high levels of abdominal aortic calcification (AAC) and a prevalent vertebral fracture – both of which can be assessed via lateral spine radiographs – are at increased risk of hip, clinical vertebral, and major osteoporotic fractures.

“The results of this study and others suggest that it may be appropriate to expand lateral spine imaging to include those with a significant pre-test probability of higher AAC being present,” wrote John T. Schousboe, MD, of the Park Nicollet Clinic and HealthPartners Institute in Bloomington, Minn. The study was published in the Journal of Bone and Mineral Research.

To determine the impact of prevalent vertebral fractures and AAC on fracture risk, the researchers assessed the lateral spine radiographs of 5,365 men who were enrolled in the Osteoporotic Fractures in Men (MrOS) study. All participants were 65 years or older, community dwelling, able to walk without assistance, and without bilateral hip arthroplasties. They split patients’ 24-point AAC (ACC-24) scores at the baseline visit into four levels: 0-1, 2-4, 5-8, and greater than 9. Self-reports of fractures were solicited from the cohort every 4 months.

Of all participants, 7.6% (n = 407) had a prevalent vertebral fracture at baseline. They were, on average, 1.5 years older than participants without a fracture; they were also more likely to be white and to have a prior nonspine fracture, along with having a lower femoral neck BMD (0.718 g/cm², compared with 0.787 g/cm²; P < .001). In addition, significantly more men with a prevalent vertebral fracture had an AAC score greater than 9 (27% vs. 21.2%).

After an average follow-up period of 12.4 years (standard deviation, 5.2), 634 men had a major osteoporotic fracture, 283 had a hip fracture, 206 had a clinical vertebral fracture, and 2,626 died without having any of the three. After adjustment for risk factors such as age, prior nonspine fracture, and prevalent vertebral fracture, men with higher AAC-24 scores had a higher risk of major osteoporotic fracture, compared with men who had scores of 0-1: a hazard ratio of 1.38 (95% confidence interval, 1.10-1.73; P < .001) for scores 2-4, a HR of 1.45 (95% CI, 1.14-1.84; P < .001) for scores 5-8, and a HR of 1.65 (95% CI, 1.29-2.10; P < .001) for scores greater than 9.

Similar findings were reported regarding risk of hip fractures: a HR of 1.54 (95% CI, 1.07-2.20; P < .001) for men with AAC-24 scores 2-4, a HR of 1.40 (95% CI, 0.96-2.06; P < .001) for scores 5-8, and a HR of 2.17 (95% CI, 1.50-3.13; P < .001) for scores greater than 9. AAC-24 score severity was not associated with a higher risk of clinical vertebral fractures.

After adjustment for risk factors and AAC-24 score, men with prevalent vertebral fractures had an increased risk of all three fracture outcomes, compared with men without any fractures at baseline: a HR of 1.56 (95% CI, 1.12-2.16; P < .001) for hip fracture, a HR of 1.85 (95% CI, 1.48-2.31; P < .001) for major osteoporotic fracture, and a HR of 2.76 (95% CI, 1.94-3.91; P < .001) for clinical vertebral fracture.

Adjusting for competing mortality produced similar results: men with higher levels of AAC had increased risk of major osteoporotic fracture and hip fracture, although AAC-24 score was not associated with higher risk of clinical vertebral fractures. Prevalent vertebral fractures were also still associated with higher risk of hip (subdistribution HR, 1.42; 95% CI, 1.01-2.00; P = .004), major osteoporotic fracture (SHR, 1.71; 95% CI, 1.36-2.14; P < .001), and clinical vertebral fracture (SHR, 2.46; 95% CI, 1.72-3.52; P < .001).

Fracture risk assessment proves to be “a nice proof of concept”

“It’s well known that prevalent fractures predict future fractures,” said Thomas M. Link, MD, PhD, chief of the musculoskeletal imaging section in the department of radiology and biomedical imaging at the University of California, San Francisco, in an interview. “The new finding is that aortic calcifications combined with prevalent fractures perform better in predicting major osteoporotic fractures. Traditionally on radiographs, we note that patients who have more calcifications in vessels have less density or calcium in the bone, so this is a nice proof of concept.”

“While the study shows excellent reproducibility, it is not clear how the AAC-24 score was validated,” he added. “Theoretically, abdominal CT could be used for this.”

Along with validation of the AAC-24 score on lateral spine radiographs, he expressed a desire that future research would be “clearer regarding how this would potentially impact patient management. Prevalent fractures already are an indication to treat patients with osteoporosis-specific drugs. How would the results of this study impact management beyond that?”

The authors acknowledged their study’s other potential limitations, including limits in their ability to estimate absolute and relative hip fracture risk in men with low AAC scores but a prevalent vertebral fracture. In addition, they noted that their cohort was “mostly white, healthy, community-dwelling older men” and therefore may not be generalizable to other populations.

