Clinical Endocrinology News

Nearly one out of five American adults with hypertension is on a prescription drug known to raise blood pressure, based on analysis of more than 27,000 people included in recent reports from the recurring National Health and Nutrition Examination Survey (NHANES).

Nearly half of these American adults had hypertension, and in this subgroup, 18.5% reported using a prescription drug known to increase blood pressure. The most widely used class of agents with this effect was antidepressants, used by 8.7%; followed by nonsteroidal anti-inflammatory drugs (NSAIDs), used by 6.5%; steroids, 1.9%; estrogens, 1.7%; and several other agents each used by fewer than 1% of the study cohort, John Vitarello, MD, said during a press briefing on reports from the upcoming annual scientific sessions of the American College of Cardiology.

He and his associates estimated that this use of prescription drugs known to raise blood pressure could be what stands in the way of some 560,000-2.2 million Americans from having their hypertension under control, depending on the exact blood pressure impact that various pressure-increasing drugs have and presuming that half of those on blood pressure increasing agents could stop them and switch to alternative agents, said Dr. Vitarello, a researcher at Beth Israel Deaconess Medical Center in Boston.

He also highlighted that the study assessed only prescription drugs and did not examine OTC drug use, which may be especially relevant for the many people who regularly take NSAIDs.

“Clinicians should review the prescription and OTC drug use of patients with hypertension and consider stopping drugs that increase blood pressure or switching the patient to alternatives” that are blood pressure neutral, Dr. Vitarello said during the briefing. He cautioned that maintaining hypertensive patients on agents that raise their blood pressure can result in “prescribing cascades” where taking drugs that boost blood pressure results in need for intensified antihypertensive treatment.
 

An opportunity for NSAID alternatives

“This study hopefully raises awareness that there is a very high use of medications that increase blood pressure, and use of OTC agents could increase the rate even higher” said Eugene Yang, MD, a cardiologist and codirector of the Cardiovascular Wellness and Prevention Program of the University of Washington, Seattle. Substituting for certain antidepressant agents may often not be realistic, but an opportunity exists for reducing NSAID use, a class also linked with an increased risk for bleeding and other adverse effects, Dr. Yang said during the briefing. Minimizing use of NSAIDs including ibuprofen and naproxen use “is something to think about,” he suggested.

“The effect of NSAIDs on blood pressure is not well studied and can vary from person to person” noted Dr. Vitarello, who added that higher NSAID dosages and more prolonged use likely increase the risk for an adverse effect on blood pressure. One reasonable option is to encourage patients to use an alternative class of pain reliever such as acetaminophen.

It remains “a challenge” to discern differences in adverse blood pressure effects, and in all adverse cardiovascular effects among different NSAIDs, said Dr. Yang. Results from “some studies show that certain NSAIDs may be safer, but other studies did not. We need to be very careful using NSAIDs because, on average, they increase blood pressure by about 3 mm Hg. We need to be mindful to try to prescribe alternative agents, like acetaminophen.”
 

A decade of data from NHANES

The analysis run by Dr. Vitarello and associates used data from 27,599 American adults included in the NHANES during 2009-2018, and focused on the 44% who either had an average blood pressure measurement of at least 130/80 mm Hg or reported having ever been told by a clinician that they had hypertension. The NHANES assessments included the prescription medications taken by each participant. The prevalence of using at least one prescription drug known to raise blood pressure was 24% among women and 14% among men, and 4% of those with hypertension were on two or more pressure-increasing agents.

The researchers based their identification of pressure-increasing prescription drugs on the list included in the 2017 guideline for managing high blood pressure from the American College of Cardiology and American Heart Association. This list specifies that the antidepressants that raise blood pressure are the monoamine oxidase inhibitors, serotonin norepinephrine reuptake inhibitors, and tricyclic antidepressants.

Dr. Vitarello and Dr. Yang had no disclosures.

mzoler@mdedge.com

Nearly one out of five American adults with hypertension is on a prescription drug known to raise blood pressure, based on analysis of more than 27,000 people included in recent reports from the recurring National Health and Nutrition Examination Survey (NHANES).

Nearly half of these American adults had hypertension, and in this subgroup, 18.5% reported using a prescription drug known to increase blood pressure. The most widely used class of agents with this effect was antidepressants, used by 8.7%; followed by nonsteroidal anti-inflammatory drugs (NSAIDs), used by 6.5%; steroids, 1.9%; estrogens, 1.7%; and several other agents each used by fewer than 1% of the study cohort, John Vitarello, MD, said during a press briefing on reports from the upcoming annual scientific sessions of the American College of Cardiology.

He and his associates estimated that this use of prescription drugs known to raise blood pressure could be what stands in the way of some 560,000-2.2 million Americans from having their hypertension under control, depending on the exact blood pressure impact that various pressure-increasing drugs have and presuming that half of those on blood pressure increasing agents could stop them and switch to alternative agents, said Dr. Vitarello, a researcher at Beth Israel Deaconess Medical Center in Boston.

He also highlighted that the study assessed only prescription drugs and did not examine OTC drug use, which may be especially relevant for the many people who regularly take NSAIDs.

“Clinicians should review the prescription and OTC drug use of patients with hypertension and consider stopping drugs that increase blood pressure or switching the patient to alternatives” that are blood pressure neutral, Dr. Vitarello said during the briefing. He cautioned that maintaining hypertensive patients on agents that raise their blood pressure can result in “prescribing cascades” where taking drugs that boost blood pressure results in need for intensified antihypertensive treatment.
 

An opportunity for NSAID alternatives

“This study hopefully raises awareness that there is a very high use of medications that increase blood pressure, and use of OTC agents could increase the rate even higher” said Eugene Yang, MD, a cardiologist and codirector of the Cardiovascular Wellness and Prevention Program of the University of Washington, Seattle. Substituting for certain antidepressant agents may often not be realistic, but an opportunity exists for reducing NSAID use, a class also linked with an increased risk for bleeding and other adverse effects, Dr. Yang said during the briefing. Minimizing use of NSAIDs including ibuprofen and naproxen use “is something to think about,” he suggested.

“The effect of NSAIDs on blood pressure is not well studied and can vary from person to person” noted Dr. Vitarello, who added that higher NSAID dosages and more prolonged use likely increase the risk for an adverse effect on blood pressure. One reasonable option is to encourage patients to use an alternative class of pain reliever such as acetaminophen.

It remains “a challenge” to discern differences in adverse blood pressure effects, and in all adverse cardiovascular effects among different NSAIDs, said Dr. Yang. Results from “some studies show that certain NSAIDs may be safer, but other studies did not. We need to be very careful using NSAIDs because, on average, they increase blood pressure by about 3 mm Hg. We need to be mindful to try to prescribe alternative agents, like acetaminophen.”
 

A decade of data from NHANES

The analysis run by Dr. Vitarello and associates used data from 27,599 American adults included in the NHANES during 2009-2018, and focused on the 44% who either had an average blood pressure measurement of at least 130/80 mm Hg or reported having ever been told by a clinician that they had hypertension. The NHANES assessments included the prescription medications taken by each participant. The prevalence of using at least one prescription drug known to raise blood pressure was 24% among women and 14% among men, and 4% of those with hypertension were on two or more pressure-increasing agents.

The researchers based their identification of pressure-increasing prescription drugs on the list included in the 2017 guideline for managing high blood pressure from the American College of Cardiology and American Heart Association. This list specifies that the antidepressants that raise blood pressure are the monoamine oxidase inhibitors, serotonin norepinephrine reuptake inhibitors, and tricyclic antidepressants.

Dr. Vitarello and Dr. Yang had no disclosures.

mzoler@mdedge.com

Nearly one out of five American adults with hypertension is on a prescription drug known to raise blood pressure, based on analysis of more than 27,000 people included in recent reports from the recurring National Health and Nutrition Examination Survey (NHANES).

Nearly half of these American adults had hypertension, and in this subgroup, 18.5% reported using a prescription drug known to increase blood pressure. The most widely used class of agents with this effect was antidepressants, used by 8.7%; followed by nonsteroidal anti-inflammatory drugs (NSAIDs), used by 6.5%; steroids, 1.9%; estrogens, 1.7%; and several other agents each used by fewer than 1% of the study cohort, John Vitarello, MD, said during a press briefing on reports from the upcoming annual scientific sessions of the American College of Cardiology.

He and his associates estimated that this use of prescription drugs known to raise blood pressure could be what stands in the way of some 560,000-2.2 million Americans from having their hypertension under control, depending on the exact blood pressure impact that various pressure-increasing drugs have and presuming that half of those on blood pressure increasing agents could stop them and switch to alternative agents, said Dr. Vitarello, a researcher at Beth Israel Deaconess Medical Center in Boston.

He also highlighted that the study assessed only prescription drugs and did not examine OTC drug use, which may be especially relevant for the many people who regularly take NSAIDs.

“Clinicians should review the prescription and OTC drug use of patients with hypertension and consider stopping drugs that increase blood pressure or switching the patient to alternatives” that are blood pressure neutral, Dr. Vitarello said during the briefing. He cautioned that maintaining hypertensive patients on agents that raise their blood pressure can result in “prescribing cascades” where taking drugs that boost blood pressure results in need for intensified antihypertensive treatment.
 

An opportunity for NSAID alternatives

“This study hopefully raises awareness that there is a very high use of medications that increase blood pressure, and use of OTC agents could increase the rate even higher” said Eugene Yang, MD, a cardiologist and codirector of the Cardiovascular Wellness and Prevention Program of the University of Washington, Seattle. Substituting for certain antidepressant agents may often not be realistic, but an opportunity exists for reducing NSAID use, a class also linked with an increased risk for bleeding and other adverse effects, Dr. Yang said during the briefing. Minimizing use of NSAIDs including ibuprofen and naproxen use “is something to think about,” he suggested.

“The effect of NSAIDs on blood pressure is not well studied and can vary from person to person” noted Dr. Vitarello, who added that higher NSAID dosages and more prolonged use likely increase the risk for an adverse effect on blood pressure. One reasonable option is to encourage patients to use an alternative class of pain reliever such as acetaminophen.

It remains “a challenge” to discern differences in adverse blood pressure effects, and in all adverse cardiovascular effects among different NSAIDs, said Dr. Yang. Results from “some studies show that certain NSAIDs may be safer, but other studies did not. We need to be very careful using NSAIDs because, on average, they increase blood pressure by about 3 mm Hg. We need to be mindful to try to prescribe alternative agents, like acetaminophen.”
 

A decade of data from NHANES

The analysis run by Dr. Vitarello and associates used data from 27,599 American adults included in the NHANES during 2009-2018, and focused on the 44% who either had an average blood pressure measurement of at least 130/80 mm Hg or reported having ever been told by a clinician that they had hypertension. The NHANES assessments included the prescription medications taken by each participant. The prevalence of using at least one prescription drug known to raise blood pressure was 24% among women and 14% among men, and 4% of those with hypertension were on two or more pressure-increasing agents.

The researchers based their identification of pressure-increasing prescription drugs on the list included in the 2017 guideline for managing high blood pressure from the American College of Cardiology and American Heart Association. This list specifies that the antidepressants that raise blood pressure are the monoamine oxidase inhibitors, serotonin norepinephrine reuptake inhibitors, and tricyclic antidepressants.

Dr. Vitarello and Dr. Yang had no disclosures.

mzoler@mdedge.com

For persons with obesity who lost a substantial amount of weight on a low-calorie diet, the combination of exercise and medication significantly improved weight-loss maintenance, and more so than either strategy alone, according to results of a randomized, head-to-head trial.

A year after starting moderate to vigorous exercise coupled with liraglutide treatment, study participants had a weight loss 9.5 kg more than those who received placebo and usual activity, study results show.

Reductions in both weight and fat loss seen with exercise and liraglutide was roughly twice as much as what was achieved at 1 year with the strategies of liraglutide or exercise alone, according to authors of the study, which appears in the New England Journal of Medicine .

Although the findings may not apply to those who can’t or won’t perform moderate to vigorous exercise, the intervention in this study was nevertheless feasible in this group of persons with obesity who had a very low level of fitness, according to the authors.
 

Hope for healthy weight loss maintenance

Investigator Signe S. Torekov, PhD, said in an interview that these results provide hope that more-intensive exercise regimens, with or without medication, can be useful and well accepted among individuals struggling with obesity.

“When we started our study, we were told, ‘you are never going to have people with obesity exercising that much, and for that long’ – but people were actually very happy about the exercise,” said Dr. Torekov, a professor in the department of biomedical sciences at the University of Copenhagen.

“If you actually set up a program where people are monitored and you have a feedback system, then exercise is an excellent component in obesity treatment that should be much more actively used – not only for its weight-lowering component, but also for improving health and quality of life,” she said in an interview.

Weight-management specialist John D. Clark, MD, PhD, said results of this study can be used to help inform patients about how successful different strategies incorporating exercise and medication may be following initial weight loss.

“When patients plateau on a consistent, calorie-restricted dietary plan, we can educate them and manage expectations about what options may be available to them after their initial weight loss,” said Dr. Clark, of the University of Texas, Dallas.

“If the patient’s goal specifically is weight loss at all costs, then I may suggest, ‘let’s consider liraglutide or liraglutide in combination with exercise,’ ” he said in an interview. “Exercise improves body composition, even if it may not on its own be as successful in the next phase of their weight-loss journey, as shown in this study.”
 

Obesity and weight-loss challenges

Although it’s not uncommon for obese patients to lose a large amount of weight, keeping the weight off is frequently a challenge unless the patient follows a structured weight maintenance program, according to Dr. Torekov and coauthors.

The rapid weight regain seen in many obese patients could be a result of reductions in total energy expenditure or increased appetite. Exercise is one strategy to sustain weight loss, though according to the authors, very few studies have looked at exercise in isolation to quantify its contribution to maintenance.

Accordingly, the present study sought to determine whether exercise, medication, or the combination thereof works best to keep weight off.

The study incorporated liraglutide, a GLP-1 receptor agonist indicated for chronic weight management, along with a reduced-calorie diet and increased physical activity, in adults with elevated body mass index and at least one weight-related comorbidity.

The investigator-initiated phase 3 trial included 215 adults with a body mass index of 32-43. Individuals with type 2 diabetes were excluded. All participants followed an 8-week, low-calorie diet comprising 800 calories per day.

Participants who lost 5% or more of their body weight were then randomized to 1 year of exercise plus liraglutide, exercise plus placebo, usual activity plus liraglutide, or usual activity plus placebo.

The exercise program – which was structured but flexible, according to investigators – included group exercise sessions that incorporated 30 minutes of indoor cycling and 15 minutes of circuit training 2 days each week. Participants wore heart rate monitors during exercise to make sure they reached targets for moderate to vigorous intensity.

Instructors trained in exercise physiology planned and monitored individualized exercise programs for each participant in the exercise-medication or exercise-only arms of the study.

Participants in all groups attended 12 one-on-one consultations where body weight was measured and dietetic support was provided.
 

Weight loss with exercise and medication

Out of 215 individuals enrolled in the study, 195 lost at least 5% of body weight and continued on to the randomized portion, the investigators reported. During the diet phase, they lost a mean of 13.1 kg, translating into a 12% mean reduction in body weight.

The mean frequency of exercise was 2.4 times per week in the exercise-plus-medication group and 2.5 times per week in the exercise-only group. About one-third of the exercise took place in the group sessions, and there was no difference in relative intensity between group and individual exercise regimens, the investigators said.

Individuals in the exercise plus medication group continued to lose more weight, such that, at the end of 1 year, the weight loss decreased even further, by a mean of –3.4 kg. By contrast, weight increased by a mean of 6.1 kg for the placebo group, adding up to a treatment difference of –9.5 kg (95% confidence interval, –13.1 to –5.9; P < .001), according to the report.

