MDedge Emergency Medicine

A new study shows apolipoprotein B (apoB) and non-HDL cholesterol – but not LDL cholesterol – are associated with increased risk for all-cause mortality and myocardial infarction in patients taking statins.

Bruce Jancin/Frontline Medical News

Moreover, apoB was a more accurate marker of all-cause mortality risk than non-HDL or LDL cholesterol and was more accurate at identifying MI risk than LDL cholesterol.

“Any patient that comes to a doctor for evaluation, if statin treatment is sufficient, the doctor should look not only at LDL cholesterol but HDL cholesterol and apoB, if its available – that is the take-home message,” senior author Børge Grønne Nordestgaard, MD, DMSC, University of Copenhagen, said in an interview.

The findings are very relevant to clinical practice because international guidelines focus on LDL cholesterol and “many doctors are brainwashed that that is the only thing they should look at, just to keep LDL cholesterol down,” he said. “I’ve worked for years with triglyceride lipoproteins, what I call remnant cholesterol, and I think that the risk is very high also when you have high remnant cholesterol.”

Previous work has shown that apoB and non-HDL cholesterol better reflect atherosclerotic cardiovascular disease risk than LDL cholesterol. This is the first study, however, to show that elevated apoB and non-HDL cholesterol are associated with a higher risk for all-cause death in statin-treated patients with low LDL cholesterol, Dr. Nordestgaard noted.

The investigators compared outcomes among 13,015 statin-treated participants in the Copenhagen General Population Study using median baseline values of 92 mg/dL for apoB, 3.1 mmol/L (120 mg/dL) for non-HDL cholesterol, and 2.3 mmol/L (89 mg/dL) for LDL cholesterol. Over a median follow-up of 8 years, there were 2,499 deaths and 537 MIs.

As reported in the Journal of the American College of Cardiology, discordant apoB above the median with LDL cholesterol below was associated with a 21% increased risk for all-cause mortality (hazard ratio, 1.21; 95% confidence interval, 1.07-1.36) and 49% increased risk for MI (HR, 1.49; 95% CI, 1.15-1.92), compared with concordant apoB and LDL cholesterol below the medians.

Similar results were found for discordant non-HDL cholesterol above the median with low LDL cholesterol for all-cause mortality (HR, 1.18; 95% CI, 1.02-1.36) and MI (1.78; 95% CI, 1.35-2.34).

No such associations with mortality or MI were observed when LDL cholesterol was above the median and apoB or non-HDL below.

Additional analyses showed that high apoB with low non-HDL cholesterol was associated with a higher risk for all-cause mortality (HR, 1.21; 95% CI, 1.03-1.41), whereas high non-HDL cholesterol with low apoB was associated with a lower risk (HR, 0.75; 95% CI, 0.62-0.92).

Current guidelines define apoB greater than 130 mg/dL as a risk modifier in patients not using statins but, the authors wrote, “based on our results, the threshold for apoB as a risk modifier in statin-treated patients should be closer to 92 mg/dL than to 130 mg/dL.”

In an accompanying editorial, Neil J. Stone, MD, and Donald Lloyd-Jones, MD, both from Northwestern University, Chicago, said that American and European guidelines acknowledge the usefulness of apoB and non-HDL cholesterol in their risk algorithms and as possible targets to indicate efficacy, but don’t give a strong recommendation for apoB to assess residual risk.

“This paper suggests that, in the next iteration, we’ve got to give a stronger thought to measuring apoB for residual risk in those with secondary prevention,” Dr. Stone, vice chair of the 2018 American Heart Association/ACC cholesterol guidelines, said in an interview.

“The whole part of the guidelines was not to focus on any one number but to focus on the clinical risk as a whole,” he said. “You can enlarge your understanding of the patient by looking at their non-HDL, which you have anyway, and in certain circumstances, for example, people with metabolic syndrome, diabetes, obesity, or high triglycerides, those people might very well benefit from an apoB to further understand their risk. This paper simply highlights that and, therefore, was very valuable.”

Dr. Stone and Dr. Lloyd-Jones, however, pointed out that statin use was self-reported and information was lacking on adherence, dose intensity, and the amount of LDL cholesterol lowering from baseline. LDL cholesterol levels were also above current recommendations for optimizing risk reduction. “If statin dosing and LDL [cholesterol] were not optimized already, then there may have been ‘room’ for non-HDL [cholesterol] and apoB to add value in understanding residual risk,” they wrote.

The editorialists suggested that sequential use, rather than regular use, of apoB and non-HDL cholesterol may be best and that incorporating this information may be particularly beneficial for patients with metabolic disorders and elevated triglycerides after statin therapy.

“Maybe this paper is a wake-up call that there are other markers out there that can tell you that you still have higher risk and need to tighten up lifestyle and maybe be more adherent,” Dr. Stone said. “I think this is a wonderful chance to say that preventive cardiology isn’t just ‘set it and forget it’.”

C. Noel Bairey Merz, MD, who coauthored the 2018 cholesterol guidelines, agreed there’s “an overexuberant focus on LDL [cholesterol] for residual risk” and highlighted a recent systematic review of statins, ezetimibe, and PCSK9 cardiovascular outcomes trials that showed very little gain from aggressively driving down LDL below 100 mg/dL, unless the patient is at extremely high risk.

“If I, as a treating cardiologist who spends a lot of time on lipids, had a patient on a high-intensity statin and they didn’t drop [their LDL cholesterol] 50% and I already had them going to cardiac rehab and they were already losing weight, would I measure apoB? Yeah, I might, to motivate them to do more or to take Vascepa,” she said.

“This study is a useful addition to a relatively important problem, which is residual risk, and really supports personalized or precision medicine,” added Bairey Merz, MD, Cedars-Sinai Medical Center, Los Angeles. “But now we have to do the work and do an intervention trial in these people and see whether these markers make a difference.”

The study was supported by Herlev and Gentofte Hospital’s Research Fund and the department of clinical biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital. Dr. Nordestgaard has had consultancies or talks sponsored by AstraZeneca, Sanofi, Regeneron, Akcea, Amarin, Amgen, Esperion, Kowa, Novartis, Novo Nordisk, and Silence Therapeutics. All other authors, Dr. Stone, and Dr. Lloyd-Jones reported no conflicts. Dr. Merz reported no relevant disclosures.

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

A new study shows apolipoprotein B (apoB) and non-HDL cholesterol – but not LDL cholesterol – are associated with increased risk for all-cause mortality and myocardial infarction in patients taking statins.

Bruce Jancin/Frontline Medical News

Moreover, apoB was a more accurate marker of all-cause mortality risk than non-HDL or LDL cholesterol and was more accurate at identifying MI risk than LDL cholesterol.

“Any patient that comes to a doctor for evaluation, if statin treatment is sufficient, the doctor should look not only at LDL cholesterol but HDL cholesterol and apoB, if its available – that is the take-home message,” senior author Børge Grønne Nordestgaard, MD, DMSC, University of Copenhagen, said in an interview.

The findings are very relevant to clinical practice because international guidelines focus on LDL cholesterol and “many doctors are brainwashed that that is the only thing they should look at, just to keep LDL cholesterol down,” he said. “I’ve worked for years with triglyceride lipoproteins, what I call remnant cholesterol, and I think that the risk is very high also when you have high remnant cholesterol.”

Previous work has shown that apoB and non-HDL cholesterol better reflect atherosclerotic cardiovascular disease risk than LDL cholesterol. This is the first study, however, to show that elevated apoB and non-HDL cholesterol are associated with a higher risk for all-cause death in statin-treated patients with low LDL cholesterol, Dr. Nordestgaard noted.

The investigators compared outcomes among 13,015 statin-treated participants in the Copenhagen General Population Study using median baseline values of 92 mg/dL for apoB, 3.1 mmol/L (120 mg/dL) for non-HDL cholesterol, and 2.3 mmol/L (89 mg/dL) for LDL cholesterol. Over a median follow-up of 8 years, there were 2,499 deaths and 537 MIs.

As reported in the Journal of the American College of Cardiology, discordant apoB above the median with LDL cholesterol below was associated with a 21% increased risk for all-cause mortality (hazard ratio, 1.21; 95% confidence interval, 1.07-1.36) and 49% increased risk for MI (HR, 1.49; 95% CI, 1.15-1.92), compared with concordant apoB and LDL cholesterol below the medians.

Similar results were found for discordant non-HDL cholesterol above the median with low LDL cholesterol for all-cause mortality (HR, 1.18; 95% CI, 1.02-1.36) and MI (1.78; 95% CI, 1.35-2.34).

No such associations with mortality or MI were observed when LDL cholesterol was above the median and apoB or non-HDL below.

Additional analyses showed that high apoB with low non-HDL cholesterol was associated with a higher risk for all-cause mortality (HR, 1.21; 95% CI, 1.03-1.41), whereas high non-HDL cholesterol with low apoB was associated with a lower risk (HR, 0.75; 95% CI, 0.62-0.92).

Current guidelines define apoB greater than 130 mg/dL as a risk modifier in patients not using statins but, the authors wrote, “based on our results, the threshold for apoB as a risk modifier in statin-treated patients should be closer to 92 mg/dL than to 130 mg/dL.”

In an accompanying editorial, Neil J. Stone, MD, and Donald Lloyd-Jones, MD, both from Northwestern University, Chicago, said that American and European guidelines acknowledge the usefulness of apoB and non-HDL cholesterol in their risk algorithms and as possible targets to indicate efficacy, but don’t give a strong recommendation for apoB to assess residual risk.

“This paper suggests that, in the next iteration, we’ve got to give a stronger thought to measuring apoB for residual risk in those with secondary prevention,” Dr. Stone, vice chair of the 2018 American Heart Association/ACC cholesterol guidelines, said in an interview.

“The whole part of the guidelines was not to focus on any one number but to focus on the clinical risk as a whole,” he said. “You can enlarge your understanding of the patient by looking at their non-HDL, which you have anyway, and in certain circumstances, for example, people with metabolic syndrome, diabetes, obesity, or high triglycerides, those people might very well benefit from an apoB to further understand their risk. This paper simply highlights that and, therefore, was very valuable.”

Dr. Stone and Dr. Lloyd-Jones, however, pointed out that statin use was self-reported and information was lacking on adherence, dose intensity, and the amount of LDL cholesterol lowering from baseline. LDL cholesterol levels were also above current recommendations for optimizing risk reduction. “If statin dosing and LDL [cholesterol] were not optimized already, then there may have been ‘room’ for non-HDL [cholesterol] and apoB to add value in understanding residual risk,” they wrote.

The editorialists suggested that sequential use, rather than regular use, of apoB and non-HDL cholesterol may be best and that incorporating this information may be particularly beneficial for patients with metabolic disorders and elevated triglycerides after statin therapy.

“Maybe this paper is a wake-up call that there are other markers out there that can tell you that you still have higher risk and need to tighten up lifestyle and maybe be more adherent,” Dr. Stone said. “I think this is a wonderful chance to say that preventive cardiology isn’t just ‘set it and forget it’.”

C. Noel Bairey Merz, MD, who coauthored the 2018 cholesterol guidelines, agreed there’s “an overexuberant focus on LDL [cholesterol] for residual risk” and highlighted a recent systematic review of statins, ezetimibe, and PCSK9 cardiovascular outcomes trials that showed very little gain from aggressively driving down LDL below 100 mg/dL, unless the patient is at extremely high risk.

“If I, as a treating cardiologist who spends a lot of time on lipids, had a patient on a high-intensity statin and they didn’t drop [their LDL cholesterol] 50% and I already had them going to cardiac rehab and they were already losing weight, would I measure apoB? Yeah, I might, to motivate them to do more or to take Vascepa,” she said.

“This study is a useful addition to a relatively important problem, which is residual risk, and really supports personalized or precision medicine,” added Bairey Merz, MD, Cedars-Sinai Medical Center, Los Angeles. “But now we have to do the work and do an intervention trial in these people and see whether these markers make a difference.”

The study was supported by Herlev and Gentofte Hospital’s Research Fund and the department of clinical biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital. Dr. Nordestgaard has had consultancies or talks sponsored by AstraZeneca, Sanofi, Regeneron, Akcea, Amarin, Amgen, Esperion, Kowa, Novartis, Novo Nordisk, and Silence Therapeutics. All other authors, Dr. Stone, and Dr. Lloyd-Jones reported no conflicts. Dr. Merz reported no relevant disclosures.

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

A new study shows apolipoprotein B (apoB) and non-HDL cholesterol – but not LDL cholesterol – are associated with increased risk for all-cause mortality and myocardial infarction in patients taking statins.

Bruce Jancin/Frontline Medical News

Moreover, apoB was a more accurate marker of all-cause mortality risk than non-HDL or LDL cholesterol and was more accurate at identifying MI risk than LDL cholesterol.

“Any patient that comes to a doctor for evaluation, if statin treatment is sufficient, the doctor should look not only at LDL cholesterol but HDL cholesterol and apoB, if its available – that is the take-home message,” senior author Børge Grønne Nordestgaard, MD, DMSC, University of Copenhagen, said in an interview.

The findings are very relevant to clinical practice because international guidelines focus on LDL cholesterol and “many doctors are brainwashed that that is the only thing they should look at, just to keep LDL cholesterol down,” he said. “I’ve worked for years with triglyceride lipoproteins, what I call remnant cholesterol, and I think that the risk is very high also when you have high remnant cholesterol.”

Previous work has shown that apoB and non-HDL cholesterol better reflect atherosclerotic cardiovascular disease risk than LDL cholesterol. This is the first study, however, to show that elevated apoB and non-HDL cholesterol are associated with a higher risk for all-cause death in statin-treated patients with low LDL cholesterol, Dr. Nordestgaard noted.

The investigators compared outcomes among 13,015 statin-treated participants in the Copenhagen General Population Study using median baseline values of 92 mg/dL for apoB, 3.1 mmol/L (120 mg/dL) for non-HDL cholesterol, and 2.3 mmol/L (89 mg/dL) for LDL cholesterol. Over a median follow-up of 8 years, there were 2,499 deaths and 537 MIs.

As reported in the Journal of the American College of Cardiology, discordant apoB above the median with LDL cholesterol below was associated with a 21% increased risk for all-cause mortality (hazard ratio, 1.21; 95% confidence interval, 1.07-1.36) and 49% increased risk for MI (HR, 1.49; 95% CI, 1.15-1.92), compared with concordant apoB and LDL cholesterol below the medians.

