In patients with myocardial infarction and anemia, a “liberal” red blood cell transfusion strategy did not significantly reduce the risk of recurrent MI or death within 30 days, compared with a “restrictive” transfusion strategy, in the 3,500-patient MINT trial.

“While not statistically significant, the results consistently favored a liberal transfusion strategy,” Jeffrey L. Carson, MD, from Robert Wood Johnson Medical School, New Brunswick, N.J., said in a press briefing.

He presented the study in a late-breaking trial session at the annual scientific sessions of the American Heart Association, and it was simultaneously published online in the New England Journal of Medicine.

“Whether to transfuse is an everyday decision faced by clinicians caring for patients with acute MI,” Dr. Carson said.

“We cannot claim that a liberal transfusion strategy is definitively superior based on our primary outcome,” he said, but “the 95% confidence interval is consistent with treatment effects corresponding to no difference between the two transfusion strategies and to a clinically relevant benefit with the liberal strategy.” 

“In contrast to other trials in other settings,” such as anemia and cardiac surgery, Dr. Carson said, “the results suggest that a liberal transfusion strategy has the potential for clinical benefit with an acceptable risk of harm.”

“A liberal transfusion strategy may be the most prudent approach to transfusion in anemic patients with MI,” he added.
 

Not a home run

Others agreed with this interpretation. Martin B. Leon, MD, from Columbia University, New York, the study discussant in the press briefing, said the study “addresses a question that is common” in clinical practice. It was well conducted, and international (although most patients were in the United States and Canada), in a very broad group of patients, designed to make the results more generalizable. The 98% follow-up was extremely good, Dr. Leon added, and the trialists achieved their goal in that they did show a difference between the two transfusion strategies.

The number needed to treat was 40 to see a benefit in the combined outcome of death or recurrent MI at 30 days, Dr. Leon said. The P value for this was .07, “right on the edge” of statistical significance.

This study is “not a home run,” for the primary outcome, he noted; however, many of the outcomes tended to be in favor of a liberal transfusion strategy. Notably, cardiovascular death, which was not a specified outcome, was significantly lower in the group who received a liberal transfusion strategy.

Although a liberal transfusion strategy was “not definitely superior” in these patients with MI and anemia, Dr. Carson said, he thinks the trial will be interpreted as favoring a liberal transfusion strategy.

C. Michael Gibson, MD, professor of medicine at Harvard Medical School, Boston, and CEO of Harvard’s Baim and PERFUSE institutes for clinical research, voiced similar views.

“Given the lack of acute harm associated with liberal transfusion and the preponderance of evidence favoring liberal transfusion in the largest trial to date,” concluded Dr. Gibson, the assigned discussant at the session, “liberal transfusion appears to be a viable management strategy, particularly among patients with non-STEMI type 1 MI and as clinical judgment dictates.”

Only three small randomized controlled trials have compared transfusion thresholds in a total of 820 patients with MI and anemia, Dr. Gibson said, a point that the trial investigators also made. The results were inconsistent between trials: the CRIT trial (n = 45) favored a restrictive strategy, the MINT pilot study (n = 110) favored a liberal one, and the REALITY trial (n = 668) showed noninferiority of a restrictive strategy, compared with a liberal strategy in 30-day MACE.  

The MINT trial was four times larger than all prior studies combined. However, most outcomes were negative or of borderline significance for benefit.

Cardiac death was more common in the restrictive group at 5.5% than the liberal group at 3.2% (risk ratio, 1.74, 95% CI, 1.26-2.40), but this was nonadjudicated, and not designated as a primary, secondary, or tertiary outcome – which the researchers also noted. Fewer than half of the deaths were classified as cardiac, which was “odd,” Dr. Gibson observed.

A restrictive transfusion strategy was associated with increased events among participants with type 1 MI (RR, 1.32, 95% CI, 1.04-1.67), he noted.

Study strengths included that 45.5% of participants were women, Dr. Gibson said. Limitations included that the trial was “somewhat underpowered.” Also, even in the restrictive group, participants received a mean of 0.7 units of packed red blood cells.

