Key clinical point: Repeated active transcranial direct current stimulation (tDCS) for at least 4 weeks significantly reduced migraine pain intensity and resulted in a trend for reduction in the duration of a migraine episode.

Major finding: Patients treated with active vs. sham tDCS showed a significantly higher reduction of pain intensity (mean difference [MD], −1.44; P less than .01) and a trend for reduction in migraine duration (MD, −1.31; P = .14).

Study details: Findings are from a meta-analysis of 5 randomized controlled trials including 104 patients with migraine with/without aura and chronic migraine who received either active or sham tDCS.

Disclosures: No information on funding was available. The authors declared no conflicts of interest.

Source: Cai G et al. J Pain Res. 2021 Apr 27. doi: 10.2147/JPR.S295704.

Key clinical point: Repeated active transcranial direct current stimulation (tDCS) for at least 4 weeks significantly reduced migraine pain intensity and resulted in a trend for reduction in the duration of a migraine episode.

Major finding: Patients treated with active vs. sham tDCS showed a significantly higher reduction of pain intensity (mean difference [MD], −1.44; P less than .01) and a trend for reduction in migraine duration (MD, −1.31; P = .14).

Study details: Findings are from a meta-analysis of 5 randomized controlled trials including 104 patients with migraine with/without aura and chronic migraine who received either active or sham tDCS.

Disclosures: No information on funding was available. The authors declared no conflicts of interest.

Source: Cai G et al. J Pain Res. 2021 Apr 27. doi: 10.2147/JPR.S295704.

Key clinical point: Repeated active transcranial direct current stimulation (tDCS) for at least 4 weeks significantly reduced migraine pain intensity and resulted in a trend for reduction in the duration of a migraine episode.

Major finding: Patients treated with active vs. sham tDCS showed a significantly higher reduction of pain intensity (mean difference [MD], −1.44; P less than .01) and a trend for reduction in migraine duration (MD, −1.31; P = .14).

Study details: Findings are from a meta-analysis of 5 randomized controlled trials including 104 patients with migraine with/without aura and chronic migraine who received either active or sham tDCS.

Disclosures: No information on funding was available. The authors declared no conflicts of interest.

Source: Cai G et al. J Pain Res. 2021 Apr 27. doi: 10.2147/JPR.S295704.

Key clinical point: Erenumab demonstrated sustained efficacy and safety through 64 weeks in patients with episodic migraine (EM) with 2-4 prior preventive treatment failures.

Major finding: Overall, the proportion of patients achieving 50% or greater reduction in monthly migraine days increased from 30.4% at weeks 13-16 to 47.3% at weeks 37-40 and remained stable through weeks 61-64 (47.1%). Overall, 6.7% of patients experienced treatment-emergent serious adverse events and 1.7% discontinued treatment because of treatment-emergent adverse events.

Study details: Findings of the first year of the ongoing 3-year open-label extension phase of LIBERTY study that evaluated monthly erenumab 140 mg in 240 patients with EM who had 2-4 prior preventive treatment failures.

Disclosures: The study was funded by Novartis Pharma AG, Basel, Switzerland. Some of the authors reported receiving grants, professional fees, consulting fees, speaking/teaching fees, and/or honoraria from; being an employee of; and/or holding stocks in various pharmaceutical companies including Novartis.

Source: Goadsby PJ et al. Neurology. 2021 Apr 28. doi: 10.1212/WNL.0000000000012029.

Key clinical point: Erenumab demonstrated sustained efficacy and safety through 64 weeks in patients with episodic migraine (EM) with 2-4 prior preventive treatment failures.

Major finding: Overall, the proportion of patients achieving 50% or greater reduction in monthly migraine days increased from 30.4% at weeks 13-16 to 47.3% at weeks 37-40 and remained stable through weeks 61-64 (47.1%). Overall, 6.7% of patients experienced treatment-emergent serious adverse events and 1.7% discontinued treatment because of treatment-emergent adverse events.

Study details: Findings of the first year of the ongoing 3-year open-label extension phase of LIBERTY study that evaluated monthly erenumab 140 mg in 240 patients with EM who had 2-4 prior preventive treatment failures.

Disclosures: The study was funded by Novartis Pharma AG, Basel, Switzerland. Some of the authors reported receiving grants, professional fees, consulting fees, speaking/teaching fees, and/or honoraria from; being an employee of; and/or holding stocks in various pharmaceutical companies including Novartis.

Source: Goadsby PJ et al. Neurology. 2021 Apr 28. doi: 10.1212/WNL.0000000000012029.

Key clinical point: Erenumab demonstrated sustained efficacy and safety through 64 weeks in patients with episodic migraine (EM) with 2-4 prior preventive treatment failures.

Major finding: Overall, the proportion of patients achieving 50% or greater reduction in monthly migraine days increased from 30.4% at weeks 13-16 to 47.3% at weeks 37-40 and remained stable through weeks 61-64 (47.1%). Overall, 6.7% of patients experienced treatment-emergent serious adverse events and 1.7% discontinued treatment because of treatment-emergent adverse events.

Study details: Findings of the first year of the ongoing 3-year open-label extension phase of LIBERTY study that evaluated monthly erenumab 140 mg in 240 patients with EM who had 2-4 prior preventive treatment failures.

Disclosures: The study was funded by Novartis Pharma AG, Basel, Switzerland. Some of the authors reported receiving grants, professional fees, consulting fees, speaking/teaching fees, and/or honoraria from; being an employee of; and/or holding stocks in various pharmaceutical companies including Novartis.

Source: Goadsby PJ et al. Neurology. 2021 Apr 28. doi: 10.1212/WNL.0000000000012029.

Key clinical point: Calcitonin gene-related peptide (CGRP) monoclonal antibody was superior to botulinum toxin in reducing the frequency of acute analgesic intake in patients with chronic migraine (CM). Treatment-related serious adverse events (SAEs) were lower with CGRP monoclonal antibody.

Major finding: CGRP monoclonal antibody was superior to botulinum toxin in reducing the frequency of acute analgesics intake (weighted mean difference, −1.31; P = .02113). Treatment-related SAEs were lower with CGRP monoclonal antibody vs. botulinum toxin (relative risk, 0.505; P = .001).

Study details: Findings are from a meta-analysis of 10 studies including 6,325 patients, which performed indirect treatment comparison between CGRP monoclonal antibody and botulinum toxin for prophylactic treatment of CM.

Disclosures: No information on funding was available. The authors declared no conflicts of interest.

Source: Lu J et al. Front Pharmacol. 2021 May 3. doi: 10.3389/fphar.2021.631204.

Key clinical point: Calcitonin gene-related peptide (CGRP) monoclonal antibody was superior to botulinum toxin in reducing the frequency of acute analgesic intake in patients with chronic migraine (CM). Treatment-related serious adverse events (SAEs) were lower with CGRP monoclonal antibody.

Major finding: CGRP monoclonal antibody was superior to botulinum toxin in reducing the frequency of acute analgesics intake (weighted mean difference, −1.31; P = .02113). Treatment-related SAEs were lower with CGRP monoclonal antibody vs. botulinum toxin (relative risk, 0.505; P = .001).

Study details: Findings are from a meta-analysis of 10 studies including 6,325 patients, which performed indirect treatment comparison between CGRP monoclonal antibody and botulinum toxin for prophylactic treatment of CM.

Disclosures: No information on funding was available. The authors declared no conflicts of interest.

Source: Lu J et al. Front Pharmacol. 2021 May 3. doi: 10.3389/fphar.2021.631204.

Key clinical point: Calcitonin gene-related peptide (CGRP) monoclonal antibody was superior to botulinum toxin in reducing the frequency of acute analgesic intake in patients with chronic migraine (CM). Treatment-related serious adverse events (SAEs) were lower with CGRP monoclonal antibody.

Major finding: CGRP monoclonal antibody was superior to botulinum toxin in reducing the frequency of acute analgesics intake (weighted mean difference, −1.31; P = .02113). Treatment-related SAEs were lower with CGRP monoclonal antibody vs. botulinum toxin (relative risk, 0.505; P = .001).

Study details: Findings are from a meta-analysis of 10 studies including 6,325 patients, which performed indirect treatment comparison between CGRP monoclonal antibody and botulinum toxin for prophylactic treatment of CM.

Disclosures: No information on funding was available. The authors declared no conflicts of interest.

Source: Lu J et al. Front Pharmacol. 2021 May 3. doi: 10.3389/fphar.2021.631204.

Key clinical point: In patients with episodic migraine (EM), erenumab reduced both monthly migraine days (MMD) and monthly migraine attacks (MMA) by a similar magnitude. However, the impact on migraine attack duration was minor.

Major finding: Erenumab 70 mg and 140 mg vs. placebo were associated with a greater reduction in MMD (least square mean percent change [LSM%], −39% and −44% vs. 22%) and MMA (LSM%, −40% and −43% vs. −26%). The percentage change from baseline in migraine attack duration was minor with erenumab 70 mg and 140 mg vs. placebo (LSM%, −7% and −8% vs. −1%).

Study details: Findings are from a post hoc analysis of phase 3 STRIVE study including 955 patients with EM who were randomly allocated to receive either erenumab 70 mg or 140 mg or placebo once monthly for 6 months.

Disclosures: The study was supported by Amgen Inc., Thousand Oaks, CA, USA. HC Diener and M Ashina reported receiving honoraria, financial support, and/or serving as a consultant, speaker, or scientific advisor or primary investigator for various sources. GPDS Lima and S Rasmussen declared being employees and holding stocks at Amgen Inc.

Source: Diener HC et al. Cephalalgia. 2021 May 3. doi: 10.1177/03331024211010308.

Key clinical point: In patients with episodic migraine (EM), erenumab reduced both monthly migraine days (MMD) and monthly migraine attacks (MMA) by a similar magnitude. However, the impact on migraine attack duration was minor.

Major finding: Erenumab 70 mg and 140 mg vs. placebo were associated with a greater reduction in MMD (least square mean percent change [LSM%], −39% and −44% vs. 22%) and MMA (LSM%, −40% and −43% vs. −26%). The percentage change from baseline in migraine attack duration was minor with erenumab 70 mg and 140 mg vs. placebo (LSM%, −7% and −8% vs. −1%).

Study details: Findings are from a post hoc analysis of phase 3 STRIVE study including 955 patients with EM who were randomly allocated to receive either erenumab 70 mg or 140 mg or placebo once monthly for 6 months.

Disclosures: The study was supported by Amgen Inc., Thousand Oaks, CA, USA. HC Diener and M Ashina reported receiving honoraria, financial support, and/or serving as a consultant, speaker, or scientific advisor or primary investigator for various sources. GPDS Lima and S Rasmussen declared being employees and holding stocks at Amgen Inc.

Source: Diener HC et al. Cephalalgia. 2021 May 3. doi: 10.1177/03331024211010308.

Key clinical point: In patients with episodic migraine (EM), erenumab reduced both monthly migraine days (MMD) and monthly migraine attacks (MMA) by a similar magnitude. However, the impact on migraine attack duration was minor.

Major finding: Erenumab 70 mg and 140 mg vs. placebo were associated with a greater reduction in MMD (least square mean percent change [LSM%], −39% and −44% vs. 22%) and MMA (LSM%, −40% and −43% vs. −26%). The percentage change from baseline in migraine attack duration was minor with erenumab 70 mg and 140 mg vs. placebo (LSM%, −7% and −8% vs. −1%).

Study details: Findings are from a post hoc analysis of phase 3 STRIVE study including 955 patients with EM who were randomly allocated to receive either erenumab 70 mg or 140 mg or placebo once monthly for 6 months.

Disclosures: The study was supported by Amgen Inc., Thousand Oaks, CA, USA. HC Diener and M Ashina reported receiving honoraria, financial support, and/or serving as a consultant, speaker, or scientific advisor or primary investigator for various sources. GPDS Lima and S Rasmussen declared being employees and holding stocks at Amgen Inc.

Source: Diener HC et al. Cephalalgia. 2021 May 3. doi: 10.1177/03331024211010308.

Patients with obesity who underwent bariatric surgery had 46% lower odds of stroke 1 year later, similar odds of stroke 3 years later, and 22% lower odds of stroke 5 years later, compared with matched control patients, in new research.

purestock/Thinkstock

Michael D. Williams, MD, presented the study findings (abstract A002) at the annual meeting of the American Society for Metabolic & Bariatric Surgery.

The findings are “very good news,” even though the protection against stroke declined further out from the surgery, John D. Scott, MD, scientific program chair of the ASMBS meeting, told this news organization.