That treatment effect was also seen, but more muted, in the exercise- and liraglutide-only groups, at –4.1 kg and –6.8 kg, respectively.

A significant treatment effect was observed for exercise plus liraglutide, compared with exercise alone, at –5.4 kg (P = .004), while the treatment effect for the combination versus liraglutide alone was not significant at –2.7 kg (P = .13), the data show.

Body-fat reduction at 52 weeks was –3.9 percentage points for exercise plus liraglutide as compared with placebo, or roughly twice the reductions seen in the exercise- and liraglutide-alone groups, the investigators said, adding that the combination preserved lean mass.

Reductions in hemoglobin A1c, which are generally thought to reduce diabetes risk, were reduced in both the liraglutide and liraglutide-exercise combination group, according to their report.

The research was supported in part by grants from the Novo Nordisk Foundation.

For persons with obesity who lost a substantial amount of weight on a low-calorie diet, the combination of exercise and medication significantly improved weight-loss maintenance, and more so than either strategy alone, according to results of a randomized, head-to-head trial.

A year after starting moderate to vigorous exercise coupled with liraglutide treatment, study participants had a weight loss 9.5 kg more than those who received placebo and usual activity, study results show.

Reductions in both weight and fat loss seen with exercise and liraglutide was roughly twice as much as what was achieved at 1 year with the strategies of liraglutide or exercise alone, according to authors of the study, which appears in the New England Journal of Medicine .

Although the findings may not apply to those who can’t or won’t perform moderate to vigorous exercise, the intervention in this study was nevertheless feasible in this group of persons with obesity who had a very low level of fitness, according to the authors.
 

Hope for healthy weight loss maintenance

Investigator Signe S. Torekov, PhD, said in an interview that these results provide hope that more-intensive exercise regimens, with or without medication, can be useful and well accepted among individuals struggling with obesity.

“When we started our study, we were told, ‘you are never going to have people with obesity exercising that much, and for that long’ – but people were actually very happy about the exercise,” said Dr. Torekov, a professor in the department of biomedical sciences at the University of Copenhagen.

“If you actually set up a program where people are monitored and you have a feedback system, then exercise is an excellent component in obesity treatment that should be much more actively used – not only for its weight-lowering component, but also for improving health and quality of life,” she said in an interview.

Weight-management specialist John D. Clark, MD, PhD, said results of this study can be used to help inform patients about how successful different strategies incorporating exercise and medication may be following initial weight loss.

“When patients plateau on a consistent, calorie-restricted dietary plan, we can educate them and manage expectations about what options may be available to them after their initial weight loss,” said Dr. Clark, of the University of Texas, Dallas.

“If the patient’s goal specifically is weight loss at all costs, then I may suggest, ‘let’s consider liraglutide or liraglutide in combination with exercise,’ ” he said in an interview. “Exercise improves body composition, even if it may not on its own be as successful in the next phase of their weight-loss journey, as shown in this study.”
 

Obesity and weight-loss challenges

Although it’s not uncommon for obese patients to lose a large amount of weight, keeping the weight off is frequently a challenge unless the patient follows a structured weight maintenance program, according to Dr. Torekov and coauthors.

The rapid weight regain seen in many obese patients could be a result of reductions in total energy expenditure or increased appetite. Exercise is one strategy to sustain weight loss, though according to the authors, very few studies have looked at exercise in isolation to quantify its contribution to maintenance.

Accordingly, the present study sought to determine whether exercise, medication, or the combination thereof works best to keep weight off.

The study incorporated liraglutide, a GLP-1 receptor agonist indicated for chronic weight management, along with a reduced-calorie diet and increased physical activity, in adults with elevated body mass index and at least one weight-related comorbidity.

The investigator-initiated phase 3 trial included 215 adults with a body mass index of 32-43. Individuals with type 2 diabetes were excluded. All participants followed an 8-week, low-calorie diet comprising 800 calories per day.

Participants who lost 5% or more of their body weight were then randomized to 1 year of exercise plus liraglutide, exercise plus placebo, usual activity plus liraglutide, or usual activity plus placebo.

The exercise program – which was structured but flexible, according to investigators – included group exercise sessions that incorporated 30 minutes of indoor cycling and 15 minutes of circuit training 2 days each week. Participants wore heart rate monitors during exercise to make sure they reached targets for moderate to vigorous intensity.

Instructors trained in exercise physiology planned and monitored individualized exercise programs for each participant in the exercise-medication or exercise-only arms of the study.

Participants in all groups attended 12 one-on-one consultations where body weight was measured and dietetic support was provided.
 

Weight loss with exercise and medication

Out of 215 individuals enrolled in the study, 195 lost at least 5% of body weight and continued on to the randomized portion, the investigators reported. During the diet phase, they lost a mean of 13.1 kg, translating into a 12% mean reduction in body weight.

The mean frequency of exercise was 2.4 times per week in the exercise-plus-medication group and 2.5 times per week in the exercise-only group. About one-third of the exercise took place in the group sessions, and there was no difference in relative intensity between group and individual exercise regimens, the investigators said.

Individuals in the exercise plus medication group continued to lose more weight, such that, at the end of 1 year, the weight loss decreased even further, by a mean of –3.4 kg. By contrast, weight increased by a mean of 6.1 kg for the placebo group, adding up to a treatment difference of –9.5 kg (95% confidence interval, –13.1 to –5.9; P < .001), according to the report.

That treatment effect was also seen, but more muted, in the exercise- and liraglutide-only groups, at –4.1 kg and –6.8 kg, respectively.

A significant treatment effect was observed for exercise plus liraglutide, compared with exercise alone, at –5.4 kg (P = .004), while the treatment effect for the combination versus liraglutide alone was not significant at –2.7 kg (P = .13), the data show.

Body-fat reduction at 52 weeks was –3.9 percentage points for exercise plus liraglutide as compared with placebo, or roughly twice the reductions seen in the exercise- and liraglutide-alone groups, the investigators said, adding that the combination preserved lean mass.

Reductions in hemoglobin A1c, which are generally thought to reduce diabetes risk, were reduced in both the liraglutide and liraglutide-exercise combination group, according to their report.

The research was supported in part by grants from the Novo Nordisk Foundation.

For persons with obesity who lost a substantial amount of weight on a low-calorie diet, the combination of exercise and medication significantly improved weight-loss maintenance, and more so than either strategy alone, according to results of a randomized, head-to-head trial.

A year after starting moderate to vigorous exercise coupled with liraglutide treatment, study participants had a weight loss 9.5 kg more than those who received placebo and usual activity, study results show.

Reductions in both weight and fat loss seen with exercise and liraglutide was roughly twice as much as what was achieved at 1 year with the strategies of liraglutide or exercise alone, according to authors of the study, which appears in the New England Journal of Medicine .

Although the findings may not apply to those who can’t or won’t perform moderate to vigorous exercise, the intervention in this study was nevertheless feasible in this group of persons with obesity who had a very low level of fitness, according to the authors.
 

Hope for healthy weight loss maintenance

Investigator Signe S. Torekov, PhD, said in an interview that these results provide hope that more-intensive exercise regimens, with or without medication, can be useful and well accepted among individuals struggling with obesity.

“When we started our study, we were told, ‘you are never going to have people with obesity exercising that much, and for that long’ – but people were actually very happy about the exercise,” said Dr. Torekov, a professor in the department of biomedical sciences at the University of Copenhagen.

“If you actually set up a program where people are monitored and you have a feedback system, then exercise is an excellent component in obesity treatment that should be much more actively used – not only for its weight-lowering component, but also for improving health and quality of life,” she said in an interview.

Weight-management specialist John D. Clark, MD, PhD, said results of this study can be used to help inform patients about how successful different strategies incorporating exercise and medication may be following initial weight loss.

“When patients plateau on a consistent, calorie-restricted dietary plan, we can educate them and manage expectations about what options may be available to them after their initial weight loss,” said Dr. Clark, of the University of Texas, Dallas.

“If the patient’s goal specifically is weight loss at all costs, then I may suggest, ‘let’s consider liraglutide or liraglutide in combination with exercise,’ ” he said in an interview. “Exercise improves body composition, even if it may not on its own be as successful in the next phase of their weight-loss journey, as shown in this study.”
 

Obesity and weight-loss challenges

Although it’s not uncommon for obese patients to lose a large amount of weight, keeping the weight off is frequently a challenge unless the patient follows a structured weight maintenance program, according to Dr. Torekov and coauthors.

The rapid weight regain seen in many obese patients could be a result of reductions in total energy expenditure or increased appetite. Exercise is one strategy to sustain weight loss, though according to the authors, very few studies have looked at exercise in isolation to quantify its contribution to maintenance.

Accordingly, the present study sought to determine whether exercise, medication, or the combination thereof works best to keep weight off.

The study incorporated liraglutide, a GLP-1 receptor agonist indicated for chronic weight management, along with a reduced-calorie diet and increased physical activity, in adults with elevated body mass index and at least one weight-related comorbidity.

The investigator-initiated phase 3 trial included 215 adults with a body mass index of 32-43. Individuals with type 2 diabetes were excluded. All participants followed an 8-week, low-calorie diet comprising 800 calories per day.

Participants who lost 5% or more of their body weight were then randomized to 1 year of exercise plus liraglutide, exercise plus placebo, usual activity plus liraglutide, or usual activity plus placebo.

The exercise program – which was structured but flexible, according to investigators – included group exercise sessions that incorporated 30 minutes of indoor cycling and 15 minutes of circuit training 2 days each week. Participants wore heart rate monitors during exercise to make sure they reached targets for moderate to vigorous intensity.

Instructors trained in exercise physiology planned and monitored individualized exercise programs for each participant in the exercise-medication or exercise-only arms of the study.

Participants in all groups attended 12 one-on-one consultations where body weight was measured and dietetic support was provided.
 

Weight loss with exercise and medication

Out of 215 individuals enrolled in the study, 195 lost at least 5% of body weight and continued on to the randomized portion, the investigators reported. During the diet phase, they lost a mean of 13.1 kg, translating into a 12% mean reduction in body weight.

The mean frequency of exercise was 2.4 times per week in the exercise-plus-medication group and 2.5 times per week in the exercise-only group. About one-third of the exercise took place in the group sessions, and there was no difference in relative intensity between group and individual exercise regimens, the investigators said.

Individuals in the exercise plus medication group continued to lose more weight, such that, at the end of 1 year, the weight loss decreased even further, by a mean of –3.4 kg. By contrast, weight increased by a mean of 6.1 kg for the placebo group, adding up to a treatment difference of –9.5 kg (95% confidence interval, –13.1 to –5.9; P < .001), according to the report.

That treatment effect was also seen, but more muted, in the exercise- and liraglutide-only groups, at –4.1 kg and –6.8 kg, respectively.

A significant treatment effect was observed for exercise plus liraglutide, compared with exercise alone, at –5.4 kg (P = .004), while the treatment effect for the combination versus liraglutide alone was not significant at –2.7 kg (P = .13), the data show.

Body-fat reduction at 52 weeks was –3.9 percentage points for exercise plus liraglutide as compared with placebo, or roughly twice the reductions seen in the exercise- and liraglutide-alone groups, the investigators said, adding that the combination preserved lean mass.

Reductions in hemoglobin A1c, which are generally thought to reduce diabetes risk, were reduced in both the liraglutide and liraglutide-exercise combination group, according to their report.

The research was supported in part by grants from the Novo Nordisk Foundation.

In 2017-2018, only one in three U.S. adults with diabetes received five basic elements of care recommended by the American Diabetes Association, new research indicates.

BakiBG

The proportions of patients who visited a physician for diabetes care and received hemoglobin A1c testing, foot and eye exams, and cholesterol testing increased from 2005 to 2018. However, this increase was primarily among those aged 65 years and older, and therefore eligible for Medicare.

“Our study suggests that providing affordable health care coverage can help ensure people with diabetes get recommended care. We also found that patients who were not receiving recommended care were more likely to be younger, newly diagnosed with diabetes, and not on diabetes medication. Clinicians can pay more attention to these patient populations to improve recommended care delivery and prevent diabetes-related complications,” lead author Jung-Im Shin, MD, said in an interview.

The data predate the COVID-19 pandemic, which has also had major effects on delivery of diabetes care, added Dr. Shin of Johns Hopkins University, Baltimore.

“Routine visits to the doctor and important screenings for retinopathy or foot examination have been postponed. People with diabetes have had to reschedule or cancel nonurgent visits, some have lost ... insurance following unemployment, and many have avoided health care facilities out of fear. We are only just beginning to understand the consequences of the pandemic on the health of people with diabetes,” Dr. Shin noted.
 

Overall improvements seen only in those aged 65 and older

The data, from 4,069 adults aged 20 years and older from the 2005-2018 National Health and Nutrition and Examination Survey (NHANES), were published online April 16, 2021, in Diabetes Care.

Dr. Shin and colleagues defined receipt of diabetes care as meeting all of the following five criteria in the past 12 months, based on the ADA Standards of Care and NHANES data availability: seeing a primary doctor for diabetes care, receiving A1c testing, receiving a foot examination, receiving an eye examination, and receiving cholesterol testing.

Over the entire 13-year period, 29.2% of respondents reported having received all five components.

That proportion increased significantly over time, from 25.0% in 2005-2006 to 34.1% in 2017-2018 (P = .004). However, among the individual components, only receiving A1c testing increased significantly over time, from 64.4% to 85.3%, in all age groups (P < .001).

Moreover, when stratified by age, receipt of all five components only increased significantly among participants aged 65 and older, from 29.3% in 2005-2006 to 44.2% in 2017-2018 (P = .001).

The proportion remained unchanged among those aged 40-64 (25.2% to 25.8%; P =  .457) and showed a nonsignificant increase in those aged 20-39 (9.9% to 26.0%; P = .401).

In adjusted analyses, older age, higher income and education, health insurance, longer duration of diabetes, use of diabetes medications, and hypercholesterolemia were significantly associated with receipt of ADA guideline–recommended diabetes care.

Factors not found to be associated with care receipt included sex, race/ethnicity, body mass index, smoking status, A1c, hypertension, cardiovascular disease, chronic kidney disease, and depressive symptoms.

Participants who received ADA guideline–recommended care were significantly more likely to achieve A1c below 7.5% (adjusted odds ratio, 1.52), blood pressure less than 140/90 mm Hg (aOR, 1.47), and LDL cholesterol below 100 mg/dL (aOR, 1.47), and to receive cholesterol-lowering medication (aOR, 1.79).

Dr. Shin said that it will be “important to study the impact of COVID-19 on diabetes care when new data are available.”

The project was supported by a research grant from Merck to Johns Hopkins University. Shin has reported receiving a grant from the National Institute of Diabetes and Digestive and Kidney Diseases. Two coauthors are Merck employees.

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

In 2017-2018, only one in three U.S. adults with diabetes received five basic elements of care recommended by the American Diabetes Association, new research indicates.

BakiBG

The proportions of patients who visited a physician for diabetes care and received hemoglobin A1c testing, foot and eye exams, and cholesterol testing increased from 2005 to 2018. However, this increase was primarily among those aged 65 years and older, and therefore eligible for Medicare.

“Our study suggests that providing affordable health care coverage can help ensure people with diabetes get recommended care. We also found that patients who were not receiving recommended care were more likely to be younger, newly diagnosed with diabetes, and not on diabetes medication. Clinicians can pay more attention to these patient populations to improve recommended care delivery and prevent diabetes-related complications,” lead author Jung-Im Shin, MD, said in an interview.

The data predate the COVID-19 pandemic, which has also had major effects on delivery of diabetes care, added Dr. Shin of Johns Hopkins University, Baltimore.

