Key clinical point: A fifth of clinically stable patients receiving intermittent ulipristal acetate (UPA) treatment for uterine fibroids needed surgery after it was suspended by the European Medicines Agency in March 2020, because of safety concerns.

Major finding: Following the suspension of UPA, 20% of patients receiving intermittent UPA needed surgery and 80% needed other medical treatments.

Study details: The data come from an analysis of 85 women who received intermittent UPA treatment until it was suspended in March 2020.

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

Source: Nicolás I et al. Gynecol Endocrinol. 2021 May 28. doi: 10.1080/09513590.2021.1929152.

Key clinical point: A fifth of clinically stable patients receiving intermittent ulipristal acetate (UPA) treatment for uterine fibroids needed surgery after it was suspended by the European Medicines Agency in March 2020, because of safety concerns.

Major finding: Following the suspension of UPA, 20% of patients receiving intermittent UPA needed surgery and 80% needed other medical treatments.

Study details: The data come from an analysis of 85 women who received intermittent UPA treatment until it was suspended in March 2020.

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

Source: Nicolás I et al. Gynecol Endocrinol. 2021 May 28. doi: 10.1080/09513590.2021.1929152.

Key clinical point: A fifth of clinically stable patients receiving intermittent ulipristal acetate (UPA) treatment for uterine fibroids needed surgery after it was suspended by the European Medicines Agency in March 2020, because of safety concerns.

Major finding: Following the suspension of UPA, 20% of patients receiving intermittent UPA needed surgery and 80% needed other medical treatments.

Study details: The data come from an analysis of 85 women who received intermittent UPA treatment until it was suspended in March 2020.

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

Source: Nicolás I et al. Gynecol Endocrinol. 2021 May 28. doi: 10.1080/09513590.2021.1929152.

Key clinical point: Application of temporary uterine tourniquet may be effective in reducing perioperative bleeding in patients with multiple, large-sized uterine fibroids in close proximity of vascular structures.

Major finding: The tourniquet applied group vs not applied group had more favorable outcomes in terms of hemoglobin drop (P = .019), hematocrit drop (P = .023), transfusion amount (P = .012), operation time (P = .044), and duration of hospitalization (P = .036).

Study details: The data come from a retrospective study involving 84 patients who underwent abdominal myomectomy and were categorized into 2 groups according to the use (n=36) or nonuse (n=48) of a temporary uterine tourniquet.

Disclosures: The study did not receive any financial support. The authors declared no conflicts of interest.

Source: Akbaba E et al. J Turk Ger Gynecol Assoc. 2021 Jun 8. doi: 10.4274/jtgga.galenos.2021.2020.0242.

Key clinical point: Application of temporary uterine tourniquet may be effective in reducing perioperative bleeding in patients with multiple, large-sized uterine fibroids in close proximity of vascular structures.

Major finding: The tourniquet applied group vs not applied group had more favorable outcomes in terms of hemoglobin drop (P = .019), hematocrit drop (P = .023), transfusion amount (P = .012), operation time (P = .044), and duration of hospitalization (P = .036).

Study details: The data come from a retrospective study involving 84 patients who underwent abdominal myomectomy and were categorized into 2 groups according to the use (n=36) or nonuse (n=48) of a temporary uterine tourniquet.

Disclosures: The study did not receive any financial support. The authors declared no conflicts of interest.

Source: Akbaba E et al. J Turk Ger Gynecol Assoc. 2021 Jun 8. doi: 10.4274/jtgga.galenos.2021.2020.0242.

Key clinical point: Application of temporary uterine tourniquet may be effective in reducing perioperative bleeding in patients with multiple, large-sized uterine fibroids in close proximity of vascular structures.

Major finding: The tourniquet applied group vs not applied group had more favorable outcomes in terms of hemoglobin drop (P = .019), hematocrit drop (P = .023), transfusion amount (P = .012), operation time (P = .044), and duration of hospitalization (P = .036).

Study details: The data come from a retrospective study involving 84 patients who underwent abdominal myomectomy and were categorized into 2 groups according to the use (n=36) or nonuse (n=48) of a temporary uterine tourniquet.

Disclosures: The study did not receive any financial support. The authors declared no conflicts of interest.

Source: Akbaba E et al. J Turk Ger Gynecol Assoc. 2021 Jun 8. doi: 10.4274/jtgga.galenos.2021.2020.0242.

Key clinical point: Ultrasound-guided microwave ablation (MWA) is a safe and effective minimally invasive treatment strategy for symptomatic uterine fibroids.

Major finding: In patients treated with MWA, uterine fibroid symptom scores decreased significantly (reduction rate, 65.9%; P less than .0001) and the quality of life scores (increasing rate, 72.0%; P less than .0001) and hemoglobin levels increased significantly (increasing rate, 30.3%; P less than .0001) from baseline to follow-up. No major adverse events were reported.

Study details: A meta-analysis of 10 studies involving 671 patients.

Disclosures: The study did not receive any funding. The authors declared no conflicts of interest.

Source: Liu L et al. J Minim Invasive Gynecol. 2021 Jun 28. doi: 10.1016/j.jmig.2021.06.020.

Key clinical point: Ultrasound-guided microwave ablation (MWA) is a safe and effective minimally invasive treatment strategy for symptomatic uterine fibroids.

Major finding: In patients treated with MWA, uterine fibroid symptom scores decreased significantly (reduction rate, 65.9%; P less than .0001) and the quality of life scores (increasing rate, 72.0%; P less than .0001) and hemoglobin levels increased significantly (increasing rate, 30.3%; P less than .0001) from baseline to follow-up. No major adverse events were reported.

Study details: A meta-analysis of 10 studies involving 671 patients.

Disclosures: The study did not receive any funding. The authors declared no conflicts of interest.

Source: Liu L et al. J Minim Invasive Gynecol. 2021 Jun 28. doi: 10.1016/j.jmig.2021.06.020.

Key clinical point: Ultrasound-guided microwave ablation (MWA) is a safe and effective minimally invasive treatment strategy for symptomatic uterine fibroids.

Major finding: In patients treated with MWA, uterine fibroid symptom scores decreased significantly (reduction rate, 65.9%; P less than .0001) and the quality of life scores (increasing rate, 72.0%; P less than .0001) and hemoglobin levels increased significantly (increasing rate, 30.3%; P less than .0001) from baseline to follow-up. No major adverse events were reported.

Study details: A meta-analysis of 10 studies involving 671 patients.

Disclosures: The study did not receive any funding. The authors declared no conflicts of interest.

Source: Liu L et al. J Minim Invasive Gynecol. 2021 Jun 28. doi: 10.1016/j.jmig.2021.06.020.

Plasma biomarkers such as amyloid-beta 40 and 42, phosphorylated tau 181 and 217, and neurofilament light hold great promise for diagnosing and determining a prognosis for Alzheimer’s disease. Such tests are likely to be widely available in the near future.

But work remains to be done to translate findings from academic studies to the more general population. A key consideration is that plasma levels of these biomarkers could be affected by other conditions, which could in turn skew test results, according to Michelle Mielke, PhD, who spoke on the topic at the 2021 Alzheimer’s Association International Conference.

“The markers, which we’ve published on as well, look really promising. But they have primarily been looked at in more specialty clinics or memory clinics, and have not been examined in the general community. The goal of this presentation was really just to take a look at this in the community, in older individuals that have multiple comorbidities, and to understand what factors might affect the levels of these markers. Because as we do go forward and develop cut points, we are going to have to consider these aspects,” said Dr. Mielke in an interview. She is a professor of epidemiology and neurology at the Mayo Clinic in Rochester, Minn.
 

Case in point

To illustrate the point, Dr. Mielke presented data from her group, which analyzed P-tau 181 and P-tau 217 data from 1,329 Mayo clinic patients. Of that total, 1,161 were cognitively unimpaired (CU), 153 had mild cognitive impairment (MCI), and 15 had dementia. The median age was 67, 55% were male, and 26% had the APOE e4 allele.

After adjustment for age and sex, there were statistically significantly elevated levels of both biomarkers among patients who had tested positive for amyloid and patients who had had a stroke or myocardial infarction, and in the presence of chronic kidney disease (CKD). There also was a trend towards an increase of biomarker levels with increasing body mass index. The differences remained even after the analysis was restricted to individuals who were amyloid negative.

The researchers then looked more closely at the impact of CKD, stroke, and MI on P-tau cut points and the ability to predict abnormal amyloid positron emission tomography (PET) scans. They defined an abnormal range as 1.96 standard deviation units beyond the mean among amyloid-negative individuals who are cognitively impaired. They excluded subjects with those risk factors and then established new cut points in the absence of the factors. The approach led to a significant change for the cutoff of P-tau 181 values, from 1.57 pg/mL or greater for individuals without stroke, MI, or CKD, and 1.75 pg/mL or greater for individuals with one such factor. There was little difference in the cutoff value for P-tau 217, from 0.25 pg/mL to 0.26 pg/mL.

Among people without a history of stroke, MI, or CKD, a P-tau 181 cutoff of 1.57 pg/mL or greater had an area under the receiving operating characteristic (AUROC) value of 0.717 (95% confidence interval, 0.691-0.744), compared with an AUROC of 0.687 (95% CI, 0.662-0.712) at a cutoff of 1.75 pg/mL or greater among people with those conditions. For P-tau 217, the values were 0.737 pg/mL (95% CI, 0.712-0.762) and 0.724 pg/mL (95% CI, 0.699-0.748), respectively.

“The sensitivity was better when they excluded those individuals with these conditions. Specificity was slightly, but not significantly, lower,” said Dr. Mielke during her talk.
 

Other considerations

Dr. Mielke added that it will be important to account for these and other factors when applying biomarkers in community settings, but they should also be considered in the context of health care disparities. Stroke, MI, and CKD are more common in African Americans, for example, suggesting that there could be racial differences in biomarker levels, though she said the difference in biomarker levels would be more likely attributable to the underlying comorbidities than race per se. “As shown, these factors can affect the consideration of an accuracy of cut points for clinical use. So I think future discussions will be needed as to how best to determine the cut points, and how to base them off of (different) populations,” said Dr. Mielke.

These sorts of refinements are important, according to Christopher Weber, PhD, who was asked for comment. “We have learned the importance of an early and accurate diagnosis. The blood test is a biomarker that does detect the hallmarks of Alzheimer’s disease sometimes up to decades before symptoms even appear,” said Dr. Weber, who is director of Global Science Initiatives at the Alzheimer’s Association.

But “there’s a lot more that we need to learn regarding when exactly to use them, who they’re appropriate for. And I think validation is the key to these blood biomarkers,” Dr. Weber added.

Dr. Mielke has been a consultant with the Brain Protection Company and Biogen. Dr. Weber has no relevant financial disclosures.

Plasma biomarkers such as amyloid-beta 40 and 42, phosphorylated tau 181 and 217, and neurofilament light hold great promise for diagnosing and determining a prognosis for Alzheimer’s disease. Such tests are likely to be widely available in the near future.

But work remains to be done to translate findings from academic studies to the more general population. A key consideration is that plasma levels of these biomarkers could be affected by other conditions, which could in turn skew test results, according to Michelle Mielke, PhD, who spoke on the topic at the 2021 Alzheimer’s Association International Conference.

“The markers, which we’ve published on as well, look really promising. But they have primarily been looked at in more specialty clinics or memory clinics, and have not been examined in the general community. The goal of this presentation was really just to take a look at this in the community, in older individuals that have multiple comorbidities, and to understand what factors might affect the levels of these markers. Because as we do go forward and develop cut points, we are going to have to consider these aspects,” said Dr. Mielke in an interview. She is a professor of epidemiology and neurology at the Mayo Clinic in Rochester, Minn.
 

Case in point

To illustrate the point, Dr. Mielke presented data from her group, which analyzed P-tau 181 and P-tau 217 data from 1,329 Mayo clinic patients. Of that total, 1,161 were cognitively unimpaired (CU), 153 had mild cognitive impairment (MCI), and 15 had dementia. The median age was 67, 55% were male, and 26% had the APOE e4 allele.

After adjustment for age and sex, there were statistically significantly elevated levels of both biomarkers among patients who had tested positive for amyloid and patients who had had a stroke or myocardial infarction, and in the presence of chronic kidney disease (CKD). There also was a trend towards an increase of biomarker levels with increasing body mass index. The differences remained even after the analysis was restricted to individuals who were amyloid negative.

The researchers then looked more closely at the impact of CKD, stroke, and MI on P-tau cut points and the ability to predict abnormal amyloid positron emission tomography (PET) scans. They defined an abnormal range as 1.96 standard deviation units beyond the mean among amyloid-negative individuals who are cognitively impaired. They excluded subjects with those risk factors and then established new cut points in the absence of the factors. The approach led to a significant change for the cutoff of P-tau 181 values, from 1.57 pg/mL or greater for individuals without stroke, MI, or CKD, and 1.75 pg/mL or greater for individuals with one such factor. There was little difference in the cutoff value for P-tau 217, from 0.25 pg/mL to 0.26 pg/mL.

Among people without a history of stroke, MI, or CKD, a P-tau 181 cutoff of 1.57 pg/mL or greater had an area under the receiving operating characteristic (AUROC) value of 0.717 (95% confidence interval, 0.691-0.744), compared with an AUROC of 0.687 (95% CI, 0.662-0.712) at a cutoff of 1.75 pg/mL or greater among people with those conditions. For P-tau 217, the values were 0.737 pg/mL (95% CI, 0.712-0.762) and 0.724 pg/mL (95% CI, 0.699-0.748), respectively.

“The sensitivity was better when they excluded those individuals with these conditions. Specificity was slightly, but not significantly, lower,” said Dr. Mielke during her talk.
 

Other considerations

Dr. Mielke added that it will be important to account for these and other factors when applying biomarkers in community settings, but they should also be considered in the context of health care disparities. Stroke, MI, and CKD are more common in African Americans, for example, suggesting that there could be racial differences in biomarker levels, though she said the difference in biomarker levels would be more likely attributable to the underlying comorbidities than race per se. “As shown, these factors can affect the consideration of an accuracy of cut points for clinical use. So I think future discussions will be needed as to how best to determine the cut points, and how to base them off of (different) populations,” said Dr. Mielke.

These sorts of refinements are important, according to Christopher Weber, PhD, who was asked for comment. “We have learned the importance of an early and accurate diagnosis. The blood test is a biomarker that does detect the hallmarks of Alzheimer’s disease sometimes up to decades before symptoms even appear,” said Dr. Weber, who is director of Global Science Initiatives at the Alzheimer’s Association.

But “there’s a lot more that we need to learn regarding when exactly to use them, who they’re appropriate for. And I think validation is the key to these blood biomarkers,” Dr. Weber added.

Dr. Mielke has been a consultant with the Brain Protection Company and Biogen. Dr. Weber has no relevant financial disclosures.