Adherence to the 10 g/dL threshold in the liberal transfusion group was moderate (86.3% at hospital discharge), which the researchers acknowledged. They noted that this was frequently caused by clinical discretion, such as concern about fluid overload, and to the timing of hospital discharge. In addition, long-term potential for harm (microchimerism) is not known.

“There was a consistent nonsignificant acute benefit for liberal transfusion and a nominal reduction in CV mortality and improved outcomes in patients with type 1 MI in exploratory analyses, in a trial that ended up underpowered,” Dr. Gibson summarized. “Long-term follow up would be helpful to evaluate chronic outcomes.”

This is a very well-conducted, high-quality, important study that will be considered a landmark trial, C. David Mazer, MD, University of Toronto and St. Michael’s Hospital, also in Toronto, said in an interview.

Unfortunately, “it was not as definitive as hoped for,” Dr. Mazer lamented. Nevertheless, “I think people may interpret it as providing support for a liberal transfusion strategy” in patients with anemia and MI, he said.

Dr. Mazer, who was not involved with this research, was a principal investigator on the TRICS-3 trial, which disputed a liberal RBC transfusion strategy in patients with anemia undergoing cardiac surgery, as previously reported.

The “Red Blood Cell Transfusion: 2023 AABB International Guidelines,” led by Dr. Carson and published in JAMA, recommend a restrictive strategy in stable patients, although these guidelines did not include the current study, Dr. Mazer observed.

In the REALITY trial, there were fewer major adverse cardiac events (MACE) events in the restrictive strategy, he noted.

MINT can be viewed as comparing a high versus low hemoglobin threshold. “It is possible that the best is in between,” he said.

Dr. Mazer also noted that MINT may have achieved significance if it was designed with a larger enrollment and a higher power (for example, 90% instead of 80%) to detect between-group difference for the primary outcome. 
 

Study rationale, design, and findings

Anemia, or low RBC count, is common in patients with MI, Dr. Carson noted. A normal hemoglobin is 13 g/dL in men and 12 g/dL in women. Administering a packed RBC transfusion only when a patient’s hemoglobin falls below 7 or 8 g/dL has been widely adopted, but it is unclear if patients with acute MI may benefit from a higher hemoglobin level.

“Blood transfusion may decrease ischemic injury by improving oxygen delivery to myocardial tissues and reduce the risk of reinfarction or death,” the researchers wrote. “Alternatively, administering more blood could result in more frequent heart failure from fluid overload, infection from immunosuppression, thrombosis from higher viscosity, and inflammation.”

From 2017 to 2023, investigators enrolled 3,504 adults aged 18 and older at 144 sites in the United States (2,157 patients), Canada (885), France (323), Brazil (105), New Zealand (25), and Australia (9).

The participants had ST-elevation or non–ST-elevation MI and hemoglobin less than 10 g/dL within 24 hours. Patients with type 1 (atherosclerotic plaque disruption), type 2 (supply-demand mismatch without atherothrombotic plaque disruption), type 4b, or type 4c MI were eligible.

They were randomly assigned to receive:

• A ‘restrictive’ transfusion strategy (1,749 patients): Transfusion was permitted but not required when a patient’s hemoglobin was less than 8 g/dL and was strongly recommended when it was less than 7 g/dL or when anginal symptoms were not controlled with medications.
• A ‘liberal’ transfusion strategy (1,755 patients): One unit of RBCs was administered after randomization, and RBCs were transfused to maintain hemoglobin 10 g/dL or higher until hospital discharge or 30 days. 

The patients had a mean age of 72 years and 46% were women. More than three-quarters (78%) were White and 14% were Black. They had frequent coexisting illnesses, about a third had a history of MI, percutaneous coronary intervention, or heart failure; 14% were on a ventilator and 12% had renal dialysis. The median duration of hospitalization was 5 days in the two groups.

