Clinical Endocrinology News

On the basis of the quality of sustained bone growth achieved with vosoritide in dwarfism, studies are underway or being considered for more diseases that impair bone growth, according to discussion that followed the presentation of a phase 3 trial extension study at the annual meeting of the Endocrine Society.

After 1 year on active therapy in the randomized trial and another year in the extension study, patients in the vosoritide group had sustained growth velocity while placebo group patients who crossed over to active therapy caught up, reported Ravi Savarirayan, MD, Murdoch Children’s Research Institute, University of Melbourne, Australia.

Moreover, the quality and type of bone growth, such as the improvement in body segment ratios over the second year of the study, support a durable benefit. Dr. Savarirayan said that improvements in activities of daily living are expected from this improvement in upper-to-lower body segment ratios, as well as the growth seen in the limbs.

Currently there is no approved pharmacologic therapy for achondroplasia in the United States. Growth hormone has been approved in Japan, but Dr. Savarirayan said its effects have been limited. Surgery such as limb lengthening is another option, but this approach is not uniformly effective and carries risks.

The 52-week results from the multinational phase 3 trial with vosoritide, which stimulates bone growth, were published last year in The Lancet. In that trial, 121 patients between the ages of 5 and 18 years with achondroplasia were randomized to vosoritide at a dose of 15 μg/kg once daily or placebo.

Over the 1-year study period, the median growth velocity for those treated with vosoritide increased from about 4 cm per year to 6 cm per year. Relative to those in the placebo arm, which did not experience any change in growth, the median growth at the end of 52 weeks was 1.75 cm/year greater (6.71 vs. 3.99 cm).
 

After crossover, placebo patients catch up

In the extension study, the placebo patients were crossed over to the active therapy and both groups were followed for an additional 52 weeks. Over this period, velocity declined modestly in those in the group initially randomized to vosoritide but climbed steeply in the placebo group so that rates after 1 year were nearly identical (5.57 vs. 5.65 cm, respectively).

“The results suggest this medication may well have a durable effect,” said Dr. Savarirayan, who believes that the benefit is derived from stimulation of the growth plates. Based on the very similar efficacy observed in the placebo group once switched to active therapy, the response to vosoritide appears to be predictable.

Of the 60 patients initially randomized to vosoritide, 58 entered the extension. Of the patients who did not remain in the study, two left due to discomfort from injection-site reactions. All 61 patients initially assigned to placebo crossed over.

“We did not see any evidence of tachyphylaxis in the randomized study or in the extension,” Dr. Savarirayan said.

Although two more patients initiated on vosoritide discontinued treatment before the end of 2 years, there were no new adverse events observed. Rather, injection-site pain, which self-resolved in all patients, appears to be the most significant side effect.

“In children, the daily subcutaneous injections can be an issue,” Dr. Savarirayan acknowledged.
 

Injection site reactions most common adverse event

In a detailed evaluation of safety in a previously published dose-finding phase 2 study, injection-site reactions were also the most common of treatment-related adverse events, but there were no episodes of anaphylaxis or other grade 3 or higher hypersensitivity reactions (N Engl J Med. 2019 Jul 4;381:25-35).

Prior to clinical trials, continuous infusion of endogenous C-type natriuretic peptide demonstrated an ability to stimulate long-bone growth in experimental studies. Vosoritide, a recombinant analogue of C-type natriuretic peptide, appears to provide the same activity but offers a longer half-life.

Based on the benefits observed in achondroplasia, other applications are now being explored.

“When you evaluate the quality of the bone growth associated with vosoritide, it is normal,” said Melita Irving, MD, a consultant in clinical genetics at the Guy’s and St .Thomas’ NHS Trust, London. Dr. Irving has been involved in other research initiatives with this therapy and she cited a variety of evidence that has supported healthy bone development, including favorable changes in markers of bone growth such as type 10 collagen.

As a result, vosoritide, which is now under review by the U.S. Food and Drug Administration for treatment of dwarfism, is being pursued for several other diseases that result in abnormal bone growth, such as hypochondroplasia. Not least, clinical studies in idiopathic short stature have reached “early stages,” Dr. Irving said.

Dr. Savarirayan and Dr. Irving report no relevant conflicts of interest.

cenews@mdedge.com

On the basis of the quality of sustained bone growth achieved with vosoritide in dwarfism, studies are underway or being considered for more diseases that impair bone growth, according to discussion that followed the presentation of a phase 3 trial extension study at the annual meeting of the Endocrine Society.

After 1 year on active therapy in the randomized trial and another year in the extension study, patients in the vosoritide group had sustained growth velocity while placebo group patients who crossed over to active therapy caught up, reported Ravi Savarirayan, MD, Murdoch Children’s Research Institute, University of Melbourne, Australia.

Moreover, the quality and type of bone growth, such as the improvement in body segment ratios over the second year of the study, support a durable benefit. Dr. Savarirayan said that improvements in activities of daily living are expected from this improvement in upper-to-lower body segment ratios, as well as the growth seen in the limbs.

Currently there is no approved pharmacologic therapy for achondroplasia in the United States. Growth hormone has been approved in Japan, but Dr. Savarirayan said its effects have been limited. Surgery such as limb lengthening is another option, but this approach is not uniformly effective and carries risks.

The 52-week results from the multinational phase 3 trial with vosoritide, which stimulates bone growth, were published last year in The Lancet. In that trial, 121 patients between the ages of 5 and 18 years with achondroplasia were randomized to vosoritide at a dose of 15 μg/kg once daily or placebo.

Over the 1-year study period, the median growth velocity for those treated with vosoritide increased from about 4 cm per year to 6 cm per year. Relative to those in the placebo arm, which did not experience any change in growth, the median growth at the end of 52 weeks was 1.75 cm/year greater (6.71 vs. 3.99 cm).
 

After crossover, placebo patients catch up

In the extension study, the placebo patients were crossed over to the active therapy and both groups were followed for an additional 52 weeks. Over this period, velocity declined modestly in those in the group initially randomized to vosoritide but climbed steeply in the placebo group so that rates after 1 year were nearly identical (5.57 vs. 5.65 cm, respectively).

“The results suggest this medication may well have a durable effect,” said Dr. Savarirayan, who believes that the benefit is derived from stimulation of the growth plates. Based on the very similar efficacy observed in the placebo group once switched to active therapy, the response to vosoritide appears to be predictable.

Of the 60 patients initially randomized to vosoritide, 58 entered the extension. Of the patients who did not remain in the study, two left due to discomfort from injection-site reactions. All 61 patients initially assigned to placebo crossed over.

“We did not see any evidence of tachyphylaxis in the randomized study or in the extension,” Dr. Savarirayan said.

Although two more patients initiated on vosoritide discontinued treatment before the end of 2 years, there were no new adverse events observed. Rather, injection-site pain, which self-resolved in all patients, appears to be the most significant side effect.

“In children, the daily subcutaneous injections can be an issue,” Dr. Savarirayan acknowledged.
 

Injection site reactions most common adverse event

In a detailed evaluation of safety in a previously published dose-finding phase 2 study, injection-site reactions were also the most common of treatment-related adverse events, but there were no episodes of anaphylaxis or other grade 3 or higher hypersensitivity reactions (N Engl J Med. 2019 Jul 4;381:25-35).

Prior to clinical trials, continuous infusion of endogenous C-type natriuretic peptide demonstrated an ability to stimulate long-bone growth in experimental studies. Vosoritide, a recombinant analogue of C-type natriuretic peptide, appears to provide the same activity but offers a longer half-life.

Based on the benefits observed in achondroplasia, other applications are now being explored.

“When you evaluate the quality of the bone growth associated with vosoritide, it is normal,” said Melita Irving, MD, a consultant in clinical genetics at the Guy’s and St .Thomas’ NHS Trust, London. Dr. Irving has been involved in other research initiatives with this therapy and she cited a variety of evidence that has supported healthy bone development, including favorable changes in markers of bone growth such as type 10 collagen.

As a result, vosoritide, which is now under review by the U.S. Food and Drug Administration for treatment of dwarfism, is being pursued for several other diseases that result in abnormal bone growth, such as hypochondroplasia. Not least, clinical studies in idiopathic short stature have reached “early stages,” Dr. Irving said.

Dr. Savarirayan and Dr. Irving report no relevant conflicts of interest.

cenews@mdedge.com

On the basis of the quality of sustained bone growth achieved with vosoritide in dwarfism, studies are underway or being considered for more diseases that impair bone growth, according to discussion that followed the presentation of a phase 3 trial extension study at the annual meeting of the Endocrine Society.

After 1 year on active therapy in the randomized trial and another year in the extension study, patients in the vosoritide group had sustained growth velocity while placebo group patients who crossed over to active therapy caught up, reported Ravi Savarirayan, MD, Murdoch Children’s Research Institute, University of Melbourne, Australia.

Moreover, the quality and type of bone growth, such as the improvement in body segment ratios over the second year of the study, support a durable benefit. Dr. Savarirayan said that improvements in activities of daily living are expected from this improvement in upper-to-lower body segment ratios, as well as the growth seen in the limbs.

Currently there is no approved pharmacologic therapy for achondroplasia in the United States. Growth hormone has been approved in Japan, but Dr. Savarirayan said its effects have been limited. Surgery such as limb lengthening is another option, but this approach is not uniformly effective and carries risks.

The 52-week results from the multinational phase 3 trial with vosoritide, which stimulates bone growth, were published last year in The Lancet. In that trial, 121 patients between the ages of 5 and 18 years with achondroplasia were randomized to vosoritide at a dose of 15 μg/kg once daily or placebo.

Over the 1-year study period, the median growth velocity for those treated with vosoritide increased from about 4 cm per year to 6 cm per year. Relative to those in the placebo arm, which did not experience any change in growth, the median growth at the end of 52 weeks was 1.75 cm/year greater (6.71 vs. 3.99 cm).
 

After crossover, placebo patients catch up

In the extension study, the placebo patients were crossed over to the active therapy and both groups were followed for an additional 52 weeks. Over this period, velocity declined modestly in those in the group initially randomized to vosoritide but climbed steeply in the placebo group so that rates after 1 year were nearly identical (5.57 vs. 5.65 cm, respectively).

“The results suggest this medication may well have a durable effect,” said Dr. Savarirayan, who believes that the benefit is derived from stimulation of the growth plates. Based on the very similar efficacy observed in the placebo group once switched to active therapy, the response to vosoritide appears to be predictable.

Of the 60 patients initially randomized to vosoritide, 58 entered the extension. Of the patients who did not remain in the study, two left due to discomfort from injection-site reactions. All 61 patients initially assigned to placebo crossed over.

“We did not see any evidence of tachyphylaxis in the randomized study or in the extension,” Dr. Savarirayan said.

Although two more patients initiated on vosoritide discontinued treatment before the end of 2 years, there were no new adverse events observed. Rather, injection-site pain, which self-resolved in all patients, appears to be the most significant side effect.

“In children, the daily subcutaneous injections can be an issue,” Dr. Savarirayan acknowledged.
 

Injection site reactions most common adverse event

In a detailed evaluation of safety in a previously published dose-finding phase 2 study, injection-site reactions were also the most common of treatment-related adverse events, but there were no episodes of anaphylaxis or other grade 3 or higher hypersensitivity reactions (N Engl J Med. 2019 Jul 4;381:25-35).

Prior to clinical trials, continuous infusion of endogenous C-type natriuretic peptide demonstrated an ability to stimulate long-bone growth in experimental studies. Vosoritide, a recombinant analogue of C-type natriuretic peptide, appears to provide the same activity but offers a longer half-life.

Based on the benefits observed in achondroplasia, other applications are now being explored.

“When you evaluate the quality of the bone growth associated with vosoritide, it is normal,” said Melita Irving, MD, a consultant in clinical genetics at the Guy’s and St .Thomas’ NHS Trust, London. Dr. Irving has been involved in other research initiatives with this therapy and she cited a variety of evidence that has supported healthy bone development, including favorable changes in markers of bone growth such as type 10 collagen.

As a result, vosoritide, which is now under review by the U.S. Food and Drug Administration for treatment of dwarfism, is being pursued for several other diseases that result in abnormal bone growth, such as hypochondroplasia. Not least, clinical studies in idiopathic short stature have reached “early stages,” Dr. Irving said.

Dr. Savarirayan and Dr. Irving report no relevant conflicts of interest.

cenews@mdedge.com

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

‘This is a first step.’

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

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

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

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

MATCHing imaging against AVS

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

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

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

SciePro/Shutterstock

Woefully low rates of PA assessment

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

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

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

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

mzoler@mdedge.com

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

‘This is a first step.’

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

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

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

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

MATCHing imaging against AVS

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

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

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

SciePro/Shutterstock

Woefully low rates of PA assessment

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

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

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

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

mzoler@mdedge.com

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

‘This is a first step.’

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

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

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

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

MATCHing imaging against AVS

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

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

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

SciePro/Shutterstock

Woefully low rates of PA assessment

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

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

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

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

mzoler@mdedge.com

The National Resident Matching Program (NRMP) announced March 19 that this year’s Main Residency Match was the largest in its history.

A total of 38,106 positions were offered, up 850 spots (2.3%) from 2020. Of those, 35,194 were first-year (PGY-1) positions, which was 928 more than the previous year (2.7%). A record 5,915 programs were part of the Match, 88 more than 2020.

“The application and recruitment cycle was upended as a result of the pandemic, yet the results of the Match continue to demonstrate strong and consistent outcomes for participants,” Donna L. Lamb, DHSc, MBA, BSN, NRMP president and CEO, said in a new release.

The report comes amid a year of Zoom interview fatigue, canceled testing, and virus fears and work-arounds, which the NMRP has never had to wrestle with since it was established in 1952.

Despite challenges, fill rates increased across the board. Of the 38,106 total positions offered, 36,179 were filled, representing a 2.6% increase over 2020. Of the 35,194 first-year positions available, 33,535 were filled, representing a 2.9% increase.

Those rates drove the percentage of all positions filled to 94.9% (up from 94.6%) and the percentage of PGY-1 positions filled to 94.8% (also up from 94.6%). There were 1,927 unfilled positions, a decline of 71 (3.6%) from 2020.
 

Primary care results strong

Of the first-year positions offered, 17,649 (49.6%) were in family medicine, internal medicine, and pediatrics. That’s an increase of 514 positions (3%) over 2020.