The investigators matched more than 56,000 patients with obesity who had bariatric surgery with an equal number of similar patients who did not have this surgery, from a large national insurance database, in what they believe is the largest study of this to date.

“Any intervention that decreases your risk of [cardiovascular] events is good news,” said Dr. Scott, a clinical professor of surgery at the University of South Carolina, Greenville, and metabolic and bariatric surgery director at Prisma Health in Greenville, S.C. “And having a 22%-45% chance of reduction in stroke risk is a very worthwhile intervention.”

Asked how this would change the way clinicians inform patients of what to expect from bariatric surgery, he said: “I would advise patients that studies like this show that surgery would not increase your risk of having a stroke.

“This is consistent with many studies that show that the risks of all macrovascular events decrease after the comorbidity reductions seen after surgery.”

According to Dr. Scott, “the next steps might include a prospective randomized trial of medical treatment versus surgery alone for [cardiovascular]/stroke outcomes, but this is unlikely.”

Similarly, Dr. Williams told this news organization that “I would tell [patients] that surgery is an effective and durable method for weight loss. It also can improve comorbid conditions, particularly diabetes and hypertension.”

Even with this study, “I’m not sure it’s appropriate to say that bariatric surgery will reduce the risk of stroke,” he cautioned.

“However, as we continue to investigate the effects of bariatric surgery, this study contributes to the greater body of knowledge that suggests that reduction in ischemic stroke risk is yet another benefit of bariatric surgery.”

The assigned discussant, Corrigan L. McBride, MD, MBA wanted to know if the lower odds ratio at 1 year might be because preoperative patient selection might eliminate patients at high risk of poor cardiovascular outcomes.

Dr. Williams, a resident at Rush Medical College, Chicago, replied that it is difficult to eliminate potential selection bias, despite best efforts, but this study shows that he can tell patients: “Having surgery is not going to increases your risk of stroke.”

“This is an important study,” Dr. McBride, professor and chief of minimally invasive surgery and bariatric surgery, University of Nebraska Medical Center, Omaha, told this news organization.

“It is the first large study to show a decreased [or no increased] risk of stroke 1, 3, and 5 years after bariatric surgery compared to matched patients, and it had enough data to look at stroke as a standalone endpoint,” Dr. McBride said. “It is important too, for patients and their physicians to understand that there is a lower chance of them having a stroke if they have surgery than if they do not.”
 

‘Important,’ ‘good news’ for stroke risk after bariatric surgery

The impact of bariatric surgery on remission of type 2 diabetes is well known, Dr. Williams noted, and other studies have reported how bariatric surgery affects the risk of major adverse cardiovascular events – a composite of stroke, myocardial infarction, coronary artery disease, and all-cause death – including a study presented in the same meeting session.

However, a very large sample size is needed to be able to demonstrate the effect of bariatric surgery on stroke, since stroke is a rare event.

The researchers analyzed data from the Mariner (PearlDiver.) all-payer insurance national claims database of patients in the United States.

They matched 56,514 patients with a body mass index over 35 kg/m² and comorbidities or a BMI of more than 40 who underwent sleeve gastrectomy or Roux-en-Y gastric bypass during 2010-2019 with 56,514 control patients who did not undergo bariatric surgery.

A year after bariatric surgery, patients in that group had a lower stroke rate than patients in the control group (0.6% vs. 1.2%), and they had close to 50% lower odds of having a stroke (odds ratio, 0.54; 95% CI, 0.47-0.61).

Three years after bariatric surgery, there were 44,948 patients in each group; the rate of stroke was 2.1% in the surgery group and 2.2% in the control group, and there was no significant difference in the odds of having a stroke (OR, 0.96; 95% CI, 0.91-1.00).

Five years after bariatric surgery, there were 27,619 patients in each group; the stroke rate was lower in the bariatric surgery group than in the control group (2.8% vs 3.6%), but reduced odds of stroke was not as great as after 1 year (OR, 0.78; 95% CI, 0.65-0.90).

Dr. Williams has no relevant financial disclosures. Dr. McBride and Dr. Scott disclosed that they are speakers/trainers/faculty advisers for Gore. Dr. Scott is also a consultant for C-SATS (part of Johnson & Johnson).

Patients with obesity who underwent bariatric surgery had 46% lower odds of stroke 1 year later, similar odds of stroke 3 years later, and 22% lower odds of stroke 5 years later, compared with matched control patients, in new research.

purestock/Thinkstock

Michael D. Williams, MD, presented the study findings (abstract A002) at the annual meeting of the American Society for Metabolic & Bariatric Surgery.

The findings are “very good news,” even though the protection against stroke declined further out from the surgery, John D. Scott, MD, scientific program chair of the ASMBS meeting, told this news organization.

The investigators matched more than 56,000 patients with obesity who had bariatric surgery with an equal number of similar patients who did not have this surgery, from a large national insurance database, in what they believe is the largest study of this to date.

“Any intervention that decreases your risk of [cardiovascular] events is good news,” said Dr. Scott, a clinical professor of surgery at the University of South Carolina, Greenville, and metabolic and bariatric surgery director at Prisma Health in Greenville, S.C. “And having a 22%-45% chance of reduction in stroke risk is a very worthwhile intervention.”

Asked how this would change the way clinicians inform patients of what to expect from bariatric surgery, he said: “I would advise patients that studies like this show that surgery would not increase your risk of having a stroke.

“This is consistent with many studies that show that the risks of all macrovascular events decrease after the comorbidity reductions seen after surgery.”

According to Dr. Scott, “the next steps might include a prospective randomized trial of medical treatment versus surgery alone for [cardiovascular]/stroke outcomes, but this is unlikely.”

Similarly, Dr. Williams told this news organization that “I would tell [patients] that surgery is an effective and durable method for weight loss. It also can improve comorbid conditions, particularly diabetes and hypertension.”

Even with this study, “I’m not sure it’s appropriate to say that bariatric surgery will reduce the risk of stroke,” he cautioned.

“However, as we continue to investigate the effects of bariatric surgery, this study contributes to the greater body of knowledge that suggests that reduction in ischemic stroke risk is yet another benefit of bariatric surgery.”

The assigned discussant, Corrigan L. McBride, MD, MBA wanted to know if the lower odds ratio at 1 year might be because preoperative patient selection might eliminate patients at high risk of poor cardiovascular outcomes.

Dr. Williams, a resident at Rush Medical College, Chicago, replied that it is difficult to eliminate potential selection bias, despite best efforts, but this study shows that he can tell patients: “Having surgery is not going to increases your risk of stroke.”

“This is an important study,” Dr. McBride, professor and chief of minimally invasive surgery and bariatric surgery, University of Nebraska Medical Center, Omaha, told this news organization.

“It is the first large study to show a decreased [or no increased] risk of stroke 1, 3, and 5 years after bariatric surgery compared to matched patients, and it had enough data to look at stroke as a standalone endpoint,” Dr. McBride said. “It is important too, for patients and their physicians to understand that there is a lower chance of them having a stroke if they have surgery than if they do not.”
 

‘Important,’ ‘good news’ for stroke risk after bariatric surgery

The impact of bariatric surgery on remission of type 2 diabetes is well known, Dr. Williams noted, and other studies have reported how bariatric surgery affects the risk of major adverse cardiovascular events – a composite of stroke, myocardial infarction, coronary artery disease, and all-cause death – including a study presented in the same meeting session.

However, a very large sample size is needed to be able to demonstrate the effect of bariatric surgery on stroke, since stroke is a rare event.

The researchers analyzed data from the Mariner (PearlDiver.) all-payer insurance national claims database of patients in the United States.

They matched 56,514 patients with a body mass index over 35 kg/m² and comorbidities or a BMI of more than 40 who underwent sleeve gastrectomy or Roux-en-Y gastric bypass during 2010-2019 with 56,514 control patients who did not undergo bariatric surgery.

A year after bariatric surgery, patients in that group had a lower stroke rate than patients in the control group (0.6% vs. 1.2%), and they had close to 50% lower odds of having a stroke (odds ratio, 0.54; 95% CI, 0.47-0.61).

Three years after bariatric surgery, there were 44,948 patients in each group; the rate of stroke was 2.1% in the surgery group and 2.2% in the control group, and there was no significant difference in the odds of having a stroke (OR, 0.96; 95% CI, 0.91-1.00).

Five years after bariatric surgery, there were 27,619 patients in each group; the stroke rate was lower in the bariatric surgery group than in the control group (2.8% vs 3.6%), but reduced odds of stroke was not as great as after 1 year (OR, 0.78; 95% CI, 0.65-0.90).

Dr. Williams has no relevant financial disclosures. Dr. McBride and Dr. Scott disclosed that they are speakers/trainers/faculty advisers for Gore. Dr. Scott is also a consultant for C-SATS (part of Johnson & Johnson).

Patients with obesity who underwent bariatric surgery had 46% lower odds of stroke 1 year later, similar odds of stroke 3 years later, and 22% lower odds of stroke 5 years later, compared with matched control patients, in new research.

purestock/Thinkstock

Michael D. Williams, MD, presented the study findings (abstract A002) at the annual meeting of the American Society for Metabolic & Bariatric Surgery.

The findings are “very good news,” even though the protection against stroke declined further out from the surgery, John D. Scott, MD, scientific program chair of the ASMBS meeting, told this news organization.

The investigators matched more than 56,000 patients with obesity who had bariatric surgery with an equal number of similar patients who did not have this surgery, from a large national insurance database, in what they believe is the largest study of this to date.

“Any intervention that decreases your risk of [cardiovascular] events is good news,” said Dr. Scott, a clinical professor of surgery at the University of South Carolina, Greenville, and metabolic and bariatric surgery director at Prisma Health in Greenville, S.C. “And having a 22%-45% chance of reduction in stroke risk is a very worthwhile intervention.”

Asked how this would change the way clinicians inform patients of what to expect from bariatric surgery, he said: “I would advise patients that studies like this show that surgery would not increase your risk of having a stroke.

“This is consistent with many studies that show that the risks of all macrovascular events decrease after the comorbidity reductions seen after surgery.”

According to Dr. Scott, “the next steps might include a prospective randomized trial of medical treatment versus surgery alone for [cardiovascular]/stroke outcomes, but this is unlikely.”

Similarly, Dr. Williams told this news organization that “I would tell [patients] that surgery is an effective and durable method for weight loss. It also can improve comorbid conditions, particularly diabetes and hypertension.”

Even with this study, “I’m not sure it’s appropriate to say that bariatric surgery will reduce the risk of stroke,” he cautioned.

“However, as we continue to investigate the effects of bariatric surgery, this study contributes to the greater body of knowledge that suggests that reduction in ischemic stroke risk is yet another benefit of bariatric surgery.”

The assigned discussant, Corrigan L. McBride, MD, MBA wanted to know if the lower odds ratio at 1 year might be because preoperative patient selection might eliminate patients at high risk of poor cardiovascular outcomes.

Dr. Williams, a resident at Rush Medical College, Chicago, replied that it is difficult to eliminate potential selection bias, despite best efforts, but this study shows that he can tell patients: “Having surgery is not going to increases your risk of stroke.”

“This is an important study,” Dr. McBride, professor and chief of minimally invasive surgery and bariatric surgery, University of Nebraska Medical Center, Omaha, told this news organization.

“It is the first large study to show a decreased [or no increased] risk of stroke 1, 3, and 5 years after bariatric surgery compared to matched patients, and it had enough data to look at stroke as a standalone endpoint,” Dr. McBride said. “It is important too, for patients and their physicians to understand that there is a lower chance of them having a stroke if they have surgery than if they do not.”
 

‘Important,’ ‘good news’ for stroke risk after bariatric surgery

The impact of bariatric surgery on remission of type 2 diabetes is well known, Dr. Williams noted, and other studies have reported how bariatric surgery affects the risk of major adverse cardiovascular events – a composite of stroke, myocardial infarction, coronary artery disease, and all-cause death – including a study presented in the same meeting session.

However, a very large sample size is needed to be able to demonstrate the effect of bariatric surgery on stroke, since stroke is a rare event.

The researchers analyzed data from the Mariner (PearlDiver.) all-payer insurance national claims database of patients in the United States.

They matched 56,514 patients with a body mass index over 35 kg/m² and comorbidities or a BMI of more than 40 who underwent sleeve gastrectomy or Roux-en-Y gastric bypass during 2010-2019 with 56,514 control patients who did not undergo bariatric surgery.

A year after bariatric surgery, patients in that group had a lower stroke rate than patients in the control group (0.6% vs. 1.2%), and they had close to 50% lower odds of having a stroke (odds ratio, 0.54; 95% CI, 0.47-0.61).