At baseline, the mean hemoglobin was 8.6 g/dL in both groups. At days 1, 2, and 3, the mean hemoglobin was 8.8, 8.9, and 8.9 g/dL, respectively, in the restrictive transfusion group, and 10.1, 10.4, and 10.5 g/dL, respectively, in the liberal transfusion group.

The mean number of transfused blood units was 0.7 units in the restrictive strategy group and 2.5 units in the liberal strategy group, roughly a 3.5-fold difference.

After adjustment for site and incomplete follow-up in 57 patients (20 with the restrictive strategy and 37 with the liberal strategy), the estimated RR for the primary outcome in the restrictive group versus the liberal group was 1.15 (P = .07).

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

In patients with myocardial infarction and anemia, a “liberal” red blood cell transfusion strategy did not significantly reduce the risk of recurrent MI or death within 30 days, compared with a “restrictive” transfusion strategy, in the 3,500-patient MINT trial.

“While not statistically significant, the results consistently favored a liberal transfusion strategy,” Jeffrey L. Carson, MD, from Robert Wood Johnson Medical School, New Brunswick, N.J., said in a press briefing.

He presented the study in a late-breaking trial session at the annual scientific sessions of the American Heart Association, and it was simultaneously published online in the New England Journal of Medicine.

“Whether to transfuse is an everyday decision faced by clinicians caring for patients with acute MI,” Dr. Carson said.

“We cannot claim that a liberal transfusion strategy is definitively superior based on our primary outcome,” he said, but “the 95% confidence interval is consistent with treatment effects corresponding to no difference between the two transfusion strategies and to a clinically relevant benefit with the liberal strategy.” 

“In contrast to other trials in other settings,” such as anemia and cardiac surgery, Dr. Carson said, “the results suggest that a liberal transfusion strategy has the potential for clinical benefit with an acceptable risk of harm.”

“A liberal transfusion strategy may be the most prudent approach to transfusion in anemic patients with MI,” he added.
 

Not a home run

Others agreed with this interpretation. Martin B. Leon, MD, from Columbia University, New York, the study discussant in the press briefing, said the study “addresses a question that is common” in clinical practice. It was well conducted, and international (although most patients were in the United States and Canada), in a very broad group of patients, designed to make the results more generalizable. The 98% follow-up was extremely good, Dr. Leon added, and the trialists achieved their goal in that they did show a difference between the two transfusion strategies.

The number needed to treat was 40 to see a benefit in the combined outcome of death or recurrent MI at 30 days, Dr. Leon said. The P value for this was .07, “right on the edge” of statistical significance.

This study is “not a home run,” for the primary outcome, he noted; however, many of the outcomes tended to be in favor of a liberal transfusion strategy. Notably, cardiovascular death, which was not a specified outcome, was significantly lower in the group who received a liberal transfusion strategy.

Although a liberal transfusion strategy was “not definitely superior” in these patients with MI and anemia, Dr. Carson said, he thinks the trial will be interpreted as favoring a liberal transfusion strategy.

C. Michael Gibson, MD, professor of medicine at Harvard Medical School, Boston, and CEO of Harvard’s Baim and PERFUSE institutes for clinical research, voiced similar views.

“Given the lack of acute harm associated with liberal transfusion and the preponderance of evidence favoring liberal transfusion in the largest trial to date,” concluded Dr. Gibson, the assigned discussant at the session, “liberal transfusion appears to be a viable management strategy, particularly among patients with non-STEMI type 1 MI and as clinical judgment dictates.”

Only three small randomized controlled trials have compared transfusion thresholds in a total of 820 patients with MI and anemia, Dr. Gibson said, a point that the trial investigators also made. The results were inconsistent between trials: the CRIT trial (n = 45) favored a restrictive strategy, the MINT pilot study (n = 110) favored a liberal one, and the REALITY trial (n = 668) showed noninferiority of a restrictive strategy, compared with a liberal strategy in 30-day MACE.  

The MINT trial was four times larger than all prior studies combined. However, most outcomes were negative or of borderline significance for benefit.