“Routine visits to the doctor and important screenings for retinopathy or foot examination have been postponed. People with diabetes have had to reschedule or cancel nonurgent visits, some have lost ... insurance following unemployment, and many have avoided health care facilities out of fear. We are only just beginning to understand the consequences of the pandemic on the health of people with diabetes,” Dr. Shin noted.
 

Overall improvements seen only in those aged 65 and older

The data, from 4,069 adults aged 20 years and older from the 2005-2018 National Health and Nutrition and Examination Survey (NHANES), were published online April 16, 2021, in Diabetes Care.

Dr. Shin and colleagues defined receipt of diabetes care as meeting all of the following five criteria in the past 12 months, based on the ADA Standards of Care and NHANES data availability: seeing a primary doctor for diabetes care, receiving A1c testing, receiving a foot examination, receiving an eye examination, and receiving cholesterol testing.

Over the entire 13-year period, 29.2% of respondents reported having received all five components.

That proportion increased significantly over time, from 25.0% in 2005-2006 to 34.1% in 2017-2018 (P = .004). However, among the individual components, only receiving A1c testing increased significantly over time, from 64.4% to 85.3%, in all age groups (P < .001).

Moreover, when stratified by age, receipt of all five components only increased significantly among participants aged 65 and older, from 29.3% in 2005-2006 to 44.2% in 2017-2018 (P = .001).

The proportion remained unchanged among those aged 40-64 (25.2% to 25.8%; P =  .457) and showed a nonsignificant increase in those aged 20-39 (9.9% to 26.0%; P = .401).

In adjusted analyses, older age, higher income and education, health insurance, longer duration of diabetes, use of diabetes medications, and hypercholesterolemia were significantly associated with receipt of ADA guideline–recommended diabetes care.

Factors not found to be associated with care receipt included sex, race/ethnicity, body mass index, smoking status, A1c, hypertension, cardiovascular disease, chronic kidney disease, and depressive symptoms.

Participants who received ADA guideline–recommended care were significantly more likely to achieve A1c below 7.5% (adjusted odds ratio, 1.52), blood pressure less than 140/90 mm Hg (aOR, 1.47), and LDL cholesterol below 100 mg/dL (aOR, 1.47), and to receive cholesterol-lowering medication (aOR, 1.79).

Dr. Shin said that it will be “important to study the impact of COVID-19 on diabetes care when new data are available.”

The project was supported by a research grant from Merck to Johns Hopkins University. Shin has reported receiving a grant from the National Institute of Diabetes and Digestive and Kidney Diseases. Two coauthors are Merck employees.

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

In 2017-2018, only one in three U.S. adults with diabetes received five basic elements of care recommended by the American Diabetes Association, new research indicates.

BakiBG

The proportions of patients who visited a physician for diabetes care and received hemoglobin A1c testing, foot and eye exams, and cholesterol testing increased from 2005 to 2018. However, this increase was primarily among those aged 65 years and older, and therefore eligible for Medicare.

“Our study suggests that providing affordable health care coverage can help ensure people with diabetes get recommended care. We also found that patients who were not receiving recommended care were more likely to be younger, newly diagnosed with diabetes, and not on diabetes medication. Clinicians can pay more attention to these patient populations to improve recommended care delivery and prevent diabetes-related complications,” lead author Jung-Im Shin, MD, said in an interview.

The data predate the COVID-19 pandemic, which has also had major effects on delivery of diabetes care, added Dr. Shin of Johns Hopkins University, Baltimore.

“Routine visits to the doctor and important screenings for retinopathy or foot examination have been postponed. People with diabetes have had to reschedule or cancel nonurgent visits, some have lost ... insurance following unemployment, and many have avoided health care facilities out of fear. We are only just beginning to understand the consequences of the pandemic on the health of people with diabetes,” Dr. Shin noted.
 

Overall improvements seen only in those aged 65 and older

The data, from 4,069 adults aged 20 years and older from the 2005-2018 National Health and Nutrition and Examination Survey (NHANES), were published online April 16, 2021, in Diabetes Care.

Dr. Shin and colleagues defined receipt of diabetes care as meeting all of the following five criteria in the past 12 months, based on the ADA Standards of Care and NHANES data availability: seeing a primary doctor for diabetes care, receiving A1c testing, receiving a foot examination, receiving an eye examination, and receiving cholesterol testing.

Over the entire 13-year period, 29.2% of respondents reported having received all five components.

That proportion increased significantly over time, from 25.0% in 2005-2006 to 34.1% in 2017-2018 (P = .004). However, among the individual components, only receiving A1c testing increased significantly over time, from 64.4% to 85.3%, in all age groups (P < .001).

Moreover, when stratified by age, receipt of all five components only increased significantly among participants aged 65 and older, from 29.3% in 2005-2006 to 44.2% in 2017-2018 (P = .001).

The proportion remained unchanged among those aged 40-64 (25.2% to 25.8%; P =  .457) and showed a nonsignificant increase in those aged 20-39 (9.9% to 26.0%; P = .401).

In adjusted analyses, older age, higher income and education, health insurance, longer duration of diabetes, use of diabetes medications, and hypercholesterolemia were significantly associated with receipt of ADA guideline–recommended diabetes care.

Factors not found to be associated with care receipt included sex, race/ethnicity, body mass index, smoking status, A1c, hypertension, cardiovascular disease, chronic kidney disease, and depressive symptoms.

Participants who received ADA guideline–recommended care were significantly more likely to achieve A1c below 7.5% (adjusted odds ratio, 1.52), blood pressure less than 140/90 mm Hg (aOR, 1.47), and LDL cholesterol below 100 mg/dL (aOR, 1.47), and to receive cholesterol-lowering medication (aOR, 1.79).

Dr. Shin said that it will be “important to study the impact of COVID-19 on diabetes care when new data are available.”

The project was supported by a research grant from Merck to Johns Hopkins University. Shin has reported receiving a grant from the National Institute of Diabetes and Digestive and Kidney Diseases. Two coauthors are Merck employees.

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

When caring for older adults with multiple chronic conditions, prioritizing patient goals is more effective and efficient than trying to address each condition in isolation, said Mary Tinetti, MD, Gladys Phillips Crofoot Professor of Medicine and Public Health and chief of geriatrics at Yale University, New Haven, Conn.

During a virtual presentation at the American College of Physicians annual Internal Medicine meeting, the gerontologist noted that primary care providers face a number of challenges when managing elderly patients with multimorbidity. These challenges include a lack of representative data in clinical trials, conflicting guideline recommendations, patient nonadherence, and decreased benefit from therapies due to competing conditions, she said.

“Trying to follow multiple guidelines can result in unintentional harms to these people with multiple conditions,” Dr. Tinetti said. She gave examples of the wide-ranging goals patients can have.

“Some [patients] will maximize the focus on function, regardless of how long they are likely to live,” Dr. Tinetti said. “Others will say symptom burden management is most important to them. And others will say they want to live as long as possible, and survival is most important, even if that means a reduction in their function. These individuals also vary in the care they are willing and able to receive to achieve the outcomes that matter most to them.”

For these reasons, Dr. Tinetti recommended patient priorities care, which she and her colleagues have been developing and implementing over the past 5-6 years.

“If the benefits and harms of addressing each condition in isolation is of uncertain benefit and potentially burdensome to both clinician and patient, and we know that patients vary in their health priorities ... then what else would you want to focus on in your 20-minute visit ... except each patient’s priorities?” Dr. Tinetti asked. “This is one solution to the challenge.”


 

What is patient priorities care?

Patient priorities care is a multidisciplinary, cyclical approach to clinical decision-making composed of three steps, Dr. Tinetti explained. First, a clinician identifies the patient’s health priorities. Second, this information is transmitted to comanaging providers, who decide which of their respective treatments are consistent with the patient’s priorities. And third, those decisions are disseminated to everyone involved in the patient’s care, both within and outside of the health care system, allowing all care providers to align with the patient’s priorities, she noted.

“Each person does that from their own expertise,” Dr. Tinetti said. “The social worker will do something different than the cardiologist, the physical therapist, the endocrinologist – but everybody is aiming at the same outcome – the patient’s priorities.”

In 2019, Dr. Tinetti led a nonrandomized clinical trial to test the feasibility of patient priorities care. The study involved 366 older adults with multimorbidity, among whom 203 received usual care, while 163 received this type of care. Patients in the latter group were twice as likely to have medications stopped, and significantly less likely to have self-management tasks added and diagnostic tests ordered.
 

How electronic health records can help

In an interview, Dr. Tinetti suggested that comanaging physicians communicate through electronic health records (EHRs), first to ensure that all care providers understand a patient’s goals, then to determine if recommended therapies align with those goals.

“It would be a little bit of a culture change to do that,” Dr. Tinetti said, “but the technology is there and it isn’t too terribly time consuming.”

She went on to suggest that primary care providers are typically best suited to coordinate this process; however, if a patient receives the majority of their care from a particular specialist, then that clinician may be the most suitable coordinator.
 

Systemic obstacles and solutions

According to Cynthia Boyd, MD, interim director of the division of geriatric medicine and gerontology, Johns Hopkins University, Baltimore, clinicians may encounter obstacles when implementing patient priorities care.

When caring for older adults with multiple chronic conditions, prioritizing patient goals is more effective and efficient than trying to address each condition in isolation, said Mary Tinetti, MD, Gladys Phillips Crofoot Professor of Medicine and Public Health and chief of geriatrics at Yale University, New Haven, Conn.

During a virtual presentation at the American College of Physicians annual Internal Medicine meeting, the gerontologist noted that primary care providers face a number of challenges when managing elderly patients with multimorbidity. These challenges include a lack of representative data in clinical trials, conflicting guideline recommendations, patient nonadherence, and decreased benefit from therapies due to competing conditions, she said.

“Trying to follow multiple guidelines can result in unintentional harms to these people with multiple conditions,” Dr. Tinetti said. She gave examples of the wide-ranging goals patients can have.

“Some [patients] will maximize the focus on function, regardless of how long they are likely to live,” Dr. Tinetti said. “Others will say symptom burden management is most important to them. And others will say they want to live as long as possible, and survival is most important, even if that means a reduction in their function. These individuals also vary in the care they are willing and able to receive to achieve the outcomes that matter most to them.”

For these reasons, Dr. Tinetti recommended patient priorities care, which she and her colleagues have been developing and implementing over the past 5-6 years.

“If the benefits and harms of addressing each condition in isolation is of uncertain benefit and potentially burdensome to both clinician and patient, and we know that patients vary in their health priorities ... then what else would you want to focus on in your 20-minute visit ... except each patient’s priorities?” Dr. Tinetti asked. “This is one solution to the challenge.”


 

What is patient priorities care?

Patient priorities care is a multidisciplinary, cyclical approach to clinical decision-making composed of three steps, Dr. Tinetti explained. First, a clinician identifies the patient’s health priorities. Second, this information is transmitted to comanaging providers, who decide which of their respective treatments are consistent with the patient’s priorities. And third, those decisions are disseminated to everyone involved in the patient’s care, both within and outside of the health care system, allowing all care providers to align with the patient’s priorities, she noted.

“Each person does that from their own expertise,” Dr. Tinetti said. “The social worker will do something different than the cardiologist, the physical therapist, the endocrinologist – but everybody is aiming at the same outcome – the patient’s priorities.”

In 2019, Dr. Tinetti led a nonrandomized clinical trial to test the feasibility of patient priorities care. The study involved 366 older adults with multimorbidity, among whom 203 received usual care, while 163 received this type of care. Patients in the latter group were twice as likely to have medications stopped, and significantly less likely to have self-management tasks added and diagnostic tests ordered.
 

How electronic health records can help

In an interview, Dr. Tinetti suggested that comanaging physicians communicate through electronic health records (EHRs), first to ensure that all care providers understand a patient’s goals, then to determine if recommended therapies align with those goals.

“It would be a little bit of a culture change to do that,” Dr. Tinetti said, “but the technology is there and it isn’t too terribly time consuming.”

She went on to suggest that primary care providers are typically best suited to coordinate this process; however, if a patient receives the majority of their care from a particular specialist, then that clinician may be the most suitable coordinator.
 

Systemic obstacles and solutions

According to Cynthia Boyd, MD, interim director of the division of geriatric medicine and gerontology, Johns Hopkins University, Baltimore, clinicians may encounter obstacles when implementing patient priorities care.

When caring for older adults with multiple chronic conditions, prioritizing patient goals is more effective and efficient than trying to address each condition in isolation, said Mary Tinetti, MD, Gladys Phillips Crofoot Professor of Medicine and Public Health and chief of geriatrics at Yale University, New Haven, Conn.

During a virtual presentation at the American College of Physicians annual Internal Medicine meeting, the gerontologist noted that primary care providers face a number of challenges when managing elderly patients with multimorbidity. These challenges include a lack of representative data in clinical trials, conflicting guideline recommendations, patient nonadherence, and decreased benefit from therapies due to competing conditions, she said.

“Trying to follow multiple guidelines can result in unintentional harms to these people with multiple conditions,” Dr. Tinetti said. She gave examples of the wide-ranging goals patients can have.

“Some [patients] will maximize the focus on function, regardless of how long they are likely to live,” Dr. Tinetti said. “Others will say symptom burden management is most important to them. And others will say they want to live as long as possible, and survival is most important, even if that means a reduction in their function. These individuals also vary in the care they are willing and able to receive to achieve the outcomes that matter most to them.”

For these reasons, Dr. Tinetti recommended patient priorities care, which she and her colleagues have been developing and implementing over the past 5-6 years.

“If the benefits and harms of addressing each condition in isolation is of uncertain benefit and potentially burdensome to both clinician and patient, and we know that patients vary in their health priorities ... then what else would you want to focus on in your 20-minute visit ... except each patient’s priorities?” Dr. Tinetti asked. “This is one solution to the challenge.”


 

What is patient priorities care?

Patient priorities care is a multidisciplinary, cyclical approach to clinical decision-making composed of three steps, Dr. Tinetti explained. First, a clinician identifies the patient’s health priorities. Second, this information is transmitted to comanaging providers, who decide which of their respective treatments are consistent with the patient’s priorities. And third, those decisions are disseminated to everyone involved in the patient’s care, both within and outside of the health care system, allowing all care providers to align with the patient’s priorities, she noted.

“Each person does that from their own expertise,” Dr. Tinetti said. “The social worker will do something different than the cardiologist, the physical therapist, the endocrinologist – but everybody is aiming at the same outcome – the patient’s priorities.”

In 2019, Dr. Tinetti led a nonrandomized clinical trial to test the feasibility of patient priorities care. The study involved 366 older adults with multimorbidity, among whom 203 received usual care, while 163 received this type of care. Patients in the latter group were twice as likely to have medications stopped, and significantly less likely to have self-management tasks added and diagnostic tests ordered.
 

How electronic health records can help

In an interview, Dr. Tinetti suggested that comanaging physicians communicate through electronic health records (EHRs), first to ensure that all care providers understand a patient’s goals, then to determine if recommended therapies align with those goals.

“It would be a little bit of a culture change to do that,” Dr. Tinetti said, “but the technology is there and it isn’t too terribly time consuming.”

She went on to suggest that primary care providers are typically best suited to coordinate this process; however, if a patient receives the majority of their care from a particular specialist, then that clinician may be the most suitable coordinator.
 

Systemic obstacles and solutions

According to Cynthia Boyd, MD, interim director of the division of geriatric medicine and gerontology, Johns Hopkins University, Baltimore, clinicians may encounter obstacles when implementing patient priorities care.