Of first-year positions offered in 2021, 16,860 (95.5%) were filled. U.S. seniors took 11,013 (65.3%) of those slots; that represents a slight decline (0.3%) from 2020. Family medicine saw a gain of 63 U.S. MD seniors who matched, and internal medicine saw a gain of 93 U.S. DO seniors who matched.
 

Some specialties filled all positions

PGY-1 specialties with 30 positions or more that filled all available positions include dermatology, medicine – emergency medicine, medicine – pediatrics, neurologic surgery, otolaryngology, integrated plastic surgery, and vascular surgery.*

PGY-1 specialties with 30 positions or more that filled more than 90% with U.S. seniors include dermatology (100%), medicine – emergency medicine (93.6%), medicine – pediatrics (93.5%), otolaryngology (93.2%), orthopedic surgery (92.8%), and integrated plastic surgery (90.4%).*

PGY-1 specialties with at least 30 positions that filled less than 50% with U.S. seniors include pathology (41.4 %) and surgery–preliminary (28%).

The number of U.S. citizen international medical graduates who submitted rank-ordered lists was 5,295, an increase of 128 (2.5%) over 2020 and the highest in 6 years; 3,152 of them matched to first-year positions, down two PGY-1 matched applicants over last year.

Full data are available on the NRMP’s website.

Correction, 3/22/21: An earlier version of this article misstated the affected specialties.

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

The National Resident Matching Program (NRMP) announced March 19 that this year’s Main Residency Match was the largest in its history.

A total of 38,106 positions were offered, up 850 spots (2.3%) from 2020. Of those, 35,194 were first-year (PGY-1) positions, which was 928 more than the previous year (2.7%). A record 5,915 programs were part of the Match, 88 more than 2020.

“The application and recruitment cycle was upended as a result of the pandemic, yet the results of the Match continue to demonstrate strong and consistent outcomes for participants,” Donna L. Lamb, DHSc, MBA, BSN, NRMP president and CEO, said in a new release.

The report comes amid a year of Zoom interview fatigue, canceled testing, and virus fears and work-arounds, which the NMRP has never had to wrestle with since it was established in 1952.

Despite challenges, fill rates increased across the board. Of the 38,106 total positions offered, 36,179 were filled, representing a 2.6% increase over 2020. Of the 35,194 first-year positions available, 33,535 were filled, representing a 2.9% increase.

Those rates drove the percentage of all positions filled to 94.9% (up from 94.6%) and the percentage of PGY-1 positions filled to 94.8% (also up from 94.6%). There were 1,927 unfilled positions, a decline of 71 (3.6%) from 2020.
 

Primary care results strong

Of the first-year positions offered, 17,649 (49.6%) were in family medicine, internal medicine, and pediatrics. That’s an increase of 514 positions (3%) over 2020.

Of first-year positions offered in 2021, 16,860 (95.5%) were filled. U.S. seniors took 11,013 (65.3%) of those slots; that represents a slight decline (0.3%) from 2020. Family medicine saw a gain of 63 U.S. MD seniors who matched, and internal medicine saw a gain of 93 U.S. DO seniors who matched.
 

Some specialties filled all positions

PGY-1 specialties with 30 positions or more that filled all available positions include dermatology, medicine – emergency medicine, medicine – pediatrics, neurologic surgery, otolaryngology, integrated plastic surgery, and vascular surgery.*

PGY-1 specialties with 30 positions or more that filled more than 90% with U.S. seniors include dermatology (100%), medicine – emergency medicine (93.6%), medicine – pediatrics (93.5%), otolaryngology (93.2%), orthopedic surgery (92.8%), and integrated plastic surgery (90.4%).*

PGY-1 specialties with at least 30 positions that filled less than 50% with U.S. seniors include pathology (41.4 %) and surgery–preliminary (28%).

The number of U.S. citizen international medical graduates who submitted rank-ordered lists was 5,295, an increase of 128 (2.5%) over 2020 and the highest in 6 years; 3,152 of them matched to first-year positions, down two PGY-1 matched applicants over last year.

Full data are available on the NRMP’s website.

Correction, 3/22/21: An earlier version of this article misstated the affected specialties.

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

The National Resident Matching Program (NRMP) announced March 19 that this year’s Main Residency Match was the largest in its history.

A total of 38,106 positions were offered, up 850 spots (2.3%) from 2020. Of those, 35,194 were first-year (PGY-1) positions, which was 928 more than the previous year (2.7%). A record 5,915 programs were part of the Match, 88 more than 2020.

“The application and recruitment cycle was upended as a result of the pandemic, yet the results of the Match continue to demonstrate strong and consistent outcomes for participants,” Donna L. Lamb, DHSc, MBA, BSN, NRMP president and CEO, said in a new release.

The report comes amid a year of Zoom interview fatigue, canceled testing, and virus fears and work-arounds, which the NMRP has never had to wrestle with since it was established in 1952.

Despite challenges, fill rates increased across the board. Of the 38,106 total positions offered, 36,179 were filled, representing a 2.6% increase over 2020. Of the 35,194 first-year positions available, 33,535 were filled, representing a 2.9% increase.

Those rates drove the percentage of all positions filled to 94.9% (up from 94.6%) and the percentage of PGY-1 positions filled to 94.8% (also up from 94.6%). There were 1,927 unfilled positions, a decline of 71 (3.6%) from 2020.
 

Primary care results strong

Of the first-year positions offered, 17,649 (49.6%) were in family medicine, internal medicine, and pediatrics. That’s an increase of 514 positions (3%) over 2020.

Of first-year positions offered in 2021, 16,860 (95.5%) were filled. U.S. seniors took 11,013 (65.3%) of those slots; that represents a slight decline (0.3%) from 2020. Family medicine saw a gain of 63 U.S. MD seniors who matched, and internal medicine saw a gain of 93 U.S. DO seniors who matched.
 

Some specialties filled all positions

PGY-1 specialties with 30 positions or more that filled all available positions include dermatology, medicine – emergency medicine, medicine – pediatrics, neurologic surgery, otolaryngology, integrated plastic surgery, and vascular surgery.*

PGY-1 specialties with 30 positions or more that filled more than 90% with U.S. seniors include dermatology (100%), medicine – emergency medicine (93.6%), medicine – pediatrics (93.5%), otolaryngology (93.2%), orthopedic surgery (92.8%), and integrated plastic surgery (90.4%).*

PGY-1 specialties with at least 30 positions that filled less than 50% with U.S. seniors include pathology (41.4 %) and surgery–preliminary (28%).

The number of U.S. citizen international medical graduates who submitted rank-ordered lists was 5,295, an increase of 128 (2.5%) over 2020 and the highest in 6 years; 3,152 of them matched to first-year positions, down two PGY-1 matched applicants over last year.

Full data are available on the NRMP’s website.

Correction, 3/22/21: An earlier version of this article misstated the affected specialties.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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



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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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



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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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



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

In my last column, I explained how I’m like Tom Brady. I’m not really. Brady is a Super Bowl–winning quarterback worth over $200 million. No, I’m like Oprah. Well, trying anyway.

Brady and Oprah, in addition to being gazillionaires, have in common that they’re arguably the GOATs (Greatest Of All Time) in their fields. Watching Oprah interview Meghan Markle and Prince Harry was like watching Tom Brady on the jumbotron – she made it look easy. Her ability to create conversation and coax information from guests is hall-of-fame good. But although they are both admirable, trying to be like Brady is useful only for next Thanksgiving when you’re trying to beat your cousins from Massachusetts in touch football. Trying to be like Oprah can help you be better in clinic tomorrow. If we break down what she’s doing, it’s just fundamentals done exceedingly well.

1. Prepare ahead. It’s clear that Oprah has binders of notes about her guests and thoroughly reviewed them before she invites them to sit down. We should do the same. Open the chart and read as much as you can before you open the door. Have important information in your head so you don’t have to break from your interview to refer to it.

2. Sprinkle pleasantry. She’d never start an interview with: So why are you here? Nor should we. Even one nonscripted question or comment can help build a little rapport before getting to the work.

3. Be brief. Oprah gets her question out fast, then gets out of the way. And as a bonus, this is the easiest place to shave a few minutes from your appointments from your own end. Think for a second before you speak and try to find the shortest route to your question. Try to keep your questions to just a sentence or two.

4. Stay on it. Once you’ve discovered something relevant, stay with it, resisting the urge to finish the review of symptoms. This is not just to make a diagnosis, but as importantly, trying to diagnose “the real reason” for the visit. Then, when the question is done, own the transition. Oprah uses: “Let’s move on.” This is a bit abrupt for us, but it can be helpful if used sparingly and gently. I might soften this a little by adding “I want to be sure we have enough time to get through everything for you.”

5. Wait. A few seconds seems an eternity on the air (and in clinic), but sometimes the silent pause is just what’s needed to help the patient expand and share.

6. Be nonjudgmental. Most of us believe we’re pretty good at this, yet, it’s sometimes a blind spot. It’s easy to blame the obese patient for his stasis dermatitis or the hidradenitis patient who hasn’t stop smoking for her cysts. It also helps to be nontransactional. If you make patients feel that you’re asking questions only to extract information, you’ll never reach Oprah level.

7. Be in the moment. It is difficult, but when possible, avoid typing notes while you’re still interviewing. We’re not just there to get the facts, we’re also trying to get the story and that sometimes takes really listening.

I’m no more like Oprah than Brady, of course. But it is more fun to close my eyes and imagine myself being her when I see my next patient. That is, until Thanksgiving. Watch out, Bedards from Attleboro.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@mdedge.com.

In my last column, I explained how I’m like Tom Brady. I’m not really. Brady is a Super Bowl–winning quarterback worth over $200 million. No, I’m like Oprah. Well, trying anyway.

Brady and Oprah, in addition to being gazillionaires, have in common that they’re arguably the GOATs (Greatest Of All Time) in their fields. Watching Oprah interview Meghan Markle and Prince Harry was like watching Tom Brady on the jumbotron – she made it look easy. Her ability to create conversation and coax information from guests is hall-of-fame good. But although they are both admirable, trying to be like Brady is useful only for next Thanksgiving when you’re trying to beat your cousins from Massachusetts in touch football. Trying to be like Oprah can help you be better in clinic tomorrow. If we break down what she’s doing, it’s just fundamentals done exceedingly well.

1. Prepare ahead. It’s clear that Oprah has binders of notes about her guests and thoroughly reviewed them before she invites them to sit down. We should do the same. Open the chart and read as much as you can before you open the door. Have important information in your head so you don’t have to break from your interview to refer to it.

2. Sprinkle pleasantry. She’d never start an interview with: So why are you here? Nor should we. Even one nonscripted question or comment can help build a little rapport before getting to the work.

3. Be brief. Oprah gets her question out fast, then gets out of the way. And as a bonus, this is the easiest place to shave a few minutes from your appointments from your own end. Think for a second before you speak and try to find the shortest route to your question. Try to keep your questions to just a sentence or two.

4. Stay on it. Once you’ve discovered something relevant, stay with it, resisting the urge to finish the review of symptoms. This is not just to make a diagnosis, but as importantly, trying to diagnose “the real reason” for the visit. Then, when the question is done, own the transition. Oprah uses: “Let’s move on.” This is a bit abrupt for us, but it can be helpful if used sparingly and gently. I might soften this a little by adding “I want to be sure we have enough time to get through everything for you.”

5. Wait. A few seconds seems an eternity on the air (and in clinic), but sometimes the silent pause is just what’s needed to help the patient expand and share.

6. Be nonjudgmental. Most of us believe we’re pretty good at this, yet, it’s sometimes a blind spot. It’s easy to blame the obese patient for his stasis dermatitis or the hidradenitis patient who hasn’t stop smoking for her cysts. It also helps to be nontransactional. If you make patients feel that you’re asking questions only to extract information, you’ll never reach Oprah level.

7. Be in the moment. It is difficult, but when possible, avoid typing notes while you’re still interviewing. We’re not just there to get the facts, we’re also trying to get the story and that sometimes takes really listening.

I’m no more like Oprah than Brady, of course. But it is more fun to close my eyes and imagine myself being her when I see my next patient. That is, until Thanksgiving. Watch out, Bedards from Attleboro.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@mdedge.com.

In my last column, I explained how I’m like Tom Brady. I’m not really. Brady is a Super Bowl–winning quarterback worth over $200 million. No, I’m like Oprah. Well, trying anyway.

Brady and Oprah, in addition to being gazillionaires, have in common that they’re arguably the GOATs (Greatest Of All Time) in their fields. Watching Oprah interview Meghan Markle and Prince Harry was like watching Tom Brady on the jumbotron – she made it look easy. Her ability to create conversation and coax information from guests is hall-of-fame good. But although they are both admirable, trying to be like Brady is useful only for next Thanksgiving when you’re trying to beat your cousins from Massachusetts in touch football. Trying to be like Oprah can help you be better in clinic tomorrow. If we break down what she’s doing, it’s just fundamentals done exceedingly well.

1. Prepare ahead. It’s clear that Oprah has binders of notes about her guests and thoroughly reviewed them before she invites them to sit down. We should do the same. Open the chart and read as much as you can before you open the door. Have important information in your head so you don’t have to break from your interview to refer to it.

2. Sprinkle pleasantry. She’d never start an interview with: So why are you here? Nor should we. Even one nonscripted question or comment can help build a little rapport before getting to the work.

3. Be brief. Oprah gets her question out fast, then gets out of the way. And as a bonus, this is the easiest place to shave a few minutes from your appointments from your own end. Think for a second before you speak and try to find the shortest route to your question. Try to keep your questions to just a sentence or two.

4. Stay on it. Once you’ve discovered something relevant, stay with it, resisting the urge to finish the review of symptoms. This is not just to make a diagnosis, but as importantly, trying to diagnose “the real reason” for the visit. Then, when the question is done, own the transition. Oprah uses: “Let’s move on.” This is a bit abrupt for us, but it can be helpful if used sparingly and gently. I might soften this a little by adding “I want to be sure we have enough time to get through everything for you.”

5. Wait. A few seconds seems an eternity on the air (and in clinic), but sometimes the silent pause is just what’s needed to help the patient expand and share.

6. Be nonjudgmental. Most of us believe we’re pretty good at this, yet, it’s sometimes a blind spot. It’s easy to blame the obese patient for his stasis dermatitis or the hidradenitis patient who hasn’t stop smoking for her cysts. It also helps to be nontransactional. If you make patients feel that you’re asking questions only to extract information, you’ll never reach Oprah level.