Three years after bariatric surgery, there were 44,948 patients in each group; the rate of stroke was 2.1% in the surgery group and 2.2% in the control group, and there was no significant difference in the odds of having a stroke (OR, 0.96; 95% CI, 0.91-1.00).

Five years after bariatric surgery, there were 27,619 patients in each group; the stroke rate was lower in the bariatric surgery group than in the control group (2.8% vs 3.6%), but reduced odds of stroke was not as great as after 1 year (OR, 0.78; 95% CI, 0.65-0.90).

Dr. Williams has no relevant financial disclosures. Dr. McBride and Dr. Scott disclosed that they are speakers/trainers/faculty advisers for Gore. Dr. Scott is also a consultant for C-SATS (part of Johnson & Johnson).

Prophylactic anticoagulation to prevent venous thromboembolism (VTE) was associated with reduced 60-day mortality in patients with COVID-19 who were ill enough to require hospitalization, a new report shows.

In a cohort study of more than 1,300 hospitalized patients with COVID-19 infection across 30 hospitals in Michigan, both prophylactic- and therapeutic-dose anticoagulation were associated with reduced in-hospital mortality; however, at 60 days, only prophylactic-dose anticoagulation remained associated with lower mortality.

And adherence was key; nonadherence, or missing 2 days or more of anticoagulation, was linked to more deaths at 60 days.

The findings, which were published online June 11 in JAMA Network Open, are final proof that a prophylactic anticoagulation strategy for the hospitalized COVID population is, indeed, the right one, Valerie M. Vaughn, MD, director of hospital medicine research at the University of Utah, Salt Lake City, said in an interview.

“We’ve probably always known that patients with COVID need prophylaxis for VTE, but we found that early on, unfortunately, that wasn’t being done,” Dr. Vaughn said.

“Now, we see that prophylactic rates have increased. We always knew to use anticoagulation prophylactically in patients who were hospitalized with infection because of their risk for VTE, so this study just drives home that proper adherence to an anticoagulation protocol improves mortality,” she said.

Dr. Vaughn was on the front lines when COVID-19 came to Michigan, where the research was conducted.

“We probably should have been anticoagulating from the get-go, but you have to remember that in the early days of COVID, the hospitals in Michigan were being overwhelmed. They didn’t have PPE. They were taking care of patients outside of their typical hospital beds or setting up field hospitals,” she said. “It was not quite as bad as New York, but at the University of Michigan, we set up four or five ICUs outside of our normal care.”

They also converted the top floor of their pediatric hospital into an ICU to take care of patients with COVID during the first surge, she added. “We didn’t know much about this disease, but faced with this influx of patients, many of whom were dying with blood clots, we had to do something.”  

Some hospitals began prophylactically anticoagulating their patients, but others hesitated before adopting the strategy. “But now we feel confident that prophylactic anticoagulation, done according to the right protocol, with no interruptions in the treatment, is beneficial,” Dr. Vaughn said.

The best medication choice is enoxaparin (Lovenox), which can be given once a day, as opposed to heparin, which needs to be given via injection three times a day, she said.

“Prophylactic dose anticoagulation is typically given by an injection under the skin, but a lot of times, I’ve had patients tell me they feel like a human pin cushion and have all these bruises from being stuck with needles every day, which I can totally relate to,” she said.

“It is important for us as clinicians to explain that we’re having to poke our patients because it is good for them and will help them fight COVID,” she added. “Also having the once-a-day option is going to be a lot better for adherence, and adherence to the protocol, not missing any days, is key to the better outcome.”

Dr. Vaughn and her team reviewed the charts of 1,351 patients (48% women, 49% Black, median age 64 [range 52-75]) who were hospitalized throughout Michigan during the first several months of the COVID-19 pandemic, from March to June 2020.

Only 18 patients (1.3%) had a confirmed VTE and 219 patients (16.2%) received treatment-dose anticoagulation.

The researchers noted that use of treatment-dose anticoagulation without imaging ranged from 0% to 29% across hospitals and increased significantly over time.

Of the 1,127 patients who received anticoagulation, 392 (34.8%) missed 2 days or more of prophylaxis.

In addition, there were varying rates of missed prophylaxis among the hospitals, from 11% to 61%, but these rates decreased markedly over time.

Missed doses were associated with a higher 60-day mortality (adjusted hazard ratio, 1.31; 95% confidence interval, 1.03-1.67), but not in-hospital mortality (aHR, 0.97; 95% CI, 0.91-1.03).

Compared with no anticoagulation, receiving any dose of anticoagulation was associated with lower in-hospital mortality.

However, only prophylactic-dose anticoagulation remained associated with lower mortality at 60 days. The adjusted hazard ratio for prophylactic-dose anticoagulation was 0.71 (95% CI, 0.51-0.90), compared with 0.92 (95% CI, 0.63-1.35) for treatment-dose anticoagulation.
 

Study boosts confidence

Despite its limitations, the study should make clinicians more confident that the use of prophylactic anticoagulation is warranted for hospitalized patients with COVID-19, write Andrew B. Dicks, MD, and Ido Weinberg, MD, from Massachusetts General Hospital, Boston, in an invited commentary.

“Practically, we still lack the granular data we need to help guide us in patient-by-patient decision-making – such as anticoagulation agent choice, dosage, and duration of therapy – especially as dictated by acuity of patient illness,” Dr. Dicks and Dr. Weinberg note.

“While we still await the data from randomized controlled trials to guide the optimal anticoagulation dose and duration, this study adds significant merit to the previously published recommendations from several different medical organizations regarding the use of prophylactic anticoagulation in hospitalized patients with COVID-19,” Dr. Dicks told this news organization.

The study was supported by Blue Cross and Blue Shield of Michigan and Blue Care Network as part of their Value Partnerships program. Dr. Vaughn has reported receiving speaking fees from Thermo Fisher Scientific. Dr. Dicks and Dr. Weinberg have reported no relevant financial relationships.

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

Prophylactic anticoagulation to prevent venous thromboembolism (VTE) was associated with reduced 60-day mortality in patients with COVID-19 who were ill enough to require hospitalization, a new report shows.

In a cohort study of more than 1,300 hospitalized patients with COVID-19 infection across 30 hospitals in Michigan, both prophylactic- and therapeutic-dose anticoagulation were associated with reduced in-hospital mortality; however, at 60 days, only prophylactic-dose anticoagulation remained associated with lower mortality.

And adherence was key; nonadherence, or missing 2 days or more of anticoagulation, was linked to more deaths at 60 days.

The findings, which were published online June 11 in JAMA Network Open, are final proof that a prophylactic anticoagulation strategy for the hospitalized COVID population is, indeed, the right one, Valerie M. Vaughn, MD, director of hospital medicine research at the University of Utah, Salt Lake City, said in an interview.

“We’ve probably always known that patients with COVID need prophylaxis for VTE, but we found that early on, unfortunately, that wasn’t being done,” Dr. Vaughn said.

“Now, we see that prophylactic rates have increased. We always knew to use anticoagulation prophylactically in patients who were hospitalized with infection because of their risk for VTE, so this study just drives home that proper adherence to an anticoagulation protocol improves mortality,” she said.

Dr. Vaughn was on the front lines when COVID-19 came to Michigan, where the research was conducted.

“We probably should have been anticoagulating from the get-go, but you have to remember that in the early days of COVID, the hospitals in Michigan were being overwhelmed. They didn’t have PPE. They were taking care of patients outside of their typical hospital beds or setting up field hospitals,” she said. “It was not quite as bad as New York, but at the University of Michigan, we set up four or five ICUs outside of our normal care.”

They also converted the top floor of their pediatric hospital into an ICU to take care of patients with COVID during the first surge, she added. “We didn’t know much about this disease, but faced with this influx of patients, many of whom were dying with blood clots, we had to do something.”  

Some hospitals began prophylactically anticoagulating their patients, but others hesitated before adopting the strategy. “But now we feel confident that prophylactic anticoagulation, done according to the right protocol, with no interruptions in the treatment, is beneficial,” Dr. Vaughn said.

The best medication choice is enoxaparin (Lovenox), which can be given once a day, as opposed to heparin, which needs to be given via injection three times a day, she said.

“Prophylactic dose anticoagulation is typically given by an injection under the skin, but a lot of times, I’ve had patients tell me they feel like a human pin cushion and have all these bruises from being stuck with needles every day, which I can totally relate to,” she said.

“It is important for us as clinicians to explain that we’re having to poke our patients because it is good for them and will help them fight COVID,” she added. “Also having the once-a-day option is going to be a lot better for adherence, and adherence to the protocol, not missing any days, is key to the better outcome.”

Dr. Vaughn and her team reviewed the charts of 1,351 patients (48% women, 49% Black, median age 64 [range 52-75]) who were hospitalized throughout Michigan during the first several months of the COVID-19 pandemic, from March to June 2020.

Only 18 patients (1.3%) had a confirmed VTE and 219 patients (16.2%) received treatment-dose anticoagulation.

The researchers noted that use of treatment-dose anticoagulation without imaging ranged from 0% to 29% across hospitals and increased significantly over time.

Of the 1,127 patients who received anticoagulation, 392 (34.8%) missed 2 days or more of prophylaxis.

In addition, there were varying rates of missed prophylaxis among the hospitals, from 11% to 61%, but these rates decreased markedly over time.

Missed doses were associated with a higher 60-day mortality (adjusted hazard ratio, 1.31; 95% confidence interval, 1.03-1.67), but not in-hospital mortality (aHR, 0.97; 95% CI, 0.91-1.03).

Compared with no anticoagulation, receiving any dose of anticoagulation was associated with lower in-hospital mortality.

However, only prophylactic-dose anticoagulation remained associated with lower mortality at 60 days. The adjusted hazard ratio for prophylactic-dose anticoagulation was 0.71 (95% CI, 0.51-0.90), compared with 0.92 (95% CI, 0.63-1.35) for treatment-dose anticoagulation.
 

Study boosts confidence

Despite its limitations, the study should make clinicians more confident that the use of prophylactic anticoagulation is warranted for hospitalized patients with COVID-19, write Andrew B. Dicks, MD, and Ido Weinberg, MD, from Massachusetts General Hospital, Boston, in an invited commentary.

“Practically, we still lack the granular data we need to help guide us in patient-by-patient decision-making – such as anticoagulation agent choice, dosage, and duration of therapy – especially as dictated by acuity of patient illness,” Dr. Dicks and Dr. Weinberg note.

“While we still await the data from randomized controlled trials to guide the optimal anticoagulation dose and duration, this study adds significant merit to the previously published recommendations from several different medical organizations regarding the use of prophylactic anticoagulation in hospitalized patients with COVID-19,” Dr. Dicks told this news organization.

The study was supported by Blue Cross and Blue Shield of Michigan and Blue Care Network as part of their Value Partnerships program. Dr. Vaughn has reported receiving speaking fees from Thermo Fisher Scientific. Dr. Dicks and Dr. Weinberg have reported no relevant financial relationships.

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

Prophylactic anticoagulation to prevent venous thromboembolism (VTE) was associated with reduced 60-day mortality in patients with COVID-19 who were ill enough to require hospitalization, a new report shows.

In a cohort study of more than 1,300 hospitalized patients with COVID-19 infection across 30 hospitals in Michigan, both prophylactic- and therapeutic-dose anticoagulation were associated with reduced in-hospital mortality; however, at 60 days, only prophylactic-dose anticoagulation remained associated with lower mortality.

And adherence was key; nonadherence, or missing 2 days or more of anticoagulation, was linked to more deaths at 60 days.

The findings, which were published online June 11 in JAMA Network Open, are final proof that a prophylactic anticoagulation strategy for the hospitalized COVID population is, indeed, the right one, Valerie M. Vaughn, MD, director of hospital medicine research at the University of Utah, Salt Lake City, said in an interview.

“We’ve probably always known that patients with COVID need prophylaxis for VTE, but we found that early on, unfortunately, that wasn’t being done,” Dr. Vaughn said.

“Now, we see that prophylactic rates have increased. We always knew to use anticoagulation prophylactically in patients who were hospitalized with infection because of their risk for VTE, so this study just drives home that proper adherence to an anticoagulation protocol improves mortality,” she said.

Dr. Vaughn was on the front lines when COVID-19 came to Michigan, where the research was conducted.

“We probably should have been anticoagulating from the get-go, but you have to remember that in the early days of COVID, the hospitals in Michigan were being overwhelmed. They didn’t have PPE. They were taking care of patients outside of their typical hospital beds or setting up field hospitals,” she said. “It was not quite as bad as New York, but at the University of Michigan, we set up four or five ICUs outside of our normal care.”