Similar results were found for discordant non-HDL cholesterol above the median with low LDL cholesterol for all-cause mortality (HR, 1.18; 95% CI, 1.02-1.36) and MI (1.78; 95% CI, 1.35-2.34).

No such associations with mortality or MI were observed when LDL cholesterol was above the median and apoB or non-HDL below.

Additional analyses showed that high apoB with low non-HDL cholesterol was associated with a higher risk for all-cause mortality (HR, 1.21; 95% CI, 1.03-1.41), whereas high non-HDL cholesterol with low apoB was associated with a lower risk (HR, 0.75; 95% CI, 0.62-0.92).

Current guidelines define apoB greater than 130 mg/dL as a risk modifier in patients not using statins but, the authors wrote, “based on our results, the threshold for apoB as a risk modifier in statin-treated patients should be closer to 92 mg/dL than to 130 mg/dL.”

In an accompanying editorial, Neil J. Stone, MD, and Donald Lloyd-Jones, MD, both from Northwestern University, Chicago, said that American and European guidelines acknowledge the usefulness of apoB and non-HDL cholesterol in their risk algorithms and as possible targets to indicate efficacy, but don’t give a strong recommendation for apoB to assess residual risk.

“This paper suggests that, in the next iteration, we’ve got to give a stronger thought to measuring apoB for residual risk in those with secondary prevention,” Dr. Stone, vice chair of the 2018 American Heart Association/ACC cholesterol guidelines, said in an interview.

“The whole part of the guidelines was not to focus on any one number but to focus on the clinical risk as a whole,” he said. “You can enlarge your understanding of the patient by looking at their non-HDL, which you have anyway, and in certain circumstances, for example, people with metabolic syndrome, diabetes, obesity, or high triglycerides, those people might very well benefit from an apoB to further understand their risk. This paper simply highlights that and, therefore, was very valuable.”

Dr. Stone and Dr. Lloyd-Jones, however, pointed out that statin use was self-reported and information was lacking on adherence, dose intensity, and the amount of LDL cholesterol lowering from baseline. LDL cholesterol levels were also above current recommendations for optimizing risk reduction. “If statin dosing and LDL [cholesterol] were not optimized already, then there may have been ‘room’ for non-HDL [cholesterol] and apoB to add value in understanding residual risk,” they wrote.

The editorialists suggested that sequential use, rather than regular use, of apoB and non-HDL cholesterol may be best and that incorporating this information may be particularly beneficial for patients with metabolic disorders and elevated triglycerides after statin therapy.

“Maybe this paper is a wake-up call that there are other markers out there that can tell you that you still have higher risk and need to tighten up lifestyle and maybe be more adherent,” Dr. Stone said. “I think this is a wonderful chance to say that preventive cardiology isn’t just ‘set it and forget it’.”

C. Noel Bairey Merz, MD, who coauthored the 2018 cholesterol guidelines, agreed there’s “an overexuberant focus on LDL [cholesterol] for residual risk” and highlighted a recent systematic review of statins, ezetimibe, and PCSK9 cardiovascular outcomes trials that showed very little gain from aggressively driving down LDL below 100 mg/dL, unless the patient is at extremely high risk.

“If I, as a treating cardiologist who spends a lot of time on lipids, had a patient on a high-intensity statin and they didn’t drop [their LDL cholesterol] 50% and I already had them going to cardiac rehab and they were already losing weight, would I measure apoB? Yeah, I might, to motivate them to do more or to take Vascepa,” she said.

“This study is a useful addition to a relatively important problem, which is residual risk, and really supports personalized or precision medicine,” added Bairey Merz, MD, Cedars-Sinai Medical Center, Los Angeles. “But now we have to do the work and do an intervention trial in these people and see whether these markers make a difference.”

The study was supported by Herlev and Gentofte Hospital’s Research Fund and the department of clinical biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital. Dr. Nordestgaard has had consultancies or talks sponsored by AstraZeneca, Sanofi, Regeneron, Akcea, Amarin, Amgen, Esperion, Kowa, Novartis, Novo Nordisk, and Silence Therapeutics. All other authors, Dr. Stone, and Dr. Lloyd-Jones reported no conflicts. Dr. Merz reported no relevant disclosures.

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

Among patients who undergo surgery for hidradenitis suppurativa (HS), wide excision and flap-based reconstruction are associated with lower postsurgical recurrence, yet these options should be balanced against potentially higher morbidity of extensive procedures.

Those are among the key findings of a systematic review and meta-analysis published online in Dermatologic Surgery.

“There is a major need to better understand the best surgical approaches to HS,” one of the study authors, Christopher Sayed, MD, associate professor of dermatology at the University of North Carolina at Chapel Hill, said in an interview. Previous studies have mostly reviewed outcomes for procedure types in individual cohorts, “but no recent reports have combined and analyzed data from recent studies.”

When Dr. Sayed and colleagues set out to summarize the literature on HS surgery regarding patient characteristics, surgical approaches, and study quality, as well as compare postsurgical recurrence rates, the most recent meta-analysis on postoperative recurrence rates of HS included studies published between 1990 and 2015. “In the past few years, surgical management of HS has become an increasingly popular area of study,” corresponding author Ashley Riddle, MD, MPH, who is currently an internal medicine resident at the Carolinas Medical Center, Charlotte, said in an interview. “We sought to provide an updated picture of the HS surgical landscape by analyzing studies published between 2004 to 2019. We also limited our analysis to studies with follow-up periods of greater than 1 year and included information on disease severity, adverse events, and patient satisfaction when available.”

Of 715 relevant studies identified in the medical literature, the researchers included 59 in the review and 33 in the meta-analysis. Of these 59 studies, 56 were case series, 2 were randomized, controlled trials, and one was a retrospective cohort study.

Of the 50 studies reporting gender and age at time of surgery, 61% of patients were female and their average age was 37 years. Of the 25 studies that reported Hurley scores, 73% had Hurley stage 3 HS. Of the 38 studies reporting the number of procedures per anatomic region, the most commonly operated on regions were the axilla (59%) and the inguinal region (20%).

The researchers found that 22 studies of wide excision had the lowest pooled recurrence rate at 8%, while local excision had the highest pooled recurrence rate at 34%. Meanwhile, among studies of wide/radical excision, flap repair had a pooled recurrence rate of 0%, while delayed primary closure had the highest pooled recurrence rate at 38%.

“Extensive excisions of HS seem to portend a lower risk of postoperative recurrence, but there are many approaches available that may be more appropriate for certain patients,” Dr. Riddle said. “The influence of patient factors such as comorbidities and disease severity on surgical outcomes is unclear and is a potential area of future study.”

Dr. Sayed, an author of the 2019 North American guidelines for the clinical management of HS, pointed out that most studies in the review and meta-analysis included patients who had diabetes, were on biologics or other therapy, were actively smoking, or had other comorbidities that sometimes influence surgeons to delay surgical treatment because they consider it elective. “Most studies indicated minimal or no risk of significant complications relating to these factors, so they should ideally not become obstacles for patients interested in surgical care,” he said.

Dr. Riddle said that she was surprised by how relatively few studies had been published on more conservative surgical approaches such as skin tissue–sparing excision with electrosurgical peeling, deroofing, local excision, and CO₂ laser–based evaporation.

The researchers acknowledged certain limitations of their work, including the high risk of bias for most included studies. “Almost all studies were retrospective with substantial methodological limitations, and there were no head-to-head comparisons of different surgical approaches,” Dr. Riddle said. “Patient comorbidities and postoperative complications were variably reported.”

Dr. Sayed disclosed that he is a speaker for AbbVie and Novartis; an investigator for AbbVie, Novartis, InflaRx, and UCB; and on the advisory board of AbbVie and InflaRx. The remaining authors reported having no financial disclosures.

[email protected]

Among patients who undergo surgery for hidradenitis suppurativa (HS), wide excision and flap-based reconstruction are associated with lower postsurgical recurrence, yet these options should be balanced against potentially higher morbidity of extensive procedures.

Those are among the key findings of a systematic review and meta-analysis published online in Dermatologic Surgery.

“There is a major need to better understand the best surgical approaches to HS,” one of the study authors, Christopher Sayed, MD, associate professor of dermatology at the University of North Carolina at Chapel Hill, said in an interview. Previous studies have mostly reviewed outcomes for procedure types in individual cohorts, “but no recent reports have combined and analyzed data from recent studies.”

When Dr. Sayed and colleagues set out to summarize the literature on HS surgery regarding patient characteristics, surgical approaches, and study quality, as well as compare postsurgical recurrence rates, the most recent meta-analysis on postoperative recurrence rates of HS included studies published between 1990 and 2015. “In the past few years, surgical management of HS has become an increasingly popular area of study,” corresponding author Ashley Riddle, MD, MPH, who is currently an internal medicine resident at the Carolinas Medical Center, Charlotte, said in an interview. “We sought to provide an updated picture of the HS surgical landscape by analyzing studies published between 2004 to 2019. We also limited our analysis to studies with follow-up periods of greater than 1 year and included information on disease severity, adverse events, and patient satisfaction when available.”

Of 715 relevant studies identified in the medical literature, the researchers included 59 in the review and 33 in the meta-analysis. Of these 59 studies, 56 were case series, 2 were randomized, controlled trials, and one was a retrospective cohort study.

Of the 50 studies reporting gender and age at time of surgery, 61% of patients were female and their average age was 37 years. Of the 25 studies that reported Hurley scores, 73% had Hurley stage 3 HS. Of the 38 studies reporting the number of procedures per anatomic region, the most commonly operated on regions were the axilla (59%) and the inguinal region (20%).

The researchers found that 22 studies of wide excision had the lowest pooled recurrence rate at 8%, while local excision had the highest pooled recurrence rate at 34%. Meanwhile, among studies of wide/radical excision, flap repair had a pooled recurrence rate of 0%, while delayed primary closure had the highest pooled recurrence rate at 38%.

“Extensive excisions of HS seem to portend a lower risk of postoperative recurrence, but there are many approaches available that may be more appropriate for certain patients,” Dr. Riddle said. “The influence of patient factors such as comorbidities and disease severity on surgical outcomes is unclear and is a potential area of future study.”

Dr. Sayed, an author of the 2019 North American guidelines for the clinical management of HS, pointed out that most studies in the review and meta-analysis included patients who had diabetes, were on biologics or other therapy, were actively smoking, or had other comorbidities that sometimes influence surgeons to delay surgical treatment because they consider it elective. “Most studies indicated minimal or no risk of significant complications relating to these factors, so they should ideally not become obstacles for patients interested in surgical care,” he said.

Dr. Riddle said that she was surprised by how relatively few studies had been published on more conservative surgical approaches such as skin tissue–sparing excision with electrosurgical peeling, deroofing, local excision, and CO₂ laser–based evaporation.

The researchers acknowledged certain limitations of their work, including the high risk of bias for most included studies. “Almost all studies were retrospective with substantial methodological limitations, and there were no head-to-head comparisons of different surgical approaches,” Dr. Riddle said. “Patient comorbidities and postoperative complications were variably reported.”

Dr. Sayed disclosed that he is a speaker for AbbVie and Novartis; an investigator for AbbVie, Novartis, InflaRx, and UCB; and on the advisory board of AbbVie and InflaRx. The remaining authors reported having no financial disclosures.

[email protected]

Among patients who undergo surgery for hidradenitis suppurativa (HS), wide excision and flap-based reconstruction are associated with lower postsurgical recurrence, yet these options should be balanced against potentially higher morbidity of extensive procedures.

Those are among the key findings of a systematic review and meta-analysis published online in Dermatologic Surgery.

“There is a major need to better understand the best surgical approaches to HS,” one of the study authors, Christopher Sayed, MD, associate professor of dermatology at the University of North Carolina at Chapel Hill, said in an interview. Previous studies have mostly reviewed outcomes for procedure types in individual cohorts, “but no recent reports have combined and analyzed data from recent studies.”

When Dr. Sayed and colleagues set out to summarize the literature on HS surgery regarding patient characteristics, surgical approaches, and study quality, as well as compare postsurgical recurrence rates, the most recent meta-analysis on postoperative recurrence rates of HS included studies published between 1990 and 2015. “In the past few years, surgical management of HS has become an increasingly popular area of study,” corresponding author Ashley Riddle, MD, MPH, who is currently an internal medicine resident at the Carolinas Medical Center, Charlotte, said in an interview. “We sought to provide an updated picture of the HS surgical landscape by analyzing studies published between 2004 to 2019. We also limited our analysis to studies with follow-up periods of greater than 1 year and included information on disease severity, adverse events, and patient satisfaction when available.”

Of 715 relevant studies identified in the medical literature, the researchers included 59 in the review and 33 in the meta-analysis. Of these 59 studies, 56 were case series, 2 were randomized, controlled trials, and one was a retrospective cohort study.

Of the 50 studies reporting gender and age at time of surgery, 61% of patients were female and their average age was 37 years. Of the 25 studies that reported Hurley scores, 73% had Hurley stage 3 HS. Of the 38 studies reporting the number of procedures per anatomic region, the most commonly operated on regions were the axilla (59%) and the inguinal region (20%).

The researchers found that 22 studies of wide excision had the lowest pooled recurrence rate at 8%, while local excision had the highest pooled recurrence rate at 34%. Meanwhile, among studies of wide/radical excision, flap repair had a pooled recurrence rate of 0%, while delayed primary closure had the highest pooled recurrence rate at 38%.

“Extensive excisions of HS seem to portend a lower risk of postoperative recurrence, but there are many approaches available that may be more appropriate for certain patients,” Dr. Riddle said. “The influence of patient factors such as comorbidities and disease severity on surgical outcomes is unclear and is a potential area of future study.”

Dr. Sayed, an author of the 2019 North American guidelines for the clinical management of HS, pointed out that most studies in the review and meta-analysis included patients who had diabetes, were on biologics or other therapy, were actively smoking, or had other comorbidities that sometimes influence surgeons to delay surgical treatment because they consider it elective. “Most studies indicated minimal or no risk of significant complications relating to these factors, so they should ideally not become obstacles for patients interested in surgical care,” he said.

Dr. Riddle said that she was surprised by how relatively few studies had been published on more conservative surgical approaches such as skin tissue–sparing excision with electrosurgical peeling, deroofing, local excision, and CO₂ laser–based evaporation.

The researchers acknowledged certain limitations of their work, including the high risk of bias for most included studies. “Almost all studies were retrospective with substantial methodological limitations, and there were no head-to-head comparisons of different surgical approaches,” Dr. Riddle said. “Patient comorbidities and postoperative complications were variably reported.”