The study was supported by the National Institutes of Health, including grants from the National Institute on Aging, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the National Center for Advancing Translational Sciences, and the NIH Roadmap for Medical Research. One author reported being supported by a National Heart Foundation of Australia Future Leader Fellowship. The others disclosed no potential conflicts of interest.

Family physician Mitchell A. Kaminski, MD, MBA, was still awash in feelings of joy and relief at recently being vaccinated against COVID-19 when a patient’s comments stopped him cold. The patient, a middle-aged man with several comorbidities had just declined the pneumonia vaccine – and he added, without prompting, that he wouldn’t be getting the COVID vaccine either. This patient had heard getting vaccinated could kill him.

Dr. Kaminski countered with medical facts, including that the very rare side effects hadn’t killed anyone in the United States but COVID was killing thousands of people every day. “Well then, I’ll just risk getting COVID,” Dr. Kaminski recalled the patient saying. Conversation over.

That experience caused Dr. Kaminski, who is program director for population health at Thomas Jefferson University, Philadelphia, to rethink the way he talks to patients who are uncertain or skeptical about getting a COVID-19 vaccine. Now, if he saw that patient who seemed fearful of dying from a vaccination, Dr. Kaminski said he would be more curious.

Instead of outright contradicting the beliefs of a patient who is reluctant to get vaccinated, Dr. Kaminski now gently asks about the reasons for their discomfort and offers information about the vaccines. But mostly, he listens.

©Sean Warren/iStockphoto.com

Conversations between physicians and patients about the risks that come with getting a COVID-19 vaccine are becoming more common in general as eligibility for immunizations expands. Physicians are using a variety of methods to communicate about the safety and importance of getting vaccinated that they think will lead to more of their patients getting a COVID-19 vaccine.

About 80% of Americans say that they are most likely to turn to doctors, nurses and other health professionals for help in deciding whether to get the COVID vaccine, according to research by the Kaiser Family Foundation.
 

Getting beyond the distrust

While patients often feel a strong connection with their health providers, distrust in the medical establishment still exists, especially among some populations. The Kaiser Family Foundation reported that a third of Black respondents are taking a “wait-and-see” approach, while 23% said they will get it only if it’s required – or not at all.

Distrust persists from historical racist events in medicine, such as the infamous Tuskegee experiments in which treatment was withheld from Black men with syphilis. But physicians shouldn’t assume that all Black patients have the same reasons for vaccine hesitancy, said Krys Foster, MD, MPH, a family physician at Thomas Jefferson University.

“In my experience caring for patients who are uncertain or have concerns about receiving the vaccine, I’ve learned that many are just seeking more information, or even my approval to say that it is safe to proceed given their medical history,” she said.

Sources such as the COVID Racial Data Tracker have found that Black Americans have a higher COVID death rate than other racial or ethnic groups, making vaccination even more vital. Yet fear of the vaccine could be triggered by misinformation that can be found in various places online, Dr. Foster said.

To encourage people to get vaccinated and dispel false information, Dr. Foster takes time to discuss how safe it is to get a COVID-19 vaccine and the vaccines’ side effects, then quickly pivots to discussing how to get vaccinated.

It can be difficult for some people to find appointments or access testing sites. The failure to get the vaccine shouldn’t automatically be attributed to “hesitancy,” she said. “The onus is on the medical community to help fix the health injustices inflicted on communities of color by providing equitable information and access and stop placing blame on them for having the ‘wrong’ vaccine attitude.”
 

Give your testimonial

Jamie Loehr, MD, of Cayuga Family Medicine in Ithaca, N.Y., said he has always had a higher-than-average number of patients who refused or delayed their children’s vaccines. He does not kick them out of his practice but politely continues to educate them about the vaccines.

When patients ask Dr. Loehr if he trusts the vaccine, he responds with confidence: “I not only believe in it, I got it and I recommend it to anyone who can possibly get it.”

He was surprised recently when a mother who has expressed reluctance to vaccinate her young children came for a checkup and told him she had already received a COVID vaccine. “She made the decision on her own that this was important enough that she wanted to get it,” he said.
 

Health care worker hesitancy

Some health care workers’ unease about being at the front of the line for vaccines may be another source of vaccine hesitancy among members of the general population that physicians need to address. In a survey of almost 3,500 health care workers conducted in October and November 2020 and published in January 2021 in Vaccines, only about a third (36%) said they would get the vaccine as soon as it became available. By mid- to late-February, 54% of health care workers reported having been vaccinated and another 10% planned to get the vaccine as soon as possible, according to the Kaiser Family Foundation COVID-19 Vaccine Monitor.

Resolving doubts about the vaccines requires a thoughtful approach toward health care colleagues, said Eileen Barrett, MD, MPH, an internist and hospitalist who was a coauthor of the Vaccines paper and who serves on the editorial advisory board of Internal Medicine News. “We should meet people where they are and do our best to hear their concerns, listening thoughtfully without condescension. Validate how important their role is in endorsing vaccination and also validate asking questions.”