They also converted the top floor of their pediatric hospital into an ICU to take care of patients with COVID during the first surge, she added. “We didn’t know much about this disease, but faced with this influx of patients, many of whom were dying with blood clots, we had to do something.”  

Some hospitals began prophylactically anticoagulating their patients, but others hesitated before adopting the strategy. “But now we feel confident that prophylactic anticoagulation, done according to the right protocol, with no interruptions in the treatment, is beneficial,” Dr. Vaughn said.

The best medication choice is enoxaparin (Lovenox), which can be given once a day, as opposed to heparin, which needs to be given via injection three times a day, she said.

“Prophylactic dose anticoagulation is typically given by an injection under the skin, but a lot of times, I’ve had patients tell me they feel like a human pin cushion and have all these bruises from being stuck with needles every day, which I can totally relate to,” she said.

“It is important for us as clinicians to explain that we’re having to poke our patients because it is good for them and will help them fight COVID,” she added. “Also having the once-a-day option is going to be a lot better for adherence, and adherence to the protocol, not missing any days, is key to the better outcome.”

Dr. Vaughn and her team reviewed the charts of 1,351 patients (48% women, 49% Black, median age 64 [range 52-75]) who were hospitalized throughout Michigan during the first several months of the COVID-19 pandemic, from March to June 2020.

Only 18 patients (1.3%) had a confirmed VTE and 219 patients (16.2%) received treatment-dose anticoagulation.

The researchers noted that use of treatment-dose anticoagulation without imaging ranged from 0% to 29% across hospitals and increased significantly over time.

Of the 1,127 patients who received anticoagulation, 392 (34.8%) missed 2 days or more of prophylaxis.

In addition, there were varying rates of missed prophylaxis among the hospitals, from 11% to 61%, but these rates decreased markedly over time.

Missed doses were associated with a higher 60-day mortality (adjusted hazard ratio, 1.31; 95% confidence interval, 1.03-1.67), but not in-hospital mortality (aHR, 0.97; 95% CI, 0.91-1.03).

Compared with no anticoagulation, receiving any dose of anticoagulation was associated with lower in-hospital mortality.

However, only prophylactic-dose anticoagulation remained associated with lower mortality at 60 days. The adjusted hazard ratio for prophylactic-dose anticoagulation was 0.71 (95% CI, 0.51-0.90), compared with 0.92 (95% CI, 0.63-1.35) for treatment-dose anticoagulation.
 

Study boosts confidence

Despite its limitations, the study should make clinicians more confident that the use of prophylactic anticoagulation is warranted for hospitalized patients with COVID-19, write Andrew B. Dicks, MD, and Ido Weinberg, MD, from Massachusetts General Hospital, Boston, in an invited commentary.

“Practically, we still lack the granular data we need to help guide us in patient-by-patient decision-making – such as anticoagulation agent choice, dosage, and duration of therapy – especially as dictated by acuity of patient illness,” Dr. Dicks and Dr. Weinberg note.

“While we still await the data from randomized controlled trials to guide the optimal anticoagulation dose and duration, this study adds significant merit to the previously published recommendations from several different medical organizations regarding the use of prophylactic anticoagulation in hospitalized patients with COVID-19,” Dr. Dicks told this news organization.

The study was supported by Blue Cross and Blue Shield of Michigan and Blue Care Network as part of their Value Partnerships program. Dr. Vaughn has reported receiving speaking fees from Thermo Fisher Scientific. Dr. Dicks and Dr. Weinberg have reported no relevant financial relationships.

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

In the absence of formal clinical trials, pediatricians are racing to determine the efficacy and risks of currently used therapies for the SARS-CoV-2–linked multisystem inflammatory syndrome in children (MIS-C).

That requires rapid pragmatic evaluation of therapies. Two real-world observational studies published online June 16 in The New England Journal of Medicine do that, with differing results.

In the Overcoming COVID-19 study, investigators assessed initial therapy and outcomes for patients with MIS-C using surveillance data from 58 pediatric hospitals nationwide.

The results suggest that patients with MIS-C who were younger than 21 years of age and who were initially treated with intravenous immunoglobulin (IVIG) plus glucocorticoids fared better in terms of cardiovascular function.

The study included 518 children (median age, 8.7 years) who were admitted to the hospital between March and October 2020 and who received at least one immunomodulatory therapy. In a propensity score–matched analysis, those given IVIG plus glucocorticoids (n = 103) had a lower risk for the primary outcome of cardiovascular dysfunction on or after day 2 than those given IVIG alone (n = 103), at 17% versus 31% (risk ratio, 0.56; 95% confidence interval, 0.34-0.94).

Risks for individual aspects of the study’s composite outcome were also lower with IVIG plus glucocorticoids. Left ventricular dysfunction occurred in 8% and 17%, respectively (RR, 0.46; 95% CI, 0.19-1.15). Shock requiring vasopressor use emerged in 13% and 24%, respectively (RR, 0.54; 95% CI, 0.29-1.00).

In addition, there were fewer cases in which adjunctive therapy was given on day one among those who received combination therapy than among those who received IVIG alone, at 34% versus 70% (RR, 0.49; 95% CI, 0.36-0.65), but the risk for fever was not lower on or after day two (31% and 40%, respectively; RR, 0.78; 95% CI, 0.53-1.13).

Lead author Mary Beth F. Son, MD, director of the rheumatology program at Boston Children’s Hospital, who is also associate professor of pediatrics at Harvard Medical School, stressed that the study did not assess which MIS-C patients should receive treatment. “Rather, we studied children who had been treated with one of two initial regimens and then assessed short-term outcomes,” she told this news organization.

Going forward, it will be important to study which children should receive immunomodulatory treatment, Dr. Son said. “Specifically, can the less ill children receive IVIG alone or no treatment? This is an unanswered question at the moment, which could be addressed with a randomized controlled trial.”

Future directions, she added, will include assessing long-term cardiac outcomes for patients with MIS-C as well as studying outpatient regimens, especially those that involve steroids.

Earlier this year, French investigators found better outcomes with combined corticosteroids and IVIG than with IVIG alone. They suggested that combination therapy should be the standard of care, given the present state of therapeutic knowledge.
 

Maybe not so standard

Different results emerged, however, from an international study of MIS-C that compared three, rather than two, treatment approaches. Collaborators from the Best Available Treatment Study for MIS-C (BATS) evaluated data for 614 children with suspected MIS-C between June 2020 and February 2021 in 32 countries and found no substantial differences in recovery among children whose primary treatment was IVIG alone, IVIG plus glucocorticoids, or glucocorticoids alone.

The study by Andrew J. McArdle, MB BChir, MSC, a clinical research fellow at Imperial College London, and colleagues was published June 16 in The New England Journal of Medicine.

In the BATS cohort, 246 received IVIG alone, 208 received IVIG plus glucocorticoids, and 99 received glucocorticoids alone. Twenty-two patients received other combinations, including biologics, and 39 received no immunomodulatory therapy.

Among patients who were included in the primary analysis, death occurred or inotropic or ventilatory support was employed in 56 of 180 of the patients who received IVIG plus glucocorticoids, compared with 44 of 211 patients treated with IVIG alone, for an adjusted odds ratio (aOR) of 0.77 (95% CI, 0.33-1.82). Among those who received glucocorticoids alone, 17 of 83 met the primary endpoint of death or inotropic or ventilatory support, for an aOR relative to IVIG alone of 0.54 (95% CI, 0.22-1.33).

After adjustments, the likelihood for reduced disease severity was similar in the two groups relative to IVIG alone, at 0.90 for IVIG plus glucocorticoids and 0.93 for glucocorticoids alone. Time to reduction in disease severity was also comparable across all groups.

Some of the differences between the U.S. study and the global studies could be the result of the larger size of the international cohort and possibly a difference in the strains of virus in the United States and abroad, according to S. Sexson Tejtel, MD, PhD, MPH, a pediatric cardiologist at Texas Children’s Hospital and an assistant professor at Baylor College of Medicine, Houston, Texas. “Some strains make children sicker than others, and they’re going to need more treatment,” said Dr. Sexson Tejtel, who was not involved in either study.

Dr. Sexson Tejtel also noted that the U.S. researchers did not assess outcomes among children treated with steroids alone. “It would be interesting to know what steroids alone look like in the U.S. MIS-C population,” she said in an interview.

BATS corresponding author Michael Levin, MBE, PhD, FRCPCH, an Imperial College professor of pediatrics and international child health, told this news organization that the differing results may have arisen because of the international study’s three-treatment focus, its wider spectrum of patients, and its different endpoints: Death and inotropic support on or after day 2, versus echocardiographic left ventricular dysfunction or inotropic usage.

Regardless of the differences between the two studies, neither establishes the most effective single or combination treatment, writes Roberta L. DeBiasi, MD, of the Division of Pediatric Infectious Diseases at Children’s National Hospital and Research Institute and George Washington University, Washington, in an accompanying editorial. “Specifically, neither study was powered to include an evaluation of approaches that steer away from broad immunosuppression with glucocorticoids and that focus on more targeted and titratable treatments with biologic agents, such as anakinra and infliximab,” she writes.

Dr. DeBiasi adds that long-term follow-up studies of cardiac and noncardiac outcomes in these patients will launch soon. “Meanwhile, continued collaboration across centers is essential to decreasing the short-term incidence of death and complications,” she writes.

“It will be interesting as we apply results from these studies as they come out to see how they change our practice,” Dr. Sexson Tejtel said. “And it would be good to have some randomized clinical trials.”

For Dr. Levin, the bottom line is that all three treatments are associated with recovery for a majority of children. “This is good news for clinicians who have been guessing which treatment to use,” he said. “Both studies are attempts to provide doctors with some evidence on which to base treatment decisions and are not the final answer. Our study is ongoing, and with larger numbers of patients it may give clearer answers.”

The Overcoming COVID-19 study was funded by the U.S. Centers for Disease Control and Prevention. Several coauthors have reported support from industry outside of the submitted work. BATS was funded by the European Union’s Horizons 2020 Program. The study authors have disclosed no relevant financial relationships. One coauthor’s spouse is employed by GlaxoSmithKline. Dr. DeBiasi and Dr. Sexson Tejtel have disclosed no relevant financial relationships.

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

In the absence of formal clinical trials, pediatricians are racing to determine the efficacy and risks of currently used therapies for the SARS-CoV-2–linked multisystem inflammatory syndrome in children (MIS-C).

That requires rapid pragmatic evaluation of therapies. Two real-world observational studies published online June 16 in The New England Journal of Medicine do that, with differing results.

In the Overcoming COVID-19 study, investigators assessed initial therapy and outcomes for patients with MIS-C using surveillance data from 58 pediatric hospitals nationwide.

The results suggest that patients with MIS-C who were younger than 21 years of age and who were initially treated with intravenous immunoglobulin (IVIG) plus glucocorticoids fared better in terms of cardiovascular function.

The study included 518 children (median age, 8.7 years) who were admitted to the hospital between March and October 2020 and who received at least one immunomodulatory therapy. In a propensity score–matched analysis, those given IVIG plus glucocorticoids (n = 103) had a lower risk for the primary outcome of cardiovascular dysfunction on or after day 2 than those given IVIG alone (n = 103), at 17% versus 31% (risk ratio, 0.56; 95% confidence interval, 0.34-0.94).

Risks for individual aspects of the study’s composite outcome were also lower with IVIG plus glucocorticoids. Left ventricular dysfunction occurred in 8% and 17%, respectively (RR, 0.46; 95% CI, 0.19-1.15). Shock requiring vasopressor use emerged in 13% and 24%, respectively (RR, 0.54; 95% CI, 0.29-1.00).

In addition, there were fewer cases in which adjunctive therapy was given on day one among those who received combination therapy than among those who received IVIG alone, at 34% versus 70% (RR, 0.49; 95% CI, 0.36-0.65), but the risk for fever was not lower on or after day two (31% and 40%, respectively; RR, 0.78; 95% CI, 0.53-1.13).

Lead author Mary Beth F. Son, MD, director of the rheumatology program at Boston Children’s Hospital, who is also associate professor of pediatrics at Harvard Medical School, stressed that the study did not assess which MIS-C patients should receive treatment. “Rather, we studied children who had been treated with one of two initial regimens and then assessed short-term outcomes,” she told this news organization.

Going forward, it will be important to study which children should receive immunomodulatory treatment, Dr. Son said. “Specifically, can the less ill children receive IVIG alone or no treatment? This is an unanswered question at the moment, which could be addressed with a randomized controlled trial.”