Dr. Sayed disclosed that he is a speaker for AbbVie and Novartis; an investigator for AbbVie, Novartis, InflaRx, and UCB; and on the advisory board of AbbVie and InflaRx. The remaining authors reported having no financial disclosures.

[email protected]

Patients with suspected large-vessel occlusion stroke who were taken directly to the angiography suite, bypassing the emergency department, received endovascular treatment faster and had better 90-day functional outcomes in a new study.

Results of the ANGIO-CAT trial were presented at the International Stroke Conference sponsored by the American Heart Association.

The study involved patients suspected of having a large-vessel occlusion, as assessed in the prehospital setting by paramedics using the Rapid Arterial Occlusion Evaluation (RACE) score.

In his presentation, Manuel Requena, PhD, a neurologist and neurointerventionalist fellow at Vall d’Hebron Hospital, Barcelona, explained that, if patients were within 6 hours of symptom onset with a RACE scale score greater than 4, paramedics called ahead to a stroke neurologist, who met the patient directly at the hospital.

If on clinical examination the National Institutes of Health Stroke Scale (NIHSS) score was greater than 10, patients could be enrolled into the study. Upon enrollment, they were randomly assigned either to be taken directly to the angiography suite or to receive standard care.
 

Bypassing the emergency department

Dr. Requena noted that, at his center, patients who receive standard care are transferred to the CT imaging suite, where they are evaluated with noncontrast CT and CT angiography. CT perfusion is also performed if the treating physician deems it necessary.

If a large-vessel occlusion is confirmed, patients are then transferred to the angiography suite for endovascular treatment. He added that in many centers, patients are evaluated in the ED before undergoing CT scanning.

Patients in the direct angiography group received a “flat-panel” noncontrast CT in the angiography suite to rule out intracranial hemorrhage or a large, established infarct. The large-vessel occlusion would be confirmed by arteriography before the endovascular procedure was performed.

After CT scanning, patients received thrombolysis as recommended in the guidelines.

The current interim analysis includes the 174 patients who have been enrolled so far in the study. The median RACE score for these patients was 7, and the median NIHSS score was 17. Large-vessel occlusion was confirmed in 84% of patients, and 8% had an intracerebral hemorrhage.

Results showed that of the 147 patients who received endovascular therapy, puncture time was shorter for those who were taken directly to angiography (median, 18 min vs. 42 min), as was time to reperfusion (median, 57 min vs. 84 min).

The primary outcome was a shift analysis of the Modified Rankin Scale functional outcome scale at 90 days (odds of 1-point improvement or more). In the direct angiography group, the adjusted odds ratio for an improved functional outcome was 2.2 (95% confidence interval, 1.2-.1).

There were no significant differences in safety endpoints. There was a trend toward more procedural complications in those receiving endovascular therapy in the direct angiography group (8.1% vs. 2.7%; P = .6), but there was also a trend toward lower 90-day mortality in this group (20.2% vs. 32.9%; P = .07)

Dr. Requena reported no significant difference in safety outcomes among those with a hemorrhagic stroke.

“Our study is the first clinical trial that shows the superiority of direct transfer to an angiography suite,” said Dr. Requena. “Our findings were close to what we expected, and we were surprised that they occurred so early in the study. We trust that they will be confirmed in ongoing, multicenter, international trials.”

Stroke patients who were transferred directly to an angiography suite were also less likely to be dependent on assistance with daily activities than were those who received the current standard of care, Dr. Requena said. “More frequent and more rapid treatment can help improve outcomes for our stroke patients.”

A limitation of this study is that the hospital had extensive experience with immediate angiography, so findings may differ at hospitals or care centers with less angiography expertise or experience, Dr. Requena said.

He added that retrospective studies conducted in hospitals in the United States, Germany, and Switzerland show that this kind of protocol can be developed in any high-volume stroke center, although multicenter, international trials are needed.
 

The cost of speed

Commenting on the ANGIO-CAT study, Michael Hill, MD, a professor at the University of Calgary (Alta.), said the 27-minute improvement in door-to-reperfusion time achieved in the study was meaningful and correlates with the degree of improved outcomes observed. “So, the improvement in speed of treatment resulting in better outcomes makes sense,” he added.

He cautioned that this strategy would only be feasible in certain centers with selected patients and that cost will be a fundamental issue.

“If you identify patients at angiography, you risk having some patients with no target large-vessel occlusion,” Dr. Hill added. “The real question is, how many of these patients without a large-vessel occlusion can the system tolerate before it becomes uneconomical and not fruitful or harmful, given that groin puncture is not totally harmless?”

The moderator of the ISC news conference on the study, Mitchell Elkind, MD, professor of neurology at Columbia University, New York, who is also president of the American Stroke Association, said the study reflects the growing recognition of the importance of speed when treating stroke. “If we can shorten time to treatment using rapid evaluation and imaging protocols, this will help save brain,” he said.

Also commenting on the study, Louisa McCullough, MD, PhD, chief of neurology at Memorial Hermann Hospital–Texas Medical Center, Houston, who is the ISC meeting chair, said she thought the study would be relevant to the United States. “Speed is really of the essence. Whenever we can reduce delays, that will make a big difference to patients.”

Referring to this study on improving hospital systems, as well as a second study that was presented at the meeting that showed benefits from delivery of prehospital thrombolysis via a mobile stroke unit, Dr. McCullough added that “we need to set up models so we can get the best of both these worlds. These studies are really leading the way on how we can change the stroke systems of care.”

The study was funded by Vall d’Hebron Research Institute. Dr. Requena disclosed no relevant financial relationships.

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

Patients with suspected large-vessel occlusion stroke who were taken directly to the angiography suite, bypassing the emergency department, received endovascular treatment faster and had better 90-day functional outcomes in a new study.

Results of the ANGIO-CAT trial were presented at the International Stroke Conference sponsored by the American Heart Association.

The study involved patients suspected of having a large-vessel occlusion, as assessed in the prehospital setting by paramedics using the Rapid Arterial Occlusion Evaluation (RACE) score.

In his presentation, Manuel Requena, PhD, a neurologist and neurointerventionalist fellow at Vall d’Hebron Hospital, Barcelona, explained that, if patients were within 6 hours of symptom onset with a RACE scale score greater than 4, paramedics called ahead to a stroke neurologist, who met the patient directly at the hospital.

If on clinical examination the National Institutes of Health Stroke Scale (NIHSS) score was greater than 10, patients could be enrolled into the study. Upon enrollment, they were randomly assigned either to be taken directly to the angiography suite or to receive standard care.
 

Bypassing the emergency department

Dr. Requena noted that, at his center, patients who receive standard care are transferred to the CT imaging suite, where they are evaluated with noncontrast CT and CT angiography. CT perfusion is also performed if the treating physician deems it necessary.

If a large-vessel occlusion is confirmed, patients are then transferred to the angiography suite for endovascular treatment. He added that in many centers, patients are evaluated in the ED before undergoing CT scanning.

Patients in the direct angiography group received a “flat-panel” noncontrast CT in the angiography suite to rule out intracranial hemorrhage or a large, established infarct. The large-vessel occlusion would be confirmed by arteriography before the endovascular procedure was performed.

After CT scanning, patients received thrombolysis as recommended in the guidelines.

The current interim analysis includes the 174 patients who have been enrolled so far in the study. The median RACE score for these patients was 7, and the median NIHSS score was 17. Large-vessel occlusion was confirmed in 84% of patients, and 8% had an intracerebral hemorrhage.

Results showed that of the 147 patients who received endovascular therapy, puncture time was shorter for those who were taken directly to angiography (median, 18 min vs. 42 min), as was time to reperfusion (median, 57 min vs. 84 min).

The primary outcome was a shift analysis of the Modified Rankin Scale functional outcome scale at 90 days (odds of 1-point improvement or more). In the direct angiography group, the adjusted odds ratio for an improved functional outcome was 2.2 (95% confidence interval, 1.2-.1).

There were no significant differences in safety endpoints. There was a trend toward more procedural complications in those receiving endovascular therapy in the direct angiography group (8.1% vs. 2.7%; P = .6), but there was also a trend toward lower 90-day mortality in this group (20.2% vs. 32.9%; P = .07)

Dr. Requena reported no significant difference in safety outcomes among those with a hemorrhagic stroke.

“Our study is the first clinical trial that shows the superiority of direct transfer to an angiography suite,” said Dr. Requena. “Our findings were close to what we expected, and we were surprised that they occurred so early in the study. We trust that they will be confirmed in ongoing, multicenter, international trials.”

Stroke patients who were transferred directly to an angiography suite were also less likely to be dependent on assistance with daily activities than were those who received the current standard of care, Dr. Requena said. “More frequent and more rapid treatment can help improve outcomes for our stroke patients.”

A limitation of this study is that the hospital had extensive experience with immediate angiography, so findings may differ at hospitals or care centers with less angiography expertise or experience, Dr. Requena said.

He added that retrospective studies conducted in hospitals in the United States, Germany, and Switzerland show that this kind of protocol can be developed in any high-volume stroke center, although multicenter, international trials are needed.
 

The cost of speed

Commenting on the ANGIO-CAT study, Michael Hill, MD, a professor at the University of Calgary (Alta.), said the 27-minute improvement in door-to-reperfusion time achieved in the study was meaningful and correlates with the degree of improved outcomes observed. “So, the improvement in speed of treatment resulting in better outcomes makes sense,” he added.

He cautioned that this strategy would only be feasible in certain centers with selected patients and that cost will be a fundamental issue.

“If you identify patients at angiography, you risk having some patients with no target large-vessel occlusion,” Dr. Hill added. “The real question is, how many of these patients without a large-vessel occlusion can the system tolerate before it becomes uneconomical and not fruitful or harmful, given that groin puncture is not totally harmless?”

The moderator of the ISC news conference on the study, Mitchell Elkind, MD, professor of neurology at Columbia University, New York, who is also president of the American Stroke Association, said the study reflects the growing recognition of the importance of speed when treating stroke. “If we can shorten time to treatment using rapid evaluation and imaging protocols, this will help save brain,” he said.

Also commenting on the study, Louisa McCullough, MD, PhD, chief of neurology at Memorial Hermann Hospital–Texas Medical Center, Houston, who is the ISC meeting chair, said she thought the study would be relevant to the United States. “Speed is really of the essence. Whenever we can reduce delays, that will make a big difference to patients.”

Referring to this study on improving hospital systems, as well as a second study that was presented at the meeting that showed benefits from delivery of prehospital thrombolysis via a mobile stroke unit, Dr. McCullough added that “we need to set up models so we can get the best of both these worlds. These studies are really leading the way on how we can change the stroke systems of care.”

The study was funded by Vall d’Hebron Research Institute. Dr. Requena disclosed no relevant financial relationships.

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

Patients with suspected large-vessel occlusion stroke who were taken directly to the angiography suite, bypassing the emergency department, received endovascular treatment faster and had better 90-day functional outcomes in a new study.

Results of the ANGIO-CAT trial were presented at the International Stroke Conference sponsored by the American Heart Association.

The study involved patients suspected of having a large-vessel occlusion, as assessed in the prehospital setting by paramedics using the Rapid Arterial Occlusion Evaluation (RACE) score.

In his presentation, Manuel Requena, PhD, a neurologist and neurointerventionalist fellow at Vall d’Hebron Hospital, Barcelona, explained that, if patients were within 6 hours of symptom onset with a RACE scale score greater than 4, paramedics called ahead to a stroke neurologist, who met the patient directly at the hospital.

If on clinical examination the National Institutes of Health Stroke Scale (NIHSS) score was greater than 10, patients could be enrolled into the study. Upon enrollment, they were randomly assigned either to be taken directly to the angiography suite or to receive standard care.
 

Bypassing the emergency department

Dr. Requena noted that, at his center, patients who receive standard care are transferred to the CT imaging suite, where they are evaluated with noncontrast CT and CT angiography. CT perfusion is also performed if the treating physician deems it necessary.

If a large-vessel occlusion is confirmed, patients are then transferred to the angiography suite for endovascular treatment. He added that in many centers, patients are evaluated in the ED before undergoing CT scanning.

Patients in the direct angiography group received a “flat-panel” noncontrast CT in the angiography suite to rule out intracranial hemorrhage or a large, established infarct. The large-vessel occlusion would be confirmed by arteriography before the endovascular procedure was performed.

After CT scanning, patients received thrombolysis as recommended in the guidelines.

The current interim analysis includes the 174 patients who have been enrolled so far in the study. The median RACE score for these patients was 7, and the median NIHSS score was 17. Large-vessel occlusion was confirmed in 84% of patients, and 8% had an intracerebral hemorrhage.

Results showed that of the 147 patients who received endovascular therapy, puncture time was shorter for those who were taken directly to angiography (median, 18 min vs. 42 min), as was time to reperfusion (median, 57 min vs. 84 min).

The primary outcome was a shift analysis of the Modified Rankin Scale functional outcome scale at 90 days (odds of 1-point improvement or more). In the direct angiography group, the adjusted odds ratio for an improved functional outcome was 2.2 (95% confidence interval, 1.2-.1).

There were no significant differences in safety endpoints. There was a trend toward more procedural complications in those receiving endovascular therapy in the direct angiography group (8.1% vs. 2.7%; P = .6), but there was also a trend toward lower 90-day mortality in this group (20.2% vs. 32.9%; P = .07)

Dr. Requena reported no significant difference in safety outcomes among those with a hemorrhagic stroke.

“Our study is the first clinical trial that shows the superiority of direct transfer to an angiography suite,” said Dr. Requena. “Our findings were close to what we expected, and we were surprised that they occurred so early in the study. We trust that they will be confirmed in ongoing, multicenter, international trials.”

Stroke patients who were transferred directly to an angiography suite were also less likely to be dependent on assistance with daily activities than were those who received the current standard of care, Dr. Requena said. “More frequent and more rapid treatment can help improve outcomes for our stroke patients.”

A limitation of this study is that the hospital had extensive experience with immediate angiography, so findings may differ at hospitals or care centers with less angiography expertise or experience, Dr. Requena said.

He added that retrospective studies conducted in hospitals in the United States, Germany, and Switzerland show that this kind of protocol can be developed in any high-volume stroke center, although multicenter, international trials are needed.
 