Cardiac death was more common in the restrictive group at 5.5% than the liberal group at 3.2% (risk ratio, 1.74, 95% CI, 1.26-2.40), but this was nonadjudicated, and not designated as a primary, secondary, or tertiary outcome – which the researchers also noted. Fewer than half of the deaths were classified as cardiac, which was “odd,” Dr. Gibson observed.

A restrictive transfusion strategy was associated with increased events among participants with type 1 MI (RR, 1.32, 95% CI, 1.04-1.67), he noted.

Study strengths included that 45.5% of participants were women, Dr. Gibson said. Limitations included that the trial was “somewhat underpowered.” Also, even in the restrictive group, participants received a mean of 0.7 units of packed red blood cells.

Adherence to the 10 g/dL threshold in the liberal transfusion group was moderate (86.3% at hospital discharge), which the researchers acknowledged. They noted that this was frequently caused by clinical discretion, such as concern about fluid overload, and to the timing of hospital discharge. In addition, long-term potential for harm (microchimerism) is not known.

“There was a consistent nonsignificant acute benefit for liberal transfusion and a nominal reduction in CV mortality and improved outcomes in patients with type 1 MI in exploratory analyses, in a trial that ended up underpowered,” Dr. Gibson summarized. “Long-term follow up would be helpful to evaluate chronic outcomes.”

This is a very well-conducted, high-quality, important study that will be considered a landmark trial, C. David Mazer, MD, University of Toronto and St. Michael’s Hospital, also in Toronto, said in an interview.

Unfortunately, “it was not as definitive as hoped for,” Dr. Mazer lamented. Nevertheless, “I think people may interpret it as providing support for a liberal transfusion strategy” in patients with anemia and MI, he said.

Dr. Mazer, who was not involved with this research, was a principal investigator on the TRICS-3 trial, which disputed a liberal RBC transfusion strategy in patients with anemia undergoing cardiac surgery, as previously reported.

The “Red Blood Cell Transfusion: 2023 AABB International Guidelines,” led by Dr. Carson and published in JAMA, recommend a restrictive strategy in stable patients, although these guidelines did not include the current study, Dr. Mazer observed.

In the REALITY trial, there were fewer major adverse cardiac events (MACE) events in the restrictive strategy, he noted.

MINT can be viewed as comparing a high versus low hemoglobin threshold. “It is possible that the best is in between,” he said.

Dr. Mazer also noted that MINT may have achieved significance if it was designed with a larger enrollment and a higher power (for example, 90% instead of 80%) to detect between-group difference for the primary outcome. 
 

Study rationale, design, and findings

Anemia, or low RBC count, is common in patients with MI, Dr. Carson noted. A normal hemoglobin is 13 g/dL in men and 12 g/dL in women. Administering a packed RBC transfusion only when a patient’s hemoglobin falls below 7 or 8 g/dL has been widely adopted, but it is unclear if patients with acute MI may benefit from a higher hemoglobin level.

“Blood transfusion may decrease ischemic injury by improving oxygen delivery to myocardial tissues and reduce the risk of reinfarction or death,” the researchers wrote. “Alternatively, administering more blood could result in more frequent heart failure from fluid overload, infection from immunosuppression, thrombosis from higher viscosity, and inflammation.”

From 2017 to 2023, investigators enrolled 3,504 adults aged 18 and older at 144 sites in the United States (2,157 patients), Canada (885), France (323), Brazil (105), New Zealand (25), and Australia (9).

The participants had ST-elevation or non–ST-elevation MI and hemoglobin less than 10 g/dL within 24 hours. Patients with type 1 (atherosclerotic plaque disruption), type 2 (supply-demand mismatch without atherothrombotic plaque disruption), type 4b, or type 4c MI were eligible.

They were randomly assigned to receive:

• A ‘restrictive’ transfusion strategy (1,749 patients): Transfusion was permitted but not required when a patient’s hemoglobin was less than 8 g/dL and was strongly recommended when it was less than 7 g/dL or when anginal symptoms were not controlled with medications.
• A ‘liberal’ transfusion strategy (1,755 patients): One unit of RBCs was administered after randomization, and RBCs were transfused to maintain hemoglobin 10 g/dL or higher until hospital discharge or 30 days. 