Future directions, she added, will include assessing long-term cardiac outcomes for patients with MIS-C as well as studying outpatient regimens, especially those that involve steroids.

Earlier this year, French investigators found better outcomes with combined corticosteroids and IVIG than with IVIG alone. They suggested that combination therapy should be the standard of care, given the present state of therapeutic knowledge.
 

Maybe not so standard

Different results emerged, however, from an international study of MIS-C that compared three, rather than two, treatment approaches. Collaborators from the Best Available Treatment Study for MIS-C (BATS) evaluated data for 614 children with suspected MIS-C between June 2020 and February 2021 in 32 countries and found no substantial differences in recovery among children whose primary treatment was IVIG alone, IVIG plus glucocorticoids, or glucocorticoids alone.

The study by Andrew J. McArdle, MB BChir, MSC, a clinical research fellow at Imperial College London, and colleagues was published June 16 in The New England Journal of Medicine.

In the BATS cohort, 246 received IVIG alone, 208 received IVIG plus glucocorticoids, and 99 received glucocorticoids alone. Twenty-two patients received other combinations, including biologics, and 39 received no immunomodulatory therapy.

Among patients who were included in the primary analysis, death occurred or inotropic or ventilatory support was employed in 56 of 180 of the patients who received IVIG plus glucocorticoids, compared with 44 of 211 patients treated with IVIG alone, for an adjusted odds ratio (aOR) of 0.77 (95% CI, 0.33-1.82). Among those who received glucocorticoids alone, 17 of 83 met the primary endpoint of death or inotropic or ventilatory support, for an aOR relative to IVIG alone of 0.54 (95% CI, 0.22-1.33).

After adjustments, the likelihood for reduced disease severity was similar in the two groups relative to IVIG alone, at 0.90 for IVIG plus glucocorticoids and 0.93 for glucocorticoids alone. Time to reduction in disease severity was also comparable across all groups.

Some of the differences between the U.S. study and the global studies could be the result of the larger size of the international cohort and possibly a difference in the strains of virus in the United States and abroad, according to S. Sexson Tejtel, MD, PhD, MPH, a pediatric cardiologist at Texas Children’s Hospital and an assistant professor at Baylor College of Medicine, Houston, Texas. “Some strains make children sicker than others, and they’re going to need more treatment,” said Dr. Sexson Tejtel, who was not involved in either study.

Dr. Sexson Tejtel also noted that the U.S. researchers did not assess outcomes among children treated with steroids alone. “It would be interesting to know what steroids alone look like in the U.S. MIS-C population,” she said in an interview.

BATS corresponding author Michael Levin, MBE, PhD, FRCPCH, an Imperial College professor of pediatrics and international child health, told this news organization that the differing results may have arisen because of the international study’s three-treatment focus, its wider spectrum of patients, and its different endpoints: Death and inotropic support on or after day 2, versus echocardiographic left ventricular dysfunction or inotropic usage.

Regardless of the differences between the two studies, neither establishes the most effective single or combination treatment, writes Roberta L. DeBiasi, MD, of the Division of Pediatric Infectious Diseases at Children’s National Hospital and Research Institute and George Washington University, Washington, in an accompanying editorial. “Specifically, neither study was powered to include an evaluation of approaches that steer away from broad immunosuppression with glucocorticoids and that focus on more targeted and titratable treatments with biologic agents, such as anakinra and infliximab,” she writes.

Dr. DeBiasi adds that long-term follow-up studies of cardiac and noncardiac outcomes in these patients will launch soon. “Meanwhile, continued collaboration across centers is essential to decreasing the short-term incidence of death and complications,” she writes.

“It will be interesting as we apply results from these studies as they come out to see how they change our practice,” Dr. Sexson Tejtel said. “And it would be good to have some randomized clinical trials.”

For Dr. Levin, the bottom line is that all three treatments are associated with recovery for a majority of children. “This is good news for clinicians who have been guessing which treatment to use,” he said. “Both studies are attempts to provide doctors with some evidence on which to base treatment decisions and are not the final answer. Our study is ongoing, and with larger numbers of patients it may give clearer answers.”

The Overcoming COVID-19 study was funded by the U.S. Centers for Disease Control and Prevention. Several coauthors have reported support from industry outside of the submitted work. BATS was funded by the European Union’s Horizons 2020 Program. The study authors have disclosed no relevant financial relationships. One coauthor’s spouse is employed by GlaxoSmithKline. Dr. DeBiasi and Dr. Sexson Tejtel have disclosed no relevant financial relationships.

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

In the absence of formal clinical trials, pediatricians are racing to determine the efficacy and risks of currently used therapies for the SARS-CoV-2–linked multisystem inflammatory syndrome in children (MIS-C).

That requires rapid pragmatic evaluation of therapies. Two real-world observational studies published online June 16 in The New England Journal of Medicine do that, with differing results.

In the Overcoming COVID-19 study, investigators assessed initial therapy and outcomes for patients with MIS-C using surveillance data from 58 pediatric hospitals nationwide.

The results suggest that patients with MIS-C who were younger than 21 years of age and who were initially treated with intravenous immunoglobulin (IVIG) plus glucocorticoids fared better in terms of cardiovascular function.

The study included 518 children (median age, 8.7 years) who were admitted to the hospital between March and October 2020 and who received at least one immunomodulatory therapy. In a propensity score–matched analysis, those given IVIG plus glucocorticoids (n = 103) had a lower risk for the primary outcome of cardiovascular dysfunction on or after day 2 than those given IVIG alone (n = 103), at 17% versus 31% (risk ratio, 0.56; 95% confidence interval, 0.34-0.94).

Risks for individual aspects of the study’s composite outcome were also lower with IVIG plus glucocorticoids. Left ventricular dysfunction occurred in 8% and 17%, respectively (RR, 0.46; 95% CI, 0.19-1.15). Shock requiring vasopressor use emerged in 13% and 24%, respectively (RR, 0.54; 95% CI, 0.29-1.00).

In addition, there were fewer cases in which adjunctive therapy was given on day one among those who received combination therapy than among those who received IVIG alone, at 34% versus 70% (RR, 0.49; 95% CI, 0.36-0.65), but the risk for fever was not lower on or after day two (31% and 40%, respectively; RR, 0.78; 95% CI, 0.53-1.13).

Lead author Mary Beth F. Son, MD, director of the rheumatology program at Boston Children’s Hospital, who is also associate professor of pediatrics at Harvard Medical School, stressed that the study did not assess which MIS-C patients should receive treatment. “Rather, we studied children who had been treated with one of two initial regimens and then assessed short-term outcomes,” she told this news organization.

Going forward, it will be important to study which children should receive immunomodulatory treatment, Dr. Son said. “Specifically, can the less ill children receive IVIG alone or no treatment? This is an unanswered question at the moment, which could be addressed with a randomized controlled trial.”

Future directions, she added, will include assessing long-term cardiac outcomes for patients with MIS-C as well as studying outpatient regimens, especially those that involve steroids.

Earlier this year, French investigators found better outcomes with combined corticosteroids and IVIG than with IVIG alone. They suggested that combination therapy should be the standard of care, given the present state of therapeutic knowledge.
 

Maybe not so standard

Different results emerged, however, from an international study of MIS-C that compared three, rather than two, treatment approaches. Collaborators from the Best Available Treatment Study for MIS-C (BATS) evaluated data for 614 children with suspected MIS-C between June 2020 and February 2021 in 32 countries and found no substantial differences in recovery among children whose primary treatment was IVIG alone, IVIG plus glucocorticoids, or glucocorticoids alone.

The study by Andrew J. McArdle, MB BChir, MSC, a clinical research fellow at Imperial College London, and colleagues was published June 16 in The New England Journal of Medicine.

In the BATS cohort, 246 received IVIG alone, 208 received IVIG plus glucocorticoids, and 99 received glucocorticoids alone. Twenty-two patients received other combinations, including biologics, and 39 received no immunomodulatory therapy.

Among patients who were included in the primary analysis, death occurred or inotropic or ventilatory support was employed in 56 of 180 of the patients who received IVIG plus glucocorticoids, compared with 44 of 211 patients treated with IVIG alone, for an adjusted odds ratio (aOR) of 0.77 (95% CI, 0.33-1.82). Among those who received glucocorticoids alone, 17 of 83 met the primary endpoint of death or inotropic or ventilatory support, for an aOR relative to IVIG alone of 0.54 (95% CI, 0.22-1.33).

After adjustments, the likelihood for reduced disease severity was similar in the two groups relative to IVIG alone, at 0.90 for IVIG plus glucocorticoids and 0.93 for glucocorticoids alone. Time to reduction in disease severity was also comparable across all groups.

Some of the differences between the U.S. study and the global studies could be the result of the larger size of the international cohort and possibly a difference in the strains of virus in the United States and abroad, according to S. Sexson Tejtel, MD, PhD, MPH, a pediatric cardiologist at Texas Children’s Hospital and an assistant professor at Baylor College of Medicine, Houston, Texas. “Some strains make children sicker than others, and they’re going to need more treatment,” said Dr. Sexson Tejtel, who was not involved in either study.

Dr. Sexson Tejtel also noted that the U.S. researchers did not assess outcomes among children treated with steroids alone. “It would be interesting to know what steroids alone look like in the U.S. MIS-C population,” she said in an interview.

BATS corresponding author Michael Levin, MBE, PhD, FRCPCH, an Imperial College professor of pediatrics and international child health, told this news organization that the differing results may have arisen because of the international study’s three-treatment focus, its wider spectrum of patients, and its different endpoints: Death and inotropic support on or after day 2, versus echocardiographic left ventricular dysfunction or inotropic usage.

Regardless of the differences between the two studies, neither establishes the most effective single or combination treatment, writes Roberta L. DeBiasi, MD, of the Division of Pediatric Infectious Diseases at Children’s National Hospital and Research Institute and George Washington University, Washington, in an accompanying editorial. “Specifically, neither study was powered to include an evaluation of approaches that steer away from broad immunosuppression with glucocorticoids and that focus on more targeted and titratable treatments with biologic agents, such as anakinra and infliximab,” she writes.

Dr. DeBiasi adds that long-term follow-up studies of cardiac and noncardiac outcomes in these patients will launch soon. “Meanwhile, continued collaboration across centers is essential to decreasing the short-term incidence of death and complications,” she writes.

“It will be interesting as we apply results from these studies as they come out to see how they change our practice,” Dr. Sexson Tejtel said. “And it would be good to have some randomized clinical trials.”

For Dr. Levin, the bottom line is that all three treatments are associated with recovery for a majority of children. “This is good news for clinicians who have been guessing which treatment to use,” he said. “Both studies are attempts to provide doctors with some evidence on which to base treatment decisions and are not the final answer. Our study is ongoing, and with larger numbers of patients it may give clearer answers.”

The Overcoming COVID-19 study was funded by the U.S. Centers for Disease Control and Prevention. Several coauthors have reported support from industry outside of the submitted work. BATS was funded by the European Union’s Horizons 2020 Program. The study authors have disclosed no relevant financial relationships. One coauthor’s spouse is employed by GlaxoSmithKline. Dr. DeBiasi and Dr. Sexson Tejtel have disclosed no relevant financial relationships.

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

A large proportion of initial Investigator Global Assessment (IGA) 0/1 or Eczema Area and Severity Index (EASI) 75 responders at week 16 maintained response with continued tralokinumab dosing every 2 weeks or every 4 weeks during a 36-week maintenance period without the use of rescue medication including topical corticosteroids, results from a pooled analysis of two trials found.

“The interesting thing here is that there weren’t major differences in the maintenance dosing, which really allows us some flexibility with maintenance dosing for this particular drug,” lead study investigator Andrew Blauvelt, MD, MBA, said during the Revolutionizing Atopic Dermatitis symposium.

Administered subcutaneously, tralokinumab is a fully human IgG4 monoclonal antibody that specifically binds to interleukin-13, a key driver of underlying inflammation in AD. In two of the drug’s pivotal phase 3 trials, ECZTRA 1 and ECZTRA 2, tralokinumab monotherapy was superior to placebo at week 16 for all primary and secondary endpoints.

The purpose of the current trial was to investigate the maintenance of efficacy after 16 weeks of tralokinumab in those who were initial responders and to assess the efficacy of reduced dosing frequency from 300 mg every 2 weeks to 300 mg every 4 weeks after a 36-week maintenance phase. Patients who used rescue medication, including topical corticosteroids, were considered to be nonresponders.