There’s power in the strong personal testimonial of physicians and other health care workers – not just to influence patients, but as a model for fellow health professionals, as well, noted Dr. Barrett, who cares for COVID-19 patients and is associate professor in the division of hospital medicine, department of internal medicine, at the University of New Mexico, Albuquerque.
 

‘Do it for your loved ones’

The Reagan-Udall Foundation, a nonprofit organization created by Congress to support the Food and Drug Administration, tested some messaging with focus groups. Participants responded favorably to this statement about why the vaccines were developed so quickly: “Vaccine development moved faster than normal because everyone’s making it their highest priority.”

People did not feel motivated to get the vaccine out of a sense of civic duty, said Susan Winckler, RPh, Esq, who is CEO of the foundation. But they did think the following was a good reason to get vaccinated: “By getting a vaccine, I could protect my children, my parents, and other loved ones.”

Physicians also can work with community influencers, such as faith leaders, to build confidence in vaccines. That’s part of the strategy of Roll Up Your Sleeves, a campaign spearheaded by agilon health, a company that partners with physician practices to develop value-based care for Medicare Advantage patients.

For example, Wilmington Health in North Carolina answered questions about the vaccines in Facebook Live events and created a Spanish-language video to boost vaccine confidence in the Latinx community. Additionally, PriMED Physicians in Dayton, Ohio, reached out to Black churches to provide a vaccine-awareness video and a PriMED doctor participated in a webinar sponsored by the Nigerian Women Cultural Organization to help dispel myths about COVID-19 and the vaccines.

“This is a way to deepen our relationship with our patients,” said Ben Kornitzer, MD, chief medical officer of agilon. “It’s helping to walk them through this door where on one side is the pandemic and social isolation and on the other side is a return to their life and loved ones.”

The messages provided by primary care physicians can be powerful and affirming, said Ms. Winckler.

“The path forward is to make a space for people to ask questions,” she continued, noting that the Reagan-Udall Foundation provides charts that show how the timeline for vaccine development was compressed without skipping any steps.

Strategies and background information on how to reinforce confidence in COVID-19 vaccines are also available on a page of the Centers for Disease Control and Prevention’s website.

None of the experts interviewed reported any relevant conflicts of interest. The Reagan-Udall Foundation has received sponsorships from Johnson & Johnson and AstraZeneca and has had a safety surveillance contract with Pfizer.

Family physician Mitchell A. Kaminski, MD, MBA, was still awash in feelings of joy and relief at recently being vaccinated against COVID-19 when a patient’s comments stopped him cold. The patient, a middle-aged man with several comorbidities had just declined the pneumonia vaccine – and he added, without prompting, that he wouldn’t be getting the COVID vaccine either. This patient had heard getting vaccinated could kill him.

Dr. Kaminski countered with medical facts, including that the very rare side effects hadn’t killed anyone in the United States but COVID was killing thousands of people every day. “Well then, I’ll just risk getting COVID,” Dr. Kaminski recalled the patient saying. Conversation over.

That experience caused Dr. Kaminski, who is program director for population health at Thomas Jefferson University, Philadelphia, to rethink the way he talks to patients who are uncertain or skeptical about getting a COVID-19 vaccine. Now, if he saw that patient who seemed fearful of dying from a vaccination, Dr. Kaminski said he would be more curious.

Instead of outright contradicting the beliefs of a patient who is reluctant to get vaccinated, Dr. Kaminski now gently asks about the reasons for their discomfort and offers information about the vaccines. But mostly, he listens.

©Sean Warren/iStockphoto.com

Conversations between physicians and patients about the risks that come with getting a COVID-19 vaccine are becoming more common in general as eligibility for immunizations expands. Physicians are using a variety of methods to communicate about the safety and importance of getting vaccinated that they think will lead to more of their patients getting a COVID-19 vaccine.

About 80% of Americans say that they are most likely to turn to doctors, nurses and other health professionals for help in deciding whether to get the COVID vaccine, according to research by the Kaiser Family Foundation.
 

Getting beyond the distrust

While patients often feel a strong connection with their health providers, distrust in the medical establishment still exists, especially among some populations. The Kaiser Family Foundation reported that a third of Black respondents are taking a “wait-and-see” approach, while 23% said they will get it only if it’s required – or not at all.

Distrust persists from historical racist events in medicine, such as the infamous Tuskegee experiments in which treatment was withheld from Black men with syphilis. But physicians shouldn’t assume that all Black patients have the same reasons for vaccine hesitancy, said Krys Foster, MD, MPH, a family physician at Thomas Jefferson University.

“In my experience caring for patients who are uncertain or have concerns about receiving the vaccine, I’ve learned that many are just seeking more information, or even my approval to say that it is safe to proceed given their medical history,” she said.