The cost of speed

Commenting on the ANGIO-CAT study, Michael Hill, MD, a professor at the University of Calgary (Alta.), said the 27-minute improvement in door-to-reperfusion time achieved in the study was meaningful and correlates with the degree of improved outcomes observed. “So, the improvement in speed of treatment resulting in better outcomes makes sense,” he added.

He cautioned that this strategy would only be feasible in certain centers with selected patients and that cost will be a fundamental issue.

“If you identify patients at angiography, you risk having some patients with no target large-vessel occlusion,” Dr. Hill added. “The real question is, how many of these patients without a large-vessel occlusion can the system tolerate before it becomes uneconomical and not fruitful or harmful, given that groin puncture is not totally harmless?”

The moderator of the ISC news conference on the study, Mitchell Elkind, MD, professor of neurology at Columbia University, New York, who is also president of the American Stroke Association, said the study reflects the growing recognition of the importance of speed when treating stroke. “If we can shorten time to treatment using rapid evaluation and imaging protocols, this will help save brain,” he said.

Also commenting on the study, Louisa McCullough, MD, PhD, chief of neurology at Memorial Hermann Hospital–Texas Medical Center, Houston, who is the ISC meeting chair, said she thought the study would be relevant to the United States. “Speed is really of the essence. Whenever we can reduce delays, that will make a big difference to patients.”

Referring to this study on improving hospital systems, as well as a second study that was presented at the meeting that showed benefits from delivery of prehospital thrombolysis via a mobile stroke unit, Dr. McCullough added that “we need to set up models so we can get the best of both these worlds. These studies are really leading the way on how we can change the stroke systems of care.”

The study was funded by Vall d’Hebron Research Institute. Dr. Requena disclosed no relevant financial relationships.

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

ACE inhibitors may be associated with an increased risk for schizophrenia and may affect psychiatric symptoms, new research suggests.

Investigators found individuals who carry a genetic variant associated with lower levels of the ACE gene and protein have increased liability to schizophrenia, suggesting that drugs that lower ACE levels or activity may do the same.

“Our findings warrant further investigation into the role of ACE in schizophrenia and closer monitoring by clinicians of individuals, especially those with schizophrenia, who may be on medication that lower ACE activity, such as ACE inhibitors,” Sonia Shah, PhD, Institute for Biomedical Sciences, University of Queensland, Brisbane, Australia, said in an interview.

The study was published online March 10, 2021, in JAMA Psychiatry.
 

Antihypertensives and mental illness

Hypertension is common in patients with psychiatric disorders and observational studies have reported associations between antihypertensive medication and these disorders, although the findings have been mixed.

Dr. Shah and colleagues estimated the potential of different antihypertensive drug classes on schizophrenia, bipolar disorder, and major depressive disorder.

In a two-sample Mendelian randomization study, they evaluated ties between a single-nucleotide variant and drug-target gene expression derived from expression quantitative trait loci data in blood (sample 1) and the SNV disease association from published case-control, genomewide association studies (sample 2).

The analyses included 40,675 patients with schizophrenia and 64,643 controls; 20,352 with bipolar disorder and 31,358 controls; and 135,458 with major depressive disorder and 344,901 controls.

The major finding was that a one standard deviation–lower expression of the ACE gene in blood was associated with lower systolic blood pressure of 4.0 mm Hg (95% confidence interval, 2.7-5.3), but also an increased risk of schizophrenia (odds ratio, 1.75; 95% CI, 1.28-2.38).
 

Could ACE inhibitors worsen symptoms or trigger episodes?

In their article, the researchers noted that, in most patients, onset of schizophrenia occurs in late adolescence or early adult life, ruling out ACE inhibitor treatment as a potential causal factor for most cases.

“However, if lower ACE levels play a causal role for schizophrenia risk, it would be reasonable to hypothesize that further lowering of ACE activity in existing patients could worsen symptoms or trigger a new episode,” they wrote.

Dr. Shah emphasized that evidence from genetic analyses alone is “not sufficient to justify changes in prescription guidelines.”

“Patients should not stop taking these medications if they are effective at controlling their blood pressure and they don’t suffer any adverse effects. But it would be reasonable to encourage greater pharmacovigilance,” she said in an interview.

“One way in which we are hoping to follow up these findings,” said Dr. Shah, “is to access electronic health record data for millions of individuals to investigate if there is evidence of increased rates of psychotic episodes in individuals who use ACE inhibitors, compared to other classes of blood pressure–lowering medication.”
 

Caution warranted

Reached for comment, Timothy Sullivan, MD, chair of psychiatry and behavioral sciences at Staten Island University Hospital in New York, noted that this is an “extremely complicated” study and urged caution in interpreting the results.

“Since most people develop schizophrenia earlier in life, before they usually develop problems with blood pressure, it’s not so much that these drugs might cause schizophrenia,” Dr. Sullivan said.

“But because of their effects on this particular gene, there’s a possibility that they might worsen symptoms or in somebody with borderline risk might cause them to develop symptoms later in life. This may apply to a relatively small number of people who develop symptoms of schizophrenia in their 40s and beyond,” he added.

That’s where “pharmacovigilance” comes into play, Dr. Sullivan said. “In other words, we should be looking at people we’re treating with these drugs to see – might we be tipping some of them into illness states that they otherwise wouldn’t experience?”

Support for the study was provided by the National Health and Medical Research Council (Australia) and U.S. National Institute for Mental Health. Dr. Shah and Dr. Sullivan disclosed no relevant financial relationships.

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

ACE inhibitors may be associated with an increased risk for schizophrenia and may affect psychiatric symptoms, new research suggests.

Investigators found individuals who carry a genetic variant associated with lower levels of the ACE gene and protein have increased liability to schizophrenia, suggesting that drugs that lower ACE levels or activity may do the same.

“Our findings warrant further investigation into the role of ACE in schizophrenia and closer monitoring by clinicians of individuals, especially those with schizophrenia, who may be on medication that lower ACE activity, such as ACE inhibitors,” Sonia Shah, PhD, Institute for Biomedical Sciences, University of Queensland, Brisbane, Australia, said in an interview.

The study was published online March 10, 2021, in JAMA Psychiatry.
 

Antihypertensives and mental illness

Hypertension is common in patients with psychiatric disorders and observational studies have reported associations between antihypertensive medication and these disorders, although the findings have been mixed.

Dr. Shah and colleagues estimated the potential of different antihypertensive drug classes on schizophrenia, bipolar disorder, and major depressive disorder.

In a two-sample Mendelian randomization study, they evaluated ties between a single-nucleotide variant and drug-target gene expression derived from expression quantitative trait loci data in blood (sample 1) and the SNV disease association from published case-control, genomewide association studies (sample 2).

The analyses included 40,675 patients with schizophrenia and 64,643 controls; 20,352 with bipolar disorder and 31,358 controls; and 135,458 with major depressive disorder and 344,901 controls.

The major finding was that a one standard deviation–lower expression of the ACE gene in blood was associated with lower systolic blood pressure of 4.0 mm Hg (95% confidence interval, 2.7-5.3), but also an increased risk of schizophrenia (odds ratio, 1.75; 95% CI, 1.28-2.38).
 

Could ACE inhibitors worsen symptoms or trigger episodes?

In their article, the researchers noted that, in most patients, onset of schizophrenia occurs in late adolescence or early adult life, ruling out ACE inhibitor treatment as a potential causal factor for most cases.

“However, if lower ACE levels play a causal role for schizophrenia risk, it would be reasonable to hypothesize that further lowering of ACE activity in existing patients could worsen symptoms or trigger a new episode,” they wrote.

Dr. Shah emphasized that evidence from genetic analyses alone is “not sufficient to justify changes in prescription guidelines.”

“Patients should not stop taking these medications if they are effective at controlling their blood pressure and they don’t suffer any adverse effects. But it would be reasonable to encourage greater pharmacovigilance,” she said in an interview.

“One way in which we are hoping to follow up these findings,” said Dr. Shah, “is to access electronic health record data for millions of individuals to investigate if there is evidence of increased rates of psychotic episodes in individuals who use ACE inhibitors, compared to other classes of blood pressure–lowering medication.”
 

Caution warranted

Reached for comment, Timothy Sullivan, MD, chair of psychiatry and behavioral sciences at Staten Island University Hospital in New York, noted that this is an “extremely complicated” study and urged caution in interpreting the results.

“Since most people develop schizophrenia earlier in life, before they usually develop problems with blood pressure, it’s not so much that these drugs might cause schizophrenia,” Dr. Sullivan said.

“But because of their effects on this particular gene, there’s a possibility that they might worsen symptoms or in somebody with borderline risk might cause them to develop symptoms later in life. This may apply to a relatively small number of people who develop symptoms of schizophrenia in their 40s and beyond,” he added.

That’s where “pharmacovigilance” comes into play, Dr. Sullivan said. “In other words, we should be looking at people we’re treating with these drugs to see – might we be tipping some of them into illness states that they otherwise wouldn’t experience?”

Support for the study was provided by the National Health and Medical Research Council (Australia) and U.S. National Institute for Mental Health. Dr. Shah and Dr. Sullivan disclosed no relevant financial relationships.

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

ACE inhibitors may be associated with an increased risk for schizophrenia and may affect psychiatric symptoms, new research suggests.

Investigators found individuals who carry a genetic variant associated with lower levels of the ACE gene and protein have increased liability to schizophrenia, suggesting that drugs that lower ACE levels or activity may do the same.

“Our findings warrant further investigation into the role of ACE in schizophrenia and closer monitoring by clinicians of individuals, especially those with schizophrenia, who may be on medication that lower ACE activity, such as ACE inhibitors,” Sonia Shah, PhD, Institute for Biomedical Sciences, University of Queensland, Brisbane, Australia, said in an interview.

The study was published online March 10, 2021, in JAMA Psychiatry.
 

Antihypertensives and mental illness

Hypertension is common in patients with psychiatric disorders and observational studies have reported associations between antihypertensive medication and these disorders, although the findings have been mixed.

Dr. Shah and colleagues estimated the potential of different antihypertensive drug classes on schizophrenia, bipolar disorder, and major depressive disorder.

In a two-sample Mendelian randomization study, they evaluated ties between a single-nucleotide variant and drug-target gene expression derived from expression quantitative trait loci data in blood (sample 1) and the SNV disease association from published case-control, genomewide association studies (sample 2).

The analyses included 40,675 patients with schizophrenia and 64,643 controls; 20,352 with bipolar disorder and 31,358 controls; and 135,458 with major depressive disorder and 344,901 controls.

The major finding was that a one standard deviation–lower expression of the ACE gene in blood was associated with lower systolic blood pressure of 4.0 mm Hg (95% confidence interval, 2.7-5.3), but also an increased risk of schizophrenia (odds ratio, 1.75; 95% CI, 1.28-2.38).
 

Could ACE inhibitors worsen symptoms or trigger episodes?

In their article, the researchers noted that, in most patients, onset of schizophrenia occurs in late adolescence or early adult life, ruling out ACE inhibitor treatment as a potential causal factor for most cases.

“However, if lower ACE levels play a causal role for schizophrenia risk, it would be reasonable to hypothesize that further lowering of ACE activity in existing patients could worsen symptoms or trigger a new episode,” they wrote.

Dr. Shah emphasized that evidence from genetic analyses alone is “not sufficient to justify changes in prescription guidelines.”

“Patients should not stop taking these medications if they are effective at controlling their blood pressure and they don’t suffer any adverse effects. But it would be reasonable to encourage greater pharmacovigilance,” she said in an interview.

“One way in which we are hoping to follow up these findings,” said Dr. Shah, “is to access electronic health record data for millions of individuals to investigate if there is evidence of increased rates of psychotic episodes in individuals who use ACE inhibitors, compared to other classes of blood pressure–lowering medication.”
 

Caution warranted

Reached for comment, Timothy Sullivan, MD, chair of psychiatry and behavioral sciences at Staten Island University Hospital in New York, noted that this is an “extremely complicated” study and urged caution in interpreting the results.

“Since most people develop schizophrenia earlier in life, before they usually develop problems with blood pressure, it’s not so much that these drugs might cause schizophrenia,” Dr. Sullivan said.

“But because of their effects on this particular gene, there’s a possibility that they might worsen symptoms or in somebody with borderline risk might cause them to develop symptoms later in life. This may apply to a relatively small number of people who develop symptoms of schizophrenia in their 40s and beyond,” he added.

That’s where “pharmacovigilance” comes into play, Dr. Sullivan said. “In other words, we should be looking at people we’re treating with these drugs to see – might we be tipping some of them into illness states that they otherwise wouldn’t experience?”

Support for the study was provided by the National Health and Medical Research Council (Australia) and U.S. National Institute for Mental Health. Dr. Shah and Dr. Sullivan disclosed no relevant financial relationships.

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

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

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

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

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

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

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

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

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

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

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

Risk of thrombosis addressed

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

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

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

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

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

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

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

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

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

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

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

‘Robust’ findings

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

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

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

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

Efficacy against variants?

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

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

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

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

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

This article was updated March 23, 2021.

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

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

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

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

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

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

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

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

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

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

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

Risk of thrombosis addressed

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

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

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

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

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

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

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

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

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

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

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

‘Robust’ findings

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

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

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

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

Efficacy against variants?

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

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

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

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

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

This article was updated March 23, 2021.

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

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

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

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

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

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

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

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

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

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

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

Risk of thrombosis addressed

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

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

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

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

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

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

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

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

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

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

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

‘Robust’ findings

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

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

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

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

Efficacy against variants?

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

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

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

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

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

This article was updated March 23, 2021.

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

To the Editor:

Hidradenitis suppurativa (HS) is a chronic inflammatory disease characterized by the development of painful abscesses, fistulous tracts, and scars. It most commonly affects the apocrine gland–bearing areas of the body such as the axillary, inguinal, and anogenital regions. With a prevalence of approximately 1%, HS can lead to notable morbidity.¹ The pathogenesis is thought to be due to occlusion of terminal hair follicles that subsequently stimulates release of proinflammatory cytokines from nearby keratinocytes. The mechanism of initial occlusion is not well understood but may be due to friction or trauma. An inflammatory mechanism of disease also has been hypothesized; however, the exact cytokine profile is not known. Treatment of HS consists of several different modalities, including oral retinoids, antibiotics, antiandrogenic therapy, and surgery.^1,2 Adalimumab is a well-known biologic that has been approved by the US Food and Drug Administration for the treatment of HS.