The patients had a mean age of 72 years and 46% were women. More than three-quarters (78%) were White and 14% were Black. They had frequent coexisting illnesses, about a third had a history of MI, percutaneous coronary intervention, or heart failure; 14% were on a ventilator and 12% had renal dialysis. The median duration of hospitalization was 5 days in the two groups.

At baseline, the mean hemoglobin was 8.6 g/dL in both groups. At days 1, 2, and 3, the mean hemoglobin was 8.8, 8.9, and 8.9 g/dL, respectively, in the restrictive transfusion group, and 10.1, 10.4, and 10.5 g/dL, respectively, in the liberal transfusion group.

The mean number of transfused blood units was 0.7 units in the restrictive strategy group and 2.5 units in the liberal strategy group, roughly a 3.5-fold difference.

After adjustment for site and incomplete follow-up in 57 patients (20 with the restrictive strategy and 37 with the liberal strategy), the estimated RR for the primary outcome in the restrictive group versus the liberal group was 1.15 (P = .07).

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

In patients with myocardial infarction and anemia, a “liberal” red blood cell transfusion strategy did not significantly reduce the risk of recurrent MI or death within 30 days, compared with a “restrictive” transfusion strategy, in the 3,500-patient MINT trial.

“While not statistically significant, the results consistently favored a liberal transfusion strategy,” Jeffrey L. Carson, MD, from Robert Wood Johnson Medical School, New Brunswick, N.J., said in a press briefing.

He presented the study in a late-breaking trial session at the annual scientific sessions of the American Heart Association, and it was simultaneously published online in the New England Journal of Medicine.

“Whether to transfuse is an everyday decision faced by clinicians caring for patients with acute MI,” Dr. Carson said.

“We cannot claim that a liberal transfusion strategy is definitively superior based on our primary outcome,” he said, but “the 95% confidence interval is consistent with treatment effects corresponding to no difference between the two transfusion strategies and to a clinically relevant benefit with the liberal strategy.” 

“In contrast to other trials in other settings,” such as anemia and cardiac surgery, Dr. Carson said, “the results suggest that a liberal transfusion strategy has the potential for clinical benefit with an acceptable risk of harm.”

“A liberal transfusion strategy may be the most prudent approach to transfusion in anemic patients with MI,” he added.
 

Not a home run

Others agreed with this interpretation. Martin B. Leon, MD, from Columbia University, New York, the study discussant in the press briefing, said the study “addresses a question that is common” in clinical practice. It was well conducted, and international (although most patients were in the United States and Canada), in a very broad group of patients, designed to make the results more generalizable. The 98% follow-up was extremely good, Dr. Leon added, and the trialists achieved their goal in that they did show a difference between the two transfusion strategies.

The number needed to treat was 40 to see a benefit in the combined outcome of death or recurrent MI at 30 days, Dr. Leon said. The P value for this was .07, “right on the edge” of statistical significance.

This study is “not a home run,” for the primary outcome, he noted; however, many of the outcomes tended to be in favor of a liberal transfusion strategy. Notably, cardiovascular death, which was not a specified outcome, was significantly lower in the group who received a liberal transfusion strategy.

Although a liberal transfusion strategy was “not definitely superior” in these patients with MI and anemia, Dr. Carson said, he thinks the trial will be interpreted as favoring a liberal transfusion strategy.

C. Michael Gibson, MD, professor of medicine at Harvard Medical School, Boston, and CEO of Harvard’s Baim and PERFUSE institutes for clinical research, voiced similar views.

“Given the lack of acute harm associated with liberal transfusion and the preponderance of evidence favoring liberal transfusion in the largest trial to date,” concluded Dr. Gibson, the assigned discussant at the session, “liberal transfusion appears to be a viable management strategy, particularly among patients with non-STEMI type 1 MI and as clinical judgment dictates.”