Sources such as the COVID Racial Data Tracker have found that Black Americans have a higher COVID death rate than other racial or ethnic groups, making vaccination even more vital. Yet fear of the vaccine could be triggered by misinformation that can be found in various places online, Dr. Foster said.

To encourage people to get vaccinated and dispel false information, Dr. Foster takes time to discuss how safe it is to get a COVID-19 vaccine and the vaccines’ side effects, then quickly pivots to discussing how to get vaccinated.

It can be difficult for some people to find appointments or access testing sites. The failure to get the vaccine shouldn’t automatically be attributed to “hesitancy,” she said. “The onus is on the medical community to help fix the health injustices inflicted on communities of color by providing equitable information and access and stop placing blame on them for having the ‘wrong’ vaccine attitude.”
 

Give your testimonial

Jamie Loehr, MD, of Cayuga Family Medicine in Ithaca, N.Y., said he has always had a higher-than-average number of patients who refused or delayed their children’s vaccines. He does not kick them out of his practice but politely continues to educate them about the vaccines.

When patients ask Dr. Loehr if he trusts the vaccine, he responds with confidence: “I not only believe in it, I got it and I recommend it to anyone who can possibly get it.”

He was surprised recently when a mother who has expressed reluctance to vaccinate her young children came for a checkup and told him she had already received a COVID vaccine. “She made the decision on her own that this was important enough that she wanted to get it,” he said.
 

Health care worker hesitancy

Some health care workers’ unease about being at the front of the line for vaccines may be another source of vaccine hesitancy among members of the general population that physicians need to address. In a survey of almost 3,500 health care workers conducted in October and November 2020 and published in January 2021 in Vaccines, only about a third (36%) said they would get the vaccine as soon as it became available. By mid- to late-February, 54% of health care workers reported having been vaccinated and another 10% planned to get the vaccine as soon as possible, according to the Kaiser Family Foundation COVID-19 Vaccine Monitor.

Resolving doubts about the vaccines requires a thoughtful approach toward health care colleagues, said Eileen Barrett, MD, MPH, an internist and hospitalist who was a coauthor of the Vaccines paper and who serves on the editorial advisory board of Internal Medicine News. “We should meet people where they are and do our best to hear their concerns, listening thoughtfully without condescension. Validate how important their role is in endorsing vaccination and also validate asking questions.”

There’s power in the strong personal testimonial of physicians and other health care workers – not just to influence patients, but as a model for fellow health professionals, as well, noted Dr. Barrett, who cares for COVID-19 patients and is associate professor in the division of hospital medicine, department of internal medicine, at the University of New Mexico, Albuquerque.
 

‘Do it for your loved ones’

The Reagan-Udall Foundation, a nonprofit organization created by Congress to support the Food and Drug Administration, tested some messaging with focus groups. Participants responded favorably to this statement about why the vaccines were developed so quickly: “Vaccine development moved faster than normal because everyone’s making it their highest priority.”

People did not feel motivated to get the vaccine out of a sense of civic duty, said Susan Winckler, RPh, Esq, who is CEO of the foundation. But they did think the following was a good reason to get vaccinated: “By getting a vaccine, I could protect my children, my parents, and other loved ones.”

Physicians also can work with community influencers, such as faith leaders, to build confidence in vaccines. That’s part of the strategy of Roll Up Your Sleeves, a campaign spearheaded by agilon health, a company that partners with physician practices to develop value-based care for Medicare Advantage patients.

For example, Wilmington Health in North Carolina answered questions about the vaccines in Facebook Live events and created a Spanish-language video to boost vaccine confidence in the Latinx community. Additionally, PriMED Physicians in Dayton, Ohio, reached out to Black churches to provide a vaccine-awareness video and a PriMED doctor participated in a webinar sponsored by the Nigerian Women Cultural Organization to help dispel myths about COVID-19 and the vaccines.

“This is a way to deepen our relationship with our patients,” said Ben Kornitzer, MD, chief medical officer of agilon. “It’s helping to walk them through this door where on one side is the pandemic and social isolation and on the other side is a return to their life and loved ones.”

The messages provided by primary care physicians can be powerful and affirming, said Ms. Winckler.

“The path forward is to make a space for people to ask questions,” she continued, noting that the Reagan-Udall Foundation provides charts that show how the timeline for vaccine development was compressed without skipping any steps.

Strategies and background information on how to reinforce confidence in COVID-19 vaccines are also available on a page of the Centers for Disease Control and Prevention’s website.

None of the experts interviewed reported any relevant conflicts of interest. The Reagan-Udall Foundation has received sponsorships from Johnson & Johnson and AstraZeneca and has had a safety surveillance contract with Pfizer.

Family physician Mitchell A. Kaminski, MD, MBA, was still awash in feelings of joy and relief at recently being vaccinated against COVID-19 when a patient’s comments stopped him cold. The patient, a middle-aged man with several comorbidities had just declined the pneumonia vaccine – and he added, without prompting, that he wouldn’t be getting the COVID vaccine either. This patient had heard getting vaccinated could kill him.