Dr. Blauvelt reported results from 1,596 adult patients with a mean age of 38 years who were randomized to tralokinumab 300 mg every 2 weeks or placebo in the initial treatment period. At baseline, the mean duration of AD was 28.2 years, 50% had severe disease based on their IGA score, and their mean Dermatology Life Quality Index score was 17.

Of these patients, 412 achieved an IGA score of 0 or 1 and/or an EASI 75 at week 16 with tralokinumab every 2 weeks and were rerandomized (2:2:1) to continue tralokinumab 300 mg every 2 weeks, tralokinumab 300 mg every 4 weeks, or placebo for 36 weeks.

The researchers found that 56%-57% of patients in the tralokinumab every 2-week dosing group maintained their IGA 0/1 and EASI 75 response at week 52, compared with 42%-50% of those who received the drug every 4 weeks. “So, there may be a population of patients who require drug every 4 weeks after initially receiving the drug every 2 weeks for the first 16 weeks,” said Dr. Blauvelt, a dermatologist who is president of Oregon Medical Research Center, Portland. “Interestingly, 26%-34% of patients on placebo maintained their IGA 0/1 and EASI 75 response a response to week 52. Perhaps those are patients who have more mild disease or more episodic disease when they started this trial.”

He also noted that time to relapse based on their IGA 0/1 and EASI 75 was prolonged with tralokinumab treatment, compared with placebo, and adverse event frequency was similar among all treatment groups (73% among those who received tralokinumab every 2 weeks, 66% among those who received tralokinumab every 4 weeks, and 70% in the placebo group).

Dr. Blauvelt concluded that a step-down in tralokinumab dosing to every 4 weeks may be an option for some patients achieving clear or almost clear skin after an initial dosing schedule of every 2 weeks.

LEO Pharma, which is developing tralokinumab, sponsored the analysis. Dr. Blauvelt reported that he is an investigator and a scientific adviser for LEO Pharma and for several other pharmaceutical companies developing treatments for AD.

[email protected]

A large proportion of initial Investigator Global Assessment (IGA) 0/1 or Eczema Area and Severity Index (EASI) 75 responders at week 16 maintained response with continued tralokinumab dosing every 2 weeks or every 4 weeks during a 36-week maintenance period without the use of rescue medication including topical corticosteroids, results from a pooled analysis of two trials found.

“The interesting thing here is that there weren’t major differences in the maintenance dosing, which really allows us some flexibility with maintenance dosing for this particular drug,” lead study investigator Andrew Blauvelt, MD, MBA, said during the Revolutionizing Atopic Dermatitis symposium.

Administered subcutaneously, tralokinumab is a fully human IgG4 monoclonal antibody that specifically binds to interleukin-13, a key driver of underlying inflammation in AD. In two of the drug’s pivotal phase 3 trials, ECZTRA 1 and ECZTRA 2, tralokinumab monotherapy was superior to placebo at week 16 for all primary and secondary endpoints.

The purpose of the current trial was to investigate the maintenance of efficacy after 16 weeks of tralokinumab in those who were initial responders and to assess the efficacy of reduced dosing frequency from 300 mg every 2 weeks to 300 mg every 4 weeks after a 36-week maintenance phase. Patients who used rescue medication, including topical corticosteroids, were considered to be nonresponders.

Dr. Blauvelt reported results from 1,596 adult patients with a mean age of 38 years who were randomized to tralokinumab 300 mg every 2 weeks or placebo in the initial treatment period. At baseline, the mean duration of AD was 28.2 years, 50% had severe disease based on their IGA score, and their mean Dermatology Life Quality Index score was 17.

Of these patients, 412 achieved an IGA score of 0 or 1 and/or an EASI 75 at week 16 with tralokinumab every 2 weeks and were rerandomized (2:2:1) to continue tralokinumab 300 mg every 2 weeks, tralokinumab 300 mg every 4 weeks, or placebo for 36 weeks.

The researchers found that 56%-57% of patients in the tralokinumab every 2-week dosing group maintained their IGA 0/1 and EASI 75 response at week 52, compared with 42%-50% of those who received the drug every 4 weeks. “So, there may be a population of patients who require drug every 4 weeks after initially receiving the drug every 2 weeks for the first 16 weeks,” said Dr. Blauvelt, a dermatologist who is president of Oregon Medical Research Center, Portland. “Interestingly, 26%-34% of patients on placebo maintained their IGA 0/1 and EASI 75 response a response to week 52. Perhaps those are patients who have more mild disease or more episodic disease when they started this trial.”

He also noted that time to relapse based on their IGA 0/1 and EASI 75 was prolonged with tralokinumab treatment, compared with placebo, and adverse event frequency was similar among all treatment groups (73% among those who received tralokinumab every 2 weeks, 66% among those who received tralokinumab every 4 weeks, and 70% in the placebo group).

Dr. Blauvelt concluded that a step-down in tralokinumab dosing to every 4 weeks may be an option for some patients achieving clear or almost clear skin after an initial dosing schedule of every 2 weeks.

LEO Pharma, which is developing tralokinumab, sponsored the analysis. Dr. Blauvelt reported that he is an investigator and a scientific adviser for LEO Pharma and for several other pharmaceutical companies developing treatments for AD.

[email protected]

A large proportion of initial Investigator Global Assessment (IGA) 0/1 or Eczema Area and Severity Index (EASI) 75 responders at week 16 maintained response with continued tralokinumab dosing every 2 weeks or every 4 weeks during a 36-week maintenance period without the use of rescue medication including topical corticosteroids, results from a pooled analysis of two trials found.

“The interesting thing here is that there weren’t major differences in the maintenance dosing, which really allows us some flexibility with maintenance dosing for this particular drug,” lead study investigator Andrew Blauvelt, MD, MBA, said during the Revolutionizing Atopic Dermatitis symposium.

Administered subcutaneously, tralokinumab is a fully human IgG4 monoclonal antibody that specifically binds to interleukin-13, a key driver of underlying inflammation in AD. In two of the drug’s pivotal phase 3 trials, ECZTRA 1 and ECZTRA 2, tralokinumab monotherapy was superior to placebo at week 16 for all primary and secondary endpoints.

The purpose of the current trial was to investigate the maintenance of efficacy after 16 weeks of tralokinumab in those who were initial responders and to assess the efficacy of reduced dosing frequency from 300 mg every 2 weeks to 300 mg every 4 weeks after a 36-week maintenance phase. Patients who used rescue medication, including topical corticosteroids, were considered to be nonresponders.

Dr. Blauvelt reported results from 1,596 adult patients with a mean age of 38 years who were randomized to tralokinumab 300 mg every 2 weeks or placebo in the initial treatment period. At baseline, the mean duration of AD was 28.2 years, 50% had severe disease based on their IGA score, and their mean Dermatology Life Quality Index score was 17.

Of these patients, 412 achieved an IGA score of 0 or 1 and/or an EASI 75 at week 16 with tralokinumab every 2 weeks and were rerandomized (2:2:1) to continue tralokinumab 300 mg every 2 weeks, tralokinumab 300 mg every 4 weeks, or placebo for 36 weeks.

The researchers found that 56%-57% of patients in the tralokinumab every 2-week dosing group maintained their IGA 0/1 and EASI 75 response at week 52, compared with 42%-50% of those who received the drug every 4 weeks. “So, there may be a population of patients who require drug every 4 weeks after initially receiving the drug every 2 weeks for the first 16 weeks,” said Dr. Blauvelt, a dermatologist who is president of Oregon Medical Research Center, Portland. “Interestingly, 26%-34% of patients on placebo maintained their IGA 0/1 and EASI 75 response a response to week 52. Perhaps those are patients who have more mild disease or more episodic disease when they started this trial.”

He also noted that time to relapse based on their IGA 0/1 and EASI 75 was prolonged with tralokinumab treatment, compared with placebo, and adverse event frequency was similar among all treatment groups (73% among those who received tralokinumab every 2 weeks, 66% among those who received tralokinumab every 4 weeks, and 70% in the placebo group).

Dr. Blauvelt concluded that a step-down in tralokinumab dosing to every 4 weeks may be an option for some patients achieving clear or almost clear skin after an initial dosing schedule of every 2 weeks.

LEO Pharma, which is developing tralokinumab, sponsored the analysis. Dr. Blauvelt reported that he is an investigator and a scientific adviser for LEO Pharma and for several other pharmaceutical companies developing treatments for AD.

[email protected]

The phenomenon of brain fog, as described by some patients with hypothyroidism despite treatment, is often associated with fatigue and cognitive symptoms and may be relieved by a variety of pharmacologic and nonpharmacologic approaches, new research suggests.

The findings come from a survey of more than 700 patients with hypothyroidism due to thyroid surgery and/or radioactive iodine therapy (RAI) or Hashimoto’s who reported having brain fog.

The survey results were presented May 29 at the American Association of Clinical Endocrinology Virtual Annual Meeting 2021 by investigators Matthew D. Ettleson, MD, and Ava Raine, of the University of Chicago, Illinois.

Many patients with hypothyroidism continue to experience symptoms despite taking thyroid hormone replacement therapy and having normal thyroid function test results.

These symptoms can include quantifiable cognitive, quality of life, and metabolic abnormalities. However, “some patients also experience vague and difficult to quantify symptoms, which they describe as brain fog,” Ms. Raine said.

The brain fog phenomenon has been described with somewhat varying features in several different chronic conditions, including postural orthostatic tachycardia syndrome, myalgic encephalomyelitis/chronic fatigue syndrome, fibromyalgia, post-menopausal syndrome, and recently, among people with “long haul” COVID-19 symptoms.

However, brain fog associated with treated hypothyroidism has not been explored in-depth, despite the fact that patients often report it, Ms. Raine noted.
 

Results will help clinicians assist patients with brain fog

Fatigue was the most prominent brain fog symptom reported in the survey, followed by forgetfulness and difficulty focusing. On the other hand, rest and relaxation were the most reported factors that alleviated symptoms, followed by thyroid hormone adjustment.

“Hopefully these findings will help clinicians to recognize and treat the symptoms of brain fog and shed light on a condition which up until now has not been very well understood,” Dr. Ettleson said.

Asked to comment, session moderator Jad G. Sfeir, MD, of the Mayo Medical School, Rochester, Minn., told this news organization: “We do see patients complain a lot about this brain fog. The question is how can I help, and what has worked for them in the past?”

“When you have symptoms that are vague, like brain fog, you don’t have a lot of objective tools to [measure], so you can’t really develop a study to see how a certain medication affects the symptoms. Relying on subjective information from patients saying what worked for them and what did not, you can draw a lot of implications to clinical practice.”

The survey results, Dr. Sfeir said, “will help direct clinicians to know what type of questions to ask patients based on the survey responses and how to make some recommendations that may help.”
 

Fatigue, memory problems, difficulty focusing characterize brain fog

The online survey was distributed to hypothyroidism support groups and through the American Thyroid Association. Of the 5,282 respondents with hypothyroidism and symptoms of brain fog, 46% (2,453) reported having experienced brain fog symptoms prior to their diagnosis of hypothyroidism.

The population analyzed for the study was the 17% (731) who reported experiencing brain fog weeks to months following a diagnosis of hypothyroidism. Of those, 33% had Hashimoto’s, 21% thyroid surgery, 11% RAI therapy, and 15.6% had both thyroid surgery and RAI.  

Brain fog symptoms were reported as occurring “frequently” by 44.5% and “all the time” by 37.0%. The composite symptom score was 22.9 out of 30.

Fatigue, or lack of energy, was the most commonly named symptom, reported by over 90% of both the thyroid surgery/RAI and Hashimoto’s groups, and as occurring “all the time” by about half in each group. Others reported by at least half of both groups included memory problems, difficulty focusing, sleep problems, and difficulties with decision-making. Other symptoms frequently cited included confusion, mood disturbance, and anxiety.

“Each ... domain was reported with some frequency by at least 85% of respondents, regardless of etiology of hypothyroidism, so it really was a high symptom burden that we were seeing, even in those whose symptoms were the least frequent,” Ms. Raine noted.

Symptom scores generally correlated with patient satisfaction scores, particularly with those of cognitive signs and difficulty focusing.
 

Lifting the fog: What do patients say helps them?

The survey asked patients what factors improved or worsened their brain fog symptoms. By far, the most frequent answer was rest/relaxation, endorsed by 58.5%. Another 10.5% listed exercise/outdoor time, but 1.5% said exercise worsened their symptoms.