Nonalcoholic fatty liver disease (NAFLD) was present in approximately two-thirds of patients who did not undergo a liver biopsy. These patients were more likely to be non-White and older, as well as have normal ALT levels, which shows potential gaps in knowledge about this population.

Shidlovski/Getty Images

Data from studies of patients diagnosed with NAFLD that require biopsy among their inclusion criteria may be subject to selection and detection bias, wrote A. Sidney Barritt, MD, of the University of North Carolina at Chapel Hill, and colleagues. The researchers sought to compare characteristics of patients with NAFLD who were diagnosed using clinical criteria and those diagnosed via liver biopsy.

In a study published in Hepatology Communications, the researchers reviewed data from TARGET-NASH, a longitudinal, observational cohort study designed to follow patients with NAFLD in clinical practice to provide data on the effectiveness of treatments.

“TARGET-NASH represents a large cohort of NAFLD patients from multiple sites and can provide us with real world information on progression of disease in patients with NAFLD and particular risk factors that may be clinically relevant,” Zachary Henry, MD, MS, of the division of gastroenterology & hepatology at the University of Virginia Health System in Charlottesville, said in an interview. “This is one of the first studies from this database, and as time goes on, we will see more large-population data like this to answer specific questions for NAFLD patient.”
 

Surprising findings

The researchers included 3,474 patients aged 18 years and older who were enrolled in the TARGET-NASH study between Aug. 1, 2016, and March 4, 2019. The study participants were classified according to severity of liver disease: nonalcoholic fatty liver (30%), nonalcoholic steatohepatitis (37%), and NAFLD cirrhosis (33%).

A total of 766 patients were diagnosed with NASH based on clinical criteria without biopsy, and all met the criteria for abnormal ALT and steatosis based on imaging. In addition, these patients had at least one secondary diagnostic criteria: body mass index greater than 30 kg/m2 (74%), type 2 diabetes (42%), and dyslipidemia (54%). Significant independent predictors of liver biopsy included younger age, White race, female gender, diabetes, and elevated levels of ALT.

Elevated ALT increased the odds of liver biopsy by 14% per 10-point rise, according to the study. A machine learning model showed that non-White patients with ALT less than 69 IU/mL had a 6% chance of liver biopsy. By comparison, White patients had a 21% chance of biopsy with ALT between 29 IU/mL and 69 IU/mL that dropped to 10% if the ALT was less than 29 IU/mL.

However, ALT remains a “suboptimal surrogate” for disease severity, the researchers noted. “How a normal ALT is defined and how a normal ALT range may vary across different laboratories may play a role in its utility as a diagnostic tool as well.”

Dr. Henry was surprised by this finding: “With the advent of noninvasive measures of fibrosis, such as the NAFLD fibrosis score, Fibrosis-4, and transient elastography, I thought these would have a more significant role in that decision as opposed to ALT levels.”

Notably, mental health diagnoses accounted for nearly half (49%) of comorbid conditions, followed by cardiovascular disease (19%), and osteoarthritis (10%). The prevalence of these conditions emphasizes the challenges of managing patients with NAFLD with diet and exercise alone because mental and physical problems may impede progress, the researchers wrote.

The study findings were limited by several factors including the inability to determine health care provider intent, as well as undocumented factors related to patients and providers that might influence a biopsy decision, such as assessment of disease severity, the researchers noted. In addition, they noted that the mostly White study population treated in specialty settings might not generalize to other populations or primary care.

However, the findings are strengthened by the large study population and real-world setting, the researchers emphasized. “These data provide context for the selection bias that may be present in many registries and randomized, controlled trials of therapies for NAFLD, where biopsy is required for inclusion,” and show potential knowledge gaps about the patient population less likely to undergo biopsy.
 

Knowledge gaps and implications

The study is important because of the need to identify patient factors that predict histologic versus clinical diagnosis of NAFLD as the number of patient registries and clinical trials for NAFLD increase, Bubu Banini, MD, of Yale University, New Haven, Conn., said in an interview. “This information helps to elucidate selection and ascertainment bias and place findings from NAFLD registries and clinical trials into context.”

Dr. Banini said that some of the findings were to be expected, while others were not.

“Historically, males and non-Whites are less likely to participate in registries and clinical trials, compared to females and Whites. However, I was surprised to find that these discrepancies further paralleled the likelihood of undergoing liver biopsy even among those who chose to participate. In addition, while mental health disorders (such as anxiety and depression) are a fairly prevalent comorbidity in patients with NAFLD, I was surprised to find that NAFLD patients with mental health disorders were more likely to undergo liver biopsy compared to those without these disorders. I would have expected the reverse,” he noted.

“These findings highlight the gaps in knowledge regarding the impact of demographic and psychosocial factors on choice and assess to care among patients with NAFLD, and the need for further studies to address these gaps,” she emphasized.

“A number of [studies] such as TARGET-NASH are doing away with the requirement for liver biopsy for participation; hence, it is less likely that selection bias related to liver biopsy would be a problem in these [studies] if clinical diagnosis is considered as a surrogate for histological diagnosis,” Dr. Banini added.

“On the contrary, many NAFLD clinical trials require liver biopsy for inclusion.” As nicely demonstrated in the current study, “this inclusion criterion may introduce selection bias,” she said. “Awareness of potential biases would hopefully inform the design and recruitment strategy for registries and clinical trials in order to overcome these issues.”

“I think the results of this study may actually point to a larger issue within medicine in general, which is a difference in care provided to minority communities,” Dr. Henry said. “Whether this is intentional, related to unconscious bias on the part of providers, or related to a significant mistrust between minority communities and their health care providers is unclear but certainly needs to be addressed.”

He noted that the purpose of TARGET-NASH is to enroll all patients with NAFLD regardless of biopsy. “Over time, as we have more data on these patients, we will have a better understanding of both diagnostic and therapeutic decisions in patients with NAFLD.”

The study was supported by Target RWE, sponsor of the TARGET-NASH study. TARGET-NASH is a collaboration of academic and community investigators and the pharmaceutical industry. Lead author Dr. Barritt had no financial conflicts to disclose, but many study coauthors disclosed relationships with multiple pharmaceutical companies, including those involved in the TARGET-NASH study. Dr. Banini currently serves on the NASH advisory board for Boehringer Ingelheim. Dr. Henry reported no disclosures, although his institution is one of the enrollment sites for TARGET-NASH.

Nonalcoholic fatty liver disease (NAFLD) was present in approximately two-thirds of patients who did not undergo a liver biopsy. These patients were more likely to be non-White and older, as well as have normal ALT levels, which shows potential gaps in knowledge about this population.

Shidlovski/Getty Images

Data from studies of patients diagnosed with NAFLD that require biopsy among their inclusion criteria may be subject to selection and detection bias, wrote A. Sidney Barritt, MD, of the University of North Carolina at Chapel Hill, and colleagues. The researchers sought to compare characteristics of patients with NAFLD who were diagnosed using clinical criteria and those diagnosed via liver biopsy.

In a study published in Hepatology Communications, the researchers reviewed data from TARGET-NASH, a longitudinal, observational cohort study designed to follow patients with NAFLD in clinical practice to provide data on the effectiveness of treatments.

“TARGET-NASH represents a large cohort of NAFLD patients from multiple sites and can provide us with real world information on progression of disease in patients with NAFLD and particular risk factors that may be clinically relevant,” Zachary Henry, MD, MS, of the division of gastroenterology & hepatology at the University of Virginia Health System in Charlottesville, said in an interview. “This is one of the first studies from this database, and as time goes on, we will see more large-population data like this to answer specific questions for NAFLD patient.”
 

Surprising findings

The researchers included 3,474 patients aged 18 years and older who were enrolled in the TARGET-NASH study between Aug. 1, 2016, and March 4, 2019. The study participants were classified according to severity of liver disease: nonalcoholic fatty liver (30%), nonalcoholic steatohepatitis (37%), and NAFLD cirrhosis (33%).

A total of 766 patients were diagnosed with NASH based on clinical criteria without biopsy, and all met the criteria for abnormal ALT and steatosis based on imaging. In addition, these patients had at least one secondary diagnostic criteria: body mass index greater than 30 kg/m2 (74%), type 2 diabetes (42%), and dyslipidemia (54%). Significant independent predictors of liver biopsy included younger age, White race, female gender, diabetes, and elevated levels of ALT.

Elevated ALT increased the odds of liver biopsy by 14% per 10-point rise, according to the study. A machine learning model showed that non-White patients with ALT less than 69 IU/mL had a 6% chance of liver biopsy. By comparison, White patients had a 21% chance of biopsy with ALT between 29 IU/mL and 69 IU/mL that dropped to 10% if the ALT was less than 29 IU/mL.

However, ALT remains a “suboptimal surrogate” for disease severity, the researchers noted. “How a normal ALT is defined and how a normal ALT range may vary across different laboratories may play a role in its utility as a diagnostic tool as well.”

Dr. Henry was surprised by this finding: “With the advent of noninvasive measures of fibrosis, such as the NAFLD fibrosis score, Fibrosis-4, and transient elastography, I thought these would have a more significant role in that decision as opposed to ALT levels.”

Notably, mental health diagnoses accounted for nearly half (49%) of comorbid conditions, followed by cardiovascular disease (19%), and osteoarthritis (10%). The prevalence of these conditions emphasizes the challenges of managing patients with NAFLD with diet and exercise alone because mental and physical problems may impede progress, the researchers wrote.

The study findings were limited by several factors including the inability to determine health care provider intent, as well as undocumented factors related to patients and providers that might influence a biopsy decision, such as assessment of disease severity, the researchers noted. In addition, they noted that the mostly White study population treated in specialty settings might not generalize to other populations or primary care.

However, the findings are strengthened by the large study population and real-world setting, the researchers emphasized. “These data provide context for the selection bias that may be present in many registries and randomized, controlled trials of therapies for NAFLD, where biopsy is required for inclusion,” and show potential knowledge gaps about the patient population less likely to undergo biopsy.
 

Knowledge gaps and implications

The study is important because of the need to identify patient factors that predict histologic versus clinical diagnosis of NAFLD as the number of patient registries and clinical trials for NAFLD increase, Bubu Banini, MD, of Yale University, New Haven, Conn., said in an interview. “This information helps to elucidate selection and ascertainment bias and place findings from NAFLD registries and clinical trials into context.”

Dr. Banini said that some of the findings were to be expected, while others were not.

“Historically, males and non-Whites are less likely to participate in registries and clinical trials, compared to females and Whites. However, I was surprised to find that these discrepancies further paralleled the likelihood of undergoing liver biopsy even among those who chose to participate. In addition, while mental health disorders (such as anxiety and depression) are a fairly prevalent comorbidity in patients with NAFLD, I was surprised to find that NAFLD patients with mental health disorders were more likely to undergo liver biopsy compared to those without these disorders. I would have expected the reverse,” he noted.

“These findings highlight the gaps in knowledge regarding the impact of demographic and psychosocial factors on choice and assess to care among patients with NAFLD, and the need for further studies to address these gaps,” she emphasized.

“A number of [studies] such as TARGET-NASH are doing away with the requirement for liver biopsy for participation; hence, it is less likely that selection bias related to liver biopsy would be a problem in these [studies] if clinical diagnosis is considered as a surrogate for histological diagnosis,” Dr. Banini added.

“On the contrary, many NAFLD clinical trials require liver biopsy for inclusion.” As nicely demonstrated in the current study, “this inclusion criterion may introduce selection bias,” she said. “Awareness of potential biases would hopefully inform the design and recruitment strategy for registries and clinical trials in order to overcome these issues.”

“I think the results of this study may actually point to a larger issue within medicine in general, which is a difference in care provided to minority communities,” Dr. Henry said. “Whether this is intentional, related to unconscious bias on the part of providers, or related to a significant mistrust between minority communities and their health care providers is unclear but certainly needs to be addressed.”

He noted that the purpose of TARGET-NASH is to enroll all patients with NAFLD regardless of biopsy. “Over time, as we have more data on these patients, we will have a better understanding of both diagnostic and therapeutic decisions in patients with NAFLD.”

The study was supported by Target RWE, sponsor of the TARGET-NASH study. TARGET-NASH is a collaboration of academic and community investigators and the pharmaceutical industry. Lead author Dr. Barritt had no financial conflicts to disclose, but many study coauthors disclosed relationships with multiple pharmaceutical companies, including those involved in the TARGET-NASH study. Dr. Banini currently serves on the NASH advisory board for Boehringer Ingelheim. Dr. Henry reported no disclosures, although his institution is one of the enrollment sites for TARGET-NASH.

Nonalcoholic fatty liver disease (NAFLD) was present in approximately two-thirds of patients who did not undergo a liver biopsy. These patients were more likely to be non-White and older, as well as have normal ALT levels, which shows potential gaps in knowledge about this population.

Shidlovski/Getty Images

Data from studies of patients diagnosed with NAFLD that require biopsy among their inclusion criteria may be subject to selection and detection bias, wrote A. Sidney Barritt, MD, of the University of North Carolina at Chapel Hill, and colleagues. The researchers sought to compare characteristics of patients with NAFLD who were diagnosed using clinical criteria and those diagnosed via liver biopsy.

In a study published in Hepatology Communications, the researchers reviewed data from TARGET-NASH, a longitudinal, observational cohort study designed to follow patients with NAFLD in clinical practice to provide data on the effectiveness of treatments.

“TARGET-NASH represents a large cohort of NAFLD patients from multiple sites and can provide us with real world information on progression of disease in patients with NAFLD and particular risk factors that may be clinically relevant,” Zachary Henry, MD, MS, of the division of gastroenterology & hepatology at the University of Virginia Health System in Charlottesville, said in an interview. “This is one of the first studies from this database, and as time goes on, we will see more large-population data like this to answer specific questions for NAFLD patient.”
 

Surprising findings

The researchers included 3,474 patients aged 18 years and older who were enrolled in the TARGET-NASH study between Aug. 1, 2016, and March 4, 2019. The study participants were classified according to severity of liver disease: nonalcoholic fatty liver (30%), nonalcoholic steatohepatitis (37%), and NAFLD cirrhosis (33%).

A total of 766 patients were diagnosed with NASH based on clinical criteria without biopsy, and all met the criteria for abnormal ALT and steatosis based on imaging. In addition, these patients had at least one secondary diagnostic criteria: body mass index greater than 30 kg/m2 (74%), type 2 diabetes (42%), and dyslipidemia (54%). Significant independent predictors of liver biopsy included younger age, White race, female gender, diabetes, and elevated levels of ALT.

Elevated ALT increased the odds of liver biopsy by 14% per 10-point rise, according to the study. A machine learning model showed that non-White patients with ALT less than 69 IU/mL had a 6% chance of liver biopsy. By comparison, White patients had a 21% chance of biopsy with ALT between 29 IU/mL and 69 IU/mL that dropped to 10% if the ALT was less than 29 IU/mL.

However, ALT remains a “suboptimal surrogate” for disease severity, the researchers noted. “How a normal ALT is defined and how a normal ALT range may vary across different laboratories may play a role in its utility as a diagnostic tool as well.”

Dr. Henry was surprised by this finding: “With the advent of noninvasive measures of fibrosis, such as the NAFLD fibrosis score, Fibrosis-4, and transient elastography, I thought these would have a more significant role in that decision as opposed to ALT levels.”

Notably, mental health diagnoses accounted for nearly half (49%) of comorbid conditions, followed by cardiovascular disease (19%), and osteoarthritis (10%). The prevalence of these conditions emphasizes the challenges of managing patients with NAFLD with diet and exercise alone because mental and physical problems may impede progress, the researchers wrote.

The study findings were limited by several factors including the inability to determine health care provider intent, as well as undocumented factors related to patients and providers that might influence a biopsy decision, such as assessment of disease severity, the researchers noted. In addition, they noted that the mostly White study population treated in specialty settings might not generalize to other populations or primary care.