Dr. Kaminski countered with medical facts, including that the very rare side effects hadn’t killed anyone in the United States but COVID was killing thousands of people every day. “Well then, I’ll just risk getting COVID,” Dr. Kaminski recalled the patient saying. Conversation over.

That experience caused Dr. Kaminski, who is program director for population health at Thomas Jefferson University, Philadelphia, to rethink the way he talks to patients who are uncertain or skeptical about getting a COVID-19 vaccine. Now, if he saw that patient who seemed fearful of dying from a vaccination, Dr. Kaminski said he would be more curious.

Instead of outright contradicting the beliefs of a patient who is reluctant to get vaccinated, Dr. Kaminski now gently asks about the reasons for their discomfort and offers information about the vaccines. But mostly, he listens.

©Sean Warren/iStockphoto.com

Conversations between physicians and patients about the risks that come with getting a COVID-19 vaccine are becoming more common in general as eligibility for immunizations expands. Physicians are using a variety of methods to communicate about the safety and importance of getting vaccinated that they think will lead to more of their patients getting a COVID-19 vaccine.

About 80% of Americans say that they are most likely to turn to doctors, nurses and other health professionals for help in deciding whether to get the COVID vaccine, according to research by the Kaiser Family Foundation.
 

Getting beyond the distrust

While patients often feel a strong connection with their health providers, distrust in the medical establishment still exists, especially among some populations. The Kaiser Family Foundation reported that a third of Black respondents are taking a “wait-and-see” approach, while 23% said they will get it only if it’s required – or not at all.

Distrust persists from historical racist events in medicine, such as the infamous Tuskegee experiments in which treatment was withheld from Black men with syphilis. But physicians shouldn’t assume that all Black patients have the same reasons for vaccine hesitancy, said Krys Foster, MD, MPH, a family physician at Thomas Jefferson University.

“In my experience caring for patients who are uncertain or have concerns about receiving the vaccine, I’ve learned that many are just seeking more information, or even my approval to say that it is safe to proceed given their medical history,” she said.

Sources such as the COVID Racial Data Tracker have found that Black Americans have a higher COVID death rate than other racial or ethnic groups, making vaccination even more vital. Yet fear of the vaccine could be triggered by misinformation that can be found in various places online, Dr. Foster said.

To encourage people to get vaccinated and dispel false information, Dr. Foster takes time to discuss how safe it is to get a COVID-19 vaccine and the vaccines’ side effects, then quickly pivots to discussing how to get vaccinated.

It can be difficult for some people to find appointments or access testing sites. The failure to get the vaccine shouldn’t automatically be attributed to “hesitancy,” she said. “The onus is on the medical community to help fix the health injustices inflicted on communities of color by providing equitable information and access and stop placing blame on them for having the ‘wrong’ vaccine attitude.”
 

Give your testimonial

Jamie Loehr, MD, of Cayuga Family Medicine in Ithaca, N.Y., said he has always had a higher-than-average number of patients who refused or delayed their children’s vaccines. He does not kick them out of his practice but politely continues to educate them about the vaccines.

When patients ask Dr. Loehr if he trusts the vaccine, he responds with confidence: “I not only believe in it, I got it and I recommend it to anyone who can possibly get it.”

He was surprised recently when a mother who has expressed reluctance to vaccinate her young children came for a checkup and told him she had already received a COVID vaccine. “She made the decision on her own that this was important enough that she wanted to get it,” he said.
 

Health care worker hesitancy

Some health care workers’ unease about being at the front of the line for vaccines may be another source of vaccine hesitancy among members of the general population that physicians need to address. In a survey of almost 3,500 health care workers conducted in October and November 2020 and published in January 2021 in Vaccines, only about a third (36%) said they would get the vaccine as soon as it became available. By mid- to late-February, 54% of health care workers reported having been vaccinated and another 10% planned to get the vaccine as soon as possible, according to the Kaiser Family Foundation COVID-19 Vaccine Monitor.

Resolving doubts about the vaccines requires a thoughtful approach toward health care colleagues, said Eileen Barrett, MD, MPH, an internist and hospitalist who was a coauthor of the Vaccines paper and who serves on the editorial advisory board of Internal Medicine News. “We should meet people where they are and do our best to hear their concerns, listening thoughtfully without condescension. Validate how important their role is in endorsing vaccination and also validate asking questions.”

There’s power in the strong personal testimonial of physicians and other health care workers – not just to influence patients, but as a model for fellow health professionals, as well, noted Dr. Barrett, who cares for COVID-19 patients and is associate professor in the division of hospital medicine, department of internal medicine, at the University of New Mexico, Albuquerque.
 

‘Do it for your loved ones’

The Reagan-Udall Foundation, a nonprofit organization created by Congress to support the Food and Drug Administration, tested some messaging with focus groups. Participants responded favorably to this statement about why the vaccines were developed so quickly: “Vaccine development moved faster than normal because everyone’s making it their highest priority.”