7. Be in the moment. It is difficult, but when possible, avoid typing notes while you’re still interviewing. We’re not just there to get the facts, we’re also trying to get the story and that sometimes takes really listening.

I’m no more like Oprah than Brady, of course. But it is more fun to close my eyes and imagine myself being her when I see my next patient. That is, until Thanksgiving. Watch out, Bedards from Attleboro.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@mdedge.com.

New analyses of both observational and genetic data have provided “convincing evidence” that type 2 diabetes is associated with an increased risk for Parkinson’s disease.

“The fact that we see the same effects in both types of analysis separately makes it more likely that these results are real – that type 2 diabetes really is a driver of Parkinson’s disease risk,” Alastair Noyce, PhD, senior author of the new studies, said in an interview.

The two analyses are reported in one paper published online March 8 in the journal Movement Disorders.

Dr. Noyce, clinical senior lecturer in the preventive neurology unit at the Wolfson Institute of Preventive Medicine, Queen Mary University of London, explained that his group is interested in risk factors for Parkinson’s disease, particularly those relevant at the population level and which might be modifiable.

“Several studies have looked at diabetes as a risk factor for Parkinson’s but very few have focused on type 2 diabetes, and, as this is such a growing health issue, we wanted to look at that in more detail,” he said.

The researchers performed two different analyses: a meta-analysis of observational studies investigating an association between type 2 diabetes and Parkinson’s; and a separate Mendelian randomization analysis of genetic data on the two conditions.

They found similar results in both studies, with the observational data suggesting type 2 diabetes was associated with a 21% increased risk for Parkinson’s disease and the genetic data suggesting an 8% increased risk. There were also hints that type 2 diabetes might also be associated with faster progression of Parkinson’s symptoms.

“I don’t think type 2 diabetes is a major cause of Parkinson’s, but it probably makes some contribution and may increase the risk of a more aggressive form of the condition,” Dr. Noyce said.

“I would say the increased risk of Parkinson’s disease attributable to type 2 diabetes may be similar to that of head injury or pesticide exposure, but it is important, as type 2 diabetes is very prevalent and is increasing,” he added.  “As we see the growth in type 2 diabetes, this could lead to a later increase in Parkinson’s, which is already one of the fastest-growing diseases worldwide.”

For the meta-analysis of observational data, the researchers included nine studies that investigated preceding type 2 diabetes specifically and its effect on the risk for Parkinson’s disease and progression.

The pooled effect estimates showed that type 2 diabetes was associated with an increased risk for Parkinson’s disease (odds ratio, 1.21; 95% confidence interval, 1.07-1.36), and there was some evidence that type 2 diabetes was associated with faster progression of motor symptoms (standardized mean difference [SMD], 0.55) and cognitive decline (SMD, −0.92).

The observational meta-analysis included seven cohort studies and two case-control studies, and these different types of studies showed different results in regard to the association between diabetes and Parkinson’s. While the cohort studies showed a detrimental effect of diabetes on Parkinson’s risk (OR, 1.29), the case-control studies suggested protective effect (OR, 0.51). 

Addressing this, Dr. Noyce noted that the case-control studies may be less reliable as they suffered more from survivor bias. “Diabetes may cause deaths in mid-life before people go on to develop Parkinson’s, and this would cause a protective effect to be seen, but we believe this to be a spurious result. Cohort studies are generally more reliable and are less susceptible to survivor bias,” he said.  

For the genetic analysis, the researchers combined results from two large publicly available genome-wide association studies – one for type 2 diabetes and one for Parkinson’s disease to assess whether individuals with a genetic tendency to type 2 diabetes had a higher risk of developing Parkinson’s.

Results showed an increased risk for Parkinson’s in those individuals with genetic variants associated with type 2 diabetes, with an odds ratio of 1.08 (P = .010). There was also some evidence of an effect on motor progression (OR, 1.10; P = .032) but not on cognitive progression.

On the possible mechanism behind this observation, Dr. Noyce noted type 2 diabetes and Parkinson’s have some similarities in biology, including abnormal protein aggregation.

In the study, the authors also suggest that circulating insulin may have a neuroprotective role, whereas systemic and local insulin resistance can influence pathways known to be important in Parkinson’s pathogenesis, including those that relate to mitochondrial dysfunction, neuroinflammation, synaptic plasticity, and mitochondrial dysfunction.

Dr. Noyce further pointed out that several drugs used for the treatment of type 2 diabetes have been repurposed as possible treatments for Parkinson’s disease and are now being tested for this new indication. “Our results support that approach and raise the idea that some of these drugs may even prevent Parkinson’s in people at risk,” he said.  

Most people who have type 2 diabetes won’t get Parkinson’s disease, he added. Other outcomes such as heart disease, kidney disease, and microvascular complications are far more likely, and the main aim of preventing and treating type 2 diabetes is to prevent these far more common outcomes. “But our data suggests that this could also have a possible benefit in reducing future Parkinson’s risk,” he said.  

Not on the horizon at present is the possibility of screening patients with type 2 diabetes for signs of early Parkinson’s, Dr. Noyce said.

“There isn’t a test for identifying presymptomatic neurodegenerative diseases such as Parkinson’s yet, but perhaps in the future there will be, and type 2 diabetes may be one risk factor to take into account when considering such screening,” he added.

This work was financially supported by grants from The Michael J. Fox Foundation; the Canadian Consortium on Neurodegeneration in Aging (CCNA); the Canada First Research Excellence Fund (CFREF), awarded to McGill University for the Healthy Brains for Healthy Lives (HBHL) initiative; and Parkinson Canada, and the Intramural Research Program of the NIH, National Institute on Aging.

Dr. Noyce reports grants from the Barts Charity, Parkinson’s UK, Aligning Science Across Parkinson’s and Michael J. Fox Foundation, and the Virginia Keiley Benefaction; and personal fees/honoraria from Britannia, BIAL, AbbVie, Global Kinetics Corporation, Profile, Biogen, Roche, and UCB outside of the submitted work.

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

New analyses of both observational and genetic data have provided “convincing evidence” that type 2 diabetes is associated with an increased risk for Parkinson’s disease.

“The fact that we see the same effects in both types of analysis separately makes it more likely that these results are real – that type 2 diabetes really is a driver of Parkinson’s disease risk,” Alastair Noyce, PhD, senior author of the new studies, said in an interview.

The two analyses are reported in one paper published online March 8 in the journal Movement Disorders.

Dr. Noyce, clinical senior lecturer in the preventive neurology unit at the Wolfson Institute of Preventive Medicine, Queen Mary University of London, explained that his group is interested in risk factors for Parkinson’s disease, particularly those relevant at the population level and which might be modifiable.

“Several studies have looked at diabetes as a risk factor for Parkinson’s but very few have focused on type 2 diabetes, and, as this is such a growing health issue, we wanted to look at that in more detail,” he said.

The researchers performed two different analyses: a meta-analysis of observational studies investigating an association between type 2 diabetes and Parkinson’s; and a separate Mendelian randomization analysis of genetic data on the two conditions.

They found similar results in both studies, with the observational data suggesting type 2 diabetes was associated with a 21% increased risk for Parkinson’s disease and the genetic data suggesting an 8% increased risk. There were also hints that type 2 diabetes might also be associated with faster progression of Parkinson’s symptoms.

“I don’t think type 2 diabetes is a major cause of Parkinson’s, but it probably makes some contribution and may increase the risk of a more aggressive form of the condition,” Dr. Noyce said.

“I would say the increased risk of Parkinson’s disease attributable to type 2 diabetes may be similar to that of head injury or pesticide exposure, but it is important, as type 2 diabetes is very prevalent and is increasing,” he added.  “As we see the growth in type 2 diabetes, this could lead to a later increase in Parkinson’s, which is already one of the fastest-growing diseases worldwide.”

For the meta-analysis of observational data, the researchers included nine studies that investigated preceding type 2 diabetes specifically and its effect on the risk for Parkinson’s disease and progression.

The pooled effect estimates showed that type 2 diabetes was associated with an increased risk for Parkinson’s disease (odds ratio, 1.21; 95% confidence interval, 1.07-1.36), and there was some evidence that type 2 diabetes was associated with faster progression of motor symptoms (standardized mean difference [SMD], 0.55) and cognitive decline (SMD, −0.92).

The observational meta-analysis included seven cohort studies and two case-control studies, and these different types of studies showed different results in regard to the association between diabetes and Parkinson’s. While the cohort studies showed a detrimental effect of diabetes on Parkinson’s risk (OR, 1.29), the case-control studies suggested protective effect (OR, 0.51). 

Addressing this, Dr. Noyce noted that the case-control studies may be less reliable as they suffered more from survivor bias. “Diabetes may cause deaths in mid-life before people go on to develop Parkinson’s, and this would cause a protective effect to be seen, but we believe this to be a spurious result. Cohort studies are generally more reliable and are less susceptible to survivor bias,” he said.  

For the genetic analysis, the researchers combined results from two large publicly available genome-wide association studies – one for type 2 diabetes and one for Parkinson’s disease to assess whether individuals with a genetic tendency to type 2 diabetes had a higher risk of developing Parkinson’s.

Results showed an increased risk for Parkinson’s in those individuals with genetic variants associated with type 2 diabetes, with an odds ratio of 1.08 (P = .010). There was also some evidence of an effect on motor progression (OR, 1.10; P = .032) but not on cognitive progression.

On the possible mechanism behind this observation, Dr. Noyce noted type 2 diabetes and Parkinson’s have some similarities in biology, including abnormal protein aggregation.

In the study, the authors also suggest that circulating insulin may have a neuroprotective role, whereas systemic and local insulin resistance can influence pathways known to be important in Parkinson’s pathogenesis, including those that relate to mitochondrial dysfunction, neuroinflammation, synaptic plasticity, and mitochondrial dysfunction.

Dr. Noyce further pointed out that several drugs used for the treatment of type 2 diabetes have been repurposed as possible treatments for Parkinson’s disease and are now being tested for this new indication. “Our results support that approach and raise the idea that some of these drugs may even prevent Parkinson’s in people at risk,” he said.  

Most people who have type 2 diabetes won’t get Parkinson’s disease, he added. Other outcomes such as heart disease, kidney disease, and microvascular complications are far more likely, and the main aim of preventing and treating type 2 diabetes is to prevent these far more common outcomes. “But our data suggests that this could also have a possible benefit in reducing future Parkinson’s risk,” he said.  

Not on the horizon at present is the possibility of screening patients with type 2 diabetes for signs of early Parkinson’s, Dr. Noyce said.

“There isn’t a test for identifying presymptomatic neurodegenerative diseases such as Parkinson’s yet, but perhaps in the future there will be, and type 2 diabetes may be one risk factor to take into account when considering such screening,” he added.

This work was financially supported by grants from The Michael J. Fox Foundation; the Canadian Consortium on Neurodegeneration in Aging (CCNA); the Canada First Research Excellence Fund (CFREF), awarded to McGill University for the Healthy Brains for Healthy Lives (HBHL) initiative; and Parkinson Canada, and the Intramural Research Program of the NIH, National Institute on Aging.

Dr. Noyce reports grants from the Barts Charity, Parkinson’s UK, Aligning Science Across Parkinson’s and Michael J. Fox Foundation, and the Virginia Keiley Benefaction; and personal fees/honoraria from Britannia, BIAL, AbbVie, Global Kinetics Corporation, Profile, Biogen, Roche, and UCB outside of the submitted work.

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

New analyses of both observational and genetic data have provided “convincing evidence” that type 2 diabetes is associated with an increased risk for Parkinson’s disease.

“The fact that we see the same effects in both types of analysis separately makes it more likely that these results are real – that type 2 diabetes really is a driver of Parkinson’s disease risk,” Alastair Noyce, PhD, senior author of the new studies, said in an interview.

The two analyses are reported in one paper published online March 8 in the journal Movement Disorders.

Dr. Noyce, clinical senior lecturer in the preventive neurology unit at the Wolfson Institute of Preventive Medicine, Queen Mary University of London, explained that his group is interested in risk factors for Parkinson’s disease, particularly those relevant at the population level and which might be modifiable.

“Several studies have looked at diabetes as a risk factor for Parkinson’s but very few have focused on type 2 diabetes, and, as this is such a growing health issue, we wanted to look at that in more detail,” he said.

The researchers performed two different analyses: a meta-analysis of observational studies investigating an association between type 2 diabetes and Parkinson’s; and a separate Mendelian randomization analysis of genetic data on the two conditions.

They found similar results in both studies, with the observational data suggesting type 2 diabetes was associated with a 21% increased risk for Parkinson’s disease and the genetic data suggesting an 8% increased risk. There were also hints that type 2 diabetes might also be associated with faster progression of Parkinson’s symptoms.

“I don’t think type 2 diabetes is a major cause of Parkinson’s, but it probably makes some contribution and may increase the risk of a more aggressive form of the condition,” Dr. Noyce said.

“I would say the increased risk of Parkinson’s disease attributable to type 2 diabetes may be similar to that of head injury or pesticide exposure, but it is important, as type 2 diabetes is very prevalent and is increasing,” he added.  “As we see the growth in type 2 diabetes, this could lead to a later increase in Parkinson’s, which is already one of the fastest-growing diseases worldwide.”

For the meta-analysis of observational data, the researchers included nine studies that investigated preceding type 2 diabetes specifically and its effect on the risk for Parkinson’s disease and progression.

The pooled effect estimates showed that type 2 diabetes was associated with an increased risk for Parkinson’s disease (odds ratio, 1.21; 95% confidence interval, 1.07-1.36), and there was some evidence that type 2 diabetes was associated with faster progression of motor symptoms (standardized mean difference [SMD], 0.55) and cognitive decline (SMD, −0.92).

The observational meta-analysis included seven cohort studies and two case-control studies, and these different types of studies showed different results in regard to the association between diabetes and Parkinson’s. While the cohort studies showed a detrimental effect of diabetes on Parkinson’s risk (OR, 1.29), the case-control studies suggested protective effect (OR, 0.51). 

Addressing this, Dr. Noyce noted that the case-control studies may be less reliable as they suffered more from survivor bias. “Diabetes may cause deaths in mid-life before people go on to develop Parkinson’s, and this would cause a protective effect to be seen, but we believe this to be a spurious result. Cohort studies are generally more reliable and are less susceptible to survivor bias,” he said.  