However, the findings are strengthened by the large study population and real-world setting, the researchers emphasized. “These data provide context for the selection bias that may be present in many registries and randomized, controlled trials of therapies for NAFLD, where biopsy is required for inclusion,” and show potential knowledge gaps about the patient population less likely to undergo biopsy.
 

Knowledge gaps and implications

The study is important because of the need to identify patient factors that predict histologic versus clinical diagnosis of NAFLD as the number of patient registries and clinical trials for NAFLD increase, Bubu Banini, MD, of Yale University, New Haven, Conn., said in an interview. “This information helps to elucidate selection and ascertainment bias and place findings from NAFLD registries and clinical trials into context.”

Dr. Banini said that some of the findings were to be expected, while others were not.

“Historically, males and non-Whites are less likely to participate in registries and clinical trials, compared to females and Whites. However, I was surprised to find that these discrepancies further paralleled the likelihood of undergoing liver biopsy even among those who chose to participate. In addition, while mental health disorders (such as anxiety and depression) are a fairly prevalent comorbidity in patients with NAFLD, I was surprised to find that NAFLD patients with mental health disorders were more likely to undergo liver biopsy compared to those without these disorders. I would have expected the reverse,” he noted.

“These findings highlight the gaps in knowledge regarding the impact of demographic and psychosocial factors on choice and assess to care among patients with NAFLD, and the need for further studies to address these gaps,” she emphasized.

“A number of [studies] such as TARGET-NASH are doing away with the requirement for liver biopsy for participation; hence, it is less likely that selection bias related to liver biopsy would be a problem in these [studies] if clinical diagnosis is considered as a surrogate for histological diagnosis,” Dr. Banini added.

“On the contrary, many NAFLD clinical trials require liver biopsy for inclusion.” As nicely demonstrated in the current study, “this inclusion criterion may introduce selection bias,” she said. “Awareness of potential biases would hopefully inform the design and recruitment strategy for registries and clinical trials in order to overcome these issues.”

“I think the results of this study may actually point to a larger issue within medicine in general, which is a difference in care provided to minority communities,” Dr. Henry said. “Whether this is intentional, related to unconscious bias on the part of providers, or related to a significant mistrust between minority communities and their health care providers is unclear but certainly needs to be addressed.”

He noted that the purpose of TARGET-NASH is to enroll all patients with NAFLD regardless of biopsy. “Over time, as we have more data on these patients, we will have a better understanding of both diagnostic and therapeutic decisions in patients with NAFLD.”

The study was supported by Target RWE, sponsor of the TARGET-NASH study. TARGET-NASH is a collaboration of academic and community investigators and the pharmaceutical industry. Lead author Dr. Barritt had no financial conflicts to disclose, but many study coauthors disclosed relationships with multiple pharmaceutical companies, including those involved in the TARGET-NASH study. Dr. Banini currently serves on the NASH advisory board for Boehringer Ingelheim. Dr. Henry reported no disclosures, although his institution is one of the enrollment sites for TARGET-NASH.

Use of mRNA COVID-19 vaccines should be considered as the preferable option in the United States rather than Johnson & Johnson’s (J&J) Janssen COVID-19 vaccine in women aged under 50 years, according to one group of experts.

The group made their recommendation in an editorial in JAMA published online April 30, 2021, accompanying a paper describing details of 12 case reports of cerebral venous sinus thrombosis (CVST) with thrombocytopenia following the J&J COVID-19 vaccine, also known as the Ad26.COV2.S vaccine.

The editorialists are Ruth A. Karron, MD, professor of international health at Johns Hopkins University, Baltimore; Nigel S. Key, MD, professor of hematology at the University of North Carolina at Chapel Hill; and Joshua M. Sharfstein, MD, associate dean for public health practice at Johns Hopkins

They noted that, after an initial pause following reports of thrombosis with thrombocytopenia syndrome (TTS) linked to the J&J vaccine, and on the recommendation of the Advisory Committee on Immunization Practices, the United States has permitted the use of the J&J vaccine in all adults with information on the risk of TTS added to educational materials.

The editorialists pointed out that no cases of TTS have been confirmed following administration of more than 180 million doses of the mRNA vaccines in the United States.

They said that, while the J&J vaccine will still be needed for individuals with allergies to components of the mRNA vaccines and for those who live in remote locations where the cold chain for transport and storage of mRNA vaccines cannot be maintained, “U.S. public health agencies and clinicians should consider recommending mRNA vaccines as safer options for those who may be at substantially higher risk for TTS after Ad26.COV2.S vaccination, currently women younger than 50 years.”

In the main JAMA paper, a group led by Isaac See, MD, Centers for Disease Control and Prevention COVID-19 Response Team, reported full details of 12 cases of CVST with thrombocytopenia following the J&J COVID-19 vaccine reported to the U.S. Vaccine Adverse Event Reporting System (VAERS).

The 12 U.S. case reports, 3 of which were fatal, show many similarities to cases described in Europe after the AstraZeneca vaccine.

The authors noted that, by April 12, approximately 7 million doses of the J&J vaccine had been given in the United States. The 12 cases of CVST and thrombocytopenia following receipt of the vaccine were reported to VAERS between March 2 and April 21. All 12 cases were in White women, 11 of whom were aged under 50 years.

As of April 25, a further two cases have been confirmed and reported to VAERS; one in a man younger than 40 years, the other in a woman aged between 40 and 59 years.

In the 12 cases reported in detail, symptoms started between 6 and 15 days post vaccination.

At least one risk factor for CVST was identified in seven patients (obesity in six, hypothyroidism in one, and use of combined oral contraceptives in one). None of the patients was pregnant or within 12 weeks post partum, had prior thrombosis, a personal or family history of thrombophilia, or documented prior exposure to heparin.

In addition to CVST, seven patients had intracerebral hemorrhage and eight had non-CVST thromboses.

One patient reported a history of SARS-CoV-2 infection approximately 4 months prior to vaccination. Of the other 11 patients, 4 had negative serologic tests and 7 were not tested.

All 12 patients were hospitalized and 10 were admitted to an ICU. At the time of the last follow-up, three patients had died (all of whom had intraparenchymal hemorrhage), three remained in the ICU, two were still hospitalized but not in an ICU, and four had been discharged home.

The authors pointed out that the U.S. cases of CVST with thrombocytopenia following the J&J vaccine have many similarities to those reported in Europe after the AstraZeneca vaccine, occurring primarily in women younger than 40 years and in patients without diagnosed thrombophilia. Both European and U.S. patients had a median platelet nadir count of 19 x 103/mcL and several also had non-CVST large-vessel thrombosis.

In the European cases of CVST with thrombocytopenia, 50% of patients died, compared with 25% of U.S. patients.

Like the European cases, the U.S. cases had positive heparin-PF4 HIT antibody enzyme-linked immunosorbent assay tests in the absence of prior exposure to heparin, as would be seen in autoimmune HIT.

However, in the initial European CVST reports, 88% of patients tested with functional platelet HIT antibody tests had positive results, compared with only 11% of the U.S. cases. But the authors noted that lack of standardization in functional platelet HIT antibody assays may lead to differences in results by different laboratories.

“It may be important to notify testing laboratories that postvaccination TTS is being evaluated, so that testing methods can be adjusted if needed,” they said.

They concluded that these case reports suggest that the pathogenesis of TTS may be similar to autoimmune HIT, triggered by the formation of antibodies directed against PF4, a constituent of platelet alpha granules released during platelet activation. In contrast to classic HIT in which exogenous heparin triggers antibody formation, in autoimmune HIT, an endogenous polyanion triggers PF4 antibody formation.

They noted that the precise mechanism of TTS in relation to COVID-19 vaccination has not yet been established. The Global Advisory Committee on Vaccine Safety has stated that a platform-specific mechanism related to adenovirus vector vaccines cannot be excluded. Both the J&J and AstraZeneca vaccines use an adenoviral vector, but they are different; J&J uses a human vector, while AstraZeneca uses a chimpanzee vector.

They also pointed out that CVST and thrombocytopenia following SARS-CoV-2 infection has been reported in at least two cases, but HIT testing was not done in these cases. There have not so far been any reports to VAERS of CVST with thrombocytopenia following mRNA COVID-19 vaccines.

The authors said these findings have important clinical and public health implications, noting that the CDC has updated its interim clinical considerations for use of authorized COVID-19 vaccines to indicate that women aged 18-49 years should be aware of the increased risk of TTS after receipt of the J&J vaccine, and to use a nonheparin anticoagulant in suspected cases.

They noted that a subacute presentation of headache is present in 90% of patients with typical CVST. While headache is a common symptom after the J&J vaccination, most headaches begin and resolve within 2 days. Whereas in the U.S. cases of CVST after vaccination, headache symptoms began at least 6 days after vaccination and persisted for at least a week for most.

“Urgent consultation with a neurologist is prudent when a patient is suspected or confirmed to have CVST. In addition, since the median time from symptom onset to hospitalization was 7 days in the U.S. CVST case series, patient and clinician education might shorten the time to clinical evaluation and therefore treatment,” they stated.

The authors also note that VAERS is a passive surveillance system, so cases of CVST with thrombocytopenia may be underreported.

In their accompanying editorial, Dr. Karron and colleagues pointed out that, in addition to the 12 patients with CVST with thrombocytopenia described in this case series, at least three patients without CVST but meeting diagnostic criteria for TTS have been reported to VAERS (as of April 21), all in women aged 18-59 years (median age, 37 years).

The editorialists reported that the rate of CVST with thrombocytopenia after the J&J vaccine is approximately 5 per million women aged 18-50 years. This is compared with a background rate of approximately 0.05-0.13 per million per month.

They said that the availability of an interim standardized case definition of this adverse effect will facilitate prospective case ascertainment through review of large linked databases and active case finding.

This will also permit greater understanding of whether individuals who are otherwise at increased risk for hypercoagulation in general and for CVST in particular (for example, women taking hormonal contraceptive medications or who are pregnant) are also at increased risk for TTS.

Obtaining this information will support dynamic country-specific assessments of the risks of each vaccine, compared with the risk of COVID-19 disease for their populations and subpopulations, they added.

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

Use of mRNA COVID-19 vaccines should be considered as the preferable option in the United States rather than Johnson & Johnson’s (J&J) Janssen COVID-19 vaccine in women aged under 50 years, according to one group of experts.

The group made their recommendation in an editorial in JAMA published online April 30, 2021, accompanying a paper describing details of 12 case reports of cerebral venous sinus thrombosis (CVST) with thrombocytopenia following the J&J COVID-19 vaccine, also known as the Ad26.COV2.S vaccine.

The editorialists are Ruth A. Karron, MD, professor of international health at Johns Hopkins University, Baltimore; Nigel S. Key, MD, professor of hematology at the University of North Carolina at Chapel Hill; and Joshua M. Sharfstein, MD, associate dean for public health practice at Johns Hopkins

They noted that, after an initial pause following reports of thrombosis with thrombocytopenia syndrome (TTS) linked to the J&J vaccine, and on the recommendation of the Advisory Committee on Immunization Practices, the United States has permitted the use of the J&J vaccine in all adults with information on the risk of TTS added to educational materials.

The editorialists pointed out that no cases of TTS have been confirmed following administration of more than 180 million doses of the mRNA vaccines in the United States.

They said that, while the J&J vaccine will still be needed for individuals with allergies to components of the mRNA vaccines and for those who live in remote locations where the cold chain for transport and storage of mRNA vaccines cannot be maintained, “U.S. public health agencies and clinicians should consider recommending mRNA vaccines as safer options for those who may be at substantially higher risk for TTS after Ad26.COV2.S vaccination, currently women younger than 50 years.”

In the main JAMA paper, a group led by Isaac See, MD, Centers for Disease Control and Prevention COVID-19 Response Team, reported full details of 12 cases of CVST with thrombocytopenia following the J&J COVID-19 vaccine reported to the U.S. Vaccine Adverse Event Reporting System (VAERS).

The 12 U.S. case reports, 3 of which were fatal, show many similarities to cases described in Europe after the AstraZeneca vaccine.

The authors noted that, by April 12, approximately 7 million doses of the J&J vaccine had been given in the United States. The 12 cases of CVST and thrombocytopenia following receipt of the vaccine were reported to VAERS between March 2 and April 21. All 12 cases were in White women, 11 of whom were aged under 50 years.

As of April 25, a further two cases have been confirmed and reported to VAERS; one in a man younger than 40 years, the other in a woman aged between 40 and 59 years.

In the 12 cases reported in detail, symptoms started between 6 and 15 days post vaccination.

At least one risk factor for CVST was identified in seven patients (obesity in six, hypothyroidism in one, and use of combined oral contraceptives in one). None of the patients was pregnant or within 12 weeks post partum, had prior thrombosis, a personal or family history of thrombophilia, or documented prior exposure to heparin.

In addition to CVST, seven patients had intracerebral hemorrhage and eight had non-CVST thromboses.

One patient reported a history of SARS-CoV-2 infection approximately 4 months prior to vaccination. Of the other 11 patients, 4 had negative serologic tests and 7 were not tested.

All 12 patients were hospitalized and 10 were admitted to an ICU. At the time of the last follow-up, three patients had died (all of whom had intraparenchymal hemorrhage), three remained in the ICU, two were still hospitalized but not in an ICU, and four had been discharged home.

The authors pointed out that the U.S. cases of CVST with thrombocytopenia following the J&J vaccine have many similarities to those reported in Europe after the AstraZeneca vaccine, occurring primarily in women younger than 40 years and in patients without diagnosed thrombophilia. Both European and U.S. patients had a median platelet nadir count of 19 x 103/mcL and several also had non-CVST large-vessel thrombosis.

In the European cases of CVST with thrombocytopenia, 50% of patients died, compared with 25% of U.S. patients.

Like the European cases, the U.S. cases had positive heparin-PF4 HIT antibody enzyme-linked immunosorbent assay tests in the absence of prior exposure to heparin, as would be seen in autoimmune HIT.

However, in the initial European CVST reports, 88% of patients tested with functional platelet HIT antibody tests had positive results, compared with only 11% of the U.S. cases. But the authors noted that lack of standardization in functional platelet HIT antibody assays may lead to differences in results by different laboratories.

“It may be important to notify testing laboratories that postvaccination TTS is being evaluated, so that testing methods can be adjusted if needed,” they said.

They concluded that these case reports suggest that the pathogenesis of TTS may be similar to autoimmune HIT, triggered by the formation of antibodies directed against PF4, a constituent of platelet alpha granules released during platelet activation. In contrast to classic HIT in which exogenous heparin triggers antibody formation, in autoimmune HIT, an endogenous polyanion triggers PF4 antibody formation.

They noted that the precise mechanism of TTS in relation to COVID-19 vaccination has not yet been established. The Global Advisory Committee on Vaccine Safety has stated that a platform-specific mechanism related to adenovirus vector vaccines cannot be excluded. Both the J&J and AstraZeneca vaccines use an adenoviral vector, but they are different; J&J uses a human vector, while AstraZeneca uses a chimpanzee vector.

They also pointed out that CVST and thrombocytopenia following SARS-CoV-2 infection has been reported in at least two cases, but HIT testing was not done in these cases. There have not so far been any reports to VAERS of CVST with thrombocytopenia following mRNA COVID-19 vaccines.

The authors said these findings have important clinical and public health implications, noting that the CDC has updated its interim clinical considerations for use of authorized COVID-19 vaccines to indicate that women aged 18-49 years should be aware of the increased risk of TTS after receipt of the J&J vaccine, and to use a nonheparin anticoagulant in suspected cases.