Plasma biomarkers such as amyloid-beta 40 and 42, phosphorylated tau 181 and 217, and neurofilament light hold great promise for diagnosing and determining a prognosis for Alzheimer’s disease. Such tests are likely to be widely available in the near future.

But work remains to be done to translate findings from academic studies to the more general population. A key consideration is that plasma levels of these biomarkers could be affected by other conditions, which could in turn skew test results, according to Michelle Mielke, PhD, who spoke on the topic at the 2021 Alzheimer’s Association International Conference.

“The markers, which we’ve published on as well, look really promising. But they have primarily been looked at in more specialty clinics or memory clinics, and have not been examined in the general community. The goal of this presentation was really just to take a look at this in the community, in older individuals that have multiple comorbidities, and to understand what factors might affect the levels of these markers. Because as we do go forward and develop cut points, we are going to have to consider these aspects,” said Dr. Mielke in an interview. She is a professor of epidemiology and neurology at the Mayo Clinic in Rochester, Minn.
 

Case in point

To illustrate the point, Dr. Mielke presented data from her group, which analyzed P-tau 181 and P-tau 217 data from 1,329 Mayo clinic patients. Of that total, 1,161 were cognitively unimpaired (CU), 153 had mild cognitive impairment (MCI), and 15 had dementia. The median age was 67, 55% were male, and 26% had the APOE e4 allele.

After adjustment for age and sex, there were statistically significantly elevated levels of both biomarkers among patients who had tested positive for amyloid and patients who had had a stroke or myocardial infarction, and in the presence of chronic kidney disease (CKD). There also was a trend towards an increase of biomarker levels with increasing body mass index. The differences remained even after the analysis was restricted to individuals who were amyloid negative.

The researchers then looked more closely at the impact of CKD, stroke, and MI on P-tau cut points and the ability to predict abnormal amyloid positron emission tomography (PET) scans. They defined an abnormal range as 1.96 standard deviation units beyond the mean among amyloid-negative individuals who are cognitively impaired. They excluded subjects with those risk factors and then established new cut points in the absence of the factors. The approach led to a significant change for the cutoff of P-tau 181 values, from 1.57 pg/mL or greater for individuals without stroke, MI, or CKD, and 1.75 pg/mL or greater for individuals with one such factor. There was little difference in the cutoff value for P-tau 217, from 0.25 pg/mL to 0.26 pg/mL.

Among people without a history of stroke, MI, or CKD, a P-tau 181 cutoff of 1.57 pg/mL or greater had an area under the receiving operating characteristic (AUROC) value of 0.717 (95% confidence interval, 0.691-0.744), compared with an AUROC of 0.687 (95% CI, 0.662-0.712) at a cutoff of 1.75 pg/mL or greater among people with those conditions. For P-tau 217, the values were 0.737 pg/mL (95% CI, 0.712-0.762) and 0.724 pg/mL (95% CI, 0.699-0.748), respectively.

“The sensitivity was better when they excluded those individuals with these conditions. Specificity was slightly, but not significantly, lower,” said Dr. Mielke during her talk.
 

Other considerations

Dr. Mielke added that it will be important to account for these and other factors when applying biomarkers in community settings, but they should also be considered in the context of health care disparities. Stroke, MI, and CKD are more common in African Americans, for example, suggesting that there could be racial differences in biomarker levels, though she said the difference in biomarker levels would be more likely attributable to the underlying comorbidities than race per se. “As shown, these factors can affect the consideration of an accuracy of cut points for clinical use. So I think future discussions will be needed as to how best to determine the cut points, and how to base them off of (different) populations,” said Dr. Mielke.

These sorts of refinements are important, according to Christopher Weber, PhD, who was asked for comment. “We have learned the importance of an early and accurate diagnosis. The blood test is a biomarker that does detect the hallmarks of Alzheimer’s disease sometimes up to decades before symptoms even appear,” said Dr. Weber, who is director of Global Science Initiatives at the Alzheimer’s Association.

But “there’s a lot more that we need to learn regarding when exactly to use them, who they’re appropriate for. And I think validation is the key to these blood biomarkers,” Dr. Weber added.

Dr. Mielke has been a consultant with the Brain Protection Company and Biogen. Dr. Weber has no relevant financial disclosures.

A Tennessee woman is suing a family physician and physician assistant (PA) after her husband’s death from COVID-19, claiming the health providers failed to properly test the man and rendered improper care that led to his demise.

Shirley Dimoh of Memphis alleges her husband Peter Dimoh, 66, received inadequate care when he presented with COVID-19 symptoms to May Medical Group in Munford, Tenn., on November 19, 2020. Physician assistant Robert Moody ordered a COVID-19 blood test for Mr. Dimoh, rather than a nasal swab test, which was sent to an Atlanta lab for analysis, according to the lawsuit.

By the time the Dimohs were informed of the positive result on November 23, Mr. Dimoh was seriously ill and showed signs of severe infection, the claim alleges. Family physician David Krapf, DO, then prescribed methocarbamol, a muscle relaxant, which the complaint claims exacerbated Mr. Dimoh’s infection, caused serious adverse reactions, and led to his death on December 16, 2020.

“Mr. Dimoh had multiple comorbid conditions and he had a positive test, he should have been referred to a specialist at a higher level of care,” said Duncan E. Ragsdale, a Memphis-based attorney representing Shirley Dimoh. “This is not something for a family physician or a physician assistant to be attempting to handle. It’s my belief this was a preventable death.”

Shirley Dimoh filed a lawsuit against May Medical Group, Moody, Krapf, and several others on June 23, 2021, in the Circuit Court of Tennessee, 13th Judicial District. She accuses the group of negligence, failure to refer, and failure to supervise, among other claims. She is requesting $5 million in damages.

May Medical Group did not return phone or email messages seeking comment for this story. The group had not issued a reply to the lawsuit as of this article’s deadline. An attorney for the practice is not yet listed in court records.
 

Wife had COVID-19 first, treated by same PA

Shirley Dimoh was the first of the couple to contract COVID-19. She visited May Medical Group with COVID-19 symptoms on November 9, according to the lawsuit. The same physician assistant allegedly prescribed antibiotics and sent Shirley Dimoh to the health department for a rapid nasal swab test. After a positive test resulted, she was prescribed more antibiotics, steroids, and other medications, according to the claim. She recovered without complications.

The plaintiff alleges the medical practice did not warn Peter Dimoh of the risk of contracting COVID-19 from contact with Shirley Dimoh or offer prophylactics against infection. Peter Dimoh had underlying conditions that included diabetes and kidney failure, according to Mr. Ragsdale.

It’s unclear why Peter Dimoh may have been prescribed methocarbamol after his positive COVID-19 test on November 23. The same day, Shirley Dimoh went to the pharmacy to pick up her husband’s prescription because he was too sick to go himself, the complaint states. Mr. Dimoh took the medication three times a day as prescribed. The methocarbamol was “unreasonably dangerous” for Mr. Dimoh at the time and caused an injury he would have not incurred otherwise, the suit claims.

On November 28, Mr. Dimoh collapsed and was taken by ambulance to Methodist Hospital in Memphis. He was treated for COVID-19 as well as bacterial pneumonia, severe sepsis, and sytemic inflammatory response syndrome, according to the complaint. He died December 16 from respiratory and heart failure.

“What’s interesting about this case is that you’ve got a good example and a bad example together,” Mr. Ragsdale said. “In other words, the good example is they treated her appropriately, she recovered. They didn’t treat him at all, he died. I don’t know how you could have a better counter position established by the same practice.”
 

Family has sued for malpractice before

Before his death, Peter Dimoh was the plaintiff in another medical negligence suit. In 2013, he sued the Center for Oral and Facial Surgery of Memphis and two oral surgeons for allegedly operating on him improperly and causing an adverse outcome.  

Mr. Dimoh underwent oral surgery on February 8, 2012, at the center. The day of his operation, Mr. Dimoh’s A1c and glucose levels were grossly elevated, according to the claim, which was also represented by Mr. Ragsdale. Surgeons concluded, incorrectly, that Mr. Dimoh’s diabetes was under control, the complaint alleges, failed to order preoperative antibiotics, operated on him, and caused a bacterial infection at the operative site. The infection allegedly resulted in osteomyelitis of Mr. Dimoh’s left mandible with a pathologic fracture.

The complaint also alleges that although Mr. Dimoh signed a consent form for the surgery, the defendants failed to obtain his consent because they were unaware his diabetes was not under control and they did not explain the risks of surgery while in such a condition. The suit alleges lack of informed consent, negligence, and gross negligence by the practice and requests $2 million in damages. 

Court documents show the suit was voluntarily withdrawn in 2018 without prejudice and reissued in 2019. In January 2021, the court was given notice of Mr. Dimoh’s death, and a motion was made to substitute another plaintiff, according to Shelby County court records.

An attorney for the Center for Oral and Facial Surgery of Memphis did not return a message seeking comment.

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

A Tennessee woman is suing a family physician and physician assistant (PA) after her husband’s death from COVID-19, claiming the health providers failed to properly test the man and rendered improper care that led to his demise.

Shirley Dimoh of Memphis alleges her husband Peter Dimoh, 66, received inadequate care when he presented with COVID-19 symptoms to May Medical Group in Munford, Tenn., on November 19, 2020. Physician assistant Robert Moody ordered a COVID-19 blood test for Mr. Dimoh, rather than a nasal swab test, which was sent to an Atlanta lab for analysis, according to the lawsuit.

By the time the Dimohs were informed of the positive result on November 23, Mr. Dimoh was seriously ill and showed signs of severe infection, the claim alleges. Family physician David Krapf, DO, then prescribed methocarbamol, a muscle relaxant, which the complaint claims exacerbated Mr. Dimoh’s infection, caused serious adverse reactions, and led to his death on December 16, 2020.

“Mr. Dimoh had multiple comorbid conditions and he had a positive test, he should have been referred to a specialist at a higher level of care,” said Duncan E. Ragsdale, a Memphis-based attorney representing Shirley Dimoh. “This is not something for a family physician or a physician assistant to be attempting to handle. It’s my belief this was a preventable death.”

Shirley Dimoh filed a lawsuit against May Medical Group, Moody, Krapf, and several others on June 23, 2021, in the Circuit Court of Tennessee, 13th Judicial District. She accuses the group of negligence, failure to refer, and failure to supervise, among other claims. She is requesting $5 million in damages.

May Medical Group did not return phone or email messages seeking comment for this story. The group had not issued a reply to the lawsuit as of this article’s deadline. An attorney for the practice is not yet listed in court records.
 

Wife had COVID-19 first, treated by same PA

Shirley Dimoh was the first of the couple to contract COVID-19. She visited May Medical Group with COVID-19 symptoms on November 9, according to the lawsuit. The same physician assistant allegedly prescribed antibiotics and sent Shirley Dimoh to the health department for a rapid nasal swab test. After a positive test resulted, she was prescribed more antibiotics, steroids, and other medications, according to the claim. She recovered without complications.

The plaintiff alleges the medical practice did not warn Peter Dimoh of the risk of contracting COVID-19 from contact with Shirley Dimoh or offer prophylactics against infection. Peter Dimoh had underlying conditions that included diabetes and kidney failure, according to Mr. Ragsdale.

It’s unclear why Peter Dimoh may have been prescribed methocarbamol after his positive COVID-19 test on November 23. The same day, Shirley Dimoh went to the pharmacy to pick up her husband’s prescription because he was too sick to go himself, the complaint states. Mr. Dimoh took the medication three times a day as prescribed. The methocarbamol was “unreasonably dangerous” for Mr. Dimoh at the time and caused an injury he would have not incurred otherwise, the suit claims.

On November 28, Mr. Dimoh collapsed and was taken by ambulance to Methodist Hospital in Memphis. He was treated for COVID-19 as well as bacterial pneumonia, severe sepsis, and sytemic inflammatory response syndrome, according to the complaint. He died December 16 from respiratory and heart failure.

“What’s interesting about this case is that you’ve got a good example and a bad example together,” Mr. Ragsdale said. “In other words, the good example is they treated her appropriately, she recovered. They didn’t treat him at all, he died. I don’t know how you could have a better counter position established by the same practice.”
 

Family has sued for malpractice before

Before his death, Peter Dimoh was the plaintiff in another medical negligence suit. In 2013, he sued the Center for Oral and Facial Surgery of Memphis and two oral surgeons for allegedly operating on him improperly and causing an adverse outcome.  

Mr. Dimoh underwent oral surgery on February 8, 2012, at the center. The day of his operation, Mr. Dimoh’s A1c and glucose levels were grossly elevated, according to the claim, which was also represented by Mr. Ragsdale. Surgeons concluded, incorrectly, that Mr. Dimoh’s diabetes was under control, the complaint alleges, failed to order preoperative antibiotics, operated on him, and caused a bacterial infection at the operative site. The infection allegedly resulted in osteomyelitis of Mr. Dimoh’s left mandible with a pathologic fracture.

The complaint also alleges that although Mr. Dimoh signed a consent form for the surgery, the defendants failed to obtain his consent because they were unaware his diabetes was not under control and they did not explain the risks of surgery while in such a condition. The suit alleges lack of informed consent, negligence, and gross negligence by the practice and requests $2 million in damages. 

Court documents show the suit was voluntarily withdrawn in 2018 without prejudice and reissued in 2019. In January 2021, the court was given notice of Mr. Dimoh’s death, and a motion was made to substitute another plaintiff, according to Shelby County court records.

An attorney for the Center for Oral and Facial Surgery of Memphis did not return a message seeking comment.

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

A Tennessee woman is suing a family physician and physician assistant (PA) after her husband’s death from COVID-19, claiming the health providers failed to properly test the man and rendered improper care that led to his demise.

Shirley Dimoh of Memphis alleges her husband Peter Dimoh, 66, received inadequate care when he presented with COVID-19 symptoms to May Medical Group in Munford, Tenn., on November 19, 2020. Physician assistant Robert Moody ordered a COVID-19 blood test for Mr. Dimoh, rather than a nasal swab test, which was sent to an Atlanta lab for analysis, according to the lawsuit.

By the time the Dimohs were informed of the positive result on November 23, Mr. Dimoh was seriously ill and showed signs of severe infection, the claim alleges. Family physician David Krapf, DO, then prescribed methocarbamol, a muscle relaxant, which the complaint claims exacerbated Mr. Dimoh’s infection, caused serious adverse reactions, and led to his death on December 16, 2020.

“Mr. Dimoh had multiple comorbid conditions and he had a positive test, he should have been referred to a specialist at a higher level of care,” said Duncan E. Ragsdale, a Memphis-based attorney representing Shirley Dimoh. “This is not something for a family physician or a physician assistant to be attempting to handle. It’s my belief this was a preventable death.”