Adalimumab is a human monoclonal antibody against tumor necrosis factor (TNF) α and is thought to improve HS by several mechanisms. Inhibition of TNF-α and other proinflammatory cytokines found in inflammatory lesions and apocrine glands directly decreases the severity of lesion size and the frequency of recurrence.³ Adalimumab also is thought to downregulate expression of keratin 6 and prevent the hyperkeratinization seen in HS.⁴ Additionally, TNF-α inhibition decreases production of IL-1, which has been shown to cause hypercornification of follicles and perpetuate HS pathogenesis.⁵

Adalimumab is considered a safe medication with a low toxicity profile and rarely is associated with serious adverse effects. The most common adverse effects are injection-site reaction, headache, and rash. However, as with any immunosuppressant, there is an elevated incidence of opportunistic infections. Anti-TNF medications have been associated with an increased incidence of viral, bacterial, and fungal infections. We present a patient who developed Candida esophagitis 6 weeks after starting treatment with adalimumab for the treatment of HS. This case highlights the development of esophageal candidiasis as a notable adverse event.

A 41-year-old woman with a history of endometriosis, adenomyosis, polycystic ovary syndrome, interstitial cystitis, asthma, fibromyalgia, depression, and Hashimoto thyroiditis presented to our dermatology clinic with active draining lesions and sinus tracts in the perivaginal area that were consistent with HS, which initially was treated with doxycycline 100 mg twice daily. She experienced minimal improvement of the HS lesions at 2-month follow-up.

Due to disease severity, adalimumab was started. The patient received a loading dose of 4 injections totaling 160 mg and 80 mg on day 15, followed by a maintenance dose of 40 mg/0.4 mL weekly. The patient reported substantial improvement of pain, and complete resolution of active lesions was noted on physical examination after 4 weeks of treatment with adalimumab.

Six weeks after adalimumab was started, the patient developed severe dysphagia. She was evaluated by a gastroenterologist and underwent endoscopy (Figure), which led to a diagnosis of esophageal candidiasis. Adalimumab was discontinued immediately thereafter. The patient started treatment with nystatin oral rinse 4 times daily and oral fluconazole 200 mg daily. The candidiasis resolved within 2 weeks; however, she experienced recurrence of HS with draining lesions in the perivaginal area approximately 8 weeks after discontinuation of adalimumab. The patient requested to restart adalimumab treatment despite the recent history of esophagitis. Adalimumab 40 mg/0.4 mL weekly was restarted along with oral fluconazole 200 mg twice weekly and nystatin oral rinse 4 times daily. This regimen resulted in complete resolution of HS symptoms within 6 weeks with no recurrence of esophageal candidiasis during 6 months of follow-up.

Patients receiving adalimumab for dermatologic or other conditions should be closely monitored for opportunistic infections. Although immunomodulatory medications offer promising therapeutic benefits in patients with HS, larger studies regarding treatment with anti-TNF agents in HS are warranted to prevent complications from treatment and promote long-term efficacy and safety.

To the Editor:

Hidradenitis suppurativa (HS) is a chronic inflammatory disease characterized by the development of painful abscesses, fistulous tracts, and scars. It most commonly affects the apocrine gland–bearing areas of the body such as the axillary, inguinal, and anogenital regions. With a prevalence of approximately 1%, HS can lead to notable morbidity.¹ The pathogenesis is thought to be due to occlusion of terminal hair follicles that subsequently stimulates release of proinflammatory cytokines from nearby keratinocytes. The mechanism of initial occlusion is not well understood but may be due to friction or trauma. An inflammatory mechanism of disease also has been hypothesized; however, the exact cytokine profile is not known. Treatment of HS consists of several different modalities, including oral retinoids, antibiotics, antiandrogenic therapy, and surgery.^1,2 Adalimumab is a well-known biologic that has been approved by the US Food and Drug Administration for the treatment of HS.

Adalimumab is a human monoclonal antibody against tumor necrosis factor (TNF) α and is thought to improve HS by several mechanisms. Inhibition of TNF-α and other proinflammatory cytokines found in inflammatory lesions and apocrine glands directly decreases the severity of lesion size and the frequency of recurrence.³ Adalimumab also is thought to downregulate expression of keratin 6 and prevent the hyperkeratinization seen in HS.⁴ Additionally, TNF-α inhibition decreases production of IL-1, which has been shown to cause hypercornification of follicles and perpetuate HS pathogenesis.⁵

Adalimumab is considered a safe medication with a low toxicity profile and rarely is associated with serious adverse effects. The most common adverse effects are injection-site reaction, headache, and rash. However, as with any immunosuppressant, there is an elevated incidence of opportunistic infections. Anti-TNF medications have been associated with an increased incidence of viral, bacterial, and fungal infections. We present a patient who developed Candida esophagitis 6 weeks after starting treatment with adalimumab for the treatment of HS. This case highlights the development of esophageal candidiasis as a notable adverse event.

A 41-year-old woman with a history of endometriosis, adenomyosis, polycystic ovary syndrome, interstitial cystitis, asthma, fibromyalgia, depression, and Hashimoto thyroiditis presented to our dermatology clinic with active draining lesions and sinus tracts in the perivaginal area that were consistent with HS, which initially was treated with doxycycline 100 mg twice daily. She experienced minimal improvement of the HS lesions at 2-month follow-up.

Due to disease severity, adalimumab was started. The patient received a loading dose of 4 injections totaling 160 mg and 80 mg on day 15, followed by a maintenance dose of 40 mg/0.4 mL weekly. The patient reported substantial improvement of pain, and complete resolution of active lesions was noted on physical examination after 4 weeks of treatment with adalimumab.

Six weeks after adalimumab was started, the patient developed severe dysphagia. She was evaluated by a gastroenterologist and underwent endoscopy (Figure), which led to a diagnosis of esophageal candidiasis. Adalimumab was discontinued immediately thereafter. The patient started treatment with nystatin oral rinse 4 times daily and oral fluconazole 200 mg daily. The candidiasis resolved within 2 weeks; however, she experienced recurrence of HS with draining lesions in the perivaginal area approximately 8 weeks after discontinuation of adalimumab. The patient requested to restart adalimumab treatment despite the recent history of esophagitis. Adalimumab 40 mg/0.4 mL weekly was restarted along with oral fluconazole 200 mg twice weekly and nystatin oral rinse 4 times daily. This regimen resulted in complete resolution of HS symptoms within 6 weeks with no recurrence of esophageal candidiasis during 6 months of follow-up.

Patients receiving adalimumab for dermatologic or other conditions should be closely monitored for opportunistic infections. Although immunomodulatory medications offer promising therapeutic benefits in patients with HS, larger studies regarding treatment with anti-TNF agents in HS are warranted to prevent complications from treatment and promote long-term efficacy and safety.

To the Editor:

Hidradenitis suppurativa (HS) is a chronic inflammatory disease characterized by the development of painful abscesses, fistulous tracts, and scars. It most commonly affects the apocrine gland–bearing areas of the body such as the axillary, inguinal, and anogenital regions. With a prevalence of approximately 1%, HS can lead to notable morbidity.¹ The pathogenesis is thought to be due to occlusion of terminal hair follicles that subsequently stimulates release of proinflammatory cytokines from nearby keratinocytes. The mechanism of initial occlusion is not well understood but may be due to friction or trauma. An inflammatory mechanism of disease also has been hypothesized; however, the exact cytokine profile is not known. Treatment of HS consists of several different modalities, including oral retinoids, antibiotics, antiandrogenic therapy, and surgery.^1,2 Adalimumab is a well-known biologic that has been approved by the US Food and Drug Administration for the treatment of HS.

Adalimumab is a human monoclonal antibody against tumor necrosis factor (TNF) α and is thought to improve HS by several mechanisms. Inhibition of TNF-α and other proinflammatory cytokines found in inflammatory lesions and apocrine glands directly decreases the severity of lesion size and the frequency of recurrence.³ Adalimumab also is thought to downregulate expression of keratin 6 and prevent the hyperkeratinization seen in HS.⁴ Additionally, TNF-α inhibition decreases production of IL-1, which has been shown to cause hypercornification of follicles and perpetuate HS pathogenesis.⁵

Adalimumab is considered a safe medication with a low toxicity profile and rarely is associated with serious adverse effects. The most common adverse effects are injection-site reaction, headache, and rash. However, as with any immunosuppressant, there is an elevated incidence of opportunistic infections. Anti-TNF medications have been associated with an increased incidence of viral, bacterial, and fungal infections. We present a patient who developed Candida esophagitis 6 weeks after starting treatment with adalimumab for the treatment of HS. This case highlights the development of esophageal candidiasis as a notable adverse event.

A 41-year-old woman with a history of endometriosis, adenomyosis, polycystic ovary syndrome, interstitial cystitis, asthma, fibromyalgia, depression, and Hashimoto thyroiditis presented to our dermatology clinic with active draining lesions and sinus tracts in the perivaginal area that were consistent with HS, which initially was treated with doxycycline 100 mg twice daily. She experienced minimal improvement of the HS lesions at 2-month follow-up.

Due to disease severity, adalimumab was started. The patient received a loading dose of 4 injections totaling 160 mg and 80 mg on day 15, followed by a maintenance dose of 40 mg/0.4 mL weekly. The patient reported substantial improvement of pain, and complete resolution of active lesions was noted on physical examination after 4 weeks of treatment with adalimumab.

Six weeks after adalimumab was started, the patient developed severe dysphagia. She was evaluated by a gastroenterologist and underwent endoscopy (Figure), which led to a diagnosis of esophageal candidiasis. Adalimumab was discontinued immediately thereafter. The patient started treatment with nystatin oral rinse 4 times daily and oral fluconazole 200 mg daily. The candidiasis resolved within 2 weeks; however, she experienced recurrence of HS with draining lesions in the perivaginal area approximately 8 weeks after discontinuation of adalimumab. The patient requested to restart adalimumab treatment despite the recent history of esophagitis. Adalimumab 40 mg/0.4 mL weekly was restarted along with oral fluconazole 200 mg twice weekly and nystatin oral rinse 4 times daily. This regimen resulted in complete resolution of HS symptoms within 6 weeks with no recurrence of esophageal candidiasis during 6 months of follow-up.

Patients receiving adalimumab for dermatologic or other conditions should be closely monitored for opportunistic infections. Although immunomodulatory medications offer promising therapeutic benefits in patients with HS, larger studies regarding treatment with anti-TNF agents in HS are warranted to prevent complications from treatment and promote long-term efficacy and safety.

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

juststock/Thinkstock

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

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

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

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

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

32% of patients taking meds that could interfere with tests

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

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

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

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

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

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

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

Nature of interference possibilities varies

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

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

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

Recommendations to counter interference

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

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

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

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

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

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

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

juststock/Thinkstock

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

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

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

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

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

32% of patients taking meds that could interfere with tests

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

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

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

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

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

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

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

Nature of interference possibilities varies

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

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

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

Recommendations to counter interference

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

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

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

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

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

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

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

juststock/Thinkstock

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

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

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

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

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

32% of patients taking meds that could interfere with tests

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

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

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

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

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

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

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

Nature of interference possibilities varies

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

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

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

Recommendations to counter interference

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

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

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

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

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

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

A noninvasive imaging method for identifying whether the source of a patient’s primary aldosteronism is from unilateral or bilateral adrenal adenomas worked as well as the standard method, invasive adrenal vein sampling, in a head-to-head comparison with 143 patients.

‘This is a first step.’

“This study is a first step. It will take lots more data for endocrinologists to buy into a scan over AVS,” commented David A. D’Alessio, MD, professor and chief of the division of endocrinology and metabolism at Duke University in Durham, N.C.

But Dr. D’Alessio also acknowledged the clear benefits from a safe and effective alternative to AVS.

“A reliable, less invasive, and less technical means of lateralizing excess aldosterone production would increase the number of people [with a unilateral PA source] going to surgery. The reality is that, if you are not a patient at the Mayo Clinic . . .or the National Institutes of Health, then AVS is a bit of crap shoot” that is very operator and institution dependent for its accuracy, Dr. D’Alessio said in an interview.

Metomidate specifically binds to key enzymes of the adrenal corticosteroid biosynthetic pathway, making it a precise targeting agent for a radioactive tag as documented almost a decade ago. One limitation is that this radiotracer labeling of metomidate has a 20-minute half life, which means it must be produced on site, thereby making the technology out of reach for locations that can’t set up this capability.

MATCHing imaging against AVS

To test the clinical utility of metomidate-based PET-CT directly against AVS, Dr. Wu and her associates enrolled 143 adults with confirmed PA and hypertension at two centers in London and one in Cambridge, England. The MATCH study cohort averaged 53 years of age; two-thirds were men, 58% were White, and 30% were Black. Their median blood pressure was 147/91 mm Hg, and they were maintained on a median of two antihypertensive drugs.

The researchers assessed every patient with both the imaging method and AVS, performed in random order and blindly scored. They then began each patient on a 1-month regimen with an MRA (usually spironolactone but eplerenone [Inspra] was also an option) to test the responsiveness of each patient’s hypertension to this drug class and to gauge their likely response to adrenalectomy. After the MRA test, the researchers assessed the lateralization tests and determined that 78 patients were appropriate candidates for unilateral adrenalectomy while the remaining 65 patients were not and continued on the MRA regimen. They recommended surgery if patients were clear positives by AVS, by PET-CT imaging, or both.

The study had four primary outcomes to assess the ability of the two diagnostic methods to predict the success of surgery based on four increasingly stringent postsurgical criteria calculated in hierarchical sequence: Partial or complete biochemical success, complete biochemical success, partial or complete clinical success (partial meaning any significant reduction in blood pressure), or complete clinical success (systolic pressure reduced to less than 135 mm Hg). Only one of the 78 patients treated with surgery failed to achieve at least a partial biochemical response.

SciePro/Shutterstock

Woefully low rates of PA assessment

But regardless of the success that PET-CT imaging has for identifying surgical candidates, the first step is to identify patients with PA, a diagnosis that’s woefully underperformed worldwide. One example: A separate report at ENDO 2021 retrospectively reviewed nearly 12,000 patients with hypertension and an indication of PA, such as treatment-resistant hypertension or early-onset hypertension, and managed at either of two university outpatient clinics in Michigan during 2010-2019. The report documented that 3% underwent PA assessment.

Diagnosis of patients with PA “is a major problem,” noted Dr. D’Alessio. “I think of PA as an underdiagnosed and undertreated condition, with a huge impact on morbidity and mortality. Any advance in this area is likely to be useful.” But, he added, “I’m dubious whether this [new imaging approach] will increase diagnosis of PA.” What’s needed is “getting more primary care physicians to do more screening” for PA among their patients with hypertension and a suggestion of a PA cause.