They noted that a subacute presentation of headache is present in 90% of patients with typical CVST. While headache is a common symptom after the J&J vaccination, most headaches begin and resolve within 2 days. Whereas in the U.S. cases of CVST after vaccination, headache symptoms began at least 6 days after vaccination and persisted for at least a week for most.

“Urgent consultation with a neurologist is prudent when a patient is suspected or confirmed to have CVST. In addition, since the median time from symptom onset to hospitalization was 7 days in the U.S. CVST case series, patient and clinician education might shorten the time to clinical evaluation and therefore treatment,” they stated.

The authors also note that VAERS is a passive surveillance system, so cases of CVST with thrombocytopenia may be underreported.

In their accompanying editorial, Dr. Karron and colleagues pointed out that, in addition to the 12 patients with CVST with thrombocytopenia described in this case series, at least three patients without CVST but meeting diagnostic criteria for TTS have been reported to VAERS (as of April 21), all in women aged 18-59 years (median age, 37 years).

The editorialists reported that the rate of CVST with thrombocytopenia after the J&J vaccine is approximately 5 per million women aged 18-50 years. This is compared with a background rate of approximately 0.05-0.13 per million per month.

They said that the availability of an interim standardized case definition of this adverse effect will facilitate prospective case ascertainment through review of large linked databases and active case finding.

This will also permit greater understanding of whether individuals who are otherwise at increased risk for hypercoagulation in general and for CVST in particular (for example, women taking hormonal contraceptive medications or who are pregnant) are also at increased risk for TTS.

Obtaining this information will support dynamic country-specific assessments of the risks of each vaccine, compared with the risk of COVID-19 disease for their populations and subpopulations, they added.

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

Use of mRNA COVID-19 vaccines should be considered as the preferable option in the United States rather than Johnson & Johnson’s (J&J) Janssen COVID-19 vaccine in women aged under 50 years, according to one group of experts.

The group made their recommendation in an editorial in JAMA published online April 30, 2021, accompanying a paper describing details of 12 case reports of cerebral venous sinus thrombosis (CVST) with thrombocytopenia following the J&J COVID-19 vaccine, also known as the Ad26.COV2.S vaccine.

The editorialists are Ruth A. Karron, MD, professor of international health at Johns Hopkins University, Baltimore; Nigel S. Key, MD, professor of hematology at the University of North Carolina at Chapel Hill; and Joshua M. Sharfstein, MD, associate dean for public health practice at Johns Hopkins

They noted that, after an initial pause following reports of thrombosis with thrombocytopenia syndrome (TTS) linked to the J&J vaccine, and on the recommendation of the Advisory Committee on Immunization Practices, the United States has permitted the use of the J&J vaccine in all adults with information on the risk of TTS added to educational materials.

The editorialists pointed out that no cases of TTS have been confirmed following administration of more than 180 million doses of the mRNA vaccines in the United States.

They said that, while the J&J vaccine will still be needed for individuals with allergies to components of the mRNA vaccines and for those who live in remote locations where the cold chain for transport and storage of mRNA vaccines cannot be maintained, “U.S. public health agencies and clinicians should consider recommending mRNA vaccines as safer options for those who may be at substantially higher risk for TTS after Ad26.COV2.S vaccination, currently women younger than 50 years.”

In the main JAMA paper, a group led by Isaac See, MD, Centers for Disease Control and Prevention COVID-19 Response Team, reported full details of 12 cases of CVST with thrombocytopenia following the J&J COVID-19 vaccine reported to the U.S. Vaccine Adverse Event Reporting System (VAERS).

The 12 U.S. case reports, 3 of which were fatal, show many similarities to cases described in Europe after the AstraZeneca vaccine.

The authors noted that, by April 12, approximately 7 million doses of the J&J vaccine had been given in the United States. The 12 cases of CVST and thrombocytopenia following receipt of the vaccine were reported to VAERS between March 2 and April 21. All 12 cases were in White women, 11 of whom were aged under 50 years.

As of April 25, a further two cases have been confirmed and reported to VAERS; one in a man younger than 40 years, the other in a woman aged between 40 and 59 years.

In the 12 cases reported in detail, symptoms started between 6 and 15 days post vaccination.

At least one risk factor for CVST was identified in seven patients (obesity in six, hypothyroidism in one, and use of combined oral contraceptives in one). None of the patients was pregnant or within 12 weeks post partum, had prior thrombosis, a personal or family history of thrombophilia, or documented prior exposure to heparin.

In addition to CVST, seven patients had intracerebral hemorrhage and eight had non-CVST thromboses.

One patient reported a history of SARS-CoV-2 infection approximately 4 months prior to vaccination. Of the other 11 patients, 4 had negative serologic tests and 7 were not tested.

All 12 patients were hospitalized and 10 were admitted to an ICU. At the time of the last follow-up, three patients had died (all of whom had intraparenchymal hemorrhage), three remained in the ICU, two were still hospitalized but not in an ICU, and four had been discharged home.

The authors pointed out that the U.S. cases of CVST with thrombocytopenia following the J&J vaccine have many similarities to those reported in Europe after the AstraZeneca vaccine, occurring primarily in women younger than 40 years and in patients without diagnosed thrombophilia. Both European and U.S. patients had a median platelet nadir count of 19 x 103/mcL and several also had non-CVST large-vessel thrombosis.

In the European cases of CVST with thrombocytopenia, 50% of patients died, compared with 25% of U.S. patients.

Like the European cases, the U.S. cases had positive heparin-PF4 HIT antibody enzyme-linked immunosorbent assay tests in the absence of prior exposure to heparin, as would be seen in autoimmune HIT.

However, in the initial European CVST reports, 88% of patients tested with functional platelet HIT antibody tests had positive results, compared with only 11% of the U.S. cases. But the authors noted that lack of standardization in functional platelet HIT antibody assays may lead to differences in results by different laboratories.

“It may be important to notify testing laboratories that postvaccination TTS is being evaluated, so that testing methods can be adjusted if needed,” they said.

They concluded that these case reports suggest that the pathogenesis of TTS may be similar to autoimmune HIT, triggered by the formation of antibodies directed against PF4, a constituent of platelet alpha granules released during platelet activation. In contrast to classic HIT in which exogenous heparin triggers antibody formation, in autoimmune HIT, an endogenous polyanion triggers PF4 antibody formation.

They noted that the precise mechanism of TTS in relation to COVID-19 vaccination has not yet been established. The Global Advisory Committee on Vaccine Safety has stated that a platform-specific mechanism related to adenovirus vector vaccines cannot be excluded. Both the J&J and AstraZeneca vaccines use an adenoviral vector, but they are different; J&J uses a human vector, while AstraZeneca uses a chimpanzee vector.

They also pointed out that CVST and thrombocytopenia following SARS-CoV-2 infection has been reported in at least two cases, but HIT testing was not done in these cases. There have not so far been any reports to VAERS of CVST with thrombocytopenia following mRNA COVID-19 vaccines.

The authors said these findings have important clinical and public health implications, noting that the CDC has updated its interim clinical considerations for use of authorized COVID-19 vaccines to indicate that women aged 18-49 years should be aware of the increased risk of TTS after receipt of the J&J vaccine, and to use a nonheparin anticoagulant in suspected cases.

They noted that a subacute presentation of headache is present in 90% of patients with typical CVST. While headache is a common symptom after the J&J vaccination, most headaches begin and resolve within 2 days. Whereas in the U.S. cases of CVST after vaccination, headache symptoms began at least 6 days after vaccination and persisted for at least a week for most.

“Urgent consultation with a neurologist is prudent when a patient is suspected or confirmed to have CVST. In addition, since the median time from symptom onset to hospitalization was 7 days in the U.S. CVST case series, patient and clinician education might shorten the time to clinical evaluation and therefore treatment,” they stated.

The authors also note that VAERS is a passive surveillance system, so cases of CVST with thrombocytopenia may be underreported.

In their accompanying editorial, Dr. Karron and colleagues pointed out that, in addition to the 12 patients with CVST with thrombocytopenia described in this case series, at least three patients without CVST but meeting diagnostic criteria for TTS have been reported to VAERS (as of April 21), all in women aged 18-59 years (median age, 37 years).

The editorialists reported that the rate of CVST with thrombocytopenia after the J&J vaccine is approximately 5 per million women aged 18-50 years. This is compared with a background rate of approximately 0.05-0.13 per million per month.

They said that the availability of an interim standardized case definition of this adverse effect will facilitate prospective case ascertainment through review of large linked databases and active case finding.

This will also permit greater understanding of whether individuals who are otherwise at increased risk for hypercoagulation in general and for CVST in particular (for example, women taking hormonal contraceptive medications or who are pregnant) are also at increased risk for TTS.

Obtaining this information will support dynamic country-specific assessments of the risks of each vaccine, compared with the risk of COVID-19 disease for their populations and subpopulations, they added.

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

The risk of severe outcomes with COVID-19 increases with excess weight in a linear manner beginning in normal body mass index ranges, with the effect apparently independent of obesity-related diseases such as diabetes, and stronger among younger people and Black persons, new research shows.

“Even a small increase in body mass index above 23 kg/m² is a risk factor for adverse outcomes after infection with SARS-CoV-2,” the authors reported.

“Excess weight is a modifiable risk factor and investment in the treatment of overweight and obesity, and long-term preventive strategies could help reduce the severity of COVID-19 disease,” they wrote.

The findings shed important new light in the ongoing efforts to understand COVID-19 effects, Krishnan Bhaskaran, PhD, said in an interview.

“These results confirm and add detail to the established links between overweight and obesity and COVID-19, and also add new information on risks among people with low BMI levels,” said Dr. Bhaskaran, an epidemiologist at the London School of Hygiene & Tropical Medicine, who authored an accompanying editorial (Lancet Diabetes Endocrinol 2021 Apr 29; doi: 10.1016/S2213-8587[21]00109-1).

Obesity has been well established as a major risk factor for poor outcomes among people with COVID-19; however, less is known about the risk of severe outcomes over the broader spectrum of excess weight, and its relationship with other factors.

For the prospective, community-based study, Carmen Piernas, PhD, of the University of Oxford (England) and colleagues evaluated data on nearly 7 million individuals registered in the U.K. QResearch database during Jan. 24–April 30, 2020.

Overall, patients had a mean BMI of 27 kg/m². Among them, 13,503 (.20%) were admitted to the hospital during the study period, 1,601 (.02%) were admitted to an ICU and 5,479 (.08%) died after testing positive for SARS-CoV-2.


 

Risk rises from BMI of 23 kg/m²

In looking at the risk of hospital admission with COVID-19, the authors found a J-shaped relationship with BMI, with the risk increased with a BMI of 20 kg/m² or lower, as well as an increased risk beginning with a BMI of 23 kg/m² – considered normal weight – or higher (hazard ratio, 1.05).

The risk of death from COVID-19 was also J-shaped, however the association with increases in BMI started higher – at 28 kg/m² (adjusted HR 1.04).

In terms of the risk of ICU admission with COVID-19, the curve was not J-shaped, with just a linear association of admission with increasing BMI beginning at 23 kg/m² (adjusted HR 1.10).

“It was surprising to see that the lowest risk of severe COVID-19 was found at a BMI of 23, and each extra BMI unit was associated with significantly higher risk, but we don’t really know yet what the reason is for this,” Dr. Piernas said in an interview.

The association between increasing BMI and risk of hospital admission for COVID-19 beginning at a BMI of 23 kg/m² was more significant among younger people aged 20-39 years than in those aged 80-100 years, with an adjusted HR for hospital admission per BMI unit above 23 kg/m² of 1.09 versus 1.01 (P < .0001).

In addition, the risk associated with BMI and hospital admission was stronger in people who were Black, compared with those who were White (1.07 vs. 1.04), as was the risk of death due to COVID-19 (1.08 vs. 1.04; P < .0001 for both).

“For the risk of death, Blacks have an 8% higher risk with each extra BMI unit, whereas Whites have a 4% increase, which is half the risk,” Dr. Piernas said.

Notably, the increased risks of hospital admission and ICU due to COVID-19 seen with increases in BMI were slightly lower among people with type 2 diabetes, hypertension, and cardiovascular disease compared with patients who did not have those comorbidities, suggesting the association with BMI is not explained by those risk factors.

Dr. Piernas speculated that the effect could reflect that people with diabetes or cardiovascular disease already have a preexisting condition which makes them more susceptible to SARS-CoV-2.

Hence, “the association with BMI in this group may not be as strong as the association found among those without those conditions, in which BMI explains a higher proportion of this increased risk, given the absence of these preexisting conditions.”

Similarly, the effect of BMI on COVID-19 outcomes in younger patients may appear stronger because their rates of other comorbidities are much lower than in older patients.

“Among older people, preexisting conditions and perhaps a weaker immune system may explain their much higher rates of severe COVID outcomes,” Dr. Piernas noted.

Furthermore, older patients may have frailty and high comorbidities that could explain their lower rates of ICU admission with COVID-19, Dr. Bhaskaran added in further comments.

The findings overall underscore that excess weight can represent a risk in COVID-19 outcomes that is, importantly, modifiable, and “suggest that supporting people to reach and maintain a healthy weight is likely to help people reduce their risk of experiencing severe outcomes from this disease, now or in any future waves,” he concluded.

Dr. Piernas and Dr. Bhaskaran had no disclosures to report. Coauthors’ disclosures are detailed in the published study.

The risk of severe outcomes with COVID-19 increases with excess weight in a linear manner beginning in normal body mass index ranges, with the effect apparently independent of obesity-related diseases such as diabetes, and stronger among younger people and Black persons, new research shows.

“Even a small increase in body mass index above 23 kg/m² is a risk factor for adverse outcomes after infection with SARS-CoV-2,” the authors reported.

“Excess weight is a modifiable risk factor and investment in the treatment of overweight and obesity, and long-term preventive strategies could help reduce the severity of COVID-19 disease,” they wrote.

The findings shed important new light in the ongoing efforts to understand COVID-19 effects, Krishnan Bhaskaran, PhD, said in an interview.

“These results confirm and add detail to the established links between overweight and obesity and COVID-19, and also add new information on risks among people with low BMI levels,” said Dr. Bhaskaran, an epidemiologist at the London School of Hygiene & Tropical Medicine, who authored an accompanying editorial (Lancet Diabetes Endocrinol 2021 Apr 29; doi: 10.1016/S2213-8587[21]00109-1).

Obesity has been well established as a major risk factor for poor outcomes among people with COVID-19; however, less is known about the risk of severe outcomes over the broader spectrum of excess weight, and its relationship with other factors.

For the prospective, community-based study, Carmen Piernas, PhD, of the University of Oxford (England) and colleagues evaluated data on nearly 7 million individuals registered in the U.K. QResearch database during Jan. 24–April 30, 2020.

Overall, patients had a mean BMI of 27 kg/m². Among them, 13,503 (.20%) were admitted to the hospital during the study period, 1,601 (.02%) were admitted to an ICU and 5,479 (.08%) died after testing positive for SARS-CoV-2.


 

Risk rises from BMI of 23 kg/m²

In looking at the risk of hospital admission with COVID-19, the authors found a J-shaped relationship with BMI, with the risk increased with a BMI of 20 kg/m² or lower, as well as an increased risk beginning with a BMI of 23 kg/m² – considered normal weight – or higher (hazard ratio, 1.05).

The risk of death from COVID-19 was also J-shaped, however the association with increases in BMI started higher – at 28 kg/m² (adjusted HR 1.04).

In terms of the risk of ICU admission with COVID-19, the curve was not J-shaped, with just a linear association of admission with increasing BMI beginning at 23 kg/m² (adjusted HR 1.10).