Shirley Dimoh filed a lawsuit against May Medical Group, Moody, Krapf, and several others on June 23, 2021, in the Circuit Court of Tennessee, 13th Judicial District. She accuses the group of negligence, failure to refer, and failure to supervise, among other claims. She is requesting $5 million in damages.

May Medical Group did not return phone or email messages seeking comment for this story. The group had not issued a reply to the lawsuit as of this article’s deadline. An attorney for the practice is not yet listed in court records.
 

Wife had COVID-19 first, treated by same PA

Shirley Dimoh was the first of the couple to contract COVID-19. She visited May Medical Group with COVID-19 symptoms on November 9, according to the lawsuit. The same physician assistant allegedly prescribed antibiotics and sent Shirley Dimoh to the health department for a rapid nasal swab test. After a positive test resulted, she was prescribed more antibiotics, steroids, and other medications, according to the claim. She recovered without complications.

The plaintiff alleges the medical practice did not warn Peter Dimoh of the risk of contracting COVID-19 from contact with Shirley Dimoh or offer prophylactics against infection. Peter Dimoh had underlying conditions that included diabetes and kidney failure, according to Mr. Ragsdale.

It’s unclear why Peter Dimoh may have been prescribed methocarbamol after his positive COVID-19 test on November 23. The same day, Shirley Dimoh went to the pharmacy to pick up her husband’s prescription because he was too sick to go himself, the complaint states. Mr. Dimoh took the medication three times a day as prescribed. The methocarbamol was “unreasonably dangerous” for Mr. Dimoh at the time and caused an injury he would have not incurred otherwise, the suit claims.

On November 28, Mr. Dimoh collapsed and was taken by ambulance to Methodist Hospital in Memphis. He was treated for COVID-19 as well as bacterial pneumonia, severe sepsis, and sytemic inflammatory response syndrome, according to the complaint. He died December 16 from respiratory and heart failure.

“What’s interesting about this case is that you’ve got a good example and a bad example together,” Mr. Ragsdale said. “In other words, the good example is they treated her appropriately, she recovered. They didn’t treat him at all, he died. I don’t know how you could have a better counter position established by the same practice.”
 

Family has sued for malpractice before

Before his death, Peter Dimoh was the plaintiff in another medical negligence suit. In 2013, he sued the Center for Oral and Facial Surgery of Memphis and two oral surgeons for allegedly operating on him improperly and causing an adverse outcome.  

Mr. Dimoh underwent oral surgery on February 8, 2012, at the center. The day of his operation, Mr. Dimoh’s A1c and glucose levels were grossly elevated, according to the claim, which was also represented by Mr. Ragsdale. Surgeons concluded, incorrectly, that Mr. Dimoh’s diabetes was under control, the complaint alleges, failed to order preoperative antibiotics, operated on him, and caused a bacterial infection at the operative site. The infection allegedly resulted in osteomyelitis of Mr. Dimoh’s left mandible with a pathologic fracture.

The complaint also alleges that although Mr. Dimoh signed a consent form for the surgery, the defendants failed to obtain his consent because they were unaware his diabetes was not under control and they did not explain the risks of surgery while in such a condition. The suit alleges lack of informed consent, negligence, and gross negligence by the practice and requests $2 million in damages. 

Court documents show the suit was voluntarily withdrawn in 2018 without prejudice and reissued in 2019. In January 2021, the court was given notice of Mr. Dimoh’s death, and a motion was made to substitute another plaintiff, according to Shelby County court records.

An attorney for the Center for Oral and Facial Surgery of Memphis did not return a message seeking comment.

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

Over the past 25 years, antiretroviral therapy (ART) has led to a dramatic decrease in HIV-associated morbidity and mortality. Patients who initiate ART today can now expect a nearly normal life expectancy.¹ Despite the overwhelming benefits of ART, some patients experience immune reconstitution inflammatory syndrome (IRIS), a disease- or pathogen-specific immune response that can mimic the presentation of an active opportunistic infection (OI). IRIS can occur at any CD4 count. However, it is most often associated with the rapid increase in CD4 count and decrease in viral load that typically follows ART initiation in patients who are severely immunocompromised and have high viral loads.^2-6

IRIS manifests in two primary ways. Paradoxical IRIS refers to the worsening of a previously diagnosed disease after ART initiation, whereas unmasking IRIS refers to the appearance of a previously undiagnosed disease following ART initiation.

The Medical Care Criteria Committee of the New York State Department of Health AIDS Institute Clinical Guidelines Program recently published an update to its guideline, Management of IRIS . This update incorporates recent data and summarizes how to identify and manage IRIS associated with several OIs. Important goals of this update were to raise awareness among healthcare providers about IRIS, including its clinical presentation, and provide treatment recommendations.
 

For most patients, ART should be started quickly

Over the past few years, rapid initiation of ART has become the new standard of care, with same-day initiation on the day of HIV diagnosis recommended whenever possible. For many years, however, the presence of an active OI was felt to justify delaying ART initiation until the OI was completely treated. This approach changed in 2009 when a randomized trial by the AIDS Clinical Trials Group demonstrated that patients who initiated ART within 2 weeks of OI diagnosis did not experience more adverse events than those who waited.⁷ Moreover, although the finding did not reach statistical significance, participants in the early ART arm appeared to experience lower mortality and progression of AIDS than those in the delayed ART arm. Therefore, patients diagnosed with most OIs can start ART as soon as they are tolerating the treatment for the OI.

Some OIs do require a delay in ART

Symptoms associated with IRIS are typically mild or moderate; life-threatening complications are rare. Most patients newly diagnosed with HIV who have an active OI can therefore initiate ART quickly. However, IRIS involving the central nervous system or eye carries a much greater risk of morbidity and mortality. OIs that do warrant a delay in ART initiation, therefore, include tuberculosis (TB) meningitis, cryptococcal meningitis, and cytomegalovirus (CMV) retinitis.

Several randomized clinical trials have found that in patients with HIV and pulmonary TB coinfection, ART should be started as soon as the patient is tolerating anti-TB therapy.^8-10 What’s more, in patients with CD4 counts less than 50 cells/microL, there is a mortality benefit when ART is initiated within 2 weeks of starting TB treatment, compared with waiting 8 weeks.

For TB meningitis, however, a clinical trial conducted in Vietnam did not show any mortality benefit when ART was started within 7 days (vs. 2 months); however, severe adverse events were more common in the immediate ART group, raising the concern that patients in that group had experienced complications of IRIS of the central nervous system.¹¹ Limited data are available to guide specific timing of ART in patients with TB meningitis, but based on the results of this trial, most clinicians wait approximately 2 months before initiating ART, and consultation with an expert is recommended.

Optimal timing of ART in patients with cryptococcal meningitis is also uncertain, and there have been contradictory results from several small studies. However, in 2014, the larger COAT trial, conducted in Uganda and South Africa, found 15% higher mortality in patients who initiated ART within 2 weeks, compared with more than 5 weeks.¹² Although exactly how long to wait is still unknown, ART should be delayed by at least 2 weeks after a patient starts antifungal therapy.

CMV-IRIS can have devastating effects, including vision loss or blindness. Therefore, ART initiation should be delayed in patients with diagnosed or strongly suspected CMV.¹³ Importantly, however, patients with advanced HIV may have asymptomatic or subclinical CMV retinitis. As a result, all patients with HIV who have CD4 counts less than 100 cells/mm³ who do not have known or strongly suspected CMV should be screened for signs of CMV by dilated ophthalmological examination as soon as possible after initiation of ART. If signs of CMV are seen on dilated exam, clinicians should consult with an experienced HIV care provider to determine if ART must be temporarily paused.
 

Diagnosing IRIS

Broadly, IRIS presents as a clinical deterioration after ART initiation, with localized tissue inflammation, with or without a systemic inflammatory response, but the presentation of IRIS varies depending on the underlying OI or illness. In most cases, IRIS occurs within 4-8 weeks of ART initiation or regimen change. A rise in CD4 count often but does not always precede IRIS and is not a diagnostic criterion. There is no diagnostic test for IRIS, and when assessing a patient for possible IRIS, clinicians should exclude HIV disease progression, new infections, OI drug resistance, OI treatment nonadherence, and drug reactions as possible causes for inflammatory signs or symptoms.

Treatment of IRIS

Most cases of IRIS are mild, and patients can be reassured that the symptoms will resolve with time. Clinicians should interrupt ART only if a patient has a severe, life-threatening case of IRIS. Unnecessary ART interruption may increase a patient’s risk of new opportunistic infections, recurring IRIS upon resumption of ART, and development of HIV-drug resistance. Any newly unmasked OIs should be treated promptly while ART is continued. For patients with severe IRIS, clinicians can use prednisone to treat inflammatory symptoms – generally for 1-2 weeks, followed by a taper as needed. Prednisone, however, should not be used in patients with cryptococcal meningitis or Kaposi sarcoma as it is associated with worse outcomes.^14-17

In patients newly diagnosed with HIV, prompt initiation of ART is, with the exceptions outlined above, the highest priority. IRIS is an unfortunate complication of ART, and patients may be discouraged when they find themselves feeling worse shortly after starting treatment. While providing supportive and symptomatic care, clinicians can reassure patients by explaining that immune reconstitution is, in fact, the goal of ART and that their symptoms do not represent the progression of HIV disease. It is hoped that with more frequent HIV testing, earlier diagnosis, and earlier ART initiation at higher CD4 counts, IRIS will become a less frequent nuisance to patients and providers. 

Dr. Brust is in the department of medicine at Albert Einstein College of Medicine/Montefiore Medical Center, New York. He reported having no relevant financial relationships. A version of this article first appeared on Medscape.com.

References

1. Marcus JL et al. JAMA Netw Open. 2020;3:e207954.

2. Breton G et al. Clin Infect Dis. 2004;39:1709-12.

3. Shelburne SA et al. Clin Infect Dis. 2005;40:1049-52.

4. Shelburne SA et al. AIDS. 2005;19:399-406.

5. Muller M et al. Lancet Infect Dis. 2010;10:251-61.

6. Novak RM et al. AIDS. 2012;26:721-30.

7. Zolopa A et al. PLoS One. 2009;4:e5575.

8. Havlir DV et al. N Engl J Med. 2011;365:1482-91.

9. Abdool Karim SS et al. N Engl J Med. 2011;365:1492-501.

10. Blanc FX et al. N Engl J Med. 2011;365:1471-81.

11. Torok ME et al. Clin Infect Dis. 2011;52:1374-83.

12. Boulware DR et al. N Engl J Med. 2014;370:2487-98.

13. Ortega-Larrocea G et al. AIDS. 2005;19:735-8.

14. Beardsley J et al. N Engl J Med. 2016;374:542-54.

15. Gill PS, Loureiro C et al.  Ann Intern Med. 1989;110:937-40.

16. Elliott AM et al. J Infect Dis. 2004;190:869-78.

17. Volkow PF et al. AIDS. 2008;22:663-5.

Over the past 25 years, antiretroviral therapy (ART) has led to a dramatic decrease in HIV-associated morbidity and mortality. Patients who initiate ART today can now expect a nearly normal life expectancy.¹ Despite the overwhelming benefits of ART, some patients experience immune reconstitution inflammatory syndrome (IRIS), a disease- or pathogen-specific immune response that can mimic the presentation of an active opportunistic infection (OI). IRIS can occur at any CD4 count. However, it is most often associated with the rapid increase in CD4 count and decrease in viral load that typically follows ART initiation in patients who are severely immunocompromised and have high viral loads.^2-6

IRIS manifests in two primary ways. Paradoxical IRIS refers to the worsening of a previously diagnosed disease after ART initiation, whereas unmasking IRIS refers to the appearance of a previously undiagnosed disease following ART initiation.

The Medical Care Criteria Committee of the New York State Department of Health AIDS Institute Clinical Guidelines Program recently published an update to its guideline, Management of IRIS . This update incorporates recent data and summarizes how to identify and manage IRIS associated with several OIs. Important goals of this update were to raise awareness among healthcare providers about IRIS, including its clinical presentation, and provide treatment recommendations.
 

For most patients, ART should be started quickly

Over the past few years, rapid initiation of ART has become the new standard of care, with same-day initiation on the day of HIV diagnosis recommended whenever possible. For many years, however, the presence of an active OI was felt to justify delaying ART initiation until the OI was completely treated. This approach changed in 2009 when a randomized trial by the AIDS Clinical Trials Group demonstrated that patients who initiated ART within 2 weeks of OI diagnosis did not experience more adverse events than those who waited.⁷ Moreover, although the finding did not reach statistical significance, participants in the early ART arm appeared to experience lower mortality and progression of AIDS than those in the delayed ART arm. Therefore, patients diagnosed with most OIs can start ART as soon as they are tolerating the treatment for the OI.

Some OIs do require a delay in ART

Symptoms associated with IRIS are typically mild or moderate; life-threatening complications are rare. Most patients newly diagnosed with HIV who have an active OI can therefore initiate ART quickly. However, IRIS involving the central nervous system or eye carries a much greater risk of morbidity and mortality. OIs that do warrant a delay in ART initiation, therefore, include tuberculosis (TB) meningitis, cryptococcal meningitis, and cytomegalovirus (CMV) retinitis.

Several randomized clinical trials have found that in patients with HIV and pulmonary TB coinfection, ART should be started as soon as the patient is tolerating anti-TB therapy.^8-10 What’s more, in patients with CD4 counts less than 50 cells/microL, there is a mortality benefit when ART is initiated within 2 weeks of starting TB treatment, compared with waiting 8 weeks.

For TB meningitis, however, a clinical trial conducted in Vietnam did not show any mortality benefit when ART was started within 7 days (vs. 2 months); however, severe adverse events were more common in the immediate ART group, raising the concern that patients in that group had experienced complications of IRIS of the central nervous system.¹¹ Limited data are available to guide specific timing of ART in patients with TB meningitis, but based on the results of this trial, most clinicians wait approximately 2 months before initiating ART, and consultation with an expert is recommended.

Optimal timing of ART in patients with cryptococcal meningitis is also uncertain, and there have been contradictory results from several small studies. However, in 2014, the larger COAT trial, conducted in Uganda and South Africa, found 15% higher mortality in patients who initiated ART within 2 weeks, compared with more than 5 weeks.¹² Although exactly how long to wait is still unknown, ART should be delayed by at least 2 weeks after a patient starts antifungal therapy.

CMV-IRIS can have devastating effects, including vision loss or blindness. Therefore, ART initiation should be delayed in patients with diagnosed or strongly suspected CMV.¹³ Importantly, however, patients with advanced HIV may have asymptomatic or subclinical CMV retinitis. As a result, all patients with HIV who have CD4 counts less than 100 cells/mm³ who do not have known or strongly suspected CMV should be screened for signs of CMV by dilated ophthalmological examination as soon as possible after initiation of ART. If signs of CMV are seen on dilated exam, clinicians should consult with an experienced HIV care provider to determine if ART must be temporarily paused.
 