“Surgical cures are glamorous, but medical management is also very effective, and we have good, inexpensive drugs to do this,” the MRAs, Dr. D’Alessio said.

The study received no commercial funding. Dr. Wu and her coauthors had no disclosures. Dr. D’Alessio has been a speaker on behalf of Novo Nordisk, a consultant to Intarcia and Lilly, and has received research funding from Lilly and Merck.
 

[email protected]

A noninvasive imaging method for identifying whether the source of a patient’s primary aldosteronism is from unilateral or bilateral adrenal adenomas worked as well as the standard method, invasive adrenal vein sampling, in a head-to-head comparison with 143 patients.

‘This is a first step.’

“This study is a first step. It will take lots more data for endocrinologists to buy into a scan over AVS,” commented David A. D’Alessio, MD, professor and chief of the division of endocrinology and metabolism at Duke University in Durham, N.C.

But Dr. D’Alessio also acknowledged the clear benefits from a safe and effective alternative to AVS.

“A reliable, less invasive, and less technical means of lateralizing excess aldosterone production would increase the number of people [with a unilateral PA source] going to surgery. The reality is that, if you are not a patient at the Mayo Clinic . . .or the National Institutes of Health, then AVS is a bit of crap shoot” that is very operator and institution dependent for its accuracy, Dr. D’Alessio said in an interview.

Metomidate specifically binds to key enzymes of the adrenal corticosteroid biosynthetic pathway, making it a precise targeting agent for a radioactive tag as documented almost a decade ago. One limitation is that this radiotracer labeling of metomidate has a 20-minute half life, which means it must be produced on site, thereby making the technology out of reach for locations that can’t set up this capability.

MATCHing imaging against AVS

To test the clinical utility of metomidate-based PET-CT directly against AVS, Dr. Wu and her associates enrolled 143 adults with confirmed PA and hypertension at two centers in London and one in Cambridge, England. The MATCH study cohort averaged 53 years of age; two-thirds were men, 58% were White, and 30% were Black. Their median blood pressure was 147/91 mm Hg, and they were maintained on a median of two antihypertensive drugs.

The researchers assessed every patient with both the imaging method and AVS, performed in random order and blindly scored. They then began each patient on a 1-month regimen with an MRA (usually spironolactone but eplerenone [Inspra] was also an option) to test the responsiveness of each patient’s hypertension to this drug class and to gauge their likely response to adrenalectomy. After the MRA test, the researchers assessed the lateralization tests and determined that 78 patients were appropriate candidates for unilateral adrenalectomy while the remaining 65 patients were not and continued on the MRA regimen. They recommended surgery if patients were clear positives by AVS, by PET-CT imaging, or both.

The study had four primary outcomes to assess the ability of the two diagnostic methods to predict the success of surgery based on four increasingly stringent postsurgical criteria calculated in hierarchical sequence: Partial or complete biochemical success, complete biochemical success, partial or complete clinical success (partial meaning any significant reduction in blood pressure), or complete clinical success (systolic pressure reduced to less than 135 mm Hg). Only one of the 78 patients treated with surgery failed to achieve at least a partial biochemical response.

SciePro/Shutterstock

Woefully low rates of PA assessment

But regardless of the success that PET-CT imaging has for identifying surgical candidates, the first step is to identify patients with PA, a diagnosis that’s woefully underperformed worldwide. One example: A separate report at ENDO 2021 retrospectively reviewed nearly 12,000 patients with hypertension and an indication of PA, such as treatment-resistant hypertension or early-onset hypertension, and managed at either of two university outpatient clinics in Michigan during 2010-2019. The report documented that 3% underwent PA assessment.

Diagnosis of patients with PA “is a major problem,” noted Dr. D’Alessio. “I think of PA as an underdiagnosed and undertreated condition, with a huge impact on morbidity and mortality. Any advance in this area is likely to be useful.” But, he added, “I’m dubious whether this [new imaging approach] will increase diagnosis of PA.” What’s needed is “getting more primary care physicians to do more screening” for PA among their patients with hypertension and a suggestion of a PA cause.

“Surgical cures are glamorous, but medical management is also very effective, and we have good, inexpensive drugs to do this,” the MRAs, Dr. D’Alessio said.

The study received no commercial funding. Dr. Wu and her coauthors had no disclosures. Dr. D’Alessio has been a speaker on behalf of Novo Nordisk, a consultant to Intarcia and Lilly, and has received research funding from Lilly and Merck.
 

[email protected]

A noninvasive imaging method for identifying whether the source of a patient’s primary aldosteronism is from unilateral or bilateral adrenal adenomas worked as well as the standard method, invasive adrenal vein sampling, in a head-to-head comparison with 143 patients.

‘This is a first step.’

“This study is a first step. It will take lots more data for endocrinologists to buy into a scan over AVS,” commented David A. D’Alessio, MD, professor and chief of the division of endocrinology and metabolism at Duke University in Durham, N.C.

But Dr. D’Alessio also acknowledged the clear benefits from a safe and effective alternative to AVS.

“A reliable, less invasive, and less technical means of lateralizing excess aldosterone production would increase the number of people [with a unilateral PA source] going to surgery. The reality is that, if you are not a patient at the Mayo Clinic . . .or the National Institutes of Health, then AVS is a bit of crap shoot” that is very operator and institution dependent for its accuracy, Dr. D’Alessio said in an interview.

Metomidate specifically binds to key enzymes of the adrenal corticosteroid biosynthetic pathway, making it a precise targeting agent for a radioactive tag as documented almost a decade ago. One limitation is that this radiotracer labeling of metomidate has a 20-minute half life, which means it must be produced on site, thereby making the technology out of reach for locations that can’t set up this capability.

MATCHing imaging against AVS

To test the clinical utility of metomidate-based PET-CT directly against AVS, Dr. Wu and her associates enrolled 143 adults with confirmed PA and hypertension at two centers in London and one in Cambridge, England. The MATCH study cohort averaged 53 years of age; two-thirds were men, 58% were White, and 30% were Black. Their median blood pressure was 147/91 mm Hg, and they were maintained on a median of two antihypertensive drugs.

The researchers assessed every patient with both the imaging method and AVS, performed in random order and blindly scored. They then began each patient on a 1-month regimen with an MRA (usually spironolactone but eplerenone [Inspra] was also an option) to test the responsiveness of each patient’s hypertension to this drug class and to gauge their likely response to adrenalectomy. After the MRA test, the researchers assessed the lateralization tests and determined that 78 patients were appropriate candidates for unilateral adrenalectomy while the remaining 65 patients were not and continued on the MRA regimen. They recommended surgery if patients were clear positives by AVS, by PET-CT imaging, or both.

The study had four primary outcomes to assess the ability of the two diagnostic methods to predict the success of surgery based on four increasingly stringent postsurgical criteria calculated in hierarchical sequence: Partial or complete biochemical success, complete biochemical success, partial or complete clinical success (partial meaning any significant reduction in blood pressure), or complete clinical success (systolic pressure reduced to less than 135 mm Hg). Only one of the 78 patients treated with surgery failed to achieve at least a partial biochemical response.

SciePro/Shutterstock

Woefully low rates of PA assessment

But regardless of the success that PET-CT imaging has for identifying surgical candidates, the first step is to identify patients with PA, a diagnosis that’s woefully underperformed worldwide. One example: A separate report at ENDO 2021 retrospectively reviewed nearly 12,000 patients with hypertension and an indication of PA, such as treatment-resistant hypertension or early-onset hypertension, and managed at either of two university outpatient clinics in Michigan during 2010-2019. The report documented that 3% underwent PA assessment.

Diagnosis of patients with PA “is a major problem,” noted Dr. D’Alessio. “I think of PA as an underdiagnosed and undertreated condition, with a huge impact on morbidity and mortality. Any advance in this area is likely to be useful.” But, he added, “I’m dubious whether this [new imaging approach] will increase diagnosis of PA.” What’s needed is “getting more primary care physicians to do more screening” for PA among their patients with hypertension and a suggestion of a PA cause.

“Surgical cures are glamorous, but medical management is also very effective, and we have good, inexpensive drugs to do this,” the MRAs, Dr. D’Alessio said.

The study received no commercial funding. Dr. Wu and her coauthors had no disclosures. Dr. D’Alessio has been a speaker on behalf of Novo Nordisk, a consultant to Intarcia and Lilly, and has received research funding from Lilly and Merck.
 

[email protected]

There may be a dose-related risk for atrial fibrillation (AFib) with omega-3 fatty acid intake, data from four randomized clinical trials suggest.

The latest trial to evaluate the association, the VITAL-RHYTHM study, showed that using a low dose of omega-3 fatty acids or a vitamin D supplement had no significant effect on the risks of developing incident AFib.

The trial, first reported at last year’s American Heart Association meeting, was  published online March 16 in the Journal of the American Medical Association.

Together with three other randomized clinical trials, however, these results suggest a possible dose-related effect of omega-3 fatty acids on the risk for AFib, an accompanying “Editor’s Note” suggests.

The note, by JAMA deputy editor Gregory Curfman, MD, points out that in the past 2 years, four randomized clinical trials have provided data on the risk of AFib with omega-3 fatty acid intake.

In the STRENGTH and REDUCE-IT trials, both of which evaluated high doses (4 g/day) of omega-3 fatty acids in patients with heart disease (or at high risk for it), there was a highly statistically significant increase in risk for AFib in the omega-3 groups vs. controls in both trials.

In the OMEMI trial in elderly patients with a recent myocardial infarction, an intermediate dose (1.8 g/day) of omega-3 fatty acids also showed an increase in AFib risk (hazard ratio, 1.84) but this was not significant. And now, the VITAL-RHYTHM trial shows no significant effect of a low dose (840 mg/day) of omega-3 fatty acids on the risk of developing AFib in a primary prevention population.

“Patients who choose to take omega-3 fatty acids, especially in high doses, should be informed of the risk of AF [AFib] and followed up for the possible development of this common and potentially hazardous arrhythmia,” Dr. Curfman concludes.

The authors of the VITAL-RHYTHM trial, led by Christine M. Albert, MD, MPH, Cedars-Sinai Medical Center, Los Angeles, Calif., explain that the trial was conducted after observational studies had shown that individuals with low blood levels of omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and vitamin D₃ have higher risks of incident AFib, but data on dietary or supplemental intake of these nutrients on AFib risk were mixed.

“To our knowledge, this study is the first randomized, placebo-controlled trial to prospectively test the effect of any intervention on incident AF and is the only trial to test alternative upstream preventive agents for AF in a large enough population over a long enough time period to provide an assessment of the plausible benefits and risks,” they write.

The VITAL-RHYTHM study was an ancillary trial embedded within the Vitamin D and Omega-3 (VITAL) trial, which used a 2 x 2 factorial design to evaluate daily supplementation with 2,000 IU of vitamin D₃ and/or 840 mg of marine omega-3 fatty acids (460 mg EPA and 380 mg DHA), in the primary prevention of cardiovascular disease and cancer in 25,871 men and women age 50 and older in the United States.

Results showed that over a median 5.3 years of treatment and follow-up, the primary endpoint of incident AFib occurred in 3.6% of the study population. For the omega-3 part of the trial, incident AFib events occurred in 3.7% of patients taking EPA/DHA vs. 3.4% of the placebo group, giving a hazard ratio of 1.09, which was not significant (P = .19).

For the vitamin D₃ vs. placebo comparison, results were very similar, with incident AFib events occurring in 3.7% vs. 3.4% of participants, respectively, giving a hazard ratio of 1.09, which was again not significant (P = .19). There was no evidence for interaction between the two study agents.

“Overall, these findings do not support the use of supplemental EPA-DHA or vitamin D₃ for the primary prevention of AFib and provide reassurance regarding lack of a major risk of AFib incidence associated with these commonly used supplements at these doses,” the authors conclude.

Noting that significant increases in AFib have been seen with much higher doses of omega-3 fatty acids in the REDUCE-IT and STRENGTH trials, they add: “Potentially, the adverse effect on AF risk may be dose related, and the higher dosages of EPA used in these other studies might account for the significant adverse effect on AF.”

The researchers say that, to their knowledge, this is the only randomized trial to assess the effect of vitamin D₃ supplementation on AFib risk and results suggest a null effect. They add that subgroup analyses in patients with vitamin D levels considered deficient (<20 ng/mL) did not suggest a benefit; however, the power to detect a benefit in this much smaller subset of the population was limited.

They point out that, while there were no significant differences in incident AFib for either omega-3 fatty acid or vitamin D in the overall study population, an increased risk for incident AFib associated with randomized treatment was observed in selected subgroups.

For omega-3 fatty acids, AFib risk was modestly increased in taller individuals, and for vitamin D₃, elevations in AFib risk were observed in younger individuals and participants who drank less alcohol.

“Although the hazard ratios and tests for interaction were significant, the P values associated with these subgroup analyses have not been adjusted for multiple comparisons. Thus, these findings should be interpreted with caution and considered hypothesis generating,” they warn.

The VITAL Rhythm Study was supported by a grant from the National Heart, Lung, and Blood Institute. Dr. Albert reported receipt of grants from St Jude Medical, Abbott, and Roche Diagnostics. Dr. Curfman reports no relevant disclosures.

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

There may be a dose-related risk for atrial fibrillation (AFib) with omega-3 fatty acid intake, data from four randomized clinical trials suggest.

The latest trial to evaluate the association, the VITAL-RHYTHM study, showed that using a low dose of omega-3 fatty acids or a vitamin D supplement had no significant effect on the risks of developing incident AFib.

The trial, first reported at last year’s American Heart Association meeting, was  published online March 16 in the Journal of the American Medical Association.

Together with three other randomized clinical trials, however, these results suggest a possible dose-related effect of omega-3 fatty acids on the risk for AFib, an accompanying “Editor’s Note” suggests.

The note, by JAMA deputy editor Gregory Curfman, MD, points out that in the past 2 years, four randomized clinical trials have provided data on the risk of AFib with omega-3 fatty acid intake.

In the STRENGTH and REDUCE-IT trials, both of which evaluated high doses (4 g/day) of omega-3 fatty acids in patients with heart disease (or at high risk for it), there was a highly statistically significant increase in risk for AFib in the omega-3 groups vs. controls in both trials.