“It was surprising to see that the lowest risk of severe COVID-19 was found at a BMI of 23, and each extra BMI unit was associated with significantly higher risk, but we don’t really know yet what the reason is for this,” Dr. Piernas said in an interview.

The association between increasing BMI and risk of hospital admission for COVID-19 beginning at a BMI of 23 kg/m² was more significant among younger people aged 20-39 years than in those aged 80-100 years, with an adjusted HR for hospital admission per BMI unit above 23 kg/m² of 1.09 versus 1.01 (P < .0001).

In addition, the risk associated with BMI and hospital admission was stronger in people who were Black, compared with those who were White (1.07 vs. 1.04), as was the risk of death due to COVID-19 (1.08 vs. 1.04; P < .0001 for both).

“For the risk of death, Blacks have an 8% higher risk with each extra BMI unit, whereas Whites have a 4% increase, which is half the risk,” Dr. Piernas said.

Notably, the increased risks of hospital admission and ICU due to COVID-19 seen with increases in BMI were slightly lower among people with type 2 diabetes, hypertension, and cardiovascular disease compared with patients who did not have those comorbidities, suggesting the association with BMI is not explained by those risk factors.

Dr. Piernas speculated that the effect could reflect that people with diabetes or cardiovascular disease already have a preexisting condition which makes them more susceptible to SARS-CoV-2.

Hence, “the association with BMI in this group may not be as strong as the association found among those without those conditions, in which BMI explains a higher proportion of this increased risk, given the absence of these preexisting conditions.”

Similarly, the effect of BMI on COVID-19 outcomes in younger patients may appear stronger because their rates of other comorbidities are much lower than in older patients.

“Among older people, preexisting conditions and perhaps a weaker immune system may explain their much higher rates of severe COVID outcomes,” Dr. Piernas noted.

Furthermore, older patients may have frailty and high comorbidities that could explain their lower rates of ICU admission with COVID-19, Dr. Bhaskaran added in further comments.

The findings overall underscore that excess weight can represent a risk in COVID-19 outcomes that is, importantly, modifiable, and “suggest that supporting people to reach and maintain a healthy weight is likely to help people reduce their risk of experiencing severe outcomes from this disease, now or in any future waves,” he concluded.

Dr. Piernas and Dr. Bhaskaran had no disclosures to report. Coauthors’ disclosures are detailed in the published study.

The risk of severe outcomes with COVID-19 increases with excess weight in a linear manner beginning in normal body mass index ranges, with the effect apparently independent of obesity-related diseases such as diabetes, and stronger among younger people and Black persons, new research shows.

“Even a small increase in body mass index above 23 kg/m² is a risk factor for adverse outcomes after infection with SARS-CoV-2,” the authors reported.

“Excess weight is a modifiable risk factor and investment in the treatment of overweight and obesity, and long-term preventive strategies could help reduce the severity of COVID-19 disease,” they wrote.

The findings shed important new light in the ongoing efforts to understand COVID-19 effects, Krishnan Bhaskaran, PhD, said in an interview.

“These results confirm and add detail to the established links between overweight and obesity and COVID-19, and also add new information on risks among people with low BMI levels,” said Dr. Bhaskaran, an epidemiologist at the London School of Hygiene & Tropical Medicine, who authored an accompanying editorial (Lancet Diabetes Endocrinol 2021 Apr 29; doi: 10.1016/S2213-8587[21]00109-1).

Obesity has been well established as a major risk factor for poor outcomes among people with COVID-19; however, less is known about the risk of severe outcomes over the broader spectrum of excess weight, and its relationship with other factors.

For the prospective, community-based study, Carmen Piernas, PhD, of the University of Oxford (England) and colleagues evaluated data on nearly 7 million individuals registered in the U.K. QResearch database during Jan. 24–April 30, 2020.

Overall, patients had a mean BMI of 27 kg/m². Among them, 13,503 (.20%) were admitted to the hospital during the study period, 1,601 (.02%) were admitted to an ICU and 5,479 (.08%) died after testing positive for SARS-CoV-2.


 

Risk rises from BMI of 23 kg/m²

In looking at the risk of hospital admission with COVID-19, the authors found a J-shaped relationship with BMI, with the risk increased with a BMI of 20 kg/m² or lower, as well as an increased risk beginning with a BMI of 23 kg/m² – considered normal weight – or higher (hazard ratio, 1.05).

The risk of death from COVID-19 was also J-shaped, however the association with increases in BMI started higher – at 28 kg/m² (adjusted HR 1.04).

In terms of the risk of ICU admission with COVID-19, the curve was not J-shaped, with just a linear association of admission with increasing BMI beginning at 23 kg/m² (adjusted HR 1.10).

“It was surprising to see that the lowest risk of severe COVID-19 was found at a BMI of 23, and each extra BMI unit was associated with significantly higher risk, but we don’t really know yet what the reason is for this,” Dr. Piernas said in an interview.

The association between increasing BMI and risk of hospital admission for COVID-19 beginning at a BMI of 23 kg/m² was more significant among younger people aged 20-39 years than in those aged 80-100 years, with an adjusted HR for hospital admission per BMI unit above 23 kg/m² of 1.09 versus 1.01 (P < .0001).

In addition, the risk associated with BMI and hospital admission was stronger in people who were Black, compared with those who were White (1.07 vs. 1.04), as was the risk of death due to COVID-19 (1.08 vs. 1.04; P < .0001 for both).

“For the risk of death, Blacks have an 8% higher risk with each extra BMI unit, whereas Whites have a 4% increase, which is half the risk,” Dr. Piernas said.

Notably, the increased risks of hospital admission and ICU due to COVID-19 seen with increases in BMI were slightly lower among people with type 2 diabetes, hypertension, and cardiovascular disease compared with patients who did not have those comorbidities, suggesting the association with BMI is not explained by those risk factors.

Dr. Piernas speculated that the effect could reflect that people with diabetes or cardiovascular disease already have a preexisting condition which makes them more susceptible to SARS-CoV-2.

Hence, “the association with BMI in this group may not be as strong as the association found among those without those conditions, in which BMI explains a higher proportion of this increased risk, given the absence of these preexisting conditions.”

Similarly, the effect of BMI on COVID-19 outcomes in younger patients may appear stronger because their rates of other comorbidities are much lower than in older patients.

“Among older people, preexisting conditions and perhaps a weaker immune system may explain their much higher rates of severe COVID outcomes,” Dr. Piernas noted.

Furthermore, older patients may have frailty and high comorbidities that could explain their lower rates of ICU admission with COVID-19, Dr. Bhaskaran added in further comments.

The findings overall underscore that excess weight can represent a risk in COVID-19 outcomes that is, importantly, modifiable, and “suggest that supporting people to reach and maintain a healthy weight is likely to help people reduce their risk of experiencing severe outcomes from this disease, now or in any future waves,” he concluded.

Dr. Piernas and Dr. Bhaskaran had no disclosures to report. Coauthors’ disclosures are detailed in the published study.

The Food and Drug Administration could expand the use of the Pfizer COVID-19 vaccine to teens early next week, The New York Times and CNN reported, both citing unnamed officials familiar with the agency’s plans.

In late March, Pfizer submitted data to the FDA showing its mRNA vaccine was 100% effective at preventing COVID-19 infection in children ages 12 to 15. Their vaccine  is already authorized for use teens and adults ages 16 and older.

The move would make about 17 million more Americans eligible for vaccination and would be a major step toward getting both adolescents and teens back into classrooms full time by next fall.

“Across the globe, we are longing for a normal life. This is especially true for our children. The initial results we have seen in the adolescent studies suggest that children are particularly well protected by vaccination, which is very encouraging given the trends we have seen in recent weeks regarding the spread of the B.1.1.7 U.K. variant,” Ugur Sahin, CEO and co-founder of Pfizer partner BioNTech, said in a March 31 press release.

Getting schools fully reopened for in-person learning has been a goal of both the Trump and Biden administrations, but it has been tricky to pull off, as some parents and teachers have been reluctant to return to classrooms with so much uncertainty about the risk and the role of children in spreading the virus.

A recent study of roughly 150,000 school-aged children in Israel found that while kids under age 10 were unlikely to catch or spread the virus as they reentered classrooms. Older children, though, were a different story. The study found that children ages 10-19 had risks of catching the virus that were as high as adults ages 20-60.

The risk for severe illness and death from COVID-19 rises with age.

Children and teens are at relatively low risk from severe outcomes after a COVID-19 infection compared to adults, but they can catch it and some will get really sick with it, especially if they have an underlying health condition, like obesity or asthma that makes them more vulnerable.

Beyond the initial infection, children can get a rare late complication called MIS-C, that while treatable, can be severe and requires hospitalization. Emerging reports also suggest there are some kids that become long haulers in much the same way adults do, dealing with lingering problems for months after they first get sick.

As new variants of the coronavirus circulate in the United States, some states have seen big increases in the number of children and teens with COVID. In Michigan, for example, which recently dealt with a spring surge of cases dominated by the B.1.1.7 variant, cases in children and teens quadrupled in April compared to February.

Beyond individual protection, vaccinating children and teens has been seen as important to achieving strong community protection, or herd immunity, against the new coronavirus.

If the FDA expands the authorization for the Pfizer vaccine, the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices will likely meet to review data on the safety and efficacy of the vaccine. The committee may then vote on new recommendations for use of the vaccine in the United States.

Not everyone agrees with the idea that American adolescents, who are at relatively low risk of bad outcomes, could get access to COVID vaccines ahead of vulnerable essential workers and seniors in other parts of the world that are still fighting the pandemic with little access to vaccines.

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

The Food and Drug Administration could expand the use of the Pfizer COVID-19 vaccine to teens early next week, The New York Times and CNN reported, both citing unnamed officials familiar with the agency’s plans.

In late March, Pfizer submitted data to the FDA showing its mRNA vaccine was 100% effective at preventing COVID-19 infection in children ages 12 to 15. Their vaccine  is already authorized for use teens and adults ages 16 and older.

The move would make about 17 million more Americans eligible for vaccination and would be a major step toward getting both adolescents and teens back into classrooms full time by next fall.

“Across the globe, we are longing for a normal life. This is especially true for our children. The initial results we have seen in the adolescent studies suggest that children are particularly well protected by vaccination, which is very encouraging given the trends we have seen in recent weeks regarding the spread of the B.1.1.7 U.K. variant,” Ugur Sahin, CEO and co-founder of Pfizer partner BioNTech, said in a March 31 press release.

Getting schools fully reopened for in-person learning has been a goal of both the Trump and Biden administrations, but it has been tricky to pull off, as some parents and teachers have been reluctant to return to classrooms with so much uncertainty about the risk and the role of children in spreading the virus.

A recent study of roughly 150,000 school-aged children in Israel found that while kids under age 10 were unlikely to catch or spread the virus as they reentered classrooms. Older children, though, were a different story. The study found that children ages 10-19 had risks of catching the virus that were as high as adults ages 20-60.

The risk for severe illness and death from COVID-19 rises with age.

Children and teens are at relatively low risk from severe outcomes after a COVID-19 infection compared to adults, but they can catch it and some will get really sick with it, especially if they have an underlying health condition, like obesity or asthma that makes them more vulnerable.

Beyond the initial infection, children can get a rare late complication called MIS-C, that while treatable, can be severe and requires hospitalization. Emerging reports also suggest there are some kids that become long haulers in much the same way adults do, dealing with lingering problems for months after they first get sick.

As new variants of the coronavirus circulate in the United States, some states have seen big increases in the number of children and teens with COVID. In Michigan, for example, which recently dealt with a spring surge of cases dominated by the B.1.1.7 variant, cases in children and teens quadrupled in April compared to February.

Beyond individual protection, vaccinating children and teens has been seen as important to achieving strong community protection, or herd immunity, against the new coronavirus.

If the FDA expands the authorization for the Pfizer vaccine, the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices will likely meet to review data on the safety and efficacy of the vaccine. The committee may then vote on new recommendations for use of the vaccine in the United States.

Not everyone agrees with the idea that American adolescents, who are at relatively low risk of bad outcomes, could get access to COVID vaccines ahead of vulnerable essential workers and seniors in other parts of the world that are still fighting the pandemic with little access to vaccines.

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

The Food and Drug Administration could expand the use of the Pfizer COVID-19 vaccine to teens early next week, The New York Times and CNN reported, both citing unnamed officials familiar with the agency’s plans.

In late March, Pfizer submitted data to the FDA showing its mRNA vaccine was 100% effective at preventing COVID-19 infection in children ages 12 to 15. Their vaccine  is already authorized for use teens and adults ages 16 and older.

The move would make about 17 million more Americans eligible for vaccination and would be a major step toward getting both adolescents and teens back into classrooms full time by next fall.

“Across the globe, we are longing for a normal life. This is especially true for our children. The initial results we have seen in the adolescent studies suggest that children are particularly well protected by vaccination, which is very encouraging given the trends we have seen in recent weeks regarding the spread of the B.1.1.7 U.K. variant,” Ugur Sahin, CEO and co-founder of Pfizer partner BioNTech, said in a March 31 press release.

Getting schools fully reopened for in-person learning has been a goal of both the Trump and Biden administrations, but it has been tricky to pull off, as some parents and teachers have been reluctant to return to classrooms with so much uncertainty about the risk and the role of children in spreading the virus.

A recent study of roughly 150,000 school-aged children in Israel found that while kids under age 10 were unlikely to catch or spread the virus as they reentered classrooms. Older children, though, were a different story. The study found that children ages 10-19 had risks of catching the virus that were as high as adults ages 20-60.

The risk for severe illness and death from COVID-19 rises with age.

Children and teens are at relatively low risk from severe outcomes after a COVID-19 infection compared to adults, but they can catch it and some will get really sick with it, especially if they have an underlying health condition, like obesity or asthma that makes them more vulnerable.

Beyond the initial infection, children can get a rare late complication called MIS-C, that while treatable, can be severe and requires hospitalization. Emerging reports also suggest there are some kids that become long haulers in much the same way adults do, dealing with lingering problems for months after they first get sick.

As new variants of the coronavirus circulate in the United States, some states have seen big increases in the number of children and teens with COVID. In Michigan, for example, which recently dealt with a spring surge of cases dominated by the B.1.1.7 variant, cases in children and teens quadrupled in April compared to February.

Beyond individual protection, vaccinating children and teens has been seen as important to achieving strong community protection, or herd immunity, against the new coronavirus.

If the FDA expands the authorization for the Pfizer vaccine, the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices will likely meet to review data on the safety and efficacy of the vaccine. The committee may then vote on new recommendations for use of the vaccine in the United States.

Not everyone agrees with the idea that American adolescents, who are at relatively low risk of bad outcomes, could get access to COVID vaccines ahead of vulnerable essential workers and seniors in other parts of the world that are still fighting the pandemic with little access to vaccines.

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

In its third voluntary recall in the past year, Acella Pharmaceuticals has announced a nationwide recall of specific lots of its popular hypothyroid treatment NP Thyroid tablets USP, this time after routine testing found the pills to be subpotent.

Specifically, the affected lots were found to contain less than 90% of the drug’s two labeled ingredients to treat hypothyroidism: liothyronine (LT3) and/or levothyroxine (LT4).

The affected lots include 15-mg, 30-mg, 60-mg, 90-mg and 120-mg formulations of NP Thyroid tablets, packed in 100-count and 7-count bottles.

The list of the specific recalled lots is published on the Food and Drug Administration website.

Acella reports that, so far, 43 reports of serious adverse events that could be related to the recall have been received.

Symptoms suggesting patients may have received a subpotent batch include the common signs of hypothyroidism, such as fatigue, increased sensitivity to cold, constipation, dry skin, puffy face, hair loss, slow heart rate, depression, swelling of the thyroid gland and/or unexplained weight gain or difficulty losing weight, Acella reports.