Diagnosing IRIS

Broadly, IRIS presents as a clinical deterioration after ART initiation, with localized tissue inflammation, with or without a systemic inflammatory response, but the presentation of IRIS varies depending on the underlying OI or illness. In most cases, IRIS occurs within 4-8 weeks of ART initiation or regimen change. A rise in CD4 count often but does not always precede IRIS and is not a diagnostic criterion. There is no diagnostic test for IRIS, and when assessing a patient for possible IRIS, clinicians should exclude HIV disease progression, new infections, OI drug resistance, OI treatment nonadherence, and drug reactions as possible causes for inflammatory signs or symptoms.

Treatment of IRIS

Most cases of IRIS are mild, and patients can be reassured that the symptoms will resolve with time. Clinicians should interrupt ART only if a patient has a severe, life-threatening case of IRIS. Unnecessary ART interruption may increase a patient’s risk of new opportunistic infections, recurring IRIS upon resumption of ART, and development of HIV-drug resistance. Any newly unmasked OIs should be treated promptly while ART is continued. For patients with severe IRIS, clinicians can use prednisone to treat inflammatory symptoms – generally for 1-2 weeks, followed by a taper as needed. Prednisone, however, should not be used in patients with cryptococcal meningitis or Kaposi sarcoma as it is associated with worse outcomes.^14-17

In patients newly diagnosed with HIV, prompt initiation of ART is, with the exceptions outlined above, the highest priority. IRIS is an unfortunate complication of ART, and patients may be discouraged when they find themselves feeling worse shortly after starting treatment. While providing supportive and symptomatic care, clinicians can reassure patients by explaining that immune reconstitution is, in fact, the goal of ART and that their symptoms do not represent the progression of HIV disease. It is hoped that with more frequent HIV testing, earlier diagnosis, and earlier ART initiation at higher CD4 counts, IRIS will become a less frequent nuisance to patients and providers. 

Dr. Brust is in the department of medicine at Albert Einstein College of Medicine/Montefiore Medical Center, New York. He reported having no relevant financial relationships. A version of this article first appeared on Medscape.com.

References

1. Marcus JL et al. JAMA Netw Open. 2020;3:e207954.

2. Breton G et al. Clin Infect Dis. 2004;39:1709-12.

3. Shelburne SA et al. Clin Infect Dis. 2005;40:1049-52.

4. Shelburne SA et al. AIDS. 2005;19:399-406.

5. Muller M et al. Lancet Infect Dis. 2010;10:251-61.

6. Novak RM et al. AIDS. 2012;26:721-30.

7. Zolopa A et al. PLoS One. 2009;4:e5575.

8. Havlir DV et al. N Engl J Med. 2011;365:1482-91.

9. Abdool Karim SS et al. N Engl J Med. 2011;365:1492-501.

10. Blanc FX et al. N Engl J Med. 2011;365:1471-81.

11. Torok ME et al. Clin Infect Dis. 2011;52:1374-83.

12. Boulware DR et al. N Engl J Med. 2014;370:2487-98.

13. Ortega-Larrocea G et al. AIDS. 2005;19:735-8.

14. Beardsley J et al. N Engl J Med. 2016;374:542-54.

15. Gill PS, Loureiro C et al.  Ann Intern Med. 1989;110:937-40.

16. Elliott AM et al. J Infect Dis. 2004;190:869-78.

17. Volkow PF et al. AIDS. 2008;22:663-5.

Over the past 25 years, antiretroviral therapy (ART) has led to a dramatic decrease in HIV-associated morbidity and mortality. Patients who initiate ART today can now expect a nearly normal life expectancy.¹ Despite the overwhelming benefits of ART, some patients experience immune reconstitution inflammatory syndrome (IRIS), a disease- or pathogen-specific immune response that can mimic the presentation of an active opportunistic infection (OI). IRIS can occur at any CD4 count. However, it is most often associated with the rapid increase in CD4 count and decrease in viral load that typically follows ART initiation in patients who are severely immunocompromised and have high viral loads.^2-6

IRIS manifests in two primary ways. Paradoxical IRIS refers to the worsening of a previously diagnosed disease after ART initiation, whereas unmasking IRIS refers to the appearance of a previously undiagnosed disease following ART initiation.

The Medical Care Criteria Committee of the New York State Department of Health AIDS Institute Clinical Guidelines Program recently published an update to its guideline, Management of IRIS . This update incorporates recent data and summarizes how to identify and manage IRIS associated with several OIs. Important goals of this update were to raise awareness among healthcare providers about IRIS, including its clinical presentation, and provide treatment recommendations.
 

For most patients, ART should be started quickly

Over the past few years, rapid initiation of ART has become the new standard of care, with same-day initiation on the day of HIV diagnosis recommended whenever possible. For many years, however, the presence of an active OI was felt to justify delaying ART initiation until the OI was completely treated. This approach changed in 2009 when a randomized trial by the AIDS Clinical Trials Group demonstrated that patients who initiated ART within 2 weeks of OI diagnosis did not experience more adverse events than those who waited.⁷ Moreover, although the finding did not reach statistical significance, participants in the early ART arm appeared to experience lower mortality and progression of AIDS than those in the delayed ART arm. Therefore, patients diagnosed with most OIs can start ART as soon as they are tolerating the treatment for the OI.

Some OIs do require a delay in ART

Symptoms associated with IRIS are typically mild or moderate; life-threatening complications are rare. Most patients newly diagnosed with HIV who have an active OI can therefore initiate ART quickly. However, IRIS involving the central nervous system or eye carries a much greater risk of morbidity and mortality. OIs that do warrant a delay in ART initiation, therefore, include tuberculosis (TB) meningitis, cryptococcal meningitis, and cytomegalovirus (CMV) retinitis.

Several randomized clinical trials have found that in patients with HIV and pulmonary TB coinfection, ART should be started as soon as the patient is tolerating anti-TB therapy.^8-10 What’s more, in patients with CD4 counts less than 50 cells/microL, there is a mortality benefit when ART is initiated within 2 weeks of starting TB treatment, compared with waiting 8 weeks.

For TB meningitis, however, a clinical trial conducted in Vietnam did not show any mortality benefit when ART was started within 7 days (vs. 2 months); however, severe adverse events were more common in the immediate ART group, raising the concern that patients in that group had experienced complications of IRIS of the central nervous system.¹¹ Limited data are available to guide specific timing of ART in patients with TB meningitis, but based on the results of this trial, most clinicians wait approximately 2 months before initiating ART, and consultation with an expert is recommended.

Optimal timing of ART in patients with cryptococcal meningitis is also uncertain, and there have been contradictory results from several small studies. However, in 2014, the larger COAT trial, conducted in Uganda and South Africa, found 15% higher mortality in patients who initiated ART within 2 weeks, compared with more than 5 weeks.¹² Although exactly how long to wait is still unknown, ART should be delayed by at least 2 weeks after a patient starts antifungal therapy.

CMV-IRIS can have devastating effects, including vision loss or blindness. Therefore, ART initiation should be delayed in patients with diagnosed or strongly suspected CMV.¹³ Importantly, however, patients with advanced HIV may have asymptomatic or subclinical CMV retinitis. As a result, all patients with HIV who have CD4 counts less than 100 cells/mm³ who do not have known or strongly suspected CMV should be screened for signs of CMV by dilated ophthalmological examination as soon as possible after initiation of ART. If signs of CMV are seen on dilated exam, clinicians should consult with an experienced HIV care provider to determine if ART must be temporarily paused.
 

Diagnosing IRIS

Broadly, IRIS presents as a clinical deterioration after ART initiation, with localized tissue inflammation, with or without a systemic inflammatory response, but the presentation of IRIS varies depending on the underlying OI or illness. In most cases, IRIS occurs within 4-8 weeks of ART initiation or regimen change. A rise in CD4 count often but does not always precede IRIS and is not a diagnostic criterion. There is no diagnostic test for IRIS, and when assessing a patient for possible IRIS, clinicians should exclude HIV disease progression, new infections, OI drug resistance, OI treatment nonadherence, and drug reactions as possible causes for inflammatory signs or symptoms.

Treatment of IRIS

Most cases of IRIS are mild, and patients can be reassured that the symptoms will resolve with time. Clinicians should interrupt ART only if a patient has a severe, life-threatening case of IRIS. Unnecessary ART interruption may increase a patient’s risk of new opportunistic infections, recurring IRIS upon resumption of ART, and development of HIV-drug resistance. Any newly unmasked OIs should be treated promptly while ART is continued. For patients with severe IRIS, clinicians can use prednisone to treat inflammatory symptoms – generally for 1-2 weeks, followed by a taper as needed. Prednisone, however, should not be used in patients with cryptococcal meningitis or Kaposi sarcoma as it is associated with worse outcomes.^14-17

In patients newly diagnosed with HIV, prompt initiation of ART is, with the exceptions outlined above, the highest priority. IRIS is an unfortunate complication of ART, and patients may be discouraged when they find themselves feeling worse shortly after starting treatment. While providing supportive and symptomatic care, clinicians can reassure patients by explaining that immune reconstitution is, in fact, the goal of ART and that their symptoms do not represent the progression of HIV disease. It is hoped that with more frequent HIV testing, earlier diagnosis, and earlier ART initiation at higher CD4 counts, IRIS will become a less frequent nuisance to patients and providers. 

Dr. Brust is in the department of medicine at Albert Einstein College of Medicine/Montefiore Medical Center, New York. He reported having no relevant financial relationships. A version of this article first appeared on Medscape.com.

References

1. Marcus JL et al. JAMA Netw Open. 2020;3:e207954.

2. Breton G et al. Clin Infect Dis. 2004;39:1709-12.

3. Shelburne SA et al. Clin Infect Dis. 2005;40:1049-52.

4. Shelburne SA et al. AIDS. 2005;19:399-406.

5. Muller M et al. Lancet Infect Dis. 2010;10:251-61.

6. Novak RM et al. AIDS. 2012;26:721-30.

7. Zolopa A et al. PLoS One. 2009;4:e5575.

8. Havlir DV et al. N Engl J Med. 2011;365:1482-91.

9. Abdool Karim SS et al. N Engl J Med. 2011;365:1492-501.

10. Blanc FX et al. N Engl J Med. 2011;365:1471-81.

11. Torok ME et al. Clin Infect Dis. 2011;52:1374-83.

12. Boulware DR et al. N Engl J Med. 2014;370:2487-98.

13. Ortega-Larrocea G et al. AIDS. 2005;19:735-8.

14. Beardsley J et al. N Engl J Med. 2016;374:542-54.

15. Gill PS, Loureiro C et al.  Ann Intern Med. 1989;110:937-40.

16. Elliott AM et al. J Infect Dis. 2004;190:869-78.

17. Volkow PF et al. AIDS. 2008;22:663-5.

A dietary supplement that mimics the effects of the high-fat, low-carbohydrate ketogenic diet is well tolerated and appears to reduce seizures in children and adults with treatment-resistant epilepsy, early research suggests. However, at least one expert has concerns.

In an open-label feasibility study, researchers assessed a liquid supplement known as K.Vita (Vitaflo International), which contains both decanoic acid and octanoic acid.

Although the study was small, the findings are promising, said coinvestigator Matthew Walker, MD, PhD, University College London Institute of Neurology, department of clinical and experimental epilepsy.

“The dietary supplement was reasonably well tolerated and while we weren’t specifically looking for efficacy here, we did see some patients had quite dramatic results in terms of reduced seizures,” Dr. Walker said.

Unlike the ketogenic diet, this dietary supplement is “very easy” to follow, involves only minor dietary modifications, and doesn’t require the intervention of a dietitian, he added.

The findings were published online July 23, 2021, in Brain Communications.
 

Key ingredients

In the ketogenic diet, the body uses body fat as its primary fuel source. The switch from carbohydrates to fat for body fuel results in built-up ketones.

Previous research shows the ketogenic diet is effective in reducing seizures in some patients with epilepsy. However, many patients find it difficult to tolerate, especially for extended periods. Dr. Walker also noted that ketones may have other long-term side effects, including osteoporosis.

He added that his team was keen to learn what elements of the ketogenic diet affect seizures. “Interestingly, we found that one of the fats used in the ketogenic diet, decanoic acid, has quite marked antiseizure effects,” Dr. Walker said.

Previous research has shown that decanoic acid, a medium-chain triglyceride–derived fatty acid, can cross the blood-brain barrier and decrease excitatory neurotransmission and network excitability in vitro.

Dr. Walker noted that ketones are necessary in order to reduce seizures.

“Rather than have a very high-fat, low-carbohydrate diet that causes ketones, we thought ‘why don’t we use a diet in which we just use mainly this fat, this decanoic acid, and avoid ketosis,’ ” he said.

The researchers then went to work developing the K.Vita dietary supplement, which mainly contains decanoic acid but also another fat, octanoic acid.
 

Assessing feasibility

The feasibility study included 61 patients (59% female) who began taking the supplement. Of these, 35 were children (aged 3-18 years) and 26 were adults. The children had Dravet syndrome or another genetically driven form of epilepsy, while most of the adults had a focal epilepsy.

All participants had failed multiple antiseizure medications – a median of 3 for children and 10 for adults who completed the trial. Of the 61 original participants, 20 (19 children and 1 adult) had tried the ketogenic diet but had stopped it for various reasons, including noncompliance and lack of efficacy.

The liquid supplement was introduced gradually. The amount administered was based on weight in the children and was a standard amount in adults, with the target being 240 mL.

Participants consumed the supplement in equal servings taken at regular intervals as part of a meal or snack. They could take it alone or mix it with yogurt or another food.

Patients with feeding tubes took the supplement immediately before or after or mixed into an enteral feed, with a water flush afterward.

Researchers provided patients and caregivers with guidance on excluding highly refined sugary foods and beverages. Starchy foods such as bread, pasta, rice, and potatoes were not restricted.

The study consisted of three visits: baseline, 5 weeks, and 12 weeks, in addition to regular phone and email contact. Participants were also asked to keep a seizure diary.
 

Highly acceptable to patients

Overall, the study withdrawal rate was 33%. After a protocol change involving a slower introduction of the supplement, there were fewer withdrawals, Dr. Walker reported. He noted that the proportion of participants who completed the study (41 of 61) is “much better than with most studies of adults following the ketogenic diet.”

The most frequently reported gastrointestinal symptoms with the supplement were bloating and constipation, but these were predominantly mild and tended to decrease over time. This, said Dr. Walker, contrasts to the ketogenic diet where side effects tend to persist.

There was no significant change in body weight or body mass index. “We did not see weight gain as a problem at all,” Dr. Walker said.