For the genetic analysis, the researchers combined results from two large publicly available genome-wide association studies – one for type 2 diabetes and one for Parkinson’s disease to assess whether individuals with a genetic tendency to type 2 diabetes had a higher risk of developing Parkinson’s.

Results showed an increased risk for Parkinson’s in those individuals with genetic variants associated with type 2 diabetes, with an odds ratio of 1.08 (P = .010). There was also some evidence of an effect on motor progression (OR, 1.10; P = .032) but not on cognitive progression.

On the possible mechanism behind this observation, Dr. Noyce noted type 2 diabetes and Parkinson’s have some similarities in biology, including abnormal protein aggregation.

In the study, the authors also suggest that circulating insulin may have a neuroprotective role, whereas systemic and local insulin resistance can influence pathways known to be important in Parkinson’s pathogenesis, including those that relate to mitochondrial dysfunction, neuroinflammation, synaptic plasticity, and mitochondrial dysfunction.

Dr. Noyce further pointed out that several drugs used for the treatment of type 2 diabetes have been repurposed as possible treatments for Parkinson’s disease and are now being tested for this new indication. “Our results support that approach and raise the idea that some of these drugs may even prevent Parkinson’s in people at risk,” he said.  

Most people who have type 2 diabetes won’t get Parkinson’s disease, he added. Other outcomes such as heart disease, kidney disease, and microvascular complications are far more likely, and the main aim of preventing and treating type 2 diabetes is to prevent these far more common outcomes. “But our data suggests that this could also have a possible benefit in reducing future Parkinson’s risk,” he said.  

Not on the horizon at present is the possibility of screening patients with type 2 diabetes for signs of early Parkinson’s, Dr. Noyce said.

“There isn’t a test for identifying presymptomatic neurodegenerative diseases such as Parkinson’s yet, but perhaps in the future there will be, and type 2 diabetes may be one risk factor to take into account when considering such screening,” he added.

This work was financially supported by grants from The Michael J. Fox Foundation; the Canadian Consortium on Neurodegeneration in Aging (CCNA); the Canada First Research Excellence Fund (CFREF), awarded to McGill University for the Healthy Brains for Healthy Lives (HBHL) initiative; and Parkinson Canada, and the Intramural Research Program of the NIH, National Institute on Aging.

Dr. Noyce reports grants from the Barts Charity, Parkinson’s UK, Aligning Science Across Parkinson’s and Michael J. Fox Foundation, and the Virginia Keiley Benefaction; and personal fees/honoraria from Britannia, BIAL, AbbVie, Global Kinetics Corporation, Profile, Biogen, Roche, and UCB outside of the submitted work.

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

The new 2021 Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guideline for blood pressure management for adults with chronic kidney disease (CKD) who are not receiving dialysis advises treating to a target systolic blood pressure of less than 120 mm Hg, provided measurements are “standardized” and that blood pressure is “measured properly.”

This blood pressure target – largely based on evidence from the Systolic Blood Pressure Intervention Trial (SPRINT) – represents “a major update” from the 2012 KDIGO guideline, which advised clinicians to treat to a target blood pressure of less than or equal to 130/80 mm Hg for patients with albuminuria or less than or equal to 140/90 mm Hg for patients without albuminuria.

The new goal is also lower than the less than 130/80 mm Hg target in the 2017 American College of Cardiology/American Heart Association guideline.

In a study of the public health implications of the guideline, Kathryn Foti, PhD, and colleagues determined that 70% of U.S. adults with CKD would now be eligible for treatment to lower blood pressure, as opposed to 50% under the previous KDIGO guideline and 56% under the ACC/AHA guideline.

“This is a major update of an influential set of guidelines for chronic kidney disease patients” at a time when blood pressure control is worsening in the United States, Dr. Foti, a postdoctoral researcher in the department of epidemiology at Johns Hopkins Bloomberg School of Public Health, Baltimore, said in a statement from her institution.

The 2021 KDIGO blood pressure guideline and executive summary and the public health implications study are published online in Kidney International.
 

First, ‘take blood pressure well’

The cochair of the new KDIGO guidelines, Alfred K. Cheung, MD, from the University of Utah, Salt Lake City, said in an interview that the guideline has “two important points.”

First, “take that blood pressure well,” he said. “That has a lot to do with patient preparation rather than any fancy instrument,” he emphasized.

Second, the guideline proposes a systolic blood pressure target of less than 120 mm Hg for most people with CKD not receiving dialysis, except for children and kidney transplant recipients. This target is “contingent on ‘standardized’ blood pressure measurement.”

The document provides a checklist for obtaining a standardized blood pressure measurement, adapted from the 2017 ACC/AHA blood pressure guidelines. It starts with the patient relaxed and sitting on a chair for more than 5 minutes.

In contrast to this measurement, a “routine” or “casual” office blood pressure measurement could be off by plus or minus 10 mm Hg, Dr. Cheung noted.

In a typical scenario, he continued, a patient cannot find a place to park, rushes into the clinic, and has his or her blood pressure checked right away, which would provide a “totally unreliable” reading. Adding a “fudge factor” (correction factor) would not provide an accurate reading.

Clinicians “would not settle for a potassium measurement that is 5.0 mmol/L plus or minus a few decimal points” to guide treatment, he pointed out.
 

Second, target 120, properly measured

“The very first chapter of the guidelines is devoted to blood pressure measurement, because we recognize if we’re going to do 120 [mm Hg] – the emphasis is on 120 measured properly – so we try to drive that point home,” Tara I. Chang, MD, guideline second author and a coauthor of the public health implications study, pointed out in an interview.

“There are a lot of other things that we base clinical decisions on where we really require some degree of precision, and blood pressure is important enough that to us it’s kind of in the same boat,” said Dr. Chang, from Stanford (Calif.) University.

“In SPRINT, people were randomized to less than less than 120 vs. less than 140 (they weren’t randomized to <130),” she noted.

“The recommendation should be widely adopted in clinical practice,” the guideline authors write, “since accurate measurements will ensure that proper guidance is being applied to the management of BP, as it is to the management of other risk factors.”
 

Still need individual treatment

Nevertheless, patients still need individualized treatment, the document stresses. “Not every patient with CKD will be appropriate to target to less than 120,” Dr. Chang said. However, “we want people to at least consider less than 120,” she added, to avoid therapeutic inertia.

“If you take the blood pressure in a standardized manner – such as in the ACCORD trial and in the SPRINT trial – even patients over 75 years old, or people over 80 years old, they have very little side effects,” Dr. Cheung noted.

“In the overall cohort,” he continued, “they do not have a significant increase in serious adverse events, do not have adverse events of postural hypotension, syncope, bradycardia, injurious falls – so people are worried about it, but it’s not borne out by the data.

“That said, I have two cautions,” Dr. Cheung noted. “One. If you drop somebody’s blood pressure rapidly over a week, you may be more likely to get in trouble. If you drop the blood pressure gradually over several weeks, several months, you’re much less likely to get into trouble.”

“Two. If the patient is old, you know the patient has carotid stenosis and already has postural dizziness, you may not want to try on that patient – but just because the patient is old is not the reason not to target 120.”
 

ACE inhibitors and ARBs beneficial in albuminuria, underused

“How do you get to less than 120? The short answer is, use whatever medications you need to – there is no necessarily right cocktail,” Dr. Chang said.

“We’ve known that angiotensin-converting enzyme (ACE) inhibitors and ARBs [angiotensin II receptor blockers] are beneficial in patients with CKD and in particular those with heavier albuminuria,” she continued. “We’ve known this for over 20 years.”

Yet, the study identified underutilization – “a persistent gap, just like blood pressure control and awareness,” she noted. “We’re just not making much headway.

“We are not recommending ACE inhibitors or ARBs for all the patients,” Dr. Cheung clarified. “If you are diabetic and have heavy proteinuria, that’s when the use of ACE inhibitors and ARBs are most indicated.”
 

Public health implications

SPRINT showed that treating to a systolic blood pressure of less than 120 mm Hg vs. less than 140 mm Hg reduced the risk for cardiovascular disease by 25% and all-cause mortality by 27% for participants with and those without CKD, Dr. Foti and colleagues stress.

They aimed to estimate how the new guideline would affect (1) the number of U.S. patients with CKD who would be eligible for blood pressure lowering treatment, and (2) the proportion of those with albuminuria who would be eligible for an ACE inhibitor or an ARB.

The researchers analyzed data from 1,699 adults with CKD (estimated glomerular filtration rate, 15-59 mL/min/1.73 m² or a urinary albumin-to-creatinine ratio of ≥30 mg/g) who participated in the 2015-2018 National Health and Nutrition Examination Survey.

Both the 2021 and 2012 KDIGO guidelines recommend that patients with albuminuria and blood pressure higher than the target value who are not kidney transplant recipients should be treated with an ACE inhibitor or an ARB.

On the basis of the new target, 78% of patients with CKD and albuminuria were eligible for ACE inhibitor/ARB treatment by the 2021 KDIGO guideline, compared with 71% by the 2012 KDIGO guideline. However, only 39% were taking one of these drugs.

These findings show that “with the new guideline and with the lower blood pressure target, you potentially have an even larger pool of people who have blood pressure that’s not under control, and a potential larger group of people who may benefit from ACE inhibitors and ARBs,” Dr. Chang said.

“Our paper is not the only one to show that we haven’t made a whole lot of progress,” she said, “and now that the bar has been lowered, there [have] to be some renewed efforts on controlling blood pressure, because we know that blood pressure control is such an important risk factor for cardiovascular outcomes.”

Dr. Foti is supported by an NIH/National Heart, Lung, and Blood Institute grant. Dr. Cheung has received consultancy fees from Amgen, Bard, Boehringer Ingelheim, Calliditas, Tricida, and UpToDate, and grant/research support from the National Institutes of Health for SPRINT (monies paid to institution). Dr. Chang has received consultancy fees from Bayer, Gilead, Janssen Research and Development, Novo Nordisk, Tricida, and Vascular Dynamics; grant/research support from AstraZeneca and Satellite Healthcare (monies paid to institution), the NIH, and the American Heart Association; is on advisory boards for AstraZeneca and Fresenius Medical Care Renal Therapies Group; and has received workshop honoraria from Fresenius. Disclosures of relevant financial relationships of the other authors are listed in the original articles.

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

The new 2021 Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guideline for blood pressure management for adults with chronic kidney disease (CKD) who are not receiving dialysis advises treating to a target systolic blood pressure of less than 120 mm Hg, provided measurements are “standardized” and that blood pressure is “measured properly.”

This blood pressure target – largely based on evidence from the Systolic Blood Pressure Intervention Trial (SPRINT) – represents “a major update” from the 2012 KDIGO guideline, which advised clinicians to treat to a target blood pressure of less than or equal to 130/80 mm Hg for patients with albuminuria or less than or equal to 140/90 mm Hg for patients without albuminuria.

The new goal is also lower than the less than 130/80 mm Hg target in the 2017 American College of Cardiology/American Heart Association guideline.

In a study of the public health implications of the guideline, Kathryn Foti, PhD, and colleagues determined that 70% of U.S. adults with CKD would now be eligible for treatment to lower blood pressure, as opposed to 50% under the previous KDIGO guideline and 56% under the ACC/AHA guideline.

“This is a major update of an influential set of guidelines for chronic kidney disease patients” at a time when blood pressure control is worsening in the United States, Dr. Foti, a postdoctoral researcher in the department of epidemiology at Johns Hopkins Bloomberg School of Public Health, Baltimore, said in a statement from her institution.

The 2021 KDIGO blood pressure guideline and executive summary and the public health implications study are published online in Kidney International.
 

First, ‘take blood pressure well’

The cochair of the new KDIGO guidelines, Alfred K. Cheung, MD, from the University of Utah, Salt Lake City, said in an interview that the guideline has “two important points.”

First, “take that blood pressure well,” he said. “That has a lot to do with patient preparation rather than any fancy instrument,” he emphasized.

Second, the guideline proposes a systolic blood pressure target of less than 120 mm Hg for most people with CKD not receiving dialysis, except for children and kidney transplant recipients. This target is “contingent on ‘standardized’ blood pressure measurement.”

The document provides a checklist for obtaining a standardized blood pressure measurement, adapted from the 2017 ACC/AHA blood pressure guidelines. It starts with the patient relaxed and sitting on a chair for more than 5 minutes.

In contrast to this measurement, a “routine” or “casual” office blood pressure measurement could be off by plus or minus 10 mm Hg, Dr. Cheung noted.

In a typical scenario, he continued, a patient cannot find a place to park, rushes into the clinic, and has his or her blood pressure checked right away, which would provide a “totally unreliable” reading. Adding a “fudge factor” (correction factor) would not provide an accurate reading.

Clinicians “would not settle for a potassium measurement that is 5.0 mmol/L plus or minus a few decimal points” to guide treatment, he pointed out.
 

Second, target 120, properly measured

“The very first chapter of the guidelines is devoted to blood pressure measurement, because we recognize if we’re going to do 120 [mm Hg] – the emphasis is on 120 measured properly – so we try to drive that point home,” Tara I. Chang, MD, guideline second author and a coauthor of the public health implications study, pointed out in an interview.

“There are a lot of other things that we base clinical decisions on where we really require some degree of precision, and blood pressure is important enough that to us it’s kind of in the same boat,” said Dr. Chang, from Stanford (Calif.) University.

“In SPRINT, people were randomized to less than less than 120 vs. less than 140 (they weren’t randomized to <130),” she noted.

“The recommendation should be widely adopted in clinical practice,” the guideline authors write, “since accurate measurements will ensure that proper guidance is being applied to the management of BP, as it is to the management of other risk factors.”
 

Still need individual treatment

Nevertheless, patients still need individualized treatment, the document stresses. “Not every patient with CKD will be appropriate to target to less than 120,” Dr. Chang said. However, “we want people to at least consider less than 120,” she added, to avoid therapeutic inertia.

“If you take the blood pressure in a standardized manner – such as in the ACCORD trial and in the SPRINT trial – even patients over 75 years old, or people over 80 years old, they have very little side effects,” Dr. Cheung noted.

“In the overall cohort,” he continued, “they do not have a significant increase in serious adverse events, do not have adverse events of postural hypotension, syncope, bradycardia, injurious falls – so people are worried about it, but it’s not borne out by the data.