“There is reasonable risk of serious injury in newborn infants or pregnant women with hypothyroidism including early miscarriage, fetal hyperthyroidism, and/or impairments to fetal neural and skeletal development,” the company cautions in the recall statement.

Acella adds that toxic cardiac manifestations of hyperthyroidism, including cardiac pain, palpitations or cardiac arrhythmia may occur in elderly patients and patients with underlying cardiac disease.

While Acella is notifying affected parties to discontinue distribution of the recalled products, it advises that patients who are currently taking NP Thyroid from the lots being recalled “should not discontinue use without contacting their healthcare provider for further guidance and/or a replacement prescription.”

In November 2020, a recall of NP Thyroid was issued after FDA testing found subpotent levels, as low as 87% of the labeled amount, of LT4 in some lots.

And earlier, in May 2020, the company recalled 13 lots of the tablets due to excessive potency, with FDA testing showing some tablets contained up to 115% of the labeled amount of LT3.

NP Thyroid is a type of desiccated animal thyroid product that was long the standard of care for hypothyroidism prior to the advent of the synthetic hypothyroidism drug, Synthroid (levothyroxine sodium), now the most commonly used hypothyroidism treatment.

On its website, Acella refers to NP Thyroid as a “natural choice for thyroid therapy,” as desiccated thyroid is commonly referred to.

However, one of the most common concerns about desiccated thyroid is a tendency to have unreliable concentrations of active ingredients, as discussed in American Thyroid Association recommendations.

The “amounts of both T4 and T3 can vary in every batch of desiccated thyroid, making it harder to keep blood levels right,” the ATA states.

“Finally, even desiccated thyroid pills have chemicals (binders) in them to hold the pill together, so they are not completely ‘natural.’ ”

Consumers with questions about the recall are advised to email Acella Pharmaceuticals at recall@acellapharma.com or call 1-888-424-4341, Monday through Friday from 8:00 am to 5:00 pm ET.
 

In its third voluntary recall in the past year, Acella Pharmaceuticals has announced a nationwide recall of specific lots of its popular hypothyroid treatment NP Thyroid tablets USP, this time after routine testing found the pills to be subpotent.

Specifically, the affected lots were found to contain less than 90% of the drug’s two labeled ingredients to treat hypothyroidism: liothyronine (LT3) and/or levothyroxine (LT4).

The affected lots include 15-mg, 30-mg, 60-mg, 90-mg and 120-mg formulations of NP Thyroid tablets, packed in 100-count and 7-count bottles.

The list of the specific recalled lots is published on the Food and Drug Administration website.

Acella reports that, so far, 43 reports of serious adverse events that could be related to the recall have been received.

Symptoms suggesting patients may have received a subpotent batch include the common signs of hypothyroidism, such as fatigue, increased sensitivity to cold, constipation, dry skin, puffy face, hair loss, slow heart rate, depression, swelling of the thyroid gland and/or unexplained weight gain or difficulty losing weight, Acella reports.

“There is reasonable risk of serious injury in newborn infants or pregnant women with hypothyroidism including early miscarriage, fetal hyperthyroidism, and/or impairments to fetal neural and skeletal development,” the company cautions in the recall statement.

Acella adds that toxic cardiac manifestations of hyperthyroidism, including cardiac pain, palpitations or cardiac arrhythmia may occur in elderly patients and patients with underlying cardiac disease.

While Acella is notifying affected parties to discontinue distribution of the recalled products, it advises that patients who are currently taking NP Thyroid from the lots being recalled “should not discontinue use without contacting their healthcare provider for further guidance and/or a replacement prescription.”

In November 2020, a recall of NP Thyroid was issued after FDA testing found subpotent levels, as low as 87% of the labeled amount, of LT4 in some lots.

And earlier, in May 2020, the company recalled 13 lots of the tablets due to excessive potency, with FDA testing showing some tablets contained up to 115% of the labeled amount of LT3.

NP Thyroid is a type of desiccated animal thyroid product that was long the standard of care for hypothyroidism prior to the advent of the synthetic hypothyroidism drug, Synthroid (levothyroxine sodium), now the most commonly used hypothyroidism treatment.

On its website, Acella refers to NP Thyroid as a “natural choice for thyroid therapy,” as desiccated thyroid is commonly referred to.

However, one of the most common concerns about desiccated thyroid is a tendency to have unreliable concentrations of active ingredients, as discussed in American Thyroid Association recommendations.

The “amounts of both T4 and T3 can vary in every batch of desiccated thyroid, making it harder to keep blood levels right,” the ATA states.

“Finally, even desiccated thyroid pills have chemicals (binders) in them to hold the pill together, so they are not completely ‘natural.’ ”

Consumers with questions about the recall are advised to email Acella Pharmaceuticals at recall@acellapharma.com or call 1-888-424-4341, Monday through Friday from 8:00 am to 5:00 pm ET.
 

In its third voluntary recall in the past year, Acella Pharmaceuticals has announced a nationwide recall of specific lots of its popular hypothyroid treatment NP Thyroid tablets USP, this time after routine testing found the pills to be subpotent.

Specifically, the affected lots were found to contain less than 90% of the drug’s two labeled ingredients to treat hypothyroidism: liothyronine (LT3) and/or levothyroxine (LT4).

The affected lots include 15-mg, 30-mg, 60-mg, 90-mg and 120-mg formulations of NP Thyroid tablets, packed in 100-count and 7-count bottles.

The list of the specific recalled lots is published on the Food and Drug Administration website.

Acella reports that, so far, 43 reports of serious adverse events that could be related to the recall have been received.

Symptoms suggesting patients may have received a subpotent batch include the common signs of hypothyroidism, such as fatigue, increased sensitivity to cold, constipation, dry skin, puffy face, hair loss, slow heart rate, depression, swelling of the thyroid gland and/or unexplained weight gain or difficulty losing weight, Acella reports.

“There is reasonable risk of serious injury in newborn infants or pregnant women with hypothyroidism including early miscarriage, fetal hyperthyroidism, and/or impairments to fetal neural and skeletal development,” the company cautions in the recall statement.

Acella adds that toxic cardiac manifestations of hyperthyroidism, including cardiac pain, palpitations or cardiac arrhythmia may occur in elderly patients and patients with underlying cardiac disease.

While Acella is notifying affected parties to discontinue distribution of the recalled products, it advises that patients who are currently taking NP Thyroid from the lots being recalled “should not discontinue use without contacting their healthcare provider for further guidance and/or a replacement prescription.”

In November 2020, a recall of NP Thyroid was issued after FDA testing found subpotent levels, as low as 87% of the labeled amount, of LT4 in some lots.

And earlier, in May 2020, the company recalled 13 lots of the tablets due to excessive potency, with FDA testing showing some tablets contained up to 115% of the labeled amount of LT3.

NP Thyroid is a type of desiccated animal thyroid product that was long the standard of care for hypothyroidism prior to the advent of the synthetic hypothyroidism drug, Synthroid (levothyroxine sodium), now the most commonly used hypothyroidism treatment.

On its website, Acella refers to NP Thyroid as a “natural choice for thyroid therapy,” as desiccated thyroid is commonly referred to.

However, one of the most common concerns about desiccated thyroid is a tendency to have unreliable concentrations of active ingredients, as discussed in American Thyroid Association recommendations.

The “amounts of both T4 and T3 can vary in every batch of desiccated thyroid, making it harder to keep blood levels right,” the ATA states.

“Finally, even desiccated thyroid pills have chemicals (binders) in them to hold the pill together, so they are not completely ‘natural.’ ”

Consumers with questions about the recall are advised to email Acella Pharmaceuticals at recall@acellapharma.com or call 1-888-424-4341, Monday through Friday from 8:00 am to 5:00 pm ET.
 

The Food and Drug Administration has approved dapagliflozin (Farxiga, AstraZeneca) to reduce the risk for kidney function decline, kidney failure, cardiovascular death, and hospitalization for heart failure in adult patients with chronic kidney disease (CKD) at risk for disease progression.

“Chronic kidney disease is an important public health issue, and there is a significant unmet need for therapies that slow disease progression and improve outcomes,” said Aliza Thompson, MD, deputy director of the division of cardiology and nephrology at the FDA’s Center for Drug Evaluation and Research. “Today’s approval of Farxiga for the treatment of chronic kidney disease is an important step forward in helping people living with kidney disease.”

Dapagliflozin was approved in 2014 to improve glycemic control in patients with diabetes mellitus, and approval was expanded in 2020 to include treatment of patients with heart failure and reduced ejection fraction, based on results of the DAPA-HF trial.

This new approval in chronic kidney disease was based on results of the DAPA-CKD trial that was stopped early in March 2020 because of efficacy of the treatment.

DAPA-CKD randomly assigned 4,304 patients with CKD but without diabetes to receive either dapagliflozin or placebo. The full study results, reported at the 2020 annual congress of the European Society of Cardiology and simultaneously published in the New England Journal of Medicine, showed that, during a median of 2.4 years, treatment with dapagliflozin led to a significant 31% relative reduction, compared with placebo in the study’s primary outcome, a composite that included at least a 50% drop in estimated glomerular filtration rate, compared with baseline, end-stage kidney disease, kidney transplant, renal death, or cardiovascular death.

Dapagliflozin treatment also cut all-cause mortality by a statistically significant relative reduction of 31%, and another secondary-endpoint analysis showed a statistically significant 29% relative reduction in the rate of cardiovascular death or heart failure hospitalization.

“Farxiga was not studied, nor is expected to be effective, in treating chronic kidney disease among patients with autosomal dominant or recessive polycystic (characterized by multiple cysts) kidney disease or among patients who require or have recently used immunosuppressive therapy to treat kidney disease,” the FDA statement noted.

Dapagliflozin should not be used by patients with a history of serious hypersensitivity reactions to this medication, or who are on dialysis, the agency added. “Serious, life-threatening cases of Fournier’s Gangrene have occurred in patients with diabetes taking Farxiga.”

Patients should consider taking a lower dose of insulin or insulin secretagogue to reduce hypoglycemic risk if they are also taking dapagliflozin. Treatment can also cause dehydration, serious urinary tract infections, genital yeast infections, and metabolic acidosis, the announcement said. “Patients should be assessed for their volume status and kidney function before starting Farxiga.”

Dapagliflozin previously received Fast Track, Breakthrough Therapy, and Priority Review designations for this new indication.

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

The Food and Drug Administration has approved dapagliflozin (Farxiga, AstraZeneca) to reduce the risk for kidney function decline, kidney failure, cardiovascular death, and hospitalization for heart failure in adult patients with chronic kidney disease (CKD) at risk for disease progression.

“Chronic kidney disease is an important public health issue, and there is a significant unmet need for therapies that slow disease progression and improve outcomes,” said Aliza Thompson, MD, deputy director of the division of cardiology and nephrology at the FDA’s Center for Drug Evaluation and Research. “Today’s approval of Farxiga for the treatment of chronic kidney disease is an important step forward in helping people living with kidney disease.”

Dapagliflozin was approved in 2014 to improve glycemic control in patients with diabetes mellitus, and approval was expanded in 2020 to include treatment of patients with heart failure and reduced ejection fraction, based on results of the DAPA-HF trial.

This new approval in chronic kidney disease was based on results of the DAPA-CKD trial that was stopped early in March 2020 because of efficacy of the treatment.

DAPA-CKD randomly assigned 4,304 patients with CKD but without diabetes to receive either dapagliflozin or placebo. The full study results, reported at the 2020 annual congress of the European Society of Cardiology and simultaneously published in the New England Journal of Medicine, showed that, during a median of 2.4 years, treatment with dapagliflozin led to a significant 31% relative reduction, compared with placebo in the study’s primary outcome, a composite that included at least a 50% drop in estimated glomerular filtration rate, compared with baseline, end-stage kidney disease, kidney transplant, renal death, or cardiovascular death.

Dapagliflozin treatment also cut all-cause mortality by a statistically significant relative reduction of 31%, and another secondary-endpoint analysis showed a statistically significant 29% relative reduction in the rate of cardiovascular death or heart failure hospitalization.

“Farxiga was not studied, nor is expected to be effective, in treating chronic kidney disease among patients with autosomal dominant or recessive polycystic (characterized by multiple cysts) kidney disease or among patients who require or have recently used immunosuppressive therapy to treat kidney disease,” the FDA statement noted.

Dapagliflozin should not be used by patients with a history of serious hypersensitivity reactions to this medication, or who are on dialysis, the agency added. “Serious, life-threatening cases of Fournier’s Gangrene have occurred in patients with diabetes taking Farxiga.”

Patients should consider taking a lower dose of insulin or insulin secretagogue to reduce hypoglycemic risk if they are also taking dapagliflozin. Treatment can also cause dehydration, serious urinary tract infections, genital yeast infections, and metabolic acidosis, the announcement said. “Patients should be assessed for their volume status and kidney function before starting Farxiga.”

Dapagliflozin previously received Fast Track, Breakthrough Therapy, and Priority Review designations for this new indication.

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

The Food and Drug Administration has approved dapagliflozin (Farxiga, AstraZeneca) to reduce the risk for kidney function decline, kidney failure, cardiovascular death, and hospitalization for heart failure in adult patients with chronic kidney disease (CKD) at risk for disease progression.

“Chronic kidney disease is an important public health issue, and there is a significant unmet need for therapies that slow disease progression and improve outcomes,” said Aliza Thompson, MD, deputy director of the division of cardiology and nephrology at the FDA’s Center for Drug Evaluation and Research. “Today’s approval of Farxiga for the treatment of chronic kidney disease is an important step forward in helping people living with kidney disease.”

Dapagliflozin was approved in 2014 to improve glycemic control in patients with diabetes mellitus, and approval was expanded in 2020 to include treatment of patients with heart failure and reduced ejection fraction, based on results of the DAPA-HF trial.

This new approval in chronic kidney disease was based on results of the DAPA-CKD trial that was stopped early in March 2020 because of efficacy of the treatment.

DAPA-CKD randomly assigned 4,304 patients with CKD but without diabetes to receive either dapagliflozin or placebo. The full study results, reported at the 2020 annual congress of the European Society of Cardiology and simultaneously published in the New England Journal of Medicine, showed that, during a median of 2.4 years, treatment with dapagliflozin led to a significant 31% relative reduction, compared with placebo in the study’s primary outcome, a composite that included at least a 50% drop in estimated glomerular filtration rate, compared with baseline, end-stage kidney disease, kidney transplant, renal death, or cardiovascular death.

Dapagliflozin treatment also cut all-cause mortality by a statistically significant relative reduction of 31%, and another secondary-endpoint analysis showed a statistically significant 29% relative reduction in the rate of cardiovascular death or heart failure hospitalization.

“Farxiga was not studied, nor is expected to be effective, in treating chronic kidney disease among patients with autosomal dominant or recessive polycystic (characterized by multiple cysts) kidney disease or among patients who require or have recently used immunosuppressive therapy to treat kidney disease,” the FDA statement noted.

Dapagliflozin should not be used by patients with a history of serious hypersensitivity reactions to this medication, or who are on dialysis, the agency added. “Serious, life-threatening cases of Fournier’s Gangrene have occurred in patients with diabetes taking Farxiga.”

Patients should consider taking a lower dose of insulin or insulin secretagogue to reduce hypoglycemic risk if they are also taking dapagliflozin. Treatment can also cause dehydration, serious urinary tract infections, genital yeast infections, and metabolic acidosis, the announcement said. “Patients should be assessed for their volume status and kidney function before starting Farxiga.”

Dapagliflozin previously received Fast Track, Breakthrough Therapy, and Priority Review designations for this new indication.

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