Of 15 caregivers and 19 adults who returned an acceptability questionnaire, 84% agreed or strongly agreed the supplement had a good flavor (strawberry); 88% liked the appearance and color; 77% liked the texture and consistency; and 88% agreed or strongly agreed it was easy to take.

About one-third of adults and two-thirds of caregivers said they believed the supplement reduced seizures.
 

50% seizure reduction

Only three children and one adult became ketotic. This is typically classified as a beta-hydroxybutyrate (BHB) greater than 1 mmol/L (10.4 mg/dL). The BHB levels detected were markedly lower than those observed in individuals following a ketogenic diet, the investigators note.

Of the 41 participants, 19 completed the diaries. There were also data from physician recordings, so researchers were able to retrieve seizure frequencies for 32 of the 41 (78%). Of these 32 patients, 14 (44%) had a 50% or greater reduction in seizures. Overall, children and adults “responded similarly,” Dr. Walker said.

He acknowledged the study numbers are small and emphasized that larger studies are needed to determine efficacy. He also hopes for a future randomized controlled trial comparing K.Vita with another supplement that contains different types of fats.

Interestingly, the product has already “passed” the regulatory approval process in the United Kingdom, so it can be labeled as a medicinal food and should be available for use at the beginning of 2022, Dr. Walker said.
 

Study concerns

Asked to comment on the findings, Daniel Goldenholz, MD, PhD, instructor in the department of neurology, Beth Israel Deaconess Medical Center, Boston, said the supplement may be helpful, but he has concerns about the study.

Many patients with epilepsy are “desperate” for therapies that will help treat their seizures, said Dr. Goldenholz, who was not involved with the research. “If there’s a dietary therapy that has the potential for being helpful, I’m loving that. I need that. My patients are begging for something that works.” It is “really exciting” that researchers are working on that goal, Dr. Goldenholz added.

However, he noted that it is too soon to start talking to patients about this new product. He also pointed out that a significant fraction of the study participants dropped out, many because they couldn’t tolerate the supplement. In addition, others didn’t produce a seizure diary.

Dr. Goldenholz and colleagues have published several studies showing that patients with no intervention at all can sometimes show a reduction in seizures compared with their baseline results.

“We found sizable 50% reductions attributable entirely to the natural fluctuations in seizure rates, rather than any therapy at all, he said.

Dr. Goldenholz added that he hopes to see future studies on this topic, and on similar therapies “with sufficient data and more reliable metrics for efficacy.”

The study was funded by Vitaflo International. Dr. Walker reports having received grants from Vitaflo International and personal fees from UCB Pharma, Eisai, and Sage. In addition, along with colleagues, he has a patent (Nutritional product) pending.

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

A dietary supplement that mimics the effects of the high-fat, low-carbohydrate ketogenic diet is well tolerated and appears to reduce seizures in children and adults with treatment-resistant epilepsy, early research suggests. However, at least one expert has concerns.

In an open-label feasibility study, researchers assessed a liquid supplement known as K.Vita (Vitaflo International), which contains both decanoic acid and octanoic acid.

Although the study was small, the findings are promising, said coinvestigator Matthew Walker, MD, PhD, University College London Institute of Neurology, department of clinical and experimental epilepsy.

“The dietary supplement was reasonably well tolerated and while we weren’t specifically looking for efficacy here, we did see some patients had quite dramatic results in terms of reduced seizures,” Dr. Walker said.

Unlike the ketogenic diet, this dietary supplement is “very easy” to follow, involves only minor dietary modifications, and doesn’t require the intervention of a dietitian, he added.

The findings were published online July 23, 2021, in Brain Communications.
 

Key ingredients

In the ketogenic diet, the body uses body fat as its primary fuel source. The switch from carbohydrates to fat for body fuel results in built-up ketones.

Previous research shows the ketogenic diet is effective in reducing seizures in some patients with epilepsy. However, many patients find it difficult to tolerate, especially for extended periods. Dr. Walker also noted that ketones may have other long-term side effects, including osteoporosis.

He added that his team was keen to learn what elements of the ketogenic diet affect seizures. “Interestingly, we found that one of the fats used in the ketogenic diet, decanoic acid, has quite marked antiseizure effects,” Dr. Walker said.

Previous research has shown that decanoic acid, a medium-chain triglyceride–derived fatty acid, can cross the blood-brain barrier and decrease excitatory neurotransmission and network excitability in vitro.

Dr. Walker noted that ketones are necessary in order to reduce seizures.

“Rather than have a very high-fat, low-carbohydrate diet that causes ketones, we thought ‘why don’t we use a diet in which we just use mainly this fat, this decanoic acid, and avoid ketosis,’ ” he said.

The researchers then went to work developing the K.Vita dietary supplement, which mainly contains decanoic acid but also another fat, octanoic acid.
 

Assessing feasibility

The feasibility study included 61 patients (59% female) who began taking the supplement. Of these, 35 were children (aged 3-18 years) and 26 were adults. The children had Dravet syndrome or another genetically driven form of epilepsy, while most of the adults had a focal epilepsy.

All participants had failed multiple antiseizure medications – a median of 3 for children and 10 for adults who completed the trial. Of the 61 original participants, 20 (19 children and 1 adult) had tried the ketogenic diet but had stopped it for various reasons, including noncompliance and lack of efficacy.

The liquid supplement was introduced gradually. The amount administered was based on weight in the children and was a standard amount in adults, with the target being 240 mL.

Participants consumed the supplement in equal servings taken at regular intervals as part of a meal or snack. They could take it alone or mix it with yogurt or another food.

Patients with feeding tubes took the supplement immediately before or after or mixed into an enteral feed, with a water flush afterward.

Researchers provided patients and caregivers with guidance on excluding highly refined sugary foods and beverages. Starchy foods such as bread, pasta, rice, and potatoes were not restricted.

The study consisted of three visits: baseline, 5 weeks, and 12 weeks, in addition to regular phone and email contact. Participants were also asked to keep a seizure diary.
 

Highly acceptable to patients

Overall, the study withdrawal rate was 33%. After a protocol change involving a slower introduction of the supplement, there were fewer withdrawals, Dr. Walker reported. He noted that the proportion of participants who completed the study (41 of 61) is “much better than with most studies of adults following the ketogenic diet.”

The most frequently reported gastrointestinal symptoms with the supplement were bloating and constipation, but these were predominantly mild and tended to decrease over time. This, said Dr. Walker, contrasts to the ketogenic diet where side effects tend to persist.

There was no significant change in body weight or body mass index. “We did not see weight gain as a problem at all,” Dr. Walker said.

Of 15 caregivers and 19 adults who returned an acceptability questionnaire, 84% agreed or strongly agreed the supplement had a good flavor (strawberry); 88% liked the appearance and color; 77% liked the texture and consistency; and 88% agreed or strongly agreed it was easy to take.

About one-third of adults and two-thirds of caregivers said they believed the supplement reduced seizures.
 

50% seizure reduction

Only three children and one adult became ketotic. This is typically classified as a beta-hydroxybutyrate (BHB) greater than 1 mmol/L (10.4 mg/dL). The BHB levels detected were markedly lower than those observed in individuals following a ketogenic diet, the investigators note.

Of the 41 participants, 19 completed the diaries. There were also data from physician recordings, so researchers were able to retrieve seizure frequencies for 32 of the 41 (78%). Of these 32 patients, 14 (44%) had a 50% or greater reduction in seizures. Overall, children and adults “responded similarly,” Dr. Walker said.

He acknowledged the study numbers are small and emphasized that larger studies are needed to determine efficacy. He also hopes for a future randomized controlled trial comparing K.Vita with another supplement that contains different types of fats.

Interestingly, the product has already “passed” the regulatory approval process in the United Kingdom, so it can be labeled as a medicinal food and should be available for use at the beginning of 2022, Dr. Walker said.
 

Study concerns

Asked to comment on the findings, Daniel Goldenholz, MD, PhD, instructor in the department of neurology, Beth Israel Deaconess Medical Center, Boston, said the supplement may be helpful, but he has concerns about the study.

Many patients with epilepsy are “desperate” for therapies that will help treat their seizures, said Dr. Goldenholz, who was not involved with the research. “If there’s a dietary therapy that has the potential for being helpful, I’m loving that. I need that. My patients are begging for something that works.” It is “really exciting” that researchers are working on that goal, Dr. Goldenholz added.

However, he noted that it is too soon to start talking to patients about this new product. He also pointed out that a significant fraction of the study participants dropped out, many because they couldn’t tolerate the supplement. In addition, others didn’t produce a seizure diary.

Dr. Goldenholz and colleagues have published several studies showing that patients with no intervention at all can sometimes show a reduction in seizures compared with their baseline results.

“We found sizable 50% reductions attributable entirely to the natural fluctuations in seizure rates, rather than any therapy at all, he said.

Dr. Goldenholz added that he hopes to see future studies on this topic, and on similar therapies “with sufficient data and more reliable metrics for efficacy.”

The study was funded by Vitaflo International. Dr. Walker reports having received grants from Vitaflo International and personal fees from UCB Pharma, Eisai, and Sage. In addition, along with colleagues, he has a patent (Nutritional product) pending.

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

A dietary supplement that mimics the effects of the high-fat, low-carbohydrate ketogenic diet is well tolerated and appears to reduce seizures in children and adults with treatment-resistant epilepsy, early research suggests. However, at least one expert has concerns.

In an open-label feasibility study, researchers assessed a liquid supplement known as K.Vita (Vitaflo International), which contains both decanoic acid and octanoic acid.

Although the study was small, the findings are promising, said coinvestigator Matthew Walker, MD, PhD, University College London Institute of Neurology, department of clinical and experimental epilepsy.

“The dietary supplement was reasonably well tolerated and while we weren’t specifically looking for efficacy here, we did see some patients had quite dramatic results in terms of reduced seizures,” Dr. Walker said.

Unlike the ketogenic diet, this dietary supplement is “very easy” to follow, involves only minor dietary modifications, and doesn’t require the intervention of a dietitian, he added.

The findings were published online July 23, 2021, in Brain Communications.
 

Key ingredients

In the ketogenic diet, the body uses body fat as its primary fuel source. The switch from carbohydrates to fat for body fuel results in built-up ketones.

Previous research shows the ketogenic diet is effective in reducing seizures in some patients with epilepsy. However, many patients find it difficult to tolerate, especially for extended periods. Dr. Walker also noted that ketones may have other long-term side effects, including osteoporosis.

He added that his team was keen to learn what elements of the ketogenic diet affect seizures. “Interestingly, we found that one of the fats used in the ketogenic diet, decanoic acid, has quite marked antiseizure effects,” Dr. Walker said.

Previous research has shown that decanoic acid, a medium-chain triglyceride–derived fatty acid, can cross the blood-brain barrier and decrease excitatory neurotransmission and network excitability in vitro.

Dr. Walker noted that ketones are necessary in order to reduce seizures.

“Rather than have a very high-fat, low-carbohydrate diet that causes ketones, we thought ‘why don’t we use a diet in which we just use mainly this fat, this decanoic acid, and avoid ketosis,’ ” he said.

The researchers then went to work developing the K.Vita dietary supplement, which mainly contains decanoic acid but also another fat, octanoic acid.
 

Assessing feasibility

The feasibility study included 61 patients (59% female) who began taking the supplement. Of these, 35 were children (aged 3-18 years) and 26 were adults. The children had Dravet syndrome or another genetically driven form of epilepsy, while most of the adults had a focal epilepsy.

All participants had failed multiple antiseizure medications – a median of 3 for children and 10 for adults who completed the trial. Of the 61 original participants, 20 (19 children and 1 adult) had tried the ketogenic diet but had stopped it for various reasons, including noncompliance and lack of efficacy.

The liquid supplement was introduced gradually. The amount administered was based on weight in the children and was a standard amount in adults, with the target being 240 mL.

Participants consumed the supplement in equal servings taken at regular intervals as part of a meal or snack. They could take it alone or mix it with yogurt or another food.

Patients with feeding tubes took the supplement immediately before or after or mixed into an enteral feed, with a water flush afterward.

Researchers provided patients and caregivers with guidance on excluding highly refined sugary foods and beverages. Starchy foods such as bread, pasta, rice, and potatoes were not restricted.

The study consisted of three visits: baseline, 5 weeks, and 12 weeks, in addition to regular phone and email contact. Participants were also asked to keep a seizure diary.
 

Highly acceptable to patients

Overall, the study withdrawal rate was 33%. After a protocol change involving a slower introduction of the supplement, there were fewer withdrawals, Dr. Walker reported. He noted that the proportion of participants who completed the study (41 of 61) is “much better than with most studies of adults following the ketogenic diet.”

The most frequently reported gastrointestinal symptoms with the supplement were bloating and constipation, but these were predominantly mild and tended to decrease over time. This, said Dr. Walker, contrasts to the ketogenic diet where side effects tend to persist.

There was no significant change in body weight or body mass index. “We did not see weight gain as a problem at all,” Dr. Walker said.

Of 15 caregivers and 19 adults who returned an acceptability questionnaire, 84% agreed or strongly agreed the supplement had a good flavor (strawberry); 88% liked the appearance and color; 77% liked the texture and consistency; and 88% agreed or strongly agreed it was easy to take.

About one-third of adults and two-thirds of caregivers said they believed the supplement reduced seizures.
 

50% seizure reduction

Only three children and one adult became ketotic. This is typically classified as a beta-hydroxybutyrate (BHB) greater than 1 mmol/L (10.4 mg/dL). The BHB levels detected were markedly lower than those observed in individuals following a ketogenic diet, the investigators note.

Of the 41 participants, 19 completed the diaries. There were also data from physician recordings, so researchers were able to retrieve seizure frequencies for 32 of the 41 (78%). Of these 32 patients, 14 (44%) had a 50% or greater reduction in seizures. Overall, children and adults “responded similarly,” Dr. Walker said.

He acknowledged the study numbers are small and emphasized that larger studies are needed to determine efficacy. He also hopes for a future randomized controlled trial comparing K.Vita with another supplement that contains different types of fats.

Interestingly, the product has already “passed” the regulatory approval process in the United Kingdom, so it can be labeled as a medicinal food and should be available for use at the beginning of 2022, Dr. Walker said.
 

Study concerns

Asked to comment on the findings, Daniel Goldenholz, MD, PhD, instructor in the department of neurology, Beth Israel Deaconess Medical Center, Boston, said the supplement may be helpful, but he has concerns about the study.

Many patients with epilepsy are “desperate” for therapies that will help treat their seizures, said Dr. Goldenholz, who was not involved with the research. “If there’s a dietary therapy that has the potential for being helpful, I’m loving that. I need that. My patients are begging for something that works.” It is “really exciting” that researchers are working on that goal, Dr. Goldenholz added.

However, he noted that it is too soon to start talking to patients about this new product. He also pointed out that a significant fraction of the study participants dropped out, many because they couldn’t tolerate the supplement. In addition, others didn’t produce a seizure diary.