“That said, I have two cautions,” Dr. Cheung noted. “One. If you drop somebody’s blood pressure rapidly over a week, you may be more likely to get in trouble. If you drop the blood pressure gradually over several weeks, several months, you’re much less likely to get into trouble.”

“Two. If the patient is old, you know the patient has carotid stenosis and already has postural dizziness, you may not want to try on that patient – but just because the patient is old is not the reason not to target 120.”
 

ACE inhibitors and ARBs beneficial in albuminuria, underused

“How do you get to less than 120? The short answer is, use whatever medications you need to – there is no necessarily right cocktail,” Dr. Chang said.

“We’ve known that angiotensin-converting enzyme (ACE) inhibitors and ARBs [angiotensin II receptor blockers] are beneficial in patients with CKD and in particular those with heavier albuminuria,” she continued. “We’ve known this for over 20 years.”

Yet, the study identified underutilization – “a persistent gap, just like blood pressure control and awareness,” she noted. “We’re just not making much headway.

“We are not recommending ACE inhibitors or ARBs for all the patients,” Dr. Cheung clarified. “If you are diabetic and have heavy proteinuria, that’s when the use of ACE inhibitors and ARBs are most indicated.”
 

Public health implications

SPRINT showed that treating to a systolic blood pressure of less than 120 mm Hg vs. less than 140 mm Hg reduced the risk for cardiovascular disease by 25% and all-cause mortality by 27% for participants with and those without CKD, Dr. Foti and colleagues stress.

They aimed to estimate how the new guideline would affect (1) the number of U.S. patients with CKD who would be eligible for blood pressure lowering treatment, and (2) the proportion of those with albuminuria who would be eligible for an ACE inhibitor or an ARB.

The researchers analyzed data from 1,699 adults with CKD (estimated glomerular filtration rate, 15-59 mL/min/1.73 m² or a urinary albumin-to-creatinine ratio of ≥30 mg/g) who participated in the 2015-2018 National Health and Nutrition Examination Survey.

Both the 2021 and 2012 KDIGO guidelines recommend that patients with albuminuria and blood pressure higher than the target value who are not kidney transplant recipients should be treated with an ACE inhibitor or an ARB.

On the basis of the new target, 78% of patients with CKD and albuminuria were eligible for ACE inhibitor/ARB treatment by the 2021 KDIGO guideline, compared with 71% by the 2012 KDIGO guideline. However, only 39% were taking one of these drugs.

These findings show that “with the new guideline and with the lower blood pressure target, you potentially have an even larger pool of people who have blood pressure that’s not under control, and a potential larger group of people who may benefit from ACE inhibitors and ARBs,” Dr. Chang said.

“Our paper is not the only one to show that we haven’t made a whole lot of progress,” she said, “and now that the bar has been lowered, there [have] to be some renewed efforts on controlling blood pressure, because we know that blood pressure control is such an important risk factor for cardiovascular outcomes.”

Dr. Foti is supported by an NIH/National Heart, Lung, and Blood Institute grant. Dr. Cheung has received consultancy fees from Amgen, Bard, Boehringer Ingelheim, Calliditas, Tricida, and UpToDate, and grant/research support from the National Institutes of Health for SPRINT (monies paid to institution). Dr. Chang has received consultancy fees from Bayer, Gilead, Janssen Research and Development, Novo Nordisk, Tricida, and Vascular Dynamics; grant/research support from AstraZeneca and Satellite Healthcare (monies paid to institution), the NIH, and the American Heart Association; is on advisory boards for AstraZeneca and Fresenius Medical Care Renal Therapies Group; and has received workshop honoraria from Fresenius. Disclosures of relevant financial relationships of the other authors are listed in the original articles.

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

The new 2021 Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guideline for blood pressure management for adults with chronic kidney disease (CKD) who are not receiving dialysis advises treating to a target systolic blood pressure of less than 120 mm Hg, provided measurements are “standardized” and that blood pressure is “measured properly.”

This blood pressure target – largely based on evidence from the Systolic Blood Pressure Intervention Trial (SPRINT) – represents “a major update” from the 2012 KDIGO guideline, which advised clinicians to treat to a target blood pressure of less than or equal to 130/80 mm Hg for patients with albuminuria or less than or equal to 140/90 mm Hg for patients without albuminuria.

The new goal is also lower than the less than 130/80 mm Hg target in the 2017 American College of Cardiology/American Heart Association guideline.

In a study of the public health implications of the guideline, Kathryn Foti, PhD, and colleagues determined that 70% of U.S. adults with CKD would now be eligible for treatment to lower blood pressure, as opposed to 50% under the previous KDIGO guideline and 56% under the ACC/AHA guideline.

“This is a major update of an influential set of guidelines for chronic kidney disease patients” at a time when blood pressure control is worsening in the United States, Dr. Foti, a postdoctoral researcher in the department of epidemiology at Johns Hopkins Bloomberg School of Public Health, Baltimore, said in a statement from her institution.

The 2021 KDIGO blood pressure guideline and executive summary and the public health implications study are published online in Kidney International.
 

First, ‘take blood pressure well’

The cochair of the new KDIGO guidelines, Alfred K. Cheung, MD, from the University of Utah, Salt Lake City, said in an interview that the guideline has “two important points.”

First, “take that blood pressure well,” he said. “That has a lot to do with patient preparation rather than any fancy instrument,” he emphasized.

Second, the guideline proposes a systolic blood pressure target of less than 120 mm Hg for most people with CKD not receiving dialysis, except for children and kidney transplant recipients. This target is “contingent on ‘standardized’ blood pressure measurement.”

The document provides a checklist for obtaining a standardized blood pressure measurement, adapted from the 2017 ACC/AHA blood pressure guidelines. It starts with the patient relaxed and sitting on a chair for more than 5 minutes.

In contrast to this measurement, a “routine” or “casual” office blood pressure measurement could be off by plus or minus 10 mm Hg, Dr. Cheung noted.

In a typical scenario, he continued, a patient cannot find a place to park, rushes into the clinic, and has his or her blood pressure checked right away, which would provide a “totally unreliable” reading. Adding a “fudge factor” (correction factor) would not provide an accurate reading.

Clinicians “would not settle for a potassium measurement that is 5.0 mmol/L plus or minus a few decimal points” to guide treatment, he pointed out.
 

Second, target 120, properly measured

“The very first chapter of the guidelines is devoted to blood pressure measurement, because we recognize if we’re going to do 120 [mm Hg] – the emphasis is on 120 measured properly – so we try to drive that point home,” Tara I. Chang, MD, guideline second author and a coauthor of the public health implications study, pointed out in an interview.

“There are a lot of other things that we base clinical decisions on where we really require some degree of precision, and blood pressure is important enough that to us it’s kind of in the same boat,” said Dr. Chang, from Stanford (Calif.) University.

“In SPRINT, people were randomized to less than less than 120 vs. less than 140 (they weren’t randomized to <130),” she noted.

“The recommendation should be widely adopted in clinical practice,” the guideline authors write, “since accurate measurements will ensure that proper guidance is being applied to the management of BP, as it is to the management of other risk factors.”
 

Still need individual treatment

Nevertheless, patients still need individualized treatment, the document stresses. “Not every patient with CKD will be appropriate to target to less than 120,” Dr. Chang said. However, “we want people to at least consider less than 120,” she added, to avoid therapeutic inertia.

“If you take the blood pressure in a standardized manner – such as in the ACCORD trial and in the SPRINT trial – even patients over 75 years old, or people over 80 years old, they have very little side effects,” Dr. Cheung noted.

“In the overall cohort,” he continued, “they do not have a significant increase in serious adverse events, do not have adverse events of postural hypotension, syncope, bradycardia, injurious falls – so people are worried about it, but it’s not borne out by the data.

“That said, I have two cautions,” Dr. Cheung noted. “One. If you drop somebody’s blood pressure rapidly over a week, you may be more likely to get in trouble. If you drop the blood pressure gradually over several weeks, several months, you’re much less likely to get into trouble.”

“Two. If the patient is old, you know the patient has carotid stenosis and already has postural dizziness, you may not want to try on that patient – but just because the patient is old is not the reason not to target 120.”
 

ACE inhibitors and ARBs beneficial in albuminuria, underused

“How do you get to less than 120? The short answer is, use whatever medications you need to – there is no necessarily right cocktail,” Dr. Chang said.

“We’ve known that angiotensin-converting enzyme (ACE) inhibitors and ARBs [angiotensin II receptor blockers] are beneficial in patients with CKD and in particular those with heavier albuminuria,” she continued. “We’ve known this for over 20 years.”

Yet, the study identified underutilization – “a persistent gap, just like blood pressure control and awareness,” she noted. “We’re just not making much headway.

“We are not recommending ACE inhibitors or ARBs for all the patients,” Dr. Cheung clarified. “If you are diabetic and have heavy proteinuria, that’s when the use of ACE inhibitors and ARBs are most indicated.”
 

Public health implications

SPRINT showed that treating to a systolic blood pressure of less than 120 mm Hg vs. less than 140 mm Hg reduced the risk for cardiovascular disease by 25% and all-cause mortality by 27% for participants with and those without CKD, Dr. Foti and colleagues stress.

They aimed to estimate how the new guideline would affect (1) the number of U.S. patients with CKD who would be eligible for blood pressure lowering treatment, and (2) the proportion of those with albuminuria who would be eligible for an ACE inhibitor or an ARB.

The researchers analyzed data from 1,699 adults with CKD (estimated glomerular filtration rate, 15-59 mL/min/1.73 m² or a urinary albumin-to-creatinine ratio of ≥30 mg/g) who participated in the 2015-2018 National Health and Nutrition Examination Survey.

Both the 2021 and 2012 KDIGO guidelines recommend that patients with albuminuria and blood pressure higher than the target value who are not kidney transplant recipients should be treated with an ACE inhibitor or an ARB.

On the basis of the new target, 78% of patients with CKD and albuminuria were eligible for ACE inhibitor/ARB treatment by the 2021 KDIGO guideline, compared with 71% by the 2012 KDIGO guideline. However, only 39% were taking one of these drugs.

These findings show that “with the new guideline and with the lower blood pressure target, you potentially have an even larger pool of people who have blood pressure that’s not under control, and a potential larger group of people who may benefit from ACE inhibitors and ARBs,” Dr. Chang said.

“Our paper is not the only one to show that we haven’t made a whole lot of progress,” she said, “and now that the bar has been lowered, there [have] to be some renewed efforts on controlling blood pressure, because we know that blood pressure control is such an important risk factor for cardiovascular outcomes.”

Dr. Foti is supported by an NIH/National Heart, Lung, and Blood Institute grant. Dr. Cheung has received consultancy fees from Amgen, Bard, Boehringer Ingelheim, Calliditas, Tricida, and UpToDate, and grant/research support from the National Institutes of Health for SPRINT (monies paid to institution). Dr. Chang has received consultancy fees from Bayer, Gilead, Janssen Research and Development, Novo Nordisk, Tricida, and Vascular Dynamics; grant/research support from AstraZeneca and Satellite Healthcare (monies paid to institution), the NIH, and the American Heart Association; is on advisory boards for AstraZeneca and Fresenius Medical Care Renal Therapies Group; and has received workshop honoraria from Fresenius. Disclosures of relevant financial relationships of the other authors are listed in the original articles.

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

New pills to treat patients with COVID-19 are currently in midstage clinical trials and, if successful, could be ready by the end of the year.

Only one treatment – remdesivir (Veklury) – has been fully approved by the U.S. Food and Drug Administration for patients in the hospital and it must be administered intravenously.

Hopes for a day when patients with COVID-19 can take a pill to rid their bodies of the virus got a boost when early trial results were presented at a medical conference.

Interim phase 2 results for the oral experimental COVID-19 drug molnupiravir, designed to do for patients with COVID-19 what oseltamivir (Tamiflu) can do for patients with the flu, were presented at the Conference on Retroviruses and Opportunistic Infections 2021 Annual Meeting, as reported by this news organization.

In the small study, the pill significantly reduced infectious virus in patients who were symptomatic and had tested positive for COVID-19 during the previous 4 days but were not hospitalized.

After 5 days of treatment, no participants who received molnupiravir had detectable virus, whereas 24% who received placebo did.

Two other oral agents are being developed by RedHill Biopharma: one for severe COVID-19 infection for hospitalized patients and one for patients at home with mild infection.

The first, opaganib (Yeliva), proceeded to a phase 2/3 global trial for hospitalized patients after the company announced top-line safety and efficacy data in December. In phase 2, the drug was shown to be safe in patients requiring oxygen and effectively reduced the need for oxygen by the end of the treatment period.

A key feature is that it is both an antiviral and an anti-inflammatory, Gilead Raday, RedHill’s chief operating officer, said in an interview. Data are expected midyear on its performance in 464 patients. The drug is being tested on top of remdesivir or in addition to dexamethasone.

The second, upamostat (RHB-107), is currently undergoing a phase 2/3 trial in the United States and is being investigated for use in nonhospitalized COVID-19 patients.

“I would expect data to be available in the second half of this year,” Mr. Raday said.

Upamostat is a novel serine protease inhibitor expected to be effective against emerging variants because it targets human cell factors involved in viral entry, according to the company.

Other drugs are being investigated in trials that are in earlier stages.
 

Urgent need for oral agents

Infectious disease specialists are watching the move toward a COVID-19 pill enthusiastically.

“We badly need an oral treatment option for COVID,” said Sarah Doernberg, MD, an infectious disease specialist from the University of California, San Francisco.

“It’s a real gap in our armamentarium for COVID in outpatient treatment, which is where most who contract COVID-19 will seek care,” she said in an interview.

Although some studies have shown the benefit of monoclonal antibodies for prevention and early treatment, there are major logistical issues because all the current options require IV administration, she explained.

“If we had a pill to treat early COVID, especially in high-risk patients, it would fill a gap,” she said, noting that a pill could help people get better faster and prevent hospital stays.

Studies of molnupiravir suggest that it decreases viral shedding in the first few days after COVID infection, Dr. Doernberg reported.

There is excitement around the drug, but it will be important to see whether the results translate into fewer people requiring hospital admission and whether people feel better faster.

“I want to see the clinical data,” Dr. Doernberg said.

She will also be watching for the upamostat and opaganib results in the coming weeks.