People did not feel motivated to get the vaccine out of a sense of civic duty, said Susan Winckler, RPh, Esq, who is CEO of the foundation. But they did think the following was a good reason to get vaccinated: “By getting a vaccine, I could protect my children, my parents, and other loved ones.”

Physicians also can work with community influencers, such as faith leaders, to build confidence in vaccines. That’s part of the strategy of Roll Up Your Sleeves, a campaign spearheaded by agilon health, a company that partners with physician practices to develop value-based care for Medicare Advantage patients.

For example, Wilmington Health in North Carolina answered questions about the vaccines in Facebook Live events and created a Spanish-language video to boost vaccine confidence in the Latinx community. Additionally, PriMED Physicians in Dayton, Ohio, reached out to Black churches to provide a vaccine-awareness video and a PriMED doctor participated in a webinar sponsored by the Nigerian Women Cultural Organization to help dispel myths about COVID-19 and the vaccines.

“This is a way to deepen our relationship with our patients,” said Ben Kornitzer, MD, chief medical officer of agilon. “It’s helping to walk them through this door where on one side is the pandemic and social isolation and on the other side is a return to their life and loved ones.”

The messages provided by primary care physicians can be powerful and affirming, said Ms. Winckler.

“The path forward is to make a space for people to ask questions,” she continued, noting that the Reagan-Udall Foundation provides charts that show how the timeline for vaccine development was compressed without skipping any steps.

Strategies and background information on how to reinforce confidence in COVID-19 vaccines are also available on a page of the Centers for Disease Control and Prevention’s website.

None of the experts interviewed reported any relevant conflicts of interest. The Reagan-Udall Foundation has received sponsorships from Johnson & Johnson and AstraZeneca and has had a safety surveillance contract with Pfizer.

Approximately a third of older patients treated with thyroid hormones report the concurrent use of medications that can interfere with the accuracy of thyroid function tests, potentially compromising treatment decisions, new research shows.

juststock/Thinkstock

“We know from previous studies that thyroid hormone use is common in older adults and that there are a multitude of medications that can interfere with thyroid function tests in different ways,” senior author Maria Papaleontiou, MD, told Medscape Medical News.

“However, to our knowledge, the extent of concurrent use of thyroid hormone and interfering medications in older adults, age 65 years and older, has not been previously explored,” added Dr. Papaleontiou, of the Division of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor.

The findings were presented as a poster during virtual ENDO 2021, the Endocrine Society’s annual meeting.

Commenting on the study, Thanh Duc Hoang, DO, an endocrinologist with the Walter Reed National Military Medical Center, in Bethesda, Md., said: “It is important for clinicians to be aware of various interactions and interferences of medications affecting the accuracy of thyroid function tests.”

“If patients are not able to discontinue the medications shortly before the bloodwork, the clinicians may consider ordering different thyroid tests or assays that avoid the interferences,” he told Medscape Medical News.
 

32% of patients taking meds that could interfere with tests

In evaluating data on 538,137 patients treated with thyroid hormones from the Corporate Data Warehouse of the Veterans Health Administration, spanning 2004-2017, first author Rachel Beeson, MD, and colleagues with the University of Michigan found most patients in the study were men (96.5%), White (77.1%), and had two or more comorbidities (62.6%).

Of this total, 170,261 (31.6%) patients treated with thyroid hormones, over a median follow-up of 56 months, were taking at least one drug that could potentially interfere with thyroid function tests.

Among the drugs with potential thyroid test interference, about 28% of patients were taking prednisone or prednisolone, 8% were taking amiodarone, and 1.42% were taking phenytoin. Other reported drugs that could potentially interfere included carbamazepine (0.91%), phenobarbital (0.15%), lithium (0.40%), and tamoxifen (0.11%).

Multivariate analysis showed that characteristics associated with those most likely to have concurrent medication use included non-Whites (OR, 1.18 vs Whites), Hispanic ethnicity (OR 1.11 vs non-Hispanic), female sex (OR 1.12 vs males), and presence of comorbidities (eg, Charlson-Deyo comorbidity score ≥ 2, OR,  2.47 vs score of 0).

Meanwhile, older patients age 85 years and over had a lower likelihood of concurrent medications interfering with thyroid tests (OR, 0.47 vs age 65-74 years).

The findings are concerning given the wide use of levothyroxine to treat hypothyroidism, which is the most widely prescribed drug in the United States.

“Our findings not only highlight the complexity of thyroid hormone management in older adults in the context of polypharmacy and multimorbidity, but they also draw attention to vulnerable groups for this practice, which included female patients, non-Whites, patients of Hispanic ethnicity, and patients with comorbidities,” Dr. Papaleontiou said.
 