In the OMEMI trial in elderly patients with a recent myocardial infarction, an intermediate dose (1.8 g/day) of omega-3 fatty acids also showed an increase in AFib risk (hazard ratio, 1.84) but this was not significant. And now, the VITAL-RHYTHM trial shows no significant effect of a low dose (840 mg/day) of omega-3 fatty acids on the risk of developing AFib in a primary prevention population.

“Patients who choose to take omega-3 fatty acids, especially in high doses, should be informed of the risk of AF [AFib] and followed up for the possible development of this common and potentially hazardous arrhythmia,” Dr. Curfman concludes.

The authors of the VITAL-RHYTHM trial, led by Christine M. Albert, MD, MPH, Cedars-Sinai Medical Center, Los Angeles, Calif., explain that the trial was conducted after observational studies had shown that individuals with low blood levels of omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and vitamin D₃ have higher risks of incident AFib, but data on dietary or supplemental intake of these nutrients on AFib risk were mixed.

“To our knowledge, this study is the first randomized, placebo-controlled trial to prospectively test the effect of any intervention on incident AF and is the only trial to test alternative upstream preventive agents for AF in a large enough population over a long enough time period to provide an assessment of the plausible benefits and risks,” they write.

The VITAL-RHYTHM study was an ancillary trial embedded within the Vitamin D and Omega-3 (VITAL) trial, which used a 2 x 2 factorial design to evaluate daily supplementation with 2,000 IU of vitamin D₃ and/or 840 mg of marine omega-3 fatty acids (460 mg EPA and 380 mg DHA), in the primary prevention of cardiovascular disease and cancer in 25,871 men and women age 50 and older in the United States.

Results showed that over a median 5.3 years of treatment and follow-up, the primary endpoint of incident AFib occurred in 3.6% of the study population. For the omega-3 part of the trial, incident AFib events occurred in 3.7% of patients taking EPA/DHA vs. 3.4% of the placebo group, giving a hazard ratio of 1.09, which was not significant (P = .19).

For the vitamin D₃ vs. placebo comparison, results were very similar, with incident AFib events occurring in 3.7% vs. 3.4% of participants, respectively, giving a hazard ratio of 1.09, which was again not significant (P = .19). There was no evidence for interaction between the two study agents.

“Overall, these findings do not support the use of supplemental EPA-DHA or vitamin D₃ for the primary prevention of AFib and provide reassurance regarding lack of a major risk of AFib incidence associated with these commonly used supplements at these doses,” the authors conclude.

Noting that significant increases in AFib have been seen with much higher doses of omega-3 fatty acids in the REDUCE-IT and STRENGTH trials, they add: “Potentially, the adverse effect on AF risk may be dose related, and the higher dosages of EPA used in these other studies might account for the significant adverse effect on AF.”

The researchers say that, to their knowledge, this is the only randomized trial to assess the effect of vitamin D₃ supplementation on AFib risk and results suggest a null effect. They add that subgroup analyses in patients with vitamin D levels considered deficient (<20 ng/mL) did not suggest a benefit; however, the power to detect a benefit in this much smaller subset of the population was limited.

They point out that, while there were no significant differences in incident AFib for either omega-3 fatty acid or vitamin D in the overall study population, an increased risk for incident AFib associated with randomized treatment was observed in selected subgroups.

For omega-3 fatty acids, AFib risk was modestly increased in taller individuals, and for vitamin D₃, elevations in AFib risk were observed in younger individuals and participants who drank less alcohol.

“Although the hazard ratios and tests for interaction were significant, the P values associated with these subgroup analyses have not been adjusted for multiple comparisons. Thus, these findings should be interpreted with caution and considered hypothesis generating,” they warn.

The VITAL Rhythm Study was supported by a grant from the National Heart, Lung, and Blood Institute. Dr. Albert reported receipt of grants from St Jude Medical, Abbott, and Roche Diagnostics. Dr. Curfman reports no relevant disclosures.

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

There may be a dose-related risk for atrial fibrillation (AFib) with omega-3 fatty acid intake, data from four randomized clinical trials suggest.

The latest trial to evaluate the association, the VITAL-RHYTHM study, showed that using a low dose of omega-3 fatty acids or a vitamin D supplement had no significant effect on the risks of developing incident AFib.

The trial, first reported at last year’s American Heart Association meeting, was  published online March 16 in the Journal of the American Medical Association.

Together with three other randomized clinical trials, however, these results suggest a possible dose-related effect of omega-3 fatty acids on the risk for AFib, an accompanying “Editor’s Note” suggests.

The note, by JAMA deputy editor Gregory Curfman, MD, points out that in the past 2 years, four randomized clinical trials have provided data on the risk of AFib with omega-3 fatty acid intake.

In the STRENGTH and REDUCE-IT trials, both of which evaluated high doses (4 g/day) of omega-3 fatty acids in patients with heart disease (or at high risk for it), there was a highly statistically significant increase in risk for AFib in the omega-3 groups vs. controls in both trials.

In the OMEMI trial in elderly patients with a recent myocardial infarction, an intermediate dose (1.8 g/day) of omega-3 fatty acids also showed an increase in AFib risk (hazard ratio, 1.84) but this was not significant. And now, the VITAL-RHYTHM trial shows no significant effect of a low dose (840 mg/day) of omega-3 fatty acids on the risk of developing AFib in a primary prevention population.

“Patients who choose to take omega-3 fatty acids, especially in high doses, should be informed of the risk of AF [AFib] and followed up for the possible development of this common and potentially hazardous arrhythmia,” Dr. Curfman concludes.

The authors of the VITAL-RHYTHM trial, led by Christine M. Albert, MD, MPH, Cedars-Sinai Medical Center, Los Angeles, Calif., explain that the trial was conducted after observational studies had shown that individuals with low blood levels of omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and vitamin D₃ have higher risks of incident AFib, but data on dietary or supplemental intake of these nutrients on AFib risk were mixed.

“To our knowledge, this study is the first randomized, placebo-controlled trial to prospectively test the effect of any intervention on incident AF and is the only trial to test alternative upstream preventive agents for AF in a large enough population over a long enough time period to provide an assessment of the plausible benefits and risks,” they write.

The VITAL-RHYTHM study was an ancillary trial embedded within the Vitamin D and Omega-3 (VITAL) trial, which used a 2 x 2 factorial design to evaluate daily supplementation with 2,000 IU of vitamin D₃ and/or 840 mg of marine omega-3 fatty acids (460 mg EPA and 380 mg DHA), in the primary prevention of cardiovascular disease and cancer in 25,871 men and women age 50 and older in the United States.

Results showed that over a median 5.3 years of treatment and follow-up, the primary endpoint of incident AFib occurred in 3.6% of the study population. For the omega-3 part of the trial, incident AFib events occurred in 3.7% of patients taking EPA/DHA vs. 3.4% of the placebo group, giving a hazard ratio of 1.09, which was not significant (P = .19).

For the vitamin D₃ vs. placebo comparison, results were very similar, with incident AFib events occurring in 3.7% vs. 3.4% of participants, respectively, giving a hazard ratio of 1.09, which was again not significant (P = .19). There was no evidence for interaction between the two study agents.

“Overall, these findings do not support the use of supplemental EPA-DHA or vitamin D₃ for the primary prevention of AFib and provide reassurance regarding lack of a major risk of AFib incidence associated with these commonly used supplements at these doses,” the authors conclude.

Noting that significant increases in AFib have been seen with much higher doses of omega-3 fatty acids in the REDUCE-IT and STRENGTH trials, they add: “Potentially, the adverse effect on AF risk may be dose related, and the higher dosages of EPA used in these other studies might account for the significant adverse effect on AF.”

The researchers say that, to their knowledge, this is the only randomized trial to assess the effect of vitamin D₃ supplementation on AFib risk and results suggest a null effect. They add that subgroup analyses in patients with vitamin D levels considered deficient (<20 ng/mL) did not suggest a benefit; however, the power to detect a benefit in this much smaller subset of the population was limited.

They point out that, while there were no significant differences in incident AFib for either omega-3 fatty acid or vitamin D in the overall study population, an increased risk for incident AFib associated with randomized treatment was observed in selected subgroups.

For omega-3 fatty acids, AFib risk was modestly increased in taller individuals, and for vitamin D₃, elevations in AFib risk were observed in younger individuals and participants who drank less alcohol.

“Although the hazard ratios and tests for interaction were significant, the P values associated with these subgroup analyses have not been adjusted for multiple comparisons. Thus, these findings should be interpreted with caution and considered hypothesis generating,” they warn.

The VITAL Rhythm Study was supported by a grant from the National Heart, Lung, and Blood Institute. Dr. Albert reported receipt of grants from St Jude Medical, Abbott, and Roche Diagnostics. Dr. Curfman reports no relevant disclosures.

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

In January, as Mississippi health officials planned for their incoming shipments of COVID-19 vaccine, they assessed the state’s most vulnerable: health care workers, of course, and elderly people in nursing homes. But among those who needed urgent protection from the virus ripping across the Magnolia State were 1 million Mississippians with obesity.

Obesity and weight-related illnesses have been deadly liabilities in the COVID era. A report released this month by the World Obesity Federation found that increased body weight is the second-greatest predictor of COVID-related hospitalization and death across the globe, trailing only old age as a risk factor.

As a fixture of life in the American South – home to 9 of the nation’s 12 heaviest states – obesity is playing a role not only in COVID outcomes, but in the calculus of the vaccination rollout. Mississippi was one of the first states to add a body mass index of 30 or more (a rough gauge of obesity tied to height and weight) to the list of qualifying medical conditions for a shot. About 40% of the state’s adults meet that definition, according to federal health survey data, and combined with the risk group already eligible for vaccination – residents 65 and older – that means fully half of Mississippi’s adults are entitled to vie for a restricted allotment of shots.

At least 29 states have green-lighted obesity for inclusion in the first phases of the vaccine rollout, according to KFF – a vast widening of eligibility that has the potential to overwhelm government efforts and heighten competition for scarce doses.

“We have a lifesaving intervention, and we don’t have enough of it,” said Jen Kates, PhD, director of global health and HIV policy for Kaiser Family Foundation. “Hard choices are being made about who should go first, and there is no right answer.”

The sheer prevalence of obesity in the nation – two in three Americans exceed what is considered a healthy weight – was a public health concern well before the pandemic. But COVID-19 dramatically fast-tracked the discussion from warnings about the long-term damage excess fat tissue can pose to heart, lung and metabolic functions to far more immediate threats.

In the United Kingdom, for example, overweight COVID patients were 67% more likely to require intensive care, and obese patients three times likelier, according to the World Obesity Federation report. A Centers for Disease Control and Prevention study released Monday found a similar trend among U.S. patients and noted that the risk of COVID-related hospitalization, ventilation and death increased with patients’ obesity level.

The counties that hug the southern Mississippi River are home to some of the most concentrated pockets of extreme obesity in the United States. Coronavirus infections began surging in Southern states early last summer, and hospitalizations rose in step.

Deaths in rural stretches of Arkansas, Louisiana, Mississippi, and Tennessee have been overshadowed by the sheer number of deaths in metropolitan areas like New York, Los Angeles, and Essex County, N.J. But as a share of the population, the coronavirus has been similarly unsparing in many Southern communities. In sparsely populated Claiborne County, Miss., on the floodplains of the Mississippi River, 30 residents – about 1 in 300 – had died as of early March. In East Feliciana Parish, La., north of Baton Rouge, with 106 deaths, about 1 in 180 had died by then.

“It’s just math. If the population is more obese and obesity clearly contributes to worse outcomes, then neighborhoods, cities, states and countries that are more obese will have a greater toll from COVID,” said Dr. James de Lemos, MD, a professor of internal medicine at UT Southwestern Medical Center in Dallas who led a study of hospitalized COVID patients published in the medical journal Circulation.

And, because in the U.S. obesity rates tend to be relatively high among African Americans and Latinos who are poor, with diminished access to health care, “it’s a triple whammy,” Dr. de Lemos said. “All these things intersect.”

Poverty and limited access to medical care are common features in the South, where residents like Michelle Antonyshyn, a former registered nurse and mother of seven in Salem, Ark., say they are afraid of the virus. Ms. Antonyshyn, 49, has obesity and debilitating pain in her knees and back, though she does not have high blood pressure or diabetes, two underlying conditions that federal health officials have determined are added risk factors for severe cases of COVID-19.

Still, she said, she “was very concerned just knowing that being obese puts you more at risk for bad outcomes such as being on a ventilator and death.” As a precaution, Ms. Antonyshyn said, she and her large brood locked down early and stopped attending church services in person, watching online instead.

“It’s not the same as having fellowship, but the risk for me was enough,” said Ms. Antonyshyn.

Governors throughout the South seem to recognize that weight can contribute to COVID-19 complications and have pushed for vaccine eligibility rules that prioritize obesity. But on the ground, local health officials are girding for having to tell newly eligible people who qualify as obese that there aren’t enough shots to go around.

In Port Gibson, Miss., Mheja Williams, MD, medical director of the Claiborne County Family Health Center, has been receiving barely enough doses to inoculate the health workers and oldest seniors in her county of 9,600. One week in early February, she received 100 doses.

Obesity and extreme obesity are endemic in Claiborne County, and health officials say the “normalization” of obesity means people often don’t register their weight as a risk factor, whether for COVID or other health issues. The risks are exacerbated by a general flouting of pandemic etiquette: Dr. Williams said that middle-aged and younger residents are not especially vigilant about physical distancing and that mask use is rare.

The rise of obesity in the United States is well documented over the past half-century, as the nation turned from a diet of fruits, vegetables and limited meats to one laden with ultra-processed foods and rich with salt, fat, sugar, and flavorings, along with copious amounts of meat, fast food, and soda. The U.S. has generally led the global obesity race, setting records as even toddlers and young children grew implausibly, dangerously overweight.

Well before COVID, obesity was a leading cause of preventable death in the United States. The National Institutes of Health declared it a disease in 1998, one that fosters heart disease, stroke, type 2 diabetes, and breast, colon, and other cancers.

Researchers say it is no coincidence that nations like the United States, the United Kingdom, and Italy, with relatively high obesity rates, have proved particularly vulnerable to the novel coronavirus.

They believe the virus may exploit underlying metabolic and physiological impairments that often exist in concert with obesity. Extra fat can lead to a cascade of metabolic disruptions, chronic systemic inflammation, and hormonal dysregulation that may thwart the body’s response to infection.