Only three small randomized controlled trials have compared transfusion thresholds in a total of 820 patients with MI and anemia, Dr. Gibson said, a point that the trial investigators also made. The results were inconsistent between trials: the CRIT trial (n = 45) favored a restrictive strategy, the MINT pilot study (n = 110) favored a liberal one, and the REALITY trial (n = 668) showed noninferiority of a restrictive strategy, compared with a liberal strategy in 30-day MACE.  

The MINT trial was four times larger than all prior studies combined. However, most outcomes were negative or of borderline significance for benefit.

Cardiac death was more common in the restrictive group at 5.5% than the liberal group at 3.2% (risk ratio, 1.74, 95% CI, 1.26-2.40), but this was nonadjudicated, and not designated as a primary, secondary, or tertiary outcome – which the researchers also noted. Fewer than half of the deaths were classified as cardiac, which was “odd,” Dr. Gibson observed.

A restrictive transfusion strategy was associated with increased events among participants with type 1 MI (RR, 1.32, 95% CI, 1.04-1.67), he noted.

Study strengths included that 45.5% of participants were women, Dr. Gibson said. Limitations included that the trial was “somewhat underpowered.” Also, even in the restrictive group, participants received a mean of 0.7 units of packed red blood cells.

Adherence to the 10 g/dL threshold in the liberal transfusion group was moderate (86.3% at hospital discharge), which the researchers acknowledged. They noted that this was frequently caused by clinical discretion, such as concern about fluid overload, and to the timing of hospital discharge. In addition, long-term potential for harm (microchimerism) is not known.

“There was a consistent nonsignificant acute benefit for liberal transfusion and a nominal reduction in CV mortality and improved outcomes in patients with type 1 MI in exploratory analyses, in a trial that ended up underpowered,” Dr. Gibson summarized. “Long-term follow up would be helpful to evaluate chronic outcomes.”

This is a very well-conducted, high-quality, important study that will be considered a landmark trial, C. David Mazer, MD, University of Toronto and St. Michael’s Hospital, also in Toronto, said in an interview.

Unfortunately, “it was not as definitive as hoped for,” Dr. Mazer lamented. Nevertheless, “I think people may interpret it as providing support for a liberal transfusion strategy” in patients with anemia and MI, he said.

Dr. Mazer, who was not involved with this research, was a principal investigator on the TRICS-3 trial, which disputed a liberal RBC transfusion strategy in patients with anemia undergoing cardiac surgery, as previously reported.

The “Red Blood Cell Transfusion: 2023 AABB International Guidelines,” led by Dr. Carson and published in JAMA, recommend a restrictive strategy in stable patients, although these guidelines did not include the current study, Dr. Mazer observed.

In the REALITY trial, there were fewer major adverse cardiac events (MACE) events in the restrictive strategy, he noted.

MINT can be viewed as comparing a high versus low hemoglobin threshold. “It is possible that the best is in between,” he said.

Dr. Mazer also noted that MINT may have achieved significance if it was designed with a larger enrollment and a higher power (for example, 90% instead of 80%) to detect between-group difference for the primary outcome. 
 

Study rationale, design, and findings

Anemia, or low RBC count, is common in patients with MI, Dr. Carson noted. A normal hemoglobin is 13 g/dL in men and 12 g/dL in women. Administering a packed RBC transfusion only when a patient’s hemoglobin falls below 7 or 8 g/dL has been widely adopted, but it is unclear if patients with acute MI may benefit from a higher hemoglobin level.

“Blood transfusion may decrease ischemic injury by improving oxygen delivery to myocardial tissues and reduce the risk of reinfarction or death,” the researchers wrote. “Alternatively, administering more blood could result in more frequent heart failure from fluid overload, infection from immunosuppression, thrombosis from higher viscosity, and inflammation.”

From 2017 to 2023, investigators enrolled 3,504 adults aged 18 and older at 144 sites in the United States (2,157 patients), Canada (885), France (323), Brazil (105), New Zealand (25), and Australia (9).