“If these drugs are successful, I think it’s possible we could use them – maybe under an emergency use authorization – this year,” she said.

Once antiviral pills are a viable option for COVID-19 treatment, questions will arise about their use, she said.

One question is whether patients who are getting remdesivir in the hospital and are ready to leave after 5 days should continue treatment with antiviral pills at home.

Another is whether the pills – if they are shown to be effective – will be helpful for COVID post exposure. That use would be important for people who do not have COVID-19 but who are in close contact with someone who does, such as a member of their household.

“We have that model,” Dr. Doernberg said. “We know that oseltamivir can be used for postexposure prophylaxis and can help to prevent development of clinical disease.”

But she cautioned that a challenge with COVID is that people are contagious very early. A pill would need to come with the ability to test for COVID-19 early and get patients linked to care immediately.

“Those are not small challenges,” she said.
 

Vaccines alone won’t end the COVID threat

Treatments are part of the “belt-and-suspenders” approach, along with vaccines to combat COVID-19, Dr. Doernberg said.

“We’re not going to eradicate COVID,” she said. “We’re still going to need treatments for people who either don’t respond to the vaccine or haven’t gotten the vaccine or developed disease despite the vaccine.”

Oral formulations are desperately needed, agreed Kenneth Johnson, PhD, professor of molecular biosciences at the University of Texas at Austin.

Right now, remdesivir treatments involve patients being hooked up to an IV for 30-120 minutes each day for 5 days. And the cost of a 5-day course of remdesivir ranges from $2340 to $3120 in the United States.

“We’re hoping we can come up with something that is a little bit easier to administer, and without as many concerns for toxic side effects,” he said.

Dr. Johnson’s team at UT-Austin recently made a key discovery about the way remdesivir stops the replication of viral RNA.

The understanding of where the virus starts to replicate in the infection chain of events and how and where it reacts with remdesivir might lead to the development of better, more concentrated pill forms of antivirals in the future, with fewer toxicities, he said.

The team used a lab dish to recreate the step-by-step process that occurs when a patient who is infected with SARS-CoV-2 receives remdesivir.

The discovery was published online in Molecular Cell in January and will be printed in the April issue of the journal.

The discovery won’t lead to an effective COVID-19 pill for our current crisis, but will be important for the next generation of drugs needed to deal with future coronaviruses, Dr. Johnson explained.

And there will be other coronaviruses, he said, noting that this one is the third in 20 years to jump from animals to humans. “It’s just a matter of time,” he said.

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

New pills to treat patients with COVID-19 are currently in midstage clinical trials and, if successful, could be ready by the end of the year.

Only one treatment – remdesivir (Veklury) – has been fully approved by the U.S. Food and Drug Administration for patients in the hospital and it must be administered intravenously.

Hopes for a day when patients with COVID-19 can take a pill to rid their bodies of the virus got a boost when early trial results were presented at a medical conference.

Interim phase 2 results for the oral experimental COVID-19 drug molnupiravir, designed to do for patients with COVID-19 what oseltamivir (Tamiflu) can do for patients with the flu, were presented at the Conference on Retroviruses and Opportunistic Infections 2021 Annual Meeting, as reported by this news organization.

In the small study, the pill significantly reduced infectious virus in patients who were symptomatic and had tested positive for COVID-19 during the previous 4 days but were not hospitalized.

After 5 days of treatment, no participants who received molnupiravir had detectable virus, whereas 24% who received placebo did.

Two other oral agents are being developed by RedHill Biopharma: one for severe COVID-19 infection for hospitalized patients and one for patients at home with mild infection.

The first, opaganib (Yeliva), proceeded to a phase 2/3 global trial for hospitalized patients after the company announced top-line safety and efficacy data in December. In phase 2, the drug was shown to be safe in patients requiring oxygen and effectively reduced the need for oxygen by the end of the treatment period.

A key feature is that it is both an antiviral and an anti-inflammatory, Gilead Raday, RedHill’s chief operating officer, said in an interview. Data are expected midyear on its performance in 464 patients. The drug is being tested on top of remdesivir or in addition to dexamethasone.

The second, upamostat (RHB-107), is currently undergoing a phase 2/3 trial in the United States and is being investigated for use in nonhospitalized COVID-19 patients.

“I would expect data to be available in the second half of this year,” Mr. Raday said.

Upamostat is a novel serine protease inhibitor expected to be effective against emerging variants because it targets human cell factors involved in viral entry, according to the company.

Other drugs are being investigated in trials that are in earlier stages.
 

Urgent need for oral agents

Infectious disease specialists are watching the move toward a COVID-19 pill enthusiastically.

“We badly need an oral treatment option for COVID,” said Sarah Doernberg, MD, an infectious disease specialist from the University of California, San Francisco.

“It’s a real gap in our armamentarium for COVID in outpatient treatment, which is where most who contract COVID-19 will seek care,” she said in an interview.

Although some studies have shown the benefit of monoclonal antibodies for prevention and early treatment, there are major logistical issues because all the current options require IV administration, she explained.

“If we had a pill to treat early COVID, especially in high-risk patients, it would fill a gap,” she said, noting that a pill could help people get better faster and prevent hospital stays.

Studies of molnupiravir suggest that it decreases viral shedding in the first few days after COVID infection, Dr. Doernberg reported.

There is excitement around the drug, but it will be important to see whether the results translate into fewer people requiring hospital admission and whether people feel better faster.

“I want to see the clinical data,” Dr. Doernberg said.

She will also be watching for the upamostat and opaganib results in the coming weeks.

“If these drugs are successful, I think it’s possible we could use them – maybe under an emergency use authorization – this year,” she said.

Once antiviral pills are a viable option for COVID-19 treatment, questions will arise about their use, she said.

One question is whether patients who are getting remdesivir in the hospital and are ready to leave after 5 days should continue treatment with antiviral pills at home.

Another is whether the pills – if they are shown to be effective – will be helpful for COVID post exposure. That use would be important for people who do not have COVID-19 but who are in close contact with someone who does, such as a member of their household.

“We have that model,” Dr. Doernberg said. “We know that oseltamivir can be used for postexposure prophylaxis and can help to prevent development of clinical disease.”

But she cautioned that a challenge with COVID is that people are contagious very early. A pill would need to come with the ability to test for COVID-19 early and get patients linked to care immediately.

“Those are not small challenges,” she said.
 

Vaccines alone won’t end the COVID threat

Treatments are part of the “belt-and-suspenders” approach, along with vaccines to combat COVID-19, Dr. Doernberg said.

“We’re not going to eradicate COVID,” she said. “We’re still going to need treatments for people who either don’t respond to the vaccine or haven’t gotten the vaccine or developed disease despite the vaccine.”

Oral formulations are desperately needed, agreed Kenneth Johnson, PhD, professor of molecular biosciences at the University of Texas at Austin.

Right now, remdesivir treatments involve patients being hooked up to an IV for 30-120 minutes each day for 5 days. And the cost of a 5-day course of remdesivir ranges from $2340 to $3120 in the United States.

“We’re hoping we can come up with something that is a little bit easier to administer, and without as many concerns for toxic side effects,” he said.

Dr. Johnson’s team at UT-Austin recently made a key discovery about the way remdesivir stops the replication of viral RNA.

The understanding of where the virus starts to replicate in the infection chain of events and how and where it reacts with remdesivir might lead to the development of better, more concentrated pill forms of antivirals in the future, with fewer toxicities, he said.

The team used a lab dish to recreate the step-by-step process that occurs when a patient who is infected with SARS-CoV-2 receives remdesivir.

The discovery was published online in Molecular Cell in January and will be printed in the April issue of the journal.

The discovery won’t lead to an effective COVID-19 pill for our current crisis, but will be important for the next generation of drugs needed to deal with future coronaviruses, Dr. Johnson explained.

And there will be other coronaviruses, he said, noting that this one is the third in 20 years to jump from animals to humans. “It’s just a matter of time,” he said.

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

New pills to treat patients with COVID-19 are currently in midstage clinical trials and, if successful, could be ready by the end of the year.

Only one treatment – remdesivir (Veklury) – has been fully approved by the U.S. Food and Drug Administration for patients in the hospital and it must be administered intravenously.

Hopes for a day when patients with COVID-19 can take a pill to rid their bodies of the virus got a boost when early trial results were presented at a medical conference.

Interim phase 2 results for the oral experimental COVID-19 drug molnupiravir, designed to do for patients with COVID-19 what oseltamivir (Tamiflu) can do for patients with the flu, were presented at the Conference on Retroviruses and Opportunistic Infections 2021 Annual Meeting, as reported by this news organization.

In the small study, the pill significantly reduced infectious virus in patients who were symptomatic and had tested positive for COVID-19 during the previous 4 days but were not hospitalized.

After 5 days of treatment, no participants who received molnupiravir had detectable virus, whereas 24% who received placebo did.

Two other oral agents are being developed by RedHill Biopharma: one for severe COVID-19 infection for hospitalized patients and one for patients at home with mild infection.

The first, opaganib (Yeliva), proceeded to a phase 2/3 global trial for hospitalized patients after the company announced top-line safety and efficacy data in December. In phase 2, the drug was shown to be safe in patients requiring oxygen and effectively reduced the need for oxygen by the end of the treatment period.

A key feature is that it is both an antiviral and an anti-inflammatory, Gilead Raday, RedHill’s chief operating officer, said in an interview. Data are expected midyear on its performance in 464 patients. The drug is being tested on top of remdesivir or in addition to dexamethasone.

The second, upamostat (RHB-107), is currently undergoing a phase 2/3 trial in the United States and is being investigated for use in nonhospitalized COVID-19 patients.

“I would expect data to be available in the second half of this year,” Mr. Raday said.

Upamostat is a novel serine protease inhibitor expected to be effective against emerging variants because it targets human cell factors involved in viral entry, according to the company.

Other drugs are being investigated in trials that are in earlier stages.
 

Urgent need for oral agents

Infectious disease specialists are watching the move toward a COVID-19 pill enthusiastically.

“We badly need an oral treatment option for COVID,” said Sarah Doernberg, MD, an infectious disease specialist from the University of California, San Francisco.

“It’s a real gap in our armamentarium for COVID in outpatient treatment, which is where most who contract COVID-19 will seek care,” she said in an interview.

Although some studies have shown the benefit of monoclonal antibodies for prevention and early treatment, there are major logistical issues because all the current options require IV administration, she explained.

“If we had a pill to treat early COVID, especially in high-risk patients, it would fill a gap,” she said, noting that a pill could help people get better faster and prevent hospital stays.

Studies of molnupiravir suggest that it decreases viral shedding in the first few days after COVID infection, Dr. Doernberg reported.

There is excitement around the drug, but it will be important to see whether the results translate into fewer people requiring hospital admission and whether people feel better faster.

“I want to see the clinical data,” Dr. Doernberg said.

She will also be watching for the upamostat and opaganib results in the coming weeks.

“If these drugs are successful, I think it’s possible we could use them – maybe under an emergency use authorization – this year,” she said.

Once antiviral pills are a viable option for COVID-19 treatment, questions will arise about their use, she said.

One question is whether patients who are getting remdesivir in the hospital and are ready to leave after 5 days should continue treatment with antiviral pills at home.

Another is whether the pills – if they are shown to be effective – will be helpful for COVID post exposure. That use would be important for people who do not have COVID-19 but who are in close contact with someone who does, such as a member of their household.

“We have that model,” Dr. Doernberg said. “We know that oseltamivir can be used for postexposure prophylaxis and can help to prevent development of clinical disease.”

But she cautioned that a challenge with COVID is that people are contagious very early. A pill would need to come with the ability to test for COVID-19 early and get patients linked to care immediately.

“Those are not small challenges,” she said.
 

Vaccines alone won’t end the COVID threat

Treatments are part of the “belt-and-suspenders” approach, along with vaccines to combat COVID-19, Dr. Doernberg said.

“We’re not going to eradicate COVID,” she said. “We’re still going to need treatments for people who either don’t respond to the vaccine or haven’t gotten the vaccine or developed disease despite the vaccine.”

Oral formulations are desperately needed, agreed Kenneth Johnson, PhD, professor of molecular biosciences at the University of Texas at Austin.

Right now, remdesivir treatments involve patients being hooked up to an IV for 30-120 minutes each day for 5 days. And the cost of a 5-day course of remdesivir ranges from $2340 to $3120 in the United States.

“We’re hoping we can come up with something that is a little bit easier to administer, and without as many concerns for toxic side effects,” he said.

Dr. Johnson’s team at UT-Austin recently made a key discovery about the way remdesivir stops the replication of viral RNA.

The understanding of where the virus starts to replicate in the infection chain of events and how and where it reacts with remdesivir might lead to the development of better, more concentrated pill forms of antivirals in the future, with fewer toxicities, he said.

The team used a lab dish to recreate the step-by-step process that occurs when a patient who is infected with SARS-CoV-2 receives remdesivir.

The discovery was published online in Molecular Cell in January and will be printed in the April issue of the journal.

The discovery won’t lead to an effective COVID-19 pill for our current crisis, but will be important for the next generation of drugs needed to deal with future coronaviruses, Dr. Johnson explained.

And there will be other coronaviruses, he said, noting that this one is the third in 20 years to jump from animals to humans. “It’s just a matter of time,” he said.

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

Patients with rheumatoid arthritis are often eager to try dietary interventions in an effort to improve their symptoms. For guidance, they turn to their rheumatologists, who typically can offer little in terms of concrete evidence-based recommendations. That’s because their training didn’t emphasize the role of nutrients in rheumatic diseases, the scientific evidence has historically been sketchy, and the topic of diet and disease is rife with fad diets, inflated Internet claims, and hucksterism.

Bruce Jancin/MDedge News

But that’s changing. Indeed, recent annual meetings of the American College of Rheumatology have featured randomized, controlled trials that bring welcome rigor to the field and provide findings of practical interest to clinicians and their patients, Orrin M. Troum, MD, said at the 2021 Rheumatology Winter Clinical Symposium.

He highlighted some of this work, including positive randomized trials of the dietary supplements Biqi – a traditional Chinese herbal medicine – as well as turmeric, along with reported progress in efforts to design a palatable anti-inflammatory diet that favorably alters the gut microbiome and systemic metabolome while improving clinical outcomes in patients with RA.