Other respiratory viruses, like influenza and SARS, which appeared in China in 2002, rely on cholesterol to spread enveloped RNA virus to neighboring cells, and researchers have proposed that a similar mechanism may play a role in the spread of the novel coronavirus.

There are also practical problems for coronavirus patients with obesity admitted to the hospital. They can be more difficult to intubate because of excess central weight pressing down on the diaphragm, making breathing with infected lungs even more difficult.

Physicians who specialize in treating patients with obesity say public health officials need to be more forthright and urgent in their messaging, telegraphing the risks of this COVID era.

“It should be explicit and direct,” said Fatima Stanford, MD, an obesity medicine specialist at Massachusetts General Hospital, Boston, and a Harvard Medical School instructor.

Dr. Stanford denounces the fat-shaming and bullying that people with obesity often experience. But telling patients – and the public – that obesity increases the risk of hospitalization and death is crucial, she said.

“I don’t think it’s stigmatizing,” she said. “If you tell them in that way, it’s not to scare you, it’s just giving information. Sometimes people are just unaware.”



KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

In January, as Mississippi health officials planned for their incoming shipments of COVID-19 vaccine, they assessed the state’s most vulnerable: health care workers, of course, and elderly people in nursing homes. But among those who needed urgent protection from the virus ripping across the Magnolia State were 1 million Mississippians with obesity.

Obesity and weight-related illnesses have been deadly liabilities in the COVID era. A report released this month by the World Obesity Federation found that increased body weight is the second-greatest predictor of COVID-related hospitalization and death across the globe, trailing only old age as a risk factor.

As a fixture of life in the American South – home to 9 of the nation’s 12 heaviest states – obesity is playing a role not only in COVID outcomes, but in the calculus of the vaccination rollout. Mississippi was one of the first states to add a body mass index of 30 or more (a rough gauge of obesity tied to height and weight) to the list of qualifying medical conditions for a shot. About 40% of the state’s adults meet that definition, according to federal health survey data, and combined with the risk group already eligible for vaccination – residents 65 and older – that means fully half of Mississippi’s adults are entitled to vie for a restricted allotment of shots.

At least 29 states have green-lighted obesity for inclusion in the first phases of the vaccine rollout, according to KFF – a vast widening of eligibility that has the potential to overwhelm government efforts and heighten competition for scarce doses.

“We have a lifesaving intervention, and we don’t have enough of it,” said Jen Kates, PhD, director of global health and HIV policy for Kaiser Family Foundation. “Hard choices are being made about who should go first, and there is no right answer.”

The sheer prevalence of obesity in the nation – two in three Americans exceed what is considered a healthy weight – was a public health concern well before the pandemic. But COVID-19 dramatically fast-tracked the discussion from warnings about the long-term damage excess fat tissue can pose to heart, lung and metabolic functions to far more immediate threats.

In the United Kingdom, for example, overweight COVID patients were 67% more likely to require intensive care, and obese patients three times likelier, according to the World Obesity Federation report. A Centers for Disease Control and Prevention study released Monday found a similar trend among U.S. patients and noted that the risk of COVID-related hospitalization, ventilation and death increased with patients’ obesity level.

The counties that hug the southern Mississippi River are home to some of the most concentrated pockets of extreme obesity in the United States. Coronavirus infections began surging in Southern states early last summer, and hospitalizations rose in step.

Deaths in rural stretches of Arkansas, Louisiana, Mississippi, and Tennessee have been overshadowed by the sheer number of deaths in metropolitan areas like New York, Los Angeles, and Essex County, N.J. But as a share of the population, the coronavirus has been similarly unsparing in many Southern communities. In sparsely populated Claiborne County, Miss., on the floodplains of the Mississippi River, 30 residents – about 1 in 300 – had died as of early March. In East Feliciana Parish, La., north of Baton Rouge, with 106 deaths, about 1 in 180 had died by then.

“It’s just math. If the population is more obese and obesity clearly contributes to worse outcomes, then neighborhoods, cities, states and countries that are more obese will have a greater toll from COVID,” said Dr. James de Lemos, MD, a professor of internal medicine at UT Southwestern Medical Center in Dallas who led a study of hospitalized COVID patients published in the medical journal Circulation.

And, because in the U.S. obesity rates tend to be relatively high among African Americans and Latinos who are poor, with diminished access to health care, “it’s a triple whammy,” Dr. de Lemos said. “All these things intersect.”

Poverty and limited access to medical care are common features in the South, where residents like Michelle Antonyshyn, a former registered nurse and mother of seven in Salem, Ark., say they are afraid of the virus. Ms. Antonyshyn, 49, has obesity and debilitating pain in her knees and back, though she does not have high blood pressure or diabetes, two underlying conditions that federal health officials have determined are added risk factors for severe cases of COVID-19.

Still, she said, she “was very concerned just knowing that being obese puts you more at risk for bad outcomes such as being on a ventilator and death.” As a precaution, Ms. Antonyshyn said, she and her large brood locked down early and stopped attending church services in person, watching online instead.

“It’s not the same as having fellowship, but the risk for me was enough,” said Ms. Antonyshyn.

Governors throughout the South seem to recognize that weight can contribute to COVID-19 complications and have pushed for vaccine eligibility rules that prioritize obesity. But on the ground, local health officials are girding for having to tell newly eligible people who qualify as obese that there aren’t enough shots to go around.

In Port Gibson, Miss., Mheja Williams, MD, medical director of the Claiborne County Family Health Center, has been receiving barely enough doses to inoculate the health workers and oldest seniors in her county of 9,600. One week in early February, she received 100 doses.

Obesity and extreme obesity are endemic in Claiborne County, and health officials say the “normalization” of obesity means people often don’t register their weight as a risk factor, whether for COVID or other health issues. The risks are exacerbated by a general flouting of pandemic etiquette: Dr. Williams said that middle-aged and younger residents are not especially vigilant about physical distancing and that mask use is rare.

The rise of obesity in the United States is well documented over the past half-century, as the nation turned from a diet of fruits, vegetables and limited meats to one laden with ultra-processed foods and rich with salt, fat, sugar, and flavorings, along with copious amounts of meat, fast food, and soda. The U.S. has generally led the global obesity race, setting records as even toddlers and young children grew implausibly, dangerously overweight.

Well before COVID, obesity was a leading cause of preventable death in the United States. The National Institutes of Health declared it a disease in 1998, one that fosters heart disease, stroke, type 2 diabetes, and breast, colon, and other cancers.

Researchers say it is no coincidence that nations like the United States, the United Kingdom, and Italy, with relatively high obesity rates, have proved particularly vulnerable to the novel coronavirus.

They believe the virus may exploit underlying metabolic and physiological impairments that often exist in concert with obesity. Extra fat can lead to a cascade of metabolic disruptions, chronic systemic inflammation, and hormonal dysregulation that may thwart the body’s response to infection.

Other respiratory viruses, like influenza and SARS, which appeared in China in 2002, rely on cholesterol to spread enveloped RNA virus to neighboring cells, and researchers have proposed that a similar mechanism may play a role in the spread of the novel coronavirus.

There are also practical problems for coronavirus patients with obesity admitted to the hospital. They can be more difficult to intubate because of excess central weight pressing down on the diaphragm, making breathing with infected lungs even more difficult.

Physicians who specialize in treating patients with obesity say public health officials need to be more forthright and urgent in their messaging, telegraphing the risks of this COVID era.

“It should be explicit and direct,” said Fatima Stanford, MD, an obesity medicine specialist at Massachusetts General Hospital, Boston, and a Harvard Medical School instructor.

Dr. Stanford denounces the fat-shaming and bullying that people with obesity often experience. But telling patients – and the public – that obesity increases the risk of hospitalization and death is crucial, she said.

“I don’t think it’s stigmatizing,” she said. “If you tell them in that way, it’s not to scare you, it’s just giving information. Sometimes people are just unaware.”



KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

In January, as Mississippi health officials planned for their incoming shipments of COVID-19 vaccine, they assessed the state’s most vulnerable: health care workers, of course, and elderly people in nursing homes. But among those who needed urgent protection from the virus ripping across the Magnolia State were 1 million Mississippians with obesity.

Obesity and weight-related illnesses have been deadly liabilities in the COVID era. A report released this month by the World Obesity Federation found that increased body weight is the second-greatest predictor of COVID-related hospitalization and death across the globe, trailing only old age as a risk factor.

As a fixture of life in the American South – home to 9 of the nation’s 12 heaviest states – obesity is playing a role not only in COVID outcomes, but in the calculus of the vaccination rollout. Mississippi was one of the first states to add a body mass index of 30 or more (a rough gauge of obesity tied to height and weight) to the list of qualifying medical conditions for a shot. About 40% of the state’s adults meet that definition, according to federal health survey data, and combined with the risk group already eligible for vaccination – residents 65 and older – that means fully half of Mississippi’s adults are entitled to vie for a restricted allotment of shots.

At least 29 states have green-lighted obesity for inclusion in the first phases of the vaccine rollout, according to KFF – a vast widening of eligibility that has the potential to overwhelm government efforts and heighten competition for scarce doses.

“We have a lifesaving intervention, and we don’t have enough of it,” said Jen Kates, PhD, director of global health and HIV policy for Kaiser Family Foundation. “Hard choices are being made about who should go first, and there is no right answer.”

The sheer prevalence of obesity in the nation – two in three Americans exceed what is considered a healthy weight – was a public health concern well before the pandemic. But COVID-19 dramatically fast-tracked the discussion from warnings about the long-term damage excess fat tissue can pose to heart, lung and metabolic functions to far more immediate threats.

In the United Kingdom, for example, overweight COVID patients were 67% more likely to require intensive care, and obese patients three times likelier, according to the World Obesity Federation report. A Centers for Disease Control and Prevention study released Monday found a similar trend among U.S. patients and noted that the risk of COVID-related hospitalization, ventilation and death increased with patients’ obesity level.

The counties that hug the southern Mississippi River are home to some of the most concentrated pockets of extreme obesity in the United States. Coronavirus infections began surging in Southern states early last summer, and hospitalizations rose in step.

Deaths in rural stretches of Arkansas, Louisiana, Mississippi, and Tennessee have been overshadowed by the sheer number of deaths in metropolitan areas like New York, Los Angeles, and Essex County, N.J. But as a share of the population, the coronavirus has been similarly unsparing in many Southern communities. In sparsely populated Claiborne County, Miss., on the floodplains of the Mississippi River, 30 residents – about 1 in 300 – had died as of early March. In East Feliciana Parish, La., north of Baton Rouge, with 106 deaths, about 1 in 180 had died by then.

“It’s just math. If the population is more obese and obesity clearly contributes to worse outcomes, then neighborhoods, cities, states and countries that are more obese will have a greater toll from COVID,” said Dr. James de Lemos, MD, a professor of internal medicine at UT Southwestern Medical Center in Dallas who led a study of hospitalized COVID patients published in the medical journal Circulation.

And, because in the U.S. obesity rates tend to be relatively high among African Americans and Latinos who are poor, with diminished access to health care, “it’s a triple whammy,” Dr. de Lemos said. “All these things intersect.”

Poverty and limited access to medical care are common features in the South, where residents like Michelle Antonyshyn, a former registered nurse and mother of seven in Salem, Ark., say they are afraid of the virus. Ms. Antonyshyn, 49, has obesity and debilitating pain in her knees and back, though she does not have high blood pressure or diabetes, two underlying conditions that federal health officials have determined are added risk factors for severe cases of COVID-19.

Still, she said, she “was very concerned just knowing that being obese puts you more at risk for bad outcomes such as being on a ventilator and death.” As a precaution, Ms. Antonyshyn said, she and her large brood locked down early and stopped attending church services in person, watching online instead.

“It’s not the same as having fellowship, but the risk for me was enough,” said Ms. Antonyshyn.

Governors throughout the South seem to recognize that weight can contribute to COVID-19 complications and have pushed for vaccine eligibility rules that prioritize obesity. But on the ground, local health officials are girding for having to tell newly eligible people who qualify as obese that there aren’t enough shots to go around.

In Port Gibson, Miss., Mheja Williams, MD, medical director of the Claiborne County Family Health Center, has been receiving barely enough doses to inoculate the health workers and oldest seniors in her county of 9,600. One week in early February, she received 100 doses.

Obesity and extreme obesity are endemic in Claiborne County, and health officials say the “normalization” of obesity means people often don’t register their weight as a risk factor, whether for COVID or other health issues. The risks are exacerbated by a general flouting of pandemic etiquette: Dr. Williams said that middle-aged and younger residents are not especially vigilant about physical distancing and that mask use is rare.

The rise of obesity in the United States is well documented over the past half-century, as the nation turned from a diet of fruits, vegetables and limited meats to one laden with ultra-processed foods and rich with salt, fat, sugar, and flavorings, along with copious amounts of meat, fast food, and soda. The U.S. has generally led the global obesity race, setting records as even toddlers and young children grew implausibly, dangerously overweight.

Well before COVID, obesity was a leading cause of preventable death in the United States. The National Institutes of Health declared it a disease in 1998, one that fosters heart disease, stroke, type 2 diabetes, and breast, colon, and other cancers.

Researchers say it is no coincidence that nations like the United States, the United Kingdom, and Italy, with relatively high obesity rates, have proved particularly vulnerable to the novel coronavirus.

They believe the virus may exploit underlying metabolic and physiological impairments that often exist in concert with obesity. Extra fat can lead to a cascade of metabolic disruptions, chronic systemic inflammation, and hormonal dysregulation that may thwart the body’s response to infection.

Other respiratory viruses, like influenza and SARS, which appeared in China in 2002, rely on cholesterol to spread enveloped RNA virus to neighboring cells, and researchers have proposed that a similar mechanism may play a role in the spread of the novel coronavirus.

There are also practical problems for coronavirus patients with obesity admitted to the hospital. They can be more difficult to intubate because of excess central weight pressing down on the diaphragm, making breathing with infected lungs even more difficult.

Physicians who specialize in treating patients with obesity say public health officials need to be more forthright and urgent in their messaging, telegraphing the risks of this COVID era.

“It should be explicit and direct,” said Fatima Stanford, MD, an obesity medicine specialist at Massachusetts General Hospital, Boston, and a Harvard Medical School instructor.

Dr. Stanford denounces the fat-shaming and bullying that people with obesity often experience. But telling patients – and the public – that obesity increases the risk of hospitalization and death is crucial, she said.

“I don’t think it’s stigmatizing,” she said. “If you tell them in that way, it’s not to scare you, it’s just giving information. Sometimes people are just unaware.”



KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.