Dr. Goldenholz and colleagues have published several studies showing that patients with no intervention at all can sometimes show a reduction in seizures compared with their baseline results.

“We found sizable 50% reductions attributable entirely to the natural fluctuations in seizure rates, rather than any therapy at all, he said.

Dr. Goldenholz added that he hopes to see future studies on this topic, and on similar therapies “with sufficient data and more reliable metrics for efficacy.”

The study was funded by Vitaflo International. Dr. Walker reports having received grants from Vitaflo International and personal fees from UCB Pharma, Eisai, and Sage. In addition, along with colleagues, he has a patent (Nutritional product) pending.

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

Younger children may be vulnerable to the reemergence of common respiratory viruses such as influenza and respiratory syncytial virus (RSV) as COVID-19 restrictions wane, experts say. The impact could be detrimental.

The COVID-19 pandemic and the implementation of preventative measures such as social distancing, travel restrictions, mask use, and shelter in place, reduced the transmission of respiratory viruses, according to the Centers for Disease Control and Prevention. However, because older infants and toddlers have not been exposed to these bugs during the pandemic, they are vulnerable to suffering severe viral infections.

“[We’ve] been in the honeymoon for 18 months,” said Christopher J. Harrison, MD, professor of pediatrics and pediatric infectious diseases at Children’s Mercy Hospitals and Clinics in Kansas City, Mo. “We are going to be coming out of the honeymoon and the children who didn’t get sick are going to start packing 2 years’ worth of infections into the next 9 months so there’s going to be twice as many as would be normal.”

The CDC issued a health advisory in June for parts of the southern United States, such as Texas, the Carolinas, and Oklahoma, encouraging broader testing for RSV – a virus that usually causes mild, cold-like symptoms and is the most common cause of bronchiolitis and pneumonia in children – among those who test negative for COVID-19. Virtually all children get an RSV infection by the time they are 2 years old, according to the CDC.

In previous years, RSV usually spread during the fall and spring seasons and usually peaked late December to mid-February. However, there’s been an offseason spike in the common illness this year, with nearly 2,000 confirmed cases each week of July.

Richard J. Webby, PhD, of the infectious diseases department at St. Jude Children’s Research Hospital, Memphis, Tenn., said that although RSV transmits more easily during the winter, the virus is able to thrive during this summer because many children have limited immunity and are more vulnerable to catching the virus than before. Population immunity normally limits a virus to circulating under its most favorable conditions, which is usually the winter. However, because there are a few more “susceptible hosts,” it gives the virus the ability to spread during a time when it typically wouldn’t be able to.

“Now we have a wider range of susceptible kids because they haven’t had that exposure over the past 18 months,” said Dr. Webby, who is on the World Health Organization’s Influenza Vaccine Composition Advisory Team. “It gives the virus more chances to transmit during conditions that are less favorable.”

Dr. Harrison said that, if children continue to take preventative measures such as wearing masks and sanitizing, they can delay catching the RSV – which can be severe in infants and young children – until they’re older and symptoms won’t be as severe.

“The swelling that these viruses cause in the trachea and the bronchial tubes is much bigger in proportion to the overall size of the tubes, so it takes less swelling to clog up the trachea or bronchial tube for the 9-month-old than it does of a 9-year-old,” Dr. Harrison said. “So if a 9-year-old was to get RSV, they’re not going to have nearly the same amount symptoms as the 9-month-old.

Dr. Harrison said delaying RSV in children was never an option before because it’s a virus that’s almost impossible to avoid.

“Hopefully, the mask means that if you get exposed, instead of getting a million virus particles from your classmate or your playmate, you may only get a couple thousand,” Dr. Harrison explained. “And maybe that’s enough that you can fight it off or it may be small enough that you get a mild infection instead of a severe infection.”

A summer surge of RSV has also occurred in Australia. A study published in Clinical Infectious Diseases found that Western Australia saw a 98% reduction in RSV cases. This suggests that COVID-19 restrictions also delayed the RSV season.

Dr. Webby said the lax in penetrative measures against COVID-19 may also affect this upcoming flu season. Usually, around 10%-30% of the population gets infected with the flu each year, but that hasn’t happened the past couple of seasons, he said.

“There might be slightly less overall immunity to these viruses,” Dr. Webby said. “When these viruses do come back, there’s a little bit more room for them to take off.”

Although a severe influenza season rebound this winter is a possibility, Australia continues to experience a historically low flu season. Dr. Harrison, who said the northern hemisphere looks at what’s happening in Australia and the rest of the “southern half of the world because their influenza season is during our summer,” hopes this is an indication that the northern hemisphere will also experience a mild season.

However, there’s no indication of how this upcoming flu season will hit the United States and there isn’t any guidance on what could happen because these historically low levels of respiratory viruses have never happened before, Dr. Webby explained.

He said that, if COVID-19’s delta variant continues to circulate during the fall and winter seasons, it will keep other viruses at low levels. This is because there is rarely a peak of activity of different viruses at the same time.

“When you get infected with the virus, your body’s immune response has this nonspecific reaction that protects you from anything else for a short period of time,” Dr. Webby explained. “When you get a lot of one virus circulating, it’s really hard for these other viruses to get into that population and sort of set off an epidemic of their own.”

To prepare for an unsure influenza season, Dr. Harrison suggests making the influenza vaccine available in August as opposed to October.

Dr. Harrison and Dr. Webby reported no conflicts of interest.

Younger children may be vulnerable to the reemergence of common respiratory viruses such as influenza and respiratory syncytial virus (RSV) as COVID-19 restrictions wane, experts say. The impact could be detrimental.

The COVID-19 pandemic and the implementation of preventative measures such as social distancing, travel restrictions, mask use, and shelter in place, reduced the transmission of respiratory viruses, according to the Centers for Disease Control and Prevention. However, because older infants and toddlers have not been exposed to these bugs during the pandemic, they are vulnerable to suffering severe viral infections.

“[We’ve] been in the honeymoon for 18 months,” said Christopher J. Harrison, MD, professor of pediatrics and pediatric infectious diseases at Children’s Mercy Hospitals and Clinics in Kansas City, Mo. “We are going to be coming out of the honeymoon and the children who didn’t get sick are going to start packing 2 years’ worth of infections into the next 9 months so there’s going to be twice as many as would be normal.”

The CDC issued a health advisory in June for parts of the southern United States, such as Texas, the Carolinas, and Oklahoma, encouraging broader testing for RSV – a virus that usually causes mild, cold-like symptoms and is the most common cause of bronchiolitis and pneumonia in children – among those who test negative for COVID-19. Virtually all children get an RSV infection by the time they are 2 years old, according to the CDC.

In previous years, RSV usually spread during the fall and spring seasons and usually peaked late December to mid-February. However, there’s been an offseason spike in the common illness this year, with nearly 2,000 confirmed cases each week of July.

Richard J. Webby, PhD, of the infectious diseases department at St. Jude Children’s Research Hospital, Memphis, Tenn., said that although RSV transmits more easily during the winter, the virus is able to thrive during this summer because many children have limited immunity and are more vulnerable to catching the virus than before. Population immunity normally limits a virus to circulating under its most favorable conditions, which is usually the winter. However, because there are a few more “susceptible hosts,” it gives the virus the ability to spread during a time when it typically wouldn’t be able to.

“Now we have a wider range of susceptible kids because they haven’t had that exposure over the past 18 months,” said Dr. Webby, who is on the World Health Organization’s Influenza Vaccine Composition Advisory Team. “It gives the virus more chances to transmit during conditions that are less favorable.”

Dr. Harrison said that, if children continue to take preventative measures such as wearing masks and sanitizing, they can delay catching the RSV – which can be severe in infants and young children – until they’re older and symptoms won’t be as severe.

“The swelling that these viruses cause in the trachea and the bronchial tubes is much bigger in proportion to the overall size of the tubes, so it takes less swelling to clog up the trachea or bronchial tube for the 9-month-old than it does of a 9-year-old,” Dr. Harrison said. “So if a 9-year-old was to get RSV, they’re not going to have nearly the same amount symptoms as the 9-month-old.

Dr. Harrison said delaying RSV in children was never an option before because it’s a virus that’s almost impossible to avoid.

“Hopefully, the mask means that if you get exposed, instead of getting a million virus particles from your classmate or your playmate, you may only get a couple thousand,” Dr. Harrison explained. “And maybe that’s enough that you can fight it off or it may be small enough that you get a mild infection instead of a severe infection.”

A summer surge of RSV has also occurred in Australia. A study published in Clinical Infectious Diseases found that Western Australia saw a 98% reduction in RSV cases. This suggests that COVID-19 restrictions also delayed the RSV season.

Dr. Webby said the lax in penetrative measures against COVID-19 may also affect this upcoming flu season. Usually, around 10%-30% of the population gets infected with the flu each year, but that hasn’t happened the past couple of seasons, he said.

“There might be slightly less overall immunity to these viruses,” Dr. Webby said. “When these viruses do come back, there’s a little bit more room for them to take off.”

Although a severe influenza season rebound this winter is a possibility, Australia continues to experience a historically low flu season. Dr. Harrison, who said the northern hemisphere looks at what’s happening in Australia and the rest of the “southern half of the world because their influenza season is during our summer,” hopes this is an indication that the northern hemisphere will also experience a mild season.

However, there’s no indication of how this upcoming flu season will hit the United States and there isn’t any guidance on what could happen because these historically low levels of respiratory viruses have never happened before, Dr. Webby explained.

He said that, if COVID-19’s delta variant continues to circulate during the fall and winter seasons, it will keep other viruses at low levels. This is because there is rarely a peak of activity of different viruses at the same time.

“When you get infected with the virus, your body’s immune response has this nonspecific reaction that protects you from anything else for a short period of time,” Dr. Webby explained. “When you get a lot of one virus circulating, it’s really hard for these other viruses to get into that population and sort of set off an epidemic of their own.”

To prepare for an unsure influenza season, Dr. Harrison suggests making the influenza vaccine available in August as opposed to October.

Dr. Harrison and Dr. Webby reported no conflicts of interest.

Younger children may be vulnerable to the reemergence of common respiratory viruses such as influenza and respiratory syncytial virus (RSV) as COVID-19 restrictions wane, experts say. The impact could be detrimental.

The COVID-19 pandemic and the implementation of preventative measures such as social distancing, travel restrictions, mask use, and shelter in place, reduced the transmission of respiratory viruses, according to the Centers for Disease Control and Prevention. However, because older infants and toddlers have not been exposed to these bugs during the pandemic, they are vulnerable to suffering severe viral infections.

“[We’ve] been in the honeymoon for 18 months,” said Christopher J. Harrison, MD, professor of pediatrics and pediatric infectious diseases at Children’s Mercy Hospitals and Clinics in Kansas City, Mo. “We are going to be coming out of the honeymoon and the children who didn’t get sick are going to start packing 2 years’ worth of infections into the next 9 months so there’s going to be twice as many as would be normal.”

The CDC issued a health advisory in June for parts of the southern United States, such as Texas, the Carolinas, and Oklahoma, encouraging broader testing for RSV – a virus that usually causes mild, cold-like symptoms and is the most common cause of bronchiolitis and pneumonia in children – among those who test negative for COVID-19. Virtually all children get an RSV infection by the time they are 2 years old, according to the CDC.

In previous years, RSV usually spread during the fall and spring seasons and usually peaked late December to mid-February. However, there’s been an offseason spike in the common illness this year, with nearly 2,000 confirmed cases each week of July.

Richard J. Webby, PhD, of the infectious diseases department at St. Jude Children’s Research Hospital, Memphis, Tenn., said that although RSV transmits more easily during the winter, the virus is able to thrive during this summer because many children have limited immunity and are more vulnerable to catching the virus than before. Population immunity normally limits a virus to circulating under its most favorable conditions, which is usually the winter. However, because there are a few more “susceptible hosts,” it gives the virus the ability to spread during a time when it typically wouldn’t be able to.

“Now we have a wider range of susceptible kids because they haven’t had that exposure over the past 18 months,” said Dr. Webby, who is on the World Health Organization’s Influenza Vaccine Composition Advisory Team. “It gives the virus more chances to transmit during conditions that are less favorable.”

Dr. Harrison said that, if children continue to take preventative measures such as wearing masks and sanitizing, they can delay catching the RSV – which can be severe in infants and young children – until they’re older and symptoms won’t be as severe.

“The swelling that these viruses cause in the trachea and the bronchial tubes is much bigger in proportion to the overall size of the tubes, so it takes less swelling to clog up the trachea or bronchial tube for the 9-month-old than it does of a 9-year-old,” Dr. Harrison said. “So if a 9-year-old was to get RSV, they’re not going to have nearly the same amount symptoms as the 9-month-old.

Dr. Harrison said delaying RSV in children was never an option before because it’s a virus that’s almost impossible to avoid.

“Hopefully, the mask means that if you get exposed, instead of getting a million virus particles from your classmate or your playmate, you may only get a couple thousand,” Dr. Harrison explained. “And maybe that’s enough that you can fight it off or it may be small enough that you get a mild infection instead of a severe infection.”

A summer surge of RSV has also occurred in Australia. A study published in Clinical Infectious Diseases found that Western Australia saw a 98% reduction in RSV cases. This suggests that COVID-19 restrictions also delayed the RSV season.

Dr. Webby said the lax in penetrative measures against COVID-19 may also affect this upcoming flu season. Usually, around 10%-30% of the population gets infected with the flu each year, but that hasn’t happened the past couple of seasons, he said.

“There might be slightly less overall immunity to these viruses,” Dr. Webby said. “When these viruses do come back, there’s a little bit more room for them to take off.”

Although a severe influenza season rebound this winter is a possibility, Australia continues to experience a historically low flu season. Dr. Harrison, who said the northern hemisphere looks at what’s happening in Australia and the rest of the “southern half of the world because their influenza season is during our summer,” hopes this is an indication that the northern hemisphere will also experience a mild season.

However, there’s no indication of how this upcoming flu season will hit the United States and there isn’t any guidance on what could happen because these historically low levels of respiratory viruses have never happened before, Dr. Webby explained.

He said that, if COVID-19’s delta variant continues to circulate during the fall and winter seasons, it will keep other viruses at low levels. This is because there is rarely a peak of activity of different viruses at the same time.

“When you get infected with the virus, your body’s immune response has this nonspecific reaction that protects you from anything else for a short period of time,” Dr. Webby explained. “When you get a lot of one virus circulating, it’s really hard for these other viruses to get into that population and sort of set off an epidemic of their own.”

To prepare for an unsure influenza season, Dr. Harrison suggests making the influenza vaccine available in August as opposed to October.

Dr. Harrison and Dr. Webby reported no conflicts of interest.

Today there are so many evidence-based drug therapies for heart failure with reduced ejection fraction (HFrEF) that physicians treating HF patients almost don’t know what to do them.