Dr. Troum, a rheumatologist at the University of Southern California, Los Angeles, and in private practice in Santa Monica, described a typical patient encounter in his clinic that appeared to resonate with his audience from throughout the country: “You can tell people to take another medicine and they’ll start shaking their head no before you’re finished. But when you say there are natural supplements that can help you, they’re saying ‘Yes!’ ”
 

RA improvement on an ITIS diet

Many physicians recommend a Mediterranean-style diet, first popularized in the landmark Seven Countries Study launched by the late Dr. Ancel Keys. This familiar plant-based regimen emphasizes liberal consumption of extra-virgin olive oil, legumes, fruits and vegetables, whole grains, fish, nuts, and moderate alcohol intake, with very limited intake of red and processed meats, refined grains, and sugar. There is strong evidence that the Mediterranean diet is cardioprotective, which is relevant to patients with RA since they are known to be at elevated cardiovascular risk.

However, investigators at the University of California, San Diego, became convinced that the Mediterranean diet is lacking in key anti-inflammatory ingredients from other parts of the world. These include ginger, green tea, black pepper, turmeric, miso, flax seeds, and tahini, all of which are backed by evidence – from animal models and/or interventional diet studies in patients – that suggests beneficial effects in pain and joint swelling in RA. The researchers also suspected that certain vegetables embraced in the Mediterranean diet – notably eggplant, tomatoes, and potatoes – might be problematic for RA patients because they contain solanine, thought to increase intestinal permeability, which might have arthritogenic effects on the gut microbiome.

The investigators set out to develop an anti-inflammatory diet they call the ITIS diet, essentially tweaking the Mediterranean-style diet by incorporating these additions and subtractions. Importantly, they designed the ITIS diet in conjunction with a multiracial local group of RA patients strongly enthusiastic about the potential for dietary interventions aimed at improving their symptoms. The patients provided feedback that enabled the investigators to fine-tune the anti-inflammatory diet so as to boost palatability and acceptance.

As an illustrative example of the ITIS diet, a typical day might start off with a homemade smoothie of parsley, pineapple, strawberries, and water, followed by a breakfast consisting of one or two corn tortillas spread with avocado, linseed oil, and sesame seeds, accompanied by green tea. Following a mid-morning snack of plain Greek-style yogurt, lunch might be a choice of a large salad, legumes with vegetables, or whole grains with vegetables. For the afternoon snack: four walnuts plus mango, banana, pear, papaya, apple, or pineapple. And for dinner, the options are vegetable soup and a protein; salad plus a protein; or miso soup, cooked vegetables, and a protein.

At the 2020 ACR annual meeting, Roxana Coras, MD, presented the positive findings of an open-label, pilot study of the ITIS diet in which 17 patients with active RA involving at least three tender and three swollen joints adopted the diet for 2 weeks . The ITIS diet turned out to be not too much of a stretch for Southern California RA patients interested in dietary complementary and alternative medicine. Many had already adopted some elements of the anti-inflammatory diet. Dietary adherence in the study was good, as monitored in food logs and by mass spectrometry metabolic profiling of fecal and plasma samples.

Eleven patients were categorized as responders to the anti-inflammatory diet as defined by at least a 50% improvement in pain scores from baseline to 2 weeks; six patients were nonresponders. In the overall study population, mean pain scores on a 0-10 visual analog scale improved from 3.9 to 2.45. Scores on the Clinical Disease Activity Index (CDAI) also improved significantly on the ITIS diet, from 29 to 12.7, reported Dr. Coras, a rheumatologist at the University of California, San Diego.

The mechanisms for the clinical improvement on the diet are under study. Significant differences in the gut microbiome and metabolome were seen between the responders and nonresponders. For example, Mollicutes were increased and Coriobacteriales decreased in clinical responders versus nonresponders. A significant increase in circulating levels of anti-inflammatory oxylipins was also seen in responders. Longer-term controlled studies of the ITIS diet are planned.

Biqi is big in China, gaining ground in the U.S.

Ayurvedic medicine in India and Chinese traditional herbal medicine have richly documented 4,500-year histories.

“It’s so common in my neck of the woods, where there are large Asian communities, for Chinese or Korean or Japanese or Indian medicines to be combined with our medicines. And if you don’t ask about them, you’re never going to find out what these patients are taking,” Dr. Troum said.

If they’re taking Biqi capsules, readily available on the Internet, be advised that there is randomized trial evidence to show that they’re using an efficacious and safe herbal medicine for RA. In China, the combination of Biqi capsules and a conventional disease-modifying antirheumatic drug such as methotrexate is now widely used for treatment of RA. And at the 2019 ACR annual meeting, Runyue Huang, MD, of Guangzhou University of Chinese Medicine, presented the results of a 24-week, randomized, multicenter, open-label clinical trial in which 70 RA patients were assigned to methotrexate plus a 1.2-g Biqi capsule twice daily or to methotrexate plus leflunomide (Arava) at 20 mg/day. The primary outcome – achievement of a 20% improvement in the ACR criteria, or ACR20 response, at week 24 – was achieved in 77% of the Biqi group, not significantly different from the 83% rate in the comparator group. However, the Biqi plus methotrexate group had significantly fewer adverse events and the combination was better tolerated than was leflunomide plus methotrexate.

In addition, a systematic review of earlier clinical trials concluded that Biqi in combination with methotrexate was more effective and had fewer adverse events than methotrexate alone.

“Biqi capsule with methotrexate appears to be a promising combination for RA if you can rest assured that what’s found in the Biqi capsule is exactly what they say. And that’s the main issue: You don’t really know what you’re getting unless it’s in a trial,” Dr. Troum said.

American RA patients embrace turmeric

Turmeric has played a prominent role in Ayurvedic medicine for millenia. The most medicinally important component of turmeric root is curcumin, which has potent anti-inflammatory and antioxidant properties. Americans with RA have gotten on the bandwagon, as demonstrated in a survey of 291 patients with RA or psoriatic arthritis presented at ACR 2020 by investigators from the University of Central Florida, Orlando. Among the respondents, 37% reported having taken curcumin, with no predilection based upon age, gender, or diagnosis. Fifty-nine percent took their curcumin in the form of capsules, with the rest took it as an oil or powder. Fifty-four percent got their curcumin at a local store.

Thirty-six percent of curcumin users reported improvement in pain after going on the herbal supplement. Twenty-five percent reported reduced swelling, 23% had less stiffness, and 16% reported improvement in fatigue. Patients taking 200-1,000 mg/day reported significantly greater improvement in symptoms than that of those taking less than 200 mg/day. Onset of benefits was slow: Patients on curcumin for a year or longer reported greater symptomatic improvement than did those on the supplement for less time.

Asked what he recommends to his RA patients who express interest in supplements aimed at achieving symptomatic improvement, Dr. Troum replied that he’s comfortable suggesting curcumin capsules at 500 mg twice daily, which should be labeled as containing black pepper extract to aid in absorption. He also recommends fish oil both for its cardioprotective benefits and because of randomized trial evidence that it enhances the chances of achieving ACR remission in patients on conventional disease-modifying antirheumatic drugs.
 

What about osteoarthritis?

Investigators with the National Institutes of Health–sponsored Osteoarthritis Initiative found in an analysis of the dietary patterns of 2,757 patients with mild to moderate knee OA who were followed annually for 6 years that participants could be grouped into two broad categories: Those who consumed what was termed the prudent diet, with high intake of fruits and vegetables, legumes, fish, and whole grains; and fans of the Western diet, characterized by lots of red meat, refined grains, and liberal consumption of French fries. Knee symptoms increased over time in dose-response fashion with greater adherence to the Western diet and decreased with higher prudent diet scores.

Also at ACR 2019, Australian investigators presented the results of the double-blind CurKOA trial, in which 70 participants with knee OA and moderate baseline effusion/synovitis by ultrasound were randomized to take a capsule containing 500 mg of turmeric root extract or identical placebo twice daily for 12 weeks. The group on turmeric plant extract experienced 9.11-mm greater reduction in knee pain on a 0- to 100-mm visual analog scale than did controls, which translates to a moderate standard effect size deemed by investigators to be “greater than other conventional pharmacologic therapies.” Overall, 63% of the turmeric group achieved a treatment response by OARSI-OMERACT criteria, a significantly better outcome than the 38% rate in controls. However, there was no significant between-group difference in knee structural measures as assessed by MRI in this relatively brief trial.

Anne M. Stevens, MD, PhD, senior director of immunology translational medicine at Janssen Pharmaceuticals and a pediatric rheumatologist at Seattle Children’s Hospital, rose from the audience to share that she recommends that her patients on high-dose curcumin not take NSAIDs because the two share a similar mechanism of action involving COX-2 inhibition, and the combination might therefore increase bleeding risk. But Dr. Troum said he hasn’t seen any increase in bleeding in his patients on both agents.

Dr. Troum has financial relationships with numerous pharmaceutical companies, but reported having no financial conflicts of interest regarding his presentation.
 

bjancin@mdedge.com

Patients with rheumatoid arthritis are often eager to try dietary interventions in an effort to improve their symptoms. For guidance, they turn to their rheumatologists, who typically can offer little in terms of concrete evidence-based recommendations. That’s because their training didn’t emphasize the role of nutrients in rheumatic diseases, the scientific evidence has historically been sketchy, and the topic of diet and disease is rife with fad diets, inflated Internet claims, and hucksterism.

Bruce Jancin/MDedge News

But that’s changing. Indeed, recent annual meetings of the American College of Rheumatology have featured randomized, controlled trials that bring welcome rigor to the field and provide findings of practical interest to clinicians and their patients, Orrin M. Troum, MD, said at the 2021 Rheumatology Winter Clinical Symposium.

He highlighted some of this work, including positive randomized trials of the dietary supplements Biqi – a traditional Chinese herbal medicine – as well as turmeric, along with reported progress in efforts to design a palatable anti-inflammatory diet that favorably alters the gut microbiome and systemic metabolome while improving clinical outcomes in patients with RA.

Dr. Troum, a rheumatologist at the University of Southern California, Los Angeles, and in private practice in Santa Monica, described a typical patient encounter in his clinic that appeared to resonate with his audience from throughout the country: “You can tell people to take another medicine and they’ll start shaking their head no before you’re finished. But when you say there are natural supplements that can help you, they’re saying ‘Yes!’ ”
 

RA improvement on an ITIS diet

Many physicians recommend a Mediterranean-style diet, first popularized in the landmark Seven Countries Study launched by the late Dr. Ancel Keys. This familiar plant-based regimen emphasizes liberal consumption of extra-virgin olive oil, legumes, fruits and vegetables, whole grains, fish, nuts, and moderate alcohol intake, with very limited intake of red and processed meats, refined grains, and sugar. There is strong evidence that the Mediterranean diet is cardioprotective, which is relevant to patients with RA since they are known to be at elevated cardiovascular risk.

However, investigators at the University of California, San Diego, became convinced that the Mediterranean diet is lacking in key anti-inflammatory ingredients from other parts of the world. These include ginger, green tea, black pepper, turmeric, miso, flax seeds, and tahini, all of which are backed by evidence – from animal models and/or interventional diet studies in patients – that suggests beneficial effects in pain and joint swelling in RA. The researchers also suspected that certain vegetables embraced in the Mediterranean diet – notably eggplant, tomatoes, and potatoes – might be problematic for RA patients because they contain solanine, thought to increase intestinal permeability, which might have arthritogenic effects on the gut microbiome.

The investigators set out to develop an anti-inflammatory diet they call the ITIS diet, essentially tweaking the Mediterranean-style diet by incorporating these additions and subtractions. Importantly, they designed the ITIS diet in conjunction with a multiracial local group of RA patients strongly enthusiastic about the potential for dietary interventions aimed at improving their symptoms. The patients provided feedback that enabled the investigators to fine-tune the anti-inflammatory diet so as to boost palatability and acceptance.

As an illustrative example of the ITIS diet, a typical day might start off with a homemade smoothie of parsley, pineapple, strawberries, and water, followed by a breakfast consisting of one or two corn tortillas spread with avocado, linseed oil, and sesame seeds, accompanied by green tea. Following a mid-morning snack of plain Greek-style yogurt, lunch might be a choice of a large salad, legumes with vegetables, or whole grains with vegetables. For the afternoon snack: four walnuts plus mango, banana, pear, papaya, apple, or pineapple. And for dinner, the options are vegetable soup and a protein; salad plus a protein; or miso soup, cooked vegetables, and a protein.

At the 2020 ACR annual meeting, Roxana Coras, MD, presented the positive findings of an open-label, pilot study of the ITIS diet in which 17 patients with active RA involving at least three tender and three swollen joints adopted the diet for 2 weeks . The ITIS diet turned out to be not too much of a stretch for Southern California RA patients interested in dietary complementary and alternative medicine. Many had already adopted some elements of the anti-inflammatory diet. Dietary adherence in the study was good, as monitored in food logs and by mass spectrometry metabolic profiling of fecal and plasma samples.

Eleven patients were categorized as responders to the anti-inflammatory diet as defined by at least a 50% improvement in pain scores from baseline to 2 weeks; six patients were nonresponders. In the overall study population, mean pain scores on a 0-10 visual analog scale improved from 3.9 to 2.45. Scores on the Clinical Disease Activity Index (CDAI) also improved significantly on the ITIS diet, from 29 to 12.7, reported Dr. Coras, a rheumatologist at the University of California, San Diego.

The mechanisms for the clinical improvement on the diet are under study. Significant differences in the gut microbiome and metabolome were seen between the responders and nonresponders. For example, Mollicutes were increased and Coriobacteriales decreased in clinical responders versus nonresponders. A significant increase in circulating levels of anti-inflammatory oxylipins was also seen in responders. Longer-term controlled studies of the ITIS diet are planned.

Biqi is big in China, gaining ground in the U.S.

Ayurvedic medicine in India and Chinese traditional herbal medicine have richly documented 4,500-year histories.

“It’s so common in my neck of the woods, where there are large Asian communities, for Chinese or Korean or Japanese or Indian medicines to be combined with our medicines. And if you don’t ask about them, you’re never going to find out what these patients are taking,” Dr. Troum said.