Nature of interference possibilities varies

Medications or supplements can interfere with thyroid function tests in a variety of ways, she explained. “Some medications could lead to a decrease in the absorption of levothyroxine, others may affect how well the pill dissolves.”

In addition, certain medications can affect the circulation of thyroid hormone in the blood and how it binds with proteins, or they can lead to decreasing thyroid hormone levels due to a variety of interactions.

And in contrast, “What is even more challenging is that some medications or supplements may appear to affect thyroid function based on lab tests when in reality they don’t actually affect thyroid function and may lead to dose adjustments unnecessarily,” Dr. Papaleontiou noted.
 

Recommendations to counter interference

Current recommendations to try to counter the effects of polypharmacy on thyroid treatment include advising patients to take thyroid hormones on an empty stomach at least 30-60 minutes prior to eating for optimal absorption.

If the patient is taking medications known to interfere with absorption of thyroid hormones, the recommendation is to space those out by at least 4 hours.

“The big challenge in older adults is that many of them do experience polypharmacy, being at risk for multiple drug-drug interactions,” Dr. Papaleontiou said.

“Physicians and patients should be vigilant and communicate closely every time there is initiation of a new medication or supplement to consider whether there may be interference.”

The authors have reported no relevant financial relationships. Dr. Hoang has reported being a speaker for Acella Pharmaceuticals.

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

Approximately a third of older patients treated with thyroid hormones report the concurrent use of medications that can interfere with the accuracy of thyroid function tests, potentially compromising treatment decisions, new research shows.

juststock/Thinkstock

“We know from previous studies that thyroid hormone use is common in older adults and that there are a multitude of medications that can interfere with thyroid function tests in different ways,” senior author Maria Papaleontiou, MD, told Medscape Medical News.

“However, to our knowledge, the extent of concurrent use of thyroid hormone and interfering medications in older adults, age 65 years and older, has not been previously explored,” added Dr. Papaleontiou, of the Division of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor.

The findings were presented as a poster during virtual ENDO 2021, the Endocrine Society’s annual meeting.

Commenting on the study, Thanh Duc Hoang, DO, an endocrinologist with the Walter Reed National Military Medical Center, in Bethesda, Md., said: “It is important for clinicians to be aware of various interactions and interferences of medications affecting the accuracy of thyroid function tests.”

“If patients are not able to discontinue the medications shortly before the bloodwork, the clinicians may consider ordering different thyroid tests or assays that avoid the interferences,” he told Medscape Medical News.
 

32% of patients taking meds that could interfere with tests

In evaluating data on 538,137 patients treated with thyroid hormones from the Corporate Data Warehouse of the Veterans Health Administration, spanning 2004-2017, first author Rachel Beeson, MD, and colleagues with the University of Michigan found most patients in the study were men (96.5%), White (77.1%), and had two or more comorbidities (62.6%).

Of this total, 170,261 (31.6%) patients treated with thyroid hormones, over a median follow-up of 56 months, were taking at least one drug that could potentially interfere with thyroid function tests.

Among the drugs with potential thyroid test interference, about 28% of patients were taking prednisone or prednisolone, 8% were taking amiodarone, and 1.42% were taking phenytoin. Other reported drugs that could potentially interfere included carbamazepine (0.91%), phenobarbital (0.15%), lithium (0.40%), and tamoxifen (0.11%).

Multivariate analysis showed that characteristics associated with those most likely to have concurrent medication use included non-Whites (OR, 1.18 vs Whites), Hispanic ethnicity (OR 1.11 vs non-Hispanic), female sex (OR 1.12 vs males), and presence of comorbidities (eg, Charlson-Deyo comorbidity score ≥ 2, OR,  2.47 vs score of 0).

Meanwhile, older patients age 85 years and over had a lower likelihood of concurrent medications interfering with thyroid tests (OR, 0.47 vs age 65-74 years).

The findings are concerning given the wide use of levothyroxine to treat hypothyroidism, which is the most widely prescribed drug in the United States.

“Our findings not only highlight the complexity of thyroid hormone management in older adults in the context of polypharmacy and multimorbidity, but they also draw attention to vulnerable groups for this practice, which included female patients, non-Whites, patients of Hispanic ethnicity, and patients with comorbidities,” Dr. Papaleontiou said.
 

Nature of interference possibilities varies

Medications or supplements can interfere with thyroid function tests in a variety of ways, she explained. “Some medications could lead to a decrease in the absorption of levothyroxine, others may affect how well the pill dissolves.”

In addition, certain medications can affect the circulation of thyroid hormone in the blood and how it binds with proteins, or they can lead to decreasing thyroid hormone levels due to a variety of interactions.

And in contrast, “What is even more challenging is that some medications or supplements may appear to affect thyroid function based on lab tests when in reality they don’t actually affect thyroid function and may lead to dose adjustments unnecessarily,” Dr. Papaleontiou noted.
 