Unspecified adjustments of thyroid medications were said to improve symptoms for 13.9%. Specific thyroid hormones reported to improve symptoms were liothyronine in 8.8%, desiccated thyroid extract in 3.1%, and levothyroxine in 2.7%. However, another 4.2% said thyroxine worsened their symptoms.

Healthy/nutritious diets were reported to improve symptoms by 6.3%, while consuming gluten, a high-sugar diet, and consuming alcohol were reported to worsen symptoms for 1.3%, 3.2%, and 1.3%, respectively. Caffeine was said to help for 3.1% and to harm by 0.6%.

Small numbers of patients reported improvements in symptoms with vitamins B12 and D, Adderall, or other stimulant medications, antidepressants, naltrexone, sun exposure, and blood glucose stability.

Other factors reported to worsen symptoms included menstruation, infection or other acute illness, pain, and “loud noise.”   

Dr. Ettleson pointed out, “For many of these patients [the brain fog] may have nothing to do with their thyroid. We saw a large proportion of patients who said they had symptoms well before they were ever diagnosed with hypothyroidism, and yet many patients have linked these brain fog symptoms to their thyroid.”

Nonetheless, he said, “I think it’s imperative for the clinician to at least engage in these conversations and not just stop when the thyroid function tests are normal. We have many lifestyle suggestions that have emerged from this study that I think physicians can put forward to patients who are dealing with this ... early in the process in addition to thyroid hormone adjustment, which may help some patients.”  

Dr. Ettleson, Ms. Raine, and Dr. Sfeir have reported no relevant financial relationships.

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

The phenomenon of brain fog, as described by some patients with hypothyroidism despite treatment, is often associated with fatigue and cognitive symptoms and may be relieved by a variety of pharmacologic and nonpharmacologic approaches, new research suggests.

The findings come from a survey of more than 700 patients with hypothyroidism due to thyroid surgery and/or radioactive iodine therapy (RAI) or Hashimoto’s who reported having brain fog.

The survey results were presented May 29 at the American Association of Clinical Endocrinology Virtual Annual Meeting 2021 by investigators Matthew D. Ettleson, MD, and Ava Raine, of the University of Chicago, Illinois.

Many patients with hypothyroidism continue to experience symptoms despite taking thyroid hormone replacement therapy and having normal thyroid function test results.

These symptoms can include quantifiable cognitive, quality of life, and metabolic abnormalities. However, “some patients also experience vague and difficult to quantify symptoms, which they describe as brain fog,” Ms. Raine said.

The brain fog phenomenon has been described with somewhat varying features in several different chronic conditions, including postural orthostatic tachycardia syndrome, myalgic encephalomyelitis/chronic fatigue syndrome, fibromyalgia, post-menopausal syndrome, and recently, among people with “long haul” COVID-19 symptoms.

However, brain fog associated with treated hypothyroidism has not been explored in-depth, despite the fact that patients often report it, Ms. Raine noted.
 

Results will help clinicians assist patients with brain fog

Fatigue was the most prominent brain fog symptom reported in the survey, followed by forgetfulness and difficulty focusing. On the other hand, rest and relaxation were the most reported factors that alleviated symptoms, followed by thyroid hormone adjustment.

“Hopefully these findings will help clinicians to recognize and treat the symptoms of brain fog and shed light on a condition which up until now has not been very well understood,” Dr. Ettleson said.

Asked to comment, session moderator Jad G. Sfeir, MD, of the Mayo Medical School, Rochester, Minn., told this news organization: “We do see patients complain a lot about this brain fog. The question is how can I help, and what has worked for them in the past?”

“When you have symptoms that are vague, like brain fog, you don’t have a lot of objective tools to [measure], so you can’t really develop a study to see how a certain medication affects the symptoms. Relying on subjective information from patients saying what worked for them and what did not, you can draw a lot of implications to clinical practice.”

The survey results, Dr. Sfeir said, “will help direct clinicians to know what type of questions to ask patients based on the survey responses and how to make some recommendations that may help.”
 

Fatigue, memory problems, difficulty focusing characterize brain fog

The online survey was distributed to hypothyroidism support groups and through the American Thyroid Association. Of the 5,282 respondents with hypothyroidism and symptoms of brain fog, 46% (2,453) reported having experienced brain fog symptoms prior to their diagnosis of hypothyroidism.

The population analyzed for the study was the 17% (731) who reported experiencing brain fog weeks to months following a diagnosis of hypothyroidism. Of those, 33% had Hashimoto’s, 21% thyroid surgery, 11% RAI therapy, and 15.6% had both thyroid surgery and RAI.  

Brain fog symptoms were reported as occurring “frequently” by 44.5% and “all the time” by 37.0%. The composite symptom score was 22.9 out of 30.

Fatigue, or lack of energy, was the most commonly named symptom, reported by over 90% of both the thyroid surgery/RAI and Hashimoto’s groups, and as occurring “all the time” by about half in each group. Others reported by at least half of both groups included memory problems, difficulty focusing, sleep problems, and difficulties with decision-making. Other symptoms frequently cited included confusion, mood disturbance, and anxiety.

“Each ... domain was reported with some frequency by at least 85% of respondents, regardless of etiology of hypothyroidism, so it really was a high symptom burden that we were seeing, even in those whose symptoms were the least frequent,” Ms. Raine noted.

Symptom scores generally correlated with patient satisfaction scores, particularly with those of cognitive signs and difficulty focusing.
 

Lifting the fog: What do patients say helps them?

The survey asked patients what factors improved or worsened their brain fog symptoms. By far, the most frequent answer was rest/relaxation, endorsed by 58.5%. Another 10.5% listed exercise/outdoor time, but 1.5% said exercise worsened their symptoms.

Unspecified adjustments of thyroid medications were said to improve symptoms for 13.9%. Specific thyroid hormones reported to improve symptoms were liothyronine in 8.8%, desiccated thyroid extract in 3.1%, and levothyroxine in 2.7%. However, another 4.2% said thyroxine worsened their symptoms.

Healthy/nutritious diets were reported to improve symptoms by 6.3%, while consuming gluten, a high-sugar diet, and consuming alcohol were reported to worsen symptoms for 1.3%, 3.2%, and 1.3%, respectively. Caffeine was said to help for 3.1% and to harm by 0.6%.

Small numbers of patients reported improvements in symptoms with vitamins B12 and D, Adderall, or other stimulant medications, antidepressants, naltrexone, sun exposure, and blood glucose stability.

Other factors reported to worsen symptoms included menstruation, infection or other acute illness, pain, and “loud noise.”   

Dr. Ettleson pointed out, “For many of these patients [the brain fog] may have nothing to do with their thyroid. We saw a large proportion of patients who said they had symptoms well before they were ever diagnosed with hypothyroidism, and yet many patients have linked these brain fog symptoms to their thyroid.”

Nonetheless, he said, “I think it’s imperative for the clinician to at least engage in these conversations and not just stop when the thyroid function tests are normal. We have many lifestyle suggestions that have emerged from this study that I think physicians can put forward to patients who are dealing with this ... early in the process in addition to thyroid hormone adjustment, which may help some patients.”  

Dr. Ettleson, Ms. Raine, and Dr. Sfeir have reported no relevant financial relationships.

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

The phenomenon of brain fog, as described by some patients with hypothyroidism despite treatment, is often associated with fatigue and cognitive symptoms and may be relieved by a variety of pharmacologic and nonpharmacologic approaches, new research suggests.

The findings come from a survey of more than 700 patients with hypothyroidism due to thyroid surgery and/or radioactive iodine therapy (RAI) or Hashimoto’s who reported having brain fog.

The survey results were presented May 29 at the American Association of Clinical Endocrinology Virtual Annual Meeting 2021 by investigators Matthew D. Ettleson, MD, and Ava Raine, of the University of Chicago, Illinois.

Many patients with hypothyroidism continue to experience symptoms despite taking thyroid hormone replacement therapy and having normal thyroid function test results.

These symptoms can include quantifiable cognitive, quality of life, and metabolic abnormalities. However, “some patients also experience vague and difficult to quantify symptoms, which they describe as brain fog,” Ms. Raine said.

The brain fog phenomenon has been described with somewhat varying features in several different chronic conditions, including postural orthostatic tachycardia syndrome, myalgic encephalomyelitis/chronic fatigue syndrome, fibromyalgia, post-menopausal syndrome, and recently, among people with “long haul” COVID-19 symptoms.

However, brain fog associated with treated hypothyroidism has not been explored in-depth, despite the fact that patients often report it, Ms. Raine noted.
 

Results will help clinicians assist patients with brain fog

Fatigue was the most prominent brain fog symptom reported in the survey, followed by forgetfulness and difficulty focusing. On the other hand, rest and relaxation were the most reported factors that alleviated symptoms, followed by thyroid hormone adjustment.

“Hopefully these findings will help clinicians to recognize and treat the symptoms of brain fog and shed light on a condition which up until now has not been very well understood,” Dr. Ettleson said.

Asked to comment, session moderator Jad G. Sfeir, MD, of the Mayo Medical School, Rochester, Minn., told this news organization: “We do see patients complain a lot about this brain fog. The question is how can I help, and what has worked for them in the past?”

“When you have symptoms that are vague, like brain fog, you don’t have a lot of objective tools to [measure], so you can’t really develop a study to see how a certain medication affects the symptoms. Relying on subjective information from patients saying what worked for them and what did not, you can draw a lot of implications to clinical practice.”

The survey results, Dr. Sfeir said, “will help direct clinicians to know what type of questions to ask patients based on the survey responses and how to make some recommendations that may help.”
 

Fatigue, memory problems, difficulty focusing characterize brain fog

The online survey was distributed to hypothyroidism support groups and through the American Thyroid Association. Of the 5,282 respondents with hypothyroidism and symptoms of brain fog, 46% (2,453) reported having experienced brain fog symptoms prior to their diagnosis of hypothyroidism.

The population analyzed for the study was the 17% (731) who reported experiencing brain fog weeks to months following a diagnosis of hypothyroidism. Of those, 33% had Hashimoto’s, 21% thyroid surgery, 11% RAI therapy, and 15.6% had both thyroid surgery and RAI.  

Brain fog symptoms were reported as occurring “frequently” by 44.5% and “all the time” by 37.0%. The composite symptom score was 22.9 out of 30.

Fatigue, or lack of energy, was the most commonly named symptom, reported by over 90% of both the thyroid surgery/RAI and Hashimoto’s groups, and as occurring “all the time” by about half in each group. Others reported by at least half of both groups included memory problems, difficulty focusing, sleep problems, and difficulties with decision-making. Other symptoms frequently cited included confusion, mood disturbance, and anxiety.

“Each ... domain was reported with some frequency by at least 85% of respondents, regardless of etiology of hypothyroidism, so it really was a high symptom burden that we were seeing, even in those whose symptoms were the least frequent,” Ms. Raine noted.

Symptom scores generally correlated with patient satisfaction scores, particularly with those of cognitive signs and difficulty focusing.
 

Lifting the fog: What do patients say helps them?

The survey asked patients what factors improved or worsened their brain fog symptoms. By far, the most frequent answer was rest/relaxation, endorsed by 58.5%. Another 10.5% listed exercise/outdoor time, but 1.5% said exercise worsened their symptoms.

Unspecified adjustments of thyroid medications were said to improve symptoms for 13.9%. Specific thyroid hormones reported to improve symptoms were liothyronine in 8.8%, desiccated thyroid extract in 3.1%, and levothyroxine in 2.7%. However, another 4.2% said thyroxine worsened their symptoms.

Healthy/nutritious diets were reported to improve symptoms by 6.3%, while consuming gluten, a high-sugar diet, and consuming alcohol were reported to worsen symptoms for 1.3%, 3.2%, and 1.3%, respectively. Caffeine was said to help for 3.1% and to harm by 0.6%.

Small numbers of patients reported improvements in symptoms with vitamins B12 and D, Adderall, or other stimulant medications, antidepressants, naltrexone, sun exposure, and blood glucose stability.

Other factors reported to worsen symptoms included menstruation, infection or other acute illness, pain, and “loud noise.”   

Dr. Ettleson pointed out, “For many of these patients [the brain fog] may have nothing to do with their thyroid. We saw a large proportion of patients who said they had symptoms well before they were ever diagnosed with hypothyroidism, and yet many patients have linked these brain fog symptoms to their thyroid.”

Nonetheless, he said, “I think it’s imperative for the clinician to at least engage in these conversations and not just stop when the thyroid function tests are normal. We have many lifestyle suggestions that have emerged from this study that I think physicians can put forward to patients who are dealing with this ... early in the process in addition to thyroid hormone adjustment, which may help some patients.”  