If they’re taking Biqi capsules, readily available on the Internet, be advised that there is randomized trial evidence to show that they’re using an efficacious and safe herbal medicine for RA. In China, the combination of Biqi capsules and a conventional disease-modifying antirheumatic drug such as methotrexate is now widely used for treatment of RA. And at the 2019 ACR annual meeting, Runyue Huang, MD, of Guangzhou University of Chinese Medicine, presented the results of a 24-week, randomized, multicenter, open-label clinical trial in which 70 RA patients were assigned to methotrexate plus a 1.2-g Biqi capsule twice daily or to methotrexate plus leflunomide (Arava) at 20 mg/day. The primary outcome – achievement of a 20% improvement in the ACR criteria, or ACR20 response, at week 24 – was achieved in 77% of the Biqi group, not significantly different from the 83% rate in the comparator group. However, the Biqi plus methotrexate group had significantly fewer adverse events and the combination was better tolerated than was leflunomide plus methotrexate.

In addition, a systematic review of earlier clinical trials concluded that Biqi in combination with methotrexate was more effective and had fewer adverse events than methotrexate alone.

“Biqi capsule with methotrexate appears to be a promising combination for RA if you can rest assured that what’s found in the Biqi capsule is exactly what they say. And that’s the main issue: You don’t really know what you’re getting unless it’s in a trial,” Dr. Troum said.

American RA patients embrace turmeric

Turmeric has played a prominent role in Ayurvedic medicine for millenia. The most medicinally important component of turmeric root is curcumin, which has potent anti-inflammatory and antioxidant properties. Americans with RA have gotten on the bandwagon, as demonstrated in a survey of 291 patients with RA or psoriatic arthritis presented at ACR 2020 by investigators from the University of Central Florida, Orlando. Among the respondents, 37% reported having taken curcumin, with no predilection based upon age, gender, or diagnosis. Fifty-nine percent took their curcumin in the form of capsules, with the rest took it as an oil or powder. Fifty-four percent got their curcumin at a local store.

Thirty-six percent of curcumin users reported improvement in pain after going on the herbal supplement. Twenty-five percent reported reduced swelling, 23% had less stiffness, and 16% reported improvement in fatigue. Patients taking 200-1,000 mg/day reported significantly greater improvement in symptoms than that of those taking less than 200 mg/day. Onset of benefits was slow: Patients on curcumin for a year or longer reported greater symptomatic improvement than did those on the supplement for less time.

Asked what he recommends to his RA patients who express interest in supplements aimed at achieving symptomatic improvement, Dr. Troum replied that he’s comfortable suggesting curcumin capsules at 500 mg twice daily, which should be labeled as containing black pepper extract to aid in absorption. He also recommends fish oil both for its cardioprotective benefits and because of randomized trial evidence that it enhances the chances of achieving ACR remission in patients on conventional disease-modifying antirheumatic drugs.
 

What about osteoarthritis?

Investigators with the National Institutes of Health–sponsored Osteoarthritis Initiative found in an analysis of the dietary patterns of 2,757 patients with mild to moderate knee OA who were followed annually for 6 years that participants could be grouped into two broad categories: Those who consumed what was termed the prudent diet, with high intake of fruits and vegetables, legumes, fish, and whole grains; and fans of the Western diet, characterized by lots of red meat, refined grains, and liberal consumption of French fries. Knee symptoms increased over time in dose-response fashion with greater adherence to the Western diet and decreased with higher prudent diet scores.

Also at ACR 2019, Australian investigators presented the results of the double-blind CurKOA trial, in which 70 participants with knee OA and moderate baseline effusion/synovitis by ultrasound were randomized to take a capsule containing 500 mg of turmeric root extract or identical placebo twice daily for 12 weeks. The group on turmeric plant extract experienced 9.11-mm greater reduction in knee pain on a 0- to 100-mm visual analog scale than did controls, which translates to a moderate standard effect size deemed by investigators to be “greater than other conventional pharmacologic therapies.” Overall, 63% of the turmeric group achieved a treatment response by OARSI-OMERACT criteria, a significantly better outcome than the 38% rate in controls. However, there was no significant between-group difference in knee structural measures as assessed by MRI in this relatively brief trial.

Anne M. Stevens, MD, PhD, senior director of immunology translational medicine at Janssen Pharmaceuticals and a pediatric rheumatologist at Seattle Children’s Hospital, rose from the audience to share that she recommends that her patients on high-dose curcumin not take NSAIDs because the two share a similar mechanism of action involving COX-2 inhibition, and the combination might therefore increase bleeding risk. But Dr. Troum said he hasn’t seen any increase in bleeding in his patients on both agents.

Dr. Troum has financial relationships with numerous pharmaceutical companies, but reported having no financial conflicts of interest regarding his presentation.
 

bjancin@mdedge.com

Patients with rheumatoid arthritis are often eager to try dietary interventions in an effort to improve their symptoms. For guidance, they turn to their rheumatologists, who typically can offer little in terms of concrete evidence-based recommendations. That’s because their training didn’t emphasize the role of nutrients in rheumatic diseases, the scientific evidence has historically been sketchy, and the topic of diet and disease is rife with fad diets, inflated Internet claims, and hucksterism.

Bruce Jancin/MDedge News

But that’s changing. Indeed, recent annual meetings of the American College of Rheumatology have featured randomized, controlled trials that bring welcome rigor to the field and provide findings of practical interest to clinicians and their patients, Orrin M. Troum, MD, said at the 2021 Rheumatology Winter Clinical Symposium.

He highlighted some of this work, including positive randomized trials of the dietary supplements Biqi – a traditional Chinese herbal medicine – as well as turmeric, along with reported progress in efforts to design a palatable anti-inflammatory diet that favorably alters the gut microbiome and systemic metabolome while improving clinical outcomes in patients with RA.

Dr. Troum, a rheumatologist at the University of Southern California, Los Angeles, and in private practice in Santa Monica, described a typical patient encounter in his clinic that appeared to resonate with his audience from throughout the country: “You can tell people to take another medicine and they’ll start shaking their head no before you’re finished. But when you say there are natural supplements that can help you, they’re saying ‘Yes!’ ”
 

RA improvement on an ITIS diet

Many physicians recommend a Mediterranean-style diet, first popularized in the landmark Seven Countries Study launched by the late Dr. Ancel Keys. This familiar plant-based regimen emphasizes liberal consumption of extra-virgin olive oil, legumes, fruits and vegetables, whole grains, fish, nuts, and moderate alcohol intake, with very limited intake of red and processed meats, refined grains, and sugar. There is strong evidence that the Mediterranean diet is cardioprotective, which is relevant to patients with RA since they are known to be at elevated cardiovascular risk.

However, investigators at the University of California, San Diego, became convinced that the Mediterranean diet is lacking in key anti-inflammatory ingredients from other parts of the world. These include ginger, green tea, black pepper, turmeric, miso, flax seeds, and tahini, all of which are backed by evidence – from animal models and/or interventional diet studies in patients – that suggests beneficial effects in pain and joint swelling in RA. The researchers also suspected that certain vegetables embraced in the Mediterranean diet – notably eggplant, tomatoes, and potatoes – might be problematic for RA patients because they contain solanine, thought to increase intestinal permeability, which might have arthritogenic effects on the gut microbiome.

The investigators set out to develop an anti-inflammatory diet they call the ITIS diet, essentially tweaking the Mediterranean-style diet by incorporating these additions and subtractions. Importantly, they designed the ITIS diet in conjunction with a multiracial local group of RA patients strongly enthusiastic about the potential for dietary interventions aimed at improving their symptoms. The patients provided feedback that enabled the investigators to fine-tune the anti-inflammatory diet so as to boost palatability and acceptance.

As an illustrative example of the ITIS diet, a typical day might start off with a homemade smoothie of parsley, pineapple, strawberries, and water, followed by a breakfast consisting of one or two corn tortillas spread with avocado, linseed oil, and sesame seeds, accompanied by green tea. Following a mid-morning snack of plain Greek-style yogurt, lunch might be a choice of a large salad, legumes with vegetables, or whole grains with vegetables. For the afternoon snack: four walnuts plus mango, banana, pear, papaya, apple, or pineapple. And for dinner, the options are vegetable soup and a protein; salad plus a protein; or miso soup, cooked vegetables, and a protein.

At the 2020 ACR annual meeting, Roxana Coras, MD, presented the positive findings of an open-label, pilot study of the ITIS diet in which 17 patients with active RA involving at least three tender and three swollen joints adopted the diet for 2 weeks . The ITIS diet turned out to be not too much of a stretch for Southern California RA patients interested in dietary complementary and alternative medicine. Many had already adopted some elements of the anti-inflammatory diet. Dietary adherence in the study was good, as monitored in food logs and by mass spectrometry metabolic profiling of fecal and plasma samples.

Eleven patients were categorized as responders to the anti-inflammatory diet as defined by at least a 50% improvement in pain scores from baseline to 2 weeks; six patients were nonresponders. In the overall study population, mean pain scores on a 0-10 visual analog scale improved from 3.9 to 2.45. Scores on the Clinical Disease Activity Index (CDAI) also improved significantly on the ITIS diet, from 29 to 12.7, reported Dr. Coras, a rheumatologist at the University of California, San Diego.

The mechanisms for the clinical improvement on the diet are under study. Significant differences in the gut microbiome and metabolome were seen between the responders and nonresponders. For example, Mollicutes were increased and Coriobacteriales decreased in clinical responders versus nonresponders. A significant increase in circulating levels of anti-inflammatory oxylipins was also seen in responders. Longer-term controlled studies of the ITIS diet are planned.

Biqi is big in China, gaining ground in the U.S.

Ayurvedic medicine in India and Chinese traditional herbal medicine have richly documented 4,500-year histories.

“It’s so common in my neck of the woods, where there are large Asian communities, for Chinese or Korean or Japanese or Indian medicines to be combined with our medicines. And if you don’t ask about them, you’re never going to find out what these patients are taking,” Dr. Troum said.

If they’re taking Biqi capsules, readily available on the Internet, be advised that there is randomized trial evidence to show that they’re using an efficacious and safe herbal medicine for RA. In China, the combination of Biqi capsules and a conventional disease-modifying antirheumatic drug such as methotrexate is now widely used for treatment of RA. And at the 2019 ACR annual meeting, Runyue Huang, MD, of Guangzhou University of Chinese Medicine, presented the results of a 24-week, randomized, multicenter, open-label clinical trial in which 70 RA patients were assigned to methotrexate plus a 1.2-g Biqi capsule twice daily or to methotrexate plus leflunomide (Arava) at 20 mg/day. The primary outcome – achievement of a 20% improvement in the ACR criteria, or ACR20 response, at week 24 – was achieved in 77% of the Biqi group, not significantly different from the 83% rate in the comparator group. However, the Biqi plus methotrexate group had significantly fewer adverse events and the combination was better tolerated than was leflunomide plus methotrexate.

In addition, a systematic review of earlier clinical trials concluded that Biqi in combination with methotrexate was more effective and had fewer adverse events than methotrexate alone.

“Biqi capsule with methotrexate appears to be a promising combination for RA if you can rest assured that what’s found in the Biqi capsule is exactly what they say. And that’s the main issue: You don’t really know what you’re getting unless it’s in a trial,” Dr. Troum said.

American RA patients embrace turmeric

Turmeric has played a prominent role in Ayurvedic medicine for millenia. The most medicinally important component of turmeric root is curcumin, which has potent anti-inflammatory and antioxidant properties. Americans with RA have gotten on the bandwagon, as demonstrated in a survey of 291 patients with RA or psoriatic arthritis presented at ACR 2020 by investigators from the University of Central Florida, Orlando. Among the respondents, 37% reported having taken curcumin, with no predilection based upon age, gender, or diagnosis. Fifty-nine percent took their curcumin in the form of capsules, with the rest took it as an oil or powder. Fifty-four percent got their curcumin at a local store.

Thirty-six percent of curcumin users reported improvement in pain after going on the herbal supplement. Twenty-five percent reported reduced swelling, 23% had less stiffness, and 16% reported improvement in fatigue. Patients taking 200-1,000 mg/day reported significantly greater improvement in symptoms than that of those taking less than 200 mg/day. Onset of benefits was slow: Patients on curcumin for a year or longer reported greater symptomatic improvement than did those on the supplement for less time.

Asked what he recommends to his RA patients who express interest in supplements aimed at achieving symptomatic improvement, Dr. Troum replied that he’s comfortable suggesting curcumin capsules at 500 mg twice daily, which should be labeled as containing black pepper extract to aid in absorption. He also recommends fish oil both for its cardioprotective benefits and because of randomized trial evidence that it enhances the chances of achieving ACR remission in patients on conventional disease-modifying antirheumatic drugs.
 

What about osteoarthritis?

Investigators with the National Institutes of Health–sponsored Osteoarthritis Initiative found in an analysis of the dietary patterns of 2,757 patients with mild to moderate knee OA who were followed annually for 6 years that participants could be grouped into two broad categories: Those who consumed what was termed the prudent diet, with high intake of fruits and vegetables, legumes, fish, and whole grains; and fans of the Western diet, characterized by lots of red meat, refined grains, and liberal consumption of French fries. Knee symptoms increased over time in dose-response fashion with greater adherence to the Western diet and decreased with higher prudent diet scores.

Also at ACR 2019, Australian investigators presented the results of the double-blind CurKOA trial, in which 70 participants with knee OA and moderate baseline effusion/synovitis by ultrasound were randomized to take a capsule containing 500 mg of turmeric root extract or identical placebo twice daily for 12 weeks. The group on turmeric plant extract experienced 9.11-mm greater reduction in knee pain on a 0- to 100-mm visual analog scale than did controls, which translates to a moderate standard effect size deemed by investigators to be “greater than other conventional pharmacologic therapies.” Overall, 63% of the turmeric group achieved a treatment response by OARSI-OMERACT criteria, a significantly better outcome than the 38% rate in controls. However, there was no significant between-group difference in knee structural measures as assessed by MRI in this relatively brief trial.

Anne M. Stevens, MD, PhD, senior director of immunology translational medicine at Janssen Pharmaceuticals and a pediatric rheumatologist at Seattle Children’s Hospital, rose from the audience to share that she recommends that her patients on high-dose curcumin not take NSAIDs because the two share a similar mechanism of action involving COX-2 inhibition, and the combination might therefore increase bleeding risk. But Dr. Troum said he hasn’t seen any increase in bleeding in his patients on both agents.

Dr. Troum has financial relationships with numerous pharmaceutical companies, but reported having no financial conflicts of interest regarding his presentation.
 

bjancin@mdedge.com