Recommendations to counter interference

Current recommendations to try to counter the effects of polypharmacy on thyroid treatment include advising patients to take thyroid hormones on an empty stomach at least 30-60 minutes prior to eating for optimal absorption.

If the patient is taking medications known to interfere with absorption of thyroid hormones, the recommendation is to space those out by at least 4 hours.

“The big challenge in older adults is that many of them do experience polypharmacy, being at risk for multiple drug-drug interactions,” Dr. Papaleontiou said.

“Physicians and patients should be vigilant and communicate closely every time there is initiation of a new medication or supplement to consider whether there may be interference.”

The authors have reported no relevant financial relationships. Dr. Hoang has reported being a speaker for Acella Pharmaceuticals.

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

Approximately a third of older patients treated with thyroid hormones report the concurrent use of medications that can interfere with the accuracy of thyroid function tests, potentially compromising treatment decisions, new research shows.

juststock/Thinkstock

“We know from previous studies that thyroid hormone use is common in older adults and that there are a multitude of medications that can interfere with thyroid function tests in different ways,” senior author Maria Papaleontiou, MD, told Medscape Medical News.

“However, to our knowledge, the extent of concurrent use of thyroid hormone and interfering medications in older adults, age 65 years and older, has not been previously explored,” added Dr. Papaleontiou, of the Division of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor.

The findings were presented as a poster during virtual ENDO 2021, the Endocrine Society’s annual meeting.

Commenting on the study, Thanh Duc Hoang, DO, an endocrinologist with the Walter Reed National Military Medical Center, in Bethesda, Md., said: “It is important for clinicians to be aware of various interactions and interferences of medications affecting the accuracy of thyroid function tests.”

“If patients are not able to discontinue the medications shortly before the bloodwork, the clinicians may consider ordering different thyroid tests or assays that avoid the interferences,” he told Medscape Medical News.
 

32% of patients taking meds that could interfere with tests

In evaluating data on 538,137 patients treated with thyroid hormones from the Corporate Data Warehouse of the Veterans Health Administration, spanning 2004-2017, first author Rachel Beeson, MD, and colleagues with the University of Michigan found most patients in the study were men (96.5%), White (77.1%), and had two or more comorbidities (62.6%).

Of this total, 170,261 (31.6%) patients treated with thyroid hormones, over a median follow-up of 56 months, were taking at least one drug that could potentially interfere with thyroid function tests.

Among the drugs with potential thyroid test interference, about 28% of patients were taking prednisone or prednisolone, 8% were taking amiodarone, and 1.42% were taking phenytoin. Other reported drugs that could potentially interfere included carbamazepine (0.91%), phenobarbital (0.15%), lithium (0.40%), and tamoxifen (0.11%).

Multivariate analysis showed that characteristics associated with those most likely to have concurrent medication use included non-Whites (OR, 1.18 vs Whites), Hispanic ethnicity (OR 1.11 vs non-Hispanic), female sex (OR 1.12 vs males), and presence of comorbidities (eg, Charlson-Deyo comorbidity score ≥ 2, OR,  2.47 vs score of 0).

Meanwhile, older patients age 85 years and over had a lower likelihood of concurrent medications interfering with thyroid tests (OR, 0.47 vs age 65-74 years).

The findings are concerning given the wide use of levothyroxine to treat hypothyroidism, which is the most widely prescribed drug in the United States.

“Our findings not only highlight the complexity of thyroid hormone management in older adults in the context of polypharmacy and multimorbidity, but they also draw attention to vulnerable groups for this practice, which included female patients, non-Whites, patients of Hispanic ethnicity, and patients with comorbidities,” Dr. Papaleontiou said.
 

Nature of interference possibilities varies

Medications or supplements can interfere with thyroid function tests in a variety of ways, she explained. “Some medications could lead to a decrease in the absorption of levothyroxine, others may affect how well the pill dissolves.”

In addition, certain medications can affect the circulation of thyroid hormone in the blood and how it binds with proteins, or they can lead to decreasing thyroid hormone levels due to a variety of interactions.

And in contrast, “What is even more challenging is that some medications or supplements may appear to affect thyroid function based on lab tests when in reality they don’t actually affect thyroid function and may lead to dose adjustments unnecessarily,” Dr. Papaleontiou noted.
 

Recommendations to counter interference

Current recommendations to try to counter the effects of polypharmacy on thyroid treatment include advising patients to take thyroid hormones on an empty stomach at least 30-60 minutes prior to eating for optimal absorption.

If the patient is taking medications known to interfere with absorption of thyroid hormones, the recommendation is to space those out by at least 4 hours.

“The big challenge in older adults is that many of them do experience polypharmacy, being at risk for multiple drug-drug interactions,” Dr. Papaleontiou said.

“Physicians and patients should be vigilant and communicate closely every time there is initiation of a new medication or supplement to consider whether there may be interference.”

The authors have reported no relevant financial relationships. Dr. Hoang has reported being a speaker for Acella Pharmaceuticals.

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