It’s an exciting new age that way, but to many vexingly unclear how best to merge the shiny new options with mainstay regimens based on time-honored renin-angiotensin system (RAS) inhibitors and beta-blockers.

To impart some clarity, the authors of a new HF guideline document recently took center stage at the Heart Failure Association of the European Society of Cardiology (ESC-HFA) annual meeting to preview their updated recommendations, with novel twists based on recent major trials, for the new age of HF pharmacotherapeutics.

The guideline committee considered the evidence base that existed “up until the end of March of this year,” Theresa A. McDonagh, MD, King’s College London, said during the presentation. The document “is now finalized, it’s with the publishers, and it will be presented in full with simultaneous publication at the ESC meeting” that starts August 27.

It describes a game plan, already followed by some clinicians in practice without official guidance, for initiating drugs from each of four classes in virtually all patients with HFrEF.
 

New indicated drugs, new perspective for HFrEF

Three of the drug categories are old acquaintances. Among them are the RAS inhibitors, which include angiotensin-receptor/neprilysin inhibitors, beta-blockers, and the mineralocorticoid receptor antagonists. The latter drugs are gaining new respect after having been underplayed in HF prescribing despite longstanding evidence of efficacy.

Completing the quartet of first-line HFrEF drug classes is a recent arrival to the HF arena, the sodium-glucose cotransporter 2 inhibitors.

“We now have new data and a simplified treatment algorithm for heart failure with reduced ejection fraction based on the early administration of the four major classes of drugs,” said Marco Metra, MD, University of Brescia (Italy), previewing the medical-therapy portions of the new guideline at the ESC-HFA sessions, which launched virtually and live in Florence, Italy, on July 29.

The new game plan offers a simple answer to a once-common but complex question: How and in what order are the different drug classes initiated in patients with HFrEF? In the new document, the stated goal is to get them all on board expeditiously and safely, by any means possible.

The guideline writers did not specify a sequence, preferring to leave that decision to physicians, said Dr. Metra, who stated only two guiding principles. The first is to consider the patient’s unique circumstances. The order in which the drugs are introduced might vary, depending on, for example, whether the patient has low or high blood pressure or renal dysfunction.

Second, “it is very important that we try to give all four classes of drugs to the patient in the shortest time possible, because this saves lives,” he said.

That there is no recommendation on sequencing the drugs has led some to the wrong interpretation that all should be started at once, observed coauthor Javed Butler, MD, MPH, University of Mississippi, Jackson, as a panelist during the presentation. Far from it, he said. “The doctor with the patient in front of you can make the best decision. The idea here is to get all the therapies on as soon as possible, as safely as possible.”

“The order in which they are introduced is not really important,” agreed Vijay Chopra, MD, Max Super Specialty Hospital Saket, New Delhi, another coauthor on the panel. “The important thing is that at least some dose of all the four drugs needs to be introduced in the first 4-6 weeks, and then up-titrated.”

Other medical therapy can be more tailored, Dr. Metra noted, such as loop diuretics for patients with congestion, iron for those with iron deficiency, and other drugs depending on whether there is, for example, atrial fibrillation or coronary disease.
 

Adoption of emerging definitions

The document adopts the emerging characterization of HFrEF by a left ventricular ejection fraction (LVEF) up to 40%.

And it will leverage an expanding evidence base for medication in a segment of patients once said to have HF with preserved ejection fraction (HFpEF), who had therefore lacked specific, guideline-directed medical therapies. Now, patients with an LVEF of 41%-49% will be said to have HF with mildly reduced ejection fraction (HFmrEF), a tweak to the recently introduced HF with “mid-range” LVEF that is designed to assert its nature as something to treat. The new document’s HFmrEF recommendations come with various class and level-of-evidence ratings.

That leaves HFpEF to be characterized by an LVEF of 50% in combination with structural or functional abnormalities associated with LV diastolic dysfunction or raised LV filling pressures, including raised natriuretic peptide levels.

The definitions are consistent with those proposed internationally by the ESC-HFA, the Heart Failure Society of America, and other groups in a statement published in March.
 

Expanded HFrEF med landscape

Since the 2016 ESC guideline on HF therapy, Dr. McDonagh said, “there’s been no substantial change in the evidence for many of the classical drugs that we use in heart failure. However, we had a lot of new and exciting evidence to consider,” especially in support of the SGLT2 inhibitors as one of the core medications in HFrEF.

The new data came from two controlled trials in particular. In DAPA-HF, patients with HFrEF who were initially without diabetes and who went on dapagliflozin (Farxiga, AstraZeneca) showed a 27% drop in cardiovascular (CV) death or worsening-HF events over a median of 18 months.

“That was followed up with very concordant results with empagliflozin [Jardiance, Boehringer Ingelheim/Eli Lilly] in HFrEF in the EMPEROR-Reduced trial,” Dr. McDonagh said. In that trial, comparable patients who took empagliflozin showed a 25% drop in a primary endpoint similar to that in DAPA-HF over the median 16-month follow-up.

Other HFrEF recommendations are for selected patients. They include ivabradine, already in the guidelines, for patients in sinus rhythm with an elevated resting heart rate who can’t take beta-blockers for whatever reason. But, Dr. McDonagh noted, “we had some new classes of drugs to consider as well.”

In particular, the oral soluble guanylate-cyclase receptor stimulator vericiguat (Verquvo) emerged about a year ago from the VICTORIA trial as a modest success for patients with HFrEF and a previous HF hospitalization. In the trial with more than 5,000 patients, treatment with vericiguat atop standard drug and device therapy was followed by a significant 10% drop in risk for CV death or HF hospitalization.

Available now or likely to be available in the United States, the European Union, Japan, and other countries, vericiguat is recommended in the new guideline for VICTORIA-like patients who don’t adequately respond to other indicated medications.
 

Little for HFpEF as newly defined

“Almost nothing is new” in the guidelines for HFpEF, Dr. Metra said. The document recommends screening for and treatment of any underlying disorder and comorbidities, plus diuretics for any congestion. “That’s what we have to date.”

But that evidence base might soon change. The new HFpEF recommendations could possibly be up-staged at the ESC sessions by the August 27 scheduled presentation of EMPEROR-Preserved, a randomized test of empagliflozin in HFpEF and – it could be said – HFmrEF. The trial entered patients with chronic HF and an LVEF greater than 40%.

Eli Lilly and Boehringer Ingelheim offered the world a peek at the results, which suggest the SGLT2 inhibitor had a positive impact on the primary endpoint of CV death or HF hospitalization. They announced the cursory top-line outcomes in early July as part of its regulatory obligations, noting that the trial had “met” its primary endpoint.

But many unknowns remain, including the degree of benefit and whether it varied among subgroups, and especially whether outcomes were different for HFmrEF than for HFpEF.
 

Upgrades for familiar agents

Still, HFmrEF gets noteworthy attention in the document. “For the first time, we have recommendations for these patients,” Dr. Metra said. “We already knew that diuretics are indicated for the treatment of congestion. But now, ACE inhibitors, ARBs, beta-blockers, mineralocorticoid antagonists, as well as sacubitril/valsartan, may be considered to improve outcomes in these patients.” Their upgrades in the new guidelines were based on review of trials in the CHARM program and of TOPCAT and PARAGON-HF, among others, he said.

The new document also includes “treatment algorithms based on phenotypes”; that is, comorbidities and less common HF precipitants. For example, “assessment of iron status is now mandated in all patients with heart failure,” Dr. Metra said.

AFFIRM-HF is the key trial in this arena, with its more than 1,100 iron-deficient patients with LVEF less than 50% who had been recently hospitalized for HF. A year of treatment with ferric carboxymaltose (Ferinject/Injectafer, Vifor) led to a 26% drop in risk for HF hospitalization, but without affecting mortality.

For those who are iron deficient, Dr. Metra said, “ferric carboxymaltose intravenously should be considered not only in patients with low ejection fraction and outpatients, but also in patients recently hospitalized for acute heart failure.”

The SGLT2 inhibitors are recommended in HFrEF patients with type 2 diabetes. And treatment with tafamidis (Vyndaqel, Pfizer) in patients with genetic or wild-type transthyretin cardiac amyloidosis gets a class I recommendation based on survival gains seen in the ATTR-ACT trial.

Also recommended is a full CV assessment for patients with cancer who are on cardiotoxic agents or otherwise might be at risk for chemotherapy cardiotoxicity. “Beta-blockers and ACE inhibitors should be considered in those who develop left ventricular systolic dysfunction after anticancer therapy,” Dr. Metra said.

The ongoing pandemic made its mark on the document’s genesis, as it has with most everything else. “For better or worse, we were a ‘COVID guideline,’ ” Dr. McDonagh said. The writing committee consisted of “a large task force of 31 individuals, including two patients,” and there were “only two face-to-face meetings prior to the first wave of COVID hitting Europe.”

The committee voted on each of the recommendations, “and we had to have agreement of more than 75% of the task force to assign a class of recommendation or level of evidence,” she said. “I think we did the best we could in the circumstances. We had the benefit of many discussions over Zoom, and I think at the end of the day we have achieved a consensus.”

With such a large body of participants and the 75% threshold for agreement, “you end up with perhaps a conservative guideline. But that’s not a bad thing for clinical practice, for guidelines to be conservative,” Dr. McDonagh said. “They’re mainly concerned with looking at evidence and safety.”

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

Today there are so many evidence-based drug therapies for heart failure with reduced ejection fraction (HFrEF) that physicians treating HF patients almost don’t know what to do them.

It’s an exciting new age that way, but to many vexingly unclear how best to merge the shiny new options with mainstay regimens based on time-honored renin-angiotensin system (RAS) inhibitors and beta-blockers.

To impart some clarity, the authors of a new HF guideline document recently took center stage at the Heart Failure Association of the European Society of Cardiology (ESC-HFA) annual meeting to preview their updated recommendations, with novel twists based on recent major trials, for the new age of HF pharmacotherapeutics.

The guideline committee considered the evidence base that existed “up until the end of March of this year,” Theresa A. McDonagh, MD, King’s College London, said during the presentation. The document “is now finalized, it’s with the publishers, and it will be presented in full with simultaneous publication at the ESC meeting” that starts August 27.

It describes a game plan, already followed by some clinicians in practice without official guidance, for initiating drugs from each of four classes in virtually all patients with HFrEF.
 

New indicated drugs, new perspective for HFrEF

Three of the drug categories are old acquaintances. Among them are the RAS inhibitors, which include angiotensin-receptor/neprilysin inhibitors, beta-blockers, and the mineralocorticoid receptor antagonists. The latter drugs are gaining new respect after having been underplayed in HF prescribing despite longstanding evidence of efficacy.

Completing the quartet of first-line HFrEF drug classes is a recent arrival to the HF arena, the sodium-glucose cotransporter 2 inhibitors.

“We now have new data and a simplified treatment algorithm for heart failure with reduced ejection fraction based on the early administration of the four major classes of drugs,” said Marco Metra, MD, University of Brescia (Italy), previewing the medical-therapy portions of the new guideline at the ESC-HFA sessions, which launched virtually and live in Florence, Italy, on July 29.

The new game plan offers a simple answer to a once-common but complex question: How and in what order are the different drug classes initiated in patients with HFrEF? In the new document, the stated goal is to get them all on board expeditiously and safely, by any means possible.

The guideline writers did not specify a sequence, preferring to leave that decision to physicians, said Dr. Metra, who stated only two guiding principles. The first is to consider the patient’s unique circumstances. The order in which the drugs are introduced might vary, depending on, for example, whether the patient has low or high blood pressure or renal dysfunction.

Second, “it is very important that we try to give all four classes of drugs to the patient in the shortest time possible, because this saves lives,” he said.

That there is no recommendation on sequencing the drugs has led some to the wrong interpretation that all should be started at once, observed coauthor Javed Butler, MD, MPH, University of Mississippi, Jackson, as a panelist during the presentation. Far from it, he said. “The doctor with the patient in front of you can make the best decision. The idea here is to get all the therapies on as soon as possible, as safely as possible.”

“The order in which they are introduced is not really important,” agreed Vijay Chopra, MD, Max Super Specialty Hospital Saket, New Delhi, another coauthor on the panel. “The important thing is that at least some dose of all the four drugs needs to be introduced in the first 4-6 weeks, and then up-titrated.”

Other medical therapy can be more tailored, Dr. Metra noted, such as loop diuretics for patients with congestion, iron for those with iron deficiency, and other drugs depending on whether there is, for example, atrial fibrillation or coronary disease.
 

Adoption of emerging definitions

The document adopts the emerging characterization of HFrEF by a left ventricular ejection fraction (LVEF) up to 40%.

And it will leverage an expanding evidence base for medication in a segment of patients once said to have HF with preserved ejection fraction (HFpEF), who had therefore lacked specific, guideline-directed medical therapies. Now, patients with an LVEF of 41%-49% will be said to have HF with mildly reduced ejection fraction (HFmrEF), a tweak to the recently introduced HF with “mid-range” LVEF that is designed to assert its nature as something to treat. The new document’s HFmrEF recommendations come with various class and level-of-evidence ratings.

That leaves HFpEF to be characterized by an LVEF of 50% in combination with structural or functional abnormalities associated with LV diastolic dysfunction or raised LV filling pressures, including raised natriuretic peptide levels.

The definitions are consistent with those proposed internationally by the ESC-HFA, the Heart Failure Society of America, and other groups in a statement published in March.
 

Expanded HFrEF med landscape

Since the 2016 ESC guideline on HF therapy, Dr. McDonagh said, “there’s been no substantial change in the evidence for many of the classical drugs that we use in heart failure. However, we had a lot of new and exciting evidence to consider,” especially in support of the SGLT2 inhibitors as one of the core medications in HFrEF.

The new data came from two controlled trials in particular. In DAPA-HF, patients with HFrEF who were initially without diabetes and who went on dapagliflozin (Farxiga, AstraZeneca) showed a 27% drop in cardiovascular (CV) death or worsening-HF events over a median of 18 months.

“That was followed up with very concordant results with empagliflozin [Jardiance, Boehringer Ingelheim/Eli Lilly] in HFrEF in the EMPEROR-Reduced trial,” Dr. McDonagh said. In that trial, comparable patients who took empagliflozin showed a 25% drop in a primary endpoint similar to that in DAPA-HF over the median 16-month follow-up.

Other HFrEF recommendations are for selected patients. They include ivabradine, already in the guidelines, for patients in sinus rhythm with an elevated resting heart rate who can’t take beta-blockers for whatever reason. But, Dr. McDonagh noted, “we had some new classes of drugs to consider as well.”

In particular, the oral soluble guanylate-cyclase receptor stimulator vericiguat (Verquvo) emerged about a year ago from the VICTORIA trial as a modest success for patients with HFrEF and a previous HF hospitalization. In the trial with more than 5,000 patients, treatment with vericiguat atop standard drug and device therapy was followed by a significant 10% drop in risk for CV death or HF hospitalization.