Dr. Ettleson, Ms. Raine, and Dr. Sfeir have reported no relevant financial relationships.

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

A delaying tactic used by some U.S. health insurers to limit coverage of bariatric surgery does not jibe with the clinical experience at one U.S. center with 461 patients who underwent primary or revisional bariatric surgery.

PhotoDisk

The tactic applies to patients with a baseline body mass index (BMI) of 35-39 kg/m² who usually also need at least one comorbidity to qualify for insurance coverage for bariatric surgery, and specifically to the subgroup for whom hypertension is the qualifying comorbidity.

Some insurers limit surgery coverage to patients with hypertension who fail to reach their goal blood pressure on agents from three different drug classes, a policy that is “extremely frustrating and dangerous,” said Yannis Raftopoulos, MD, PhD, in his presentation at the annual meeting of the American Society for Metabolic and Bariatric Surgery.

Using number of antihypertensive drugs ‘is not correct’

“Using the number of antihypertensive medications to justify surgery is not correct because blood pressure control is not [always] better when patients take two or three medications, compared with when they are taking one. This harms patients because the more severe their hypertension, the worse their control,” said Dr. Raftopoulos, director of the weight management program at Holyoke (Mass.) Medical Center.

He presented findings from a retrospective study of 461 patients who underwent either sleeve gastrectomy or laparoscopic Roux-en-Y gastric bypass at his center, including 213 (46%) diagnosed with hypertension at the time of their surgery. Within this group were 68 patients with a BMI of 35-39, which meant that they could get insurance coverage for bariatric surgery only if they also had a relevant comorbidity such as hypertension, diabetes, or severe sleep apnea.

Among these patients, 36 (17% of those with hypertension) had only hypertension as their relevant comorbidity and would not have qualified for bariatric surgery under the strictest criteria applied by some insurers that require patients to remain hypertensive despite treatment with at least three different antihypertensive medications. (These 36 patients underwent bariatric surgery because their insurance coverage did not have this restriction.)

The analyses Dr. Raftopoulos presented also documented the rate of hypertension resolution among patients in the series who had hypertension at baseline and 1-year follow-up results. Among 65 patients on one antihypertensive drug at baseline, 43 (66%) had complete resolution of their hypertension after 1 year, defined as blood pressure of less than 130/90 mm Hg while completely off antihypertensive treatment. In contrast, among 55 patients on two antihypertensive medications at baseline, 28 (51%) had complete resolution after 1 year, and among 24 patients on three or more antihypertensive medications at baseline, 3 (13%) had complete resolution 1 year after bariatric surgery, he reported.

“Patients who were treated with one oral antihypertensive medication preoperatively had a higher likelihood of postoperative hypertension resolution,” concluded Dr. Raftopoulos.

Restricting access to bariatric surgery to patients with a BMI of less than 40 based on the preoperative intensity of their antihypertensive treatment “is not supported by our data, and can be potentially harmful,” he declared.

“This study was the result of discussions about this problem with multiple insurers in my area,” he added. “This affects a good number of patients.”

Waiting for hypertension to become less treatable

The results Dr. Raftopoulos presented “are not surprising, because they confirm the hypothesis that earlier intervention in the course of a disease like hypertension is more likely to be successful,” commented Bruce D. Schirmer, MD, a professor of surgery at the University of Virginia, Charlottesville, and designated discussant for the report.

The policy followed by some health insurers to delay coverage for bariatric surgery until patients fail three medications “forces patients with more treatable hypertension to wait until their disease worsens and becomes less treatable before they can receive appropriate treatment,” he said.

Dr. Schirmer attributed the motivation for this approach to a “despicable” and “reprehensible” reason: “Actuarial calculations that show paying for curative therapy is not cost effective in the short term. The duration of a patient’s policy may not be long enough to yield a positive financial outcome, so it becomes more appropriate to deny optimal care and have patients become sicker from their disease.”

“I applaud the authors for accumulating the data that point out this unfortunate rule of some insurance companies,” Dr. Schirmer added.

The practice is comparable with an insurer requiring that a patient’s cancer must be metastatic before allowing coverage for treatment, commented Ann M. Rogers, MD, professor and director of the Penn State University surgical weight loss program in Hershey, Penn., and a moderator of the session.

Dr. Raftopoulos, Dr. Schirmer, and Dr. Rogers had no disclosures.

[email protected]

A delaying tactic used by some U.S. health insurers to limit coverage of bariatric surgery does not jibe with the clinical experience at one U.S. center with 461 patients who underwent primary or revisional bariatric surgery.

PhotoDisk

The tactic applies to patients with a baseline body mass index (BMI) of 35-39 kg/m² who usually also need at least one comorbidity to qualify for insurance coverage for bariatric surgery, and specifically to the subgroup for whom hypertension is the qualifying comorbidity.

Some insurers limit surgery coverage to patients with hypertension who fail to reach their goal blood pressure on agents from three different drug classes, a policy that is “extremely frustrating and dangerous,” said Yannis Raftopoulos, MD, PhD, in his presentation at the annual meeting of the American Society for Metabolic and Bariatric Surgery.

Using number of antihypertensive drugs ‘is not correct’

“Using the number of antihypertensive medications to justify surgery is not correct because blood pressure control is not [always] better when patients take two or three medications, compared with when they are taking one. This harms patients because the more severe their hypertension, the worse their control,” said Dr. Raftopoulos, director of the weight management program at Holyoke (Mass.) Medical Center.

He presented findings from a retrospective study of 461 patients who underwent either sleeve gastrectomy or laparoscopic Roux-en-Y gastric bypass at his center, including 213 (46%) diagnosed with hypertension at the time of their surgery. Within this group were 68 patients with a BMI of 35-39, which meant that they could get insurance coverage for bariatric surgery only if they also had a relevant comorbidity such as hypertension, diabetes, or severe sleep apnea.

Among these patients, 36 (17% of those with hypertension) had only hypertension as their relevant comorbidity and would not have qualified for bariatric surgery under the strictest criteria applied by some insurers that require patients to remain hypertensive despite treatment with at least three different antihypertensive medications. (These 36 patients underwent bariatric surgery because their insurance coverage did not have this restriction.)

The analyses Dr. Raftopoulos presented also documented the rate of hypertension resolution among patients in the series who had hypertension at baseline and 1-year follow-up results. Among 65 patients on one antihypertensive drug at baseline, 43 (66%) had complete resolution of their hypertension after 1 year, defined as blood pressure of less than 130/90 mm Hg while completely off antihypertensive treatment. In contrast, among 55 patients on two antihypertensive medications at baseline, 28 (51%) had complete resolution after 1 year, and among 24 patients on three or more antihypertensive medications at baseline, 3 (13%) had complete resolution 1 year after bariatric surgery, he reported.

“Patients who were treated with one oral antihypertensive medication preoperatively had a higher likelihood of postoperative hypertension resolution,” concluded Dr. Raftopoulos.

Restricting access to bariatric surgery to patients with a BMI of less than 40 based on the preoperative intensity of their antihypertensive treatment “is not supported by our data, and can be potentially harmful,” he declared.

“This study was the result of discussions about this problem with multiple insurers in my area,” he added. “This affects a good number of patients.”

Waiting for hypertension to become less treatable

The results Dr. Raftopoulos presented “are not surprising, because they confirm the hypothesis that earlier intervention in the course of a disease like hypertension is more likely to be successful,” commented Bruce D. Schirmer, MD, a professor of surgery at the University of Virginia, Charlottesville, and designated discussant for the report.

The policy followed by some health insurers to delay coverage for bariatric surgery until patients fail three medications “forces patients with more treatable hypertension to wait until their disease worsens and becomes less treatable before they can receive appropriate treatment,” he said.

Dr. Schirmer attributed the motivation for this approach to a “despicable” and “reprehensible” reason: “Actuarial calculations that show paying for curative therapy is not cost effective in the short term. The duration of a patient’s policy may not be long enough to yield a positive financial outcome, so it becomes more appropriate to deny optimal care and have patients become sicker from their disease.”

“I applaud the authors for accumulating the data that point out this unfortunate rule of some insurance companies,” Dr. Schirmer added.

The practice is comparable with an insurer requiring that a patient’s cancer must be metastatic before allowing coverage for treatment, commented Ann M. Rogers, MD, professor and director of the Penn State University surgical weight loss program in Hershey, Penn., and a moderator of the session.

Dr. Raftopoulos, Dr. Schirmer, and Dr. Rogers had no disclosures.

[email protected]

A delaying tactic used by some U.S. health insurers to limit coverage of bariatric surgery does not jibe with the clinical experience at one U.S. center with 461 patients who underwent primary or revisional bariatric surgery.

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The tactic applies to patients with a baseline body mass index (BMI) of 35-39 kg/m² who usually also need at least one comorbidity to qualify for insurance coverage for bariatric surgery, and specifically to the subgroup for whom hypertension is the qualifying comorbidity.

Some insurers limit surgery coverage to patients with hypertension who fail to reach their goal blood pressure on agents from three different drug classes, a policy that is “extremely frustrating and dangerous,” said Yannis Raftopoulos, MD, PhD, in his presentation at the annual meeting of the American Society for Metabolic and Bariatric Surgery.

Using number of antihypertensive drugs ‘is not correct’

“Using the number of antihypertensive medications to justify surgery is not correct because blood pressure control is not [always] better when patients take two or three medications, compared with when they are taking one. This harms patients because the more severe their hypertension, the worse their control,” said Dr. Raftopoulos, director of the weight management program at Holyoke (Mass.) Medical Center.

He presented findings from a retrospective study of 461 patients who underwent either sleeve gastrectomy or laparoscopic Roux-en-Y gastric bypass at his center, including 213 (46%) diagnosed with hypertension at the time of their surgery. Within this group were 68 patients with a BMI of 35-39, which meant that they could get insurance coverage for bariatric surgery only if they also had a relevant comorbidity such as hypertension, diabetes, or severe sleep apnea.

Among these patients, 36 (17% of those with hypertension) had only hypertension as their relevant comorbidity and would not have qualified for bariatric surgery under the strictest criteria applied by some insurers that require patients to remain hypertensive despite treatment with at least three different antihypertensive medications. (These 36 patients underwent bariatric surgery because their insurance coverage did not have this restriction.)

The analyses Dr. Raftopoulos presented also documented the rate of hypertension resolution among patients in the series who had hypertension at baseline and 1-year follow-up results. Among 65 patients on one antihypertensive drug at baseline, 43 (66%) had complete resolution of their hypertension after 1 year, defined as blood pressure of less than 130/90 mm Hg while completely off antihypertensive treatment. In contrast, among 55 patients on two antihypertensive medications at baseline, 28 (51%) had complete resolution after 1 year, and among 24 patients on three or more antihypertensive medications at baseline, 3 (13%) had complete resolution 1 year after bariatric surgery, he reported.

“Patients who were treated with one oral antihypertensive medication preoperatively had a higher likelihood of postoperative hypertension resolution,” concluded Dr. Raftopoulos.

Restricting access to bariatric surgery to patients with a BMI of less than 40 based on the preoperative intensity of their antihypertensive treatment “is not supported by our data, and can be potentially harmful,” he declared.

“This study was the result of discussions about this problem with multiple insurers in my area,” he added. “This affects a good number of patients.”

Waiting for hypertension to become less treatable

The results Dr. Raftopoulos presented “are not surprising, because they confirm the hypothesis that earlier intervention in the course of a disease like hypertension is more likely to be successful,” commented Bruce D. Schirmer, MD, a professor of surgery at the University of Virginia, Charlottesville, and designated discussant for the report.

The policy followed by some health insurers to delay coverage for bariatric surgery until patients fail three medications “forces patients with more treatable hypertension to wait until their disease worsens and becomes less treatable before they can receive appropriate treatment,” he said.

Dr. Schirmer attributed the motivation for this approach to a “despicable” and “reprehensible” reason: “Actuarial calculations that show paying for curative therapy is not cost effective in the short term. The duration of a patient’s policy may not be long enough to yield a positive financial outcome, so it becomes more appropriate to deny optimal care and have patients become sicker from their disease.”

“I applaud the authors for accumulating the data that point out this unfortunate rule of some insurance companies,” Dr. Schirmer added.

The practice is comparable with an insurer requiring that a patient’s cancer must be metastatic before allowing coverage for treatment, commented Ann M. Rogers, MD, professor and director of the Penn State University surgical weight loss program in Hershey, Penn., and a moderator of the session.

Dr. Raftopoulos, Dr. Schirmer, and Dr. Rogers had no disclosures.

[email protected]