The participants had ST-elevation or non–ST-elevation MI and hemoglobin less than 10 g/dL within 24 hours. Patients with type 1 (atherosclerotic plaque disruption), type 2 (supply-demand mismatch without atherothrombotic plaque disruption), type 4b, or type 4c MI were eligible.

They were randomly assigned to receive:

• A ‘restrictive’ transfusion strategy (1,749 patients): Transfusion was permitted but not required when a patient’s hemoglobin was less than 8 g/dL and was strongly recommended when it was less than 7 g/dL or when anginal symptoms were not controlled with medications.
• A ‘liberal’ transfusion strategy (1,755 patients): One unit of RBCs was administered after randomization, and RBCs were transfused to maintain hemoglobin 10 g/dL or higher until hospital discharge or 30 days. 

The patients had a mean age of 72 years and 46% were women. More than three-quarters (78%) were White and 14% were Black. They had frequent coexisting illnesses, about a third had a history of MI, percutaneous coronary intervention, or heart failure; 14% were on a ventilator and 12% had renal dialysis. The median duration of hospitalization was 5 days in the two groups.

At baseline, the mean hemoglobin was 8.6 g/dL in both groups. At days 1, 2, and 3, the mean hemoglobin was 8.8, 8.9, and 8.9 g/dL, respectively, in the restrictive transfusion group, and 10.1, 10.4, and 10.5 g/dL, respectively, in the liberal transfusion group.

The mean number of transfused blood units was 0.7 units in the restrictive strategy group and 2.5 units in the liberal strategy group, roughly a 3.5-fold difference.

After adjustment for site and incomplete follow-up in 57 patients (20 with the restrictive strategy and 37 with the liberal strategy), the estimated RR for the primary outcome in the restrictive group versus the liberal group was 1.15 (P = .07).

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

The dream of family practice began more than 6 decades ago with a movement toward personal physicians who have “… the feeling of warm personal regard and concern of doctor for patient, the feeling that the doctor treats people, not illnesses ….” The personal family physician helps patients “… not because of the interesting medical problems they may present but because they are human beings in need of help.”¹ One of the most influential founders of family medicine, Dr. Gayle Stephens, expounded on this idea in a series of essays that tapped into the intellectual, philosophical, historical, and moral underpinnings of our discipline.²

Following the dream and the birth of family medicine—like any organization—its lifecycle can be envisioned as proceeding through the rest of the 7 stages of organizational life (TABLE).³ Now allow me to give you some numbers. There are more than 118,000 family physicians in the United States, 784 family medicine residencies filled by 4530 medical school graduates, more than 150 departments of family medicine, multiple national family medicine organizations, and even a World Organization of Family Doctors.^4,5 The American Board of Family Medicine is the second largest medical specialty board in the country. Family doctors make up nearly 40% of our total primary care workforce.⁶ We launched the venture, got organized, made it. We are an institution.

This final issue of The Journal of Family Practice marks the end of an era of nearly 50 years of publication.

The threat at the institution stage is that we are on the precipice of “closing in.” Many factors are driving this stage: commoditization in health care, market influences and competition for patients, alternative primary care models, erosion of the patient-physician relationship (partly driven by technology), narrowing scope of care, clinician burnout, and the challenges of implementing value-based care, to name a few. You see what comes next in the TABLE.³ The good news is that there is an alternative to the “natural” progression to the ending stage: the path of renewal.³

In the lifecycle of an organization, the path of renewal starts the cycle anew, with dreaming the dream. I recently had the opportunity to visit Singapore to learn about their health system. Singapore is one of the wealthiest countries in the world. I was impressed with their many innovations, including technological ones, as well as new models of care. However, I was most impressed that the country is betting big on family medicine. Their Ministry of Health has launched an initiative they are calling Healthier SG.⁷ The goal is for “all Singaporeans to have a trusted and lifelong relationship with [their] family doctor.” Their dream is to bring personal doctoring to everyone in the country to make Singapore healthier.