Available now or likely to be available in the United States, the European Union, Japan, and other countries, vericiguat is recommended in the new guideline for VICTORIA-like patients who don’t adequately respond to other indicated medications.
 

Little for HFpEF as newly defined

“Almost nothing is new” in the guidelines for HFpEF, Dr. Metra said. The document recommends screening for and treatment of any underlying disorder and comorbidities, plus diuretics for any congestion. “That’s what we have to date.”

But that evidence base might soon change. The new HFpEF recommendations could possibly be up-staged at the ESC sessions by the August 27 scheduled presentation of EMPEROR-Preserved, a randomized test of empagliflozin in HFpEF and – it could be said – HFmrEF. The trial entered patients with chronic HF and an LVEF greater than 40%.

Eli Lilly and Boehringer Ingelheim offered the world a peek at the results, which suggest the SGLT2 inhibitor had a positive impact on the primary endpoint of CV death or HF hospitalization. They announced the cursory top-line outcomes in early July as part of its regulatory obligations, noting that the trial had “met” its primary endpoint.

But many unknowns remain, including the degree of benefit and whether it varied among subgroups, and especially whether outcomes were different for HFmrEF than for HFpEF.
 

Upgrades for familiar agents

Still, HFmrEF gets noteworthy attention in the document. “For the first time, we have recommendations for these patients,” Dr. Metra said. “We already knew that diuretics are indicated for the treatment of congestion. But now, ACE inhibitors, ARBs, beta-blockers, mineralocorticoid antagonists, as well as sacubitril/valsartan, may be considered to improve outcomes in these patients.” Their upgrades in the new guidelines were based on review of trials in the CHARM program and of TOPCAT and PARAGON-HF, among others, he said.

The new document also includes “treatment algorithms based on phenotypes”; that is, comorbidities and less common HF precipitants. For example, “assessment of iron status is now mandated in all patients with heart failure,” Dr. Metra said.

AFFIRM-HF is the key trial in this arena, with its more than 1,100 iron-deficient patients with LVEF less than 50% who had been recently hospitalized for HF. A year of treatment with ferric carboxymaltose (Ferinject/Injectafer, Vifor) led to a 26% drop in risk for HF hospitalization, but without affecting mortality.

For those who are iron deficient, Dr. Metra said, “ferric carboxymaltose intravenously should be considered not only in patients with low ejection fraction and outpatients, but also in patients recently hospitalized for acute heart failure.”

The SGLT2 inhibitors are recommended in HFrEF patients with type 2 diabetes. And treatment with tafamidis (Vyndaqel, Pfizer) in patients with genetic or wild-type transthyretin cardiac amyloidosis gets a class I recommendation based on survival gains seen in the ATTR-ACT trial.

Also recommended is a full CV assessment for patients with cancer who are on cardiotoxic agents or otherwise might be at risk for chemotherapy cardiotoxicity. “Beta-blockers and ACE inhibitors should be considered in those who develop left ventricular systolic dysfunction after anticancer therapy,” Dr. Metra said.

The ongoing pandemic made its mark on the document’s genesis, as it has with most everything else. “For better or worse, we were a ‘COVID guideline,’ ” Dr. McDonagh said. The writing committee consisted of “a large task force of 31 individuals, including two patients,” and there were “only two face-to-face meetings prior to the first wave of COVID hitting Europe.”

The committee voted on each of the recommendations, “and we had to have agreement of more than 75% of the task force to assign a class of recommendation or level of evidence,” she said. “I think we did the best we could in the circumstances. We had the benefit of many discussions over Zoom, and I think at the end of the day we have achieved a consensus.”

With such a large body of participants and the 75% threshold for agreement, “you end up with perhaps a conservative guideline. But that’s not a bad thing for clinical practice, for guidelines to be conservative,” Dr. McDonagh said. “They’re mainly concerned with looking at evidence and safety.”

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

Today there are so many evidence-based drug therapies for heart failure with reduced ejection fraction (HFrEF) that physicians treating HF patients almost don’t know what to do them.

It’s an exciting new age that way, but to many vexingly unclear how best to merge the shiny new options with mainstay regimens based on time-honored renin-angiotensin system (RAS) inhibitors and beta-blockers.

To impart some clarity, the authors of a new HF guideline document recently took center stage at the Heart Failure Association of the European Society of Cardiology (ESC-HFA) annual meeting to preview their updated recommendations, with novel twists based on recent major trials, for the new age of HF pharmacotherapeutics.

The guideline committee considered the evidence base that existed “up until the end of March of this year,” Theresa A. McDonagh, MD, King’s College London, said during the presentation. The document “is now finalized, it’s with the publishers, and it will be presented in full with simultaneous publication at the ESC meeting” that starts August 27.

It describes a game plan, already followed by some clinicians in practice without official guidance, for initiating drugs from each of four classes in virtually all patients with HFrEF.
 

New indicated drugs, new perspective for HFrEF

Three of the drug categories are old acquaintances. Among them are the RAS inhibitors, which include angiotensin-receptor/neprilysin inhibitors, beta-blockers, and the mineralocorticoid receptor antagonists. The latter drugs are gaining new respect after having been underplayed in HF prescribing despite longstanding evidence of efficacy.

Completing the quartet of first-line HFrEF drug classes is a recent arrival to the HF arena, the sodium-glucose cotransporter 2 inhibitors.

“We now have new data and a simplified treatment algorithm for heart failure with reduced ejection fraction based on the early administration of the four major classes of drugs,” said Marco Metra, MD, University of Brescia (Italy), previewing the medical-therapy portions of the new guideline at the ESC-HFA sessions, which launched virtually and live in Florence, Italy, on July 29.

The new game plan offers a simple answer to a once-common but complex question: How and in what order are the different drug classes initiated in patients with HFrEF? In the new document, the stated goal is to get them all on board expeditiously and safely, by any means possible.

The guideline writers did not specify a sequence, preferring to leave that decision to physicians, said Dr. Metra, who stated only two guiding principles. The first is to consider the patient’s unique circumstances. The order in which the drugs are introduced might vary, depending on, for example, whether the patient has low or high blood pressure or renal dysfunction.

Second, “it is very important that we try to give all four classes of drugs to the patient in the shortest time possible, because this saves lives,” he said.

That there is no recommendation on sequencing the drugs has led some to the wrong interpretation that all should be started at once, observed coauthor Javed Butler, MD, MPH, University of Mississippi, Jackson, as a panelist during the presentation. Far from it, he said. “The doctor with the patient in front of you can make the best decision. The idea here is to get all the therapies on as soon as possible, as safely as possible.”

“The order in which they are introduced is not really important,” agreed Vijay Chopra, MD, Max Super Specialty Hospital Saket, New Delhi, another coauthor on the panel. “The important thing is that at least some dose of all the four drugs needs to be introduced in the first 4-6 weeks, and then up-titrated.”

Other medical therapy can be more tailored, Dr. Metra noted, such as loop diuretics for patients with congestion, iron for those with iron deficiency, and other drugs depending on whether there is, for example, atrial fibrillation or coronary disease.
 

Adoption of emerging definitions

The document adopts the emerging characterization of HFrEF by a left ventricular ejection fraction (LVEF) up to 40%.

And it will leverage an expanding evidence base for medication in a segment of patients once said to have HF with preserved ejection fraction (HFpEF), who had therefore lacked specific, guideline-directed medical therapies. Now, patients with an LVEF of 41%-49% will be said to have HF with mildly reduced ejection fraction (HFmrEF), a tweak to the recently introduced HF with “mid-range” LVEF that is designed to assert its nature as something to treat. The new document’s HFmrEF recommendations come with various class and level-of-evidence ratings.

That leaves HFpEF to be characterized by an LVEF of 50% in combination with structural or functional abnormalities associated with LV diastolic dysfunction or raised LV filling pressures, including raised natriuretic peptide levels.

The definitions are consistent with those proposed internationally by the ESC-HFA, the Heart Failure Society of America, and other groups in a statement published in March.
 

Expanded HFrEF med landscape

Since the 2016 ESC guideline on HF therapy, Dr. McDonagh said, “there’s been no substantial change in the evidence for many of the classical drugs that we use in heart failure. However, we had a lot of new and exciting evidence to consider,” especially in support of the SGLT2 inhibitors as one of the core medications in HFrEF.

The new data came from two controlled trials in particular. In DAPA-HF, patients with HFrEF who were initially without diabetes and who went on dapagliflozin (Farxiga, AstraZeneca) showed a 27% drop in cardiovascular (CV) death or worsening-HF events over a median of 18 months.

“That was followed up with very concordant results with empagliflozin [Jardiance, Boehringer Ingelheim/Eli Lilly] in HFrEF in the EMPEROR-Reduced trial,” Dr. McDonagh said. In that trial, comparable patients who took empagliflozin showed a 25% drop in a primary endpoint similar to that in DAPA-HF over the median 16-month follow-up.

Other HFrEF recommendations are for selected patients. They include ivabradine, already in the guidelines, for patients in sinus rhythm with an elevated resting heart rate who can’t take beta-blockers for whatever reason. But, Dr. McDonagh noted, “we had some new classes of drugs to consider as well.”

In particular, the oral soluble guanylate-cyclase receptor stimulator vericiguat (Verquvo) emerged about a year ago from the VICTORIA trial as a modest success for patients with HFrEF and a previous HF hospitalization. In the trial with more than 5,000 patients, treatment with vericiguat atop standard drug and device therapy was followed by a significant 10% drop in risk for CV death or HF hospitalization.

Available now or likely to be available in the United States, the European Union, Japan, and other countries, vericiguat is recommended in the new guideline for VICTORIA-like patients who don’t adequately respond to other indicated medications.
 

Little for HFpEF as newly defined

“Almost nothing is new” in the guidelines for HFpEF, Dr. Metra said. The document recommends screening for and treatment of any underlying disorder and comorbidities, plus diuretics for any congestion. “That’s what we have to date.”

But that evidence base might soon change. The new HFpEF recommendations could possibly be up-staged at the ESC sessions by the August 27 scheduled presentation of EMPEROR-Preserved, a randomized test of empagliflozin in HFpEF and – it could be said – HFmrEF. The trial entered patients with chronic HF and an LVEF greater than 40%.

Eli Lilly and Boehringer Ingelheim offered the world a peek at the results, which suggest the SGLT2 inhibitor had a positive impact on the primary endpoint of CV death or HF hospitalization. They announced the cursory top-line outcomes in early July as part of its regulatory obligations, noting that the trial had “met” its primary endpoint.

But many unknowns remain, including the degree of benefit and whether it varied among subgroups, and especially whether outcomes were different for HFmrEF than for HFpEF.
 

Upgrades for familiar agents

Still, HFmrEF gets noteworthy attention in the document. “For the first time, we have recommendations for these patients,” Dr. Metra said. “We already knew that diuretics are indicated for the treatment of congestion. But now, ACE inhibitors, ARBs, beta-blockers, mineralocorticoid antagonists, as well as sacubitril/valsartan, may be considered to improve outcomes in these patients.” Their upgrades in the new guidelines were based on review of trials in the CHARM program and of TOPCAT and PARAGON-HF, among others, he said.

The new document also includes “treatment algorithms based on phenotypes”; that is, comorbidities and less common HF precipitants. For example, “assessment of iron status is now mandated in all patients with heart failure,” Dr. Metra said.

AFFIRM-HF is the key trial in this arena, with its more than 1,100 iron-deficient patients with LVEF less than 50% who had been recently hospitalized for HF. A year of treatment with ferric carboxymaltose (Ferinject/Injectafer, Vifor) led to a 26% drop in risk for HF hospitalization, but without affecting mortality.

For those who are iron deficient, Dr. Metra said, “ferric carboxymaltose intravenously should be considered not only in patients with low ejection fraction and outpatients, but also in patients recently hospitalized for acute heart failure.”

The SGLT2 inhibitors are recommended in HFrEF patients with type 2 diabetes. And treatment with tafamidis (Vyndaqel, Pfizer) in patients with genetic or wild-type transthyretin cardiac amyloidosis gets a class I recommendation based on survival gains seen in the ATTR-ACT trial.

Also recommended is a full CV assessment for patients with cancer who are on cardiotoxic agents or otherwise might be at risk for chemotherapy cardiotoxicity. “Beta-blockers and ACE inhibitors should be considered in those who develop left ventricular systolic dysfunction after anticancer therapy,” Dr. Metra said.

The ongoing pandemic made its mark on the document’s genesis, as it has with most everything else. “For better or worse, we were a ‘COVID guideline,’ ” Dr. McDonagh said. The writing committee consisted of “a large task force of 31 individuals, including two patients,” and there were “only two face-to-face meetings prior to the first wave of COVID hitting Europe.”

The committee voted on each of the recommendations, “and we had to have agreement of more than 75% of the task force to assign a class of recommendation or level of evidence,” she said. “I think we did the best we could in the circumstances. We had the benefit of many discussions over Zoom, and I think at the end of the day we have achieved a consensus.”

With such a large body of participants and the 75% threshold for agreement, “you end up with perhaps a conservative guideline. But that’s not a bad thing for clinical practice, for guidelines to be conservative,” Dr. McDonagh said. “They’re mainly concerned with looking at evidence and safety.”

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

A Federal Practitioner Exclusive

Topics Include:

• Asthma
• Traumatic Brain Injury
• Dementia
• Post-Traumatic Stress Disorder
• Pain
• Migraine
• Suicide/Suicide Prevention
• Depression
• Anxiety
• Substance Use Disorder
• Tobacco
• Diabetes/Cardiovascular Disease
• Diabetic Retinopathy
• COVID-19
• Vaccination
• HIV
• Cancer Screening
  
  To read the supplement click on the cover image or here 

A Federal Practitioner Exclusive

Topics Include:

• Asthma
• Traumatic Brain Injury
• Dementia
• Post-Traumatic Stress Disorder
• Pain
• Migraine
• Suicide/Suicide Prevention
• Depression
• Anxiety
• Substance Use Disorder
• Tobacco
• Diabetes/Cardiovascular Disease
• Diabetic Retinopathy
• COVID-19
• Vaccination
• HIV
• Cancer Screening
  
  To read the supplement click on the cover image or here 

A Federal Practitioner Exclusive

Topics Include:

• Asthma
• Traumatic Brain Injury
• Dementia
• Post-Traumatic Stress Disorder
• Pain
• Migraine
• Suicide/Suicide Prevention
• Depression
• Anxiety
• Substance Use Disorder
• Tobacco
• Diabetes/Cardiovascular Disease
• Diabetic Retinopathy
• COVID-19
• Vaccination
• HIV
• Cancer Screening
  
  To read the supplement click on the cover image or here