While their path of renewal is occurring halfway around the world, here at home, our path of renewal has been ignited over the past several years by the work of the Robert Graham Center; the Keystone Conferences; the American Board of Family Medicine; and the National Academies of Science, Engineering, and Medicine, among others.^8-11 These organizations are aligning around re-centering on ­patient-clinician relationships, measuring what is important, care by interprofessional teams, payment reform, professionalism, health equity, improved information technology, and adherence to the best available evidence. We are working toward the solution shop as opposed to the production line.¹² We are indeed dreaming a new dream.

While I write about this renewal, I close with an ending. This is the final issue of The Journal of Family Practice. It marks the end of an era of nearly 50 years of publication. The Journal of Family Practice has left a lasting mark, providing generations of clinicians with evidence-based, practical guidance to help care for patients as well as serving as an important venue for scholarly work by the family medicine community. Although I have had the privilege of serving the discipline as an editor-in-chief for only a brief time, I am grateful I had the opportunity. Most of all, I appreciate being on the journey of family medicine with you, renewing the dream together.

The references for this Editorial are available in the online version of the article at www.mdedge.com/familymedicine.

The dream of family practice began more than 6 decades ago with a movement toward personal physicians who have “… the feeling of warm personal regard and concern of doctor for patient, the feeling that the doctor treats people, not illnesses ….” The personal family physician helps patients “… not because of the interesting medical problems they may present but because they are human beings in need of help.”¹ One of the most influential founders of family medicine, Dr. Gayle Stephens, expounded on this idea in a series of essays that tapped into the intellectual, philosophical, historical, and moral underpinnings of our discipline.²

Following the dream and the birth of family medicine—like any organization—its lifecycle can be envisioned as proceeding through the rest of the 7 stages of organizational life (TABLE).³ Now allow me to give you some numbers. There are more than 118,000 family physicians in the United States, 784 family medicine residencies filled by 4530 medical school graduates, more than 150 departments of family medicine, multiple national family medicine organizations, and even a World Organization of Family Doctors.^4,5 The American Board of Family Medicine is the second largest medical specialty board in the country. Family doctors make up nearly 40% of our total primary care workforce.⁶ We launched the venture, got organized, made it. We are an institution.

This final issue of The Journal of Family Practice marks the end of an era of nearly 50 years of publication.

The threat at the institution stage is that we are on the precipice of “closing in.” Many factors are driving this stage: commoditization in health care, market influences and competition for patients, alternative primary care models, erosion of the patient-physician relationship (partly driven by technology), narrowing scope of care, clinician burnout, and the challenges of implementing value-based care, to name a few. You see what comes next in the TABLE.³ The good news is that there is an alternative to the “natural” progression to the ending stage: the path of renewal.³

In the lifecycle of an organization, the path of renewal starts the cycle anew, with dreaming the dream. I recently had the opportunity to visit Singapore to learn about their health system. Singapore is one of the wealthiest countries in the world. I was impressed with their many innovations, including technological ones, as well as new models of care. However, I was most impressed that the country is betting big on family medicine. Their Ministry of Health has launched an initiative they are calling Healthier SG.⁷ The goal is for “all Singaporeans to have a trusted and lifelong relationship with [their] family doctor.” Their dream is to bring personal doctoring to everyone in the country to make Singapore healthier.

While their path of renewal is occurring halfway around the world, here at home, our path of renewal has been ignited over the past several years by the work of the Robert Graham Center; the Keystone Conferences; the American Board of Family Medicine; and the National Academies of Science, Engineering, and Medicine, among others.^8-11 These organizations are aligning around re-centering on ­patient-clinician relationships, measuring what is important, care by interprofessional teams, payment reform, professionalism, health equity, improved information technology, and adherence to the best available evidence. We are working toward the solution shop as opposed to the production line.¹² We are indeed dreaming a new dream.

While I write about this renewal, I close with an ending. This is the final issue of The Journal of Family Practice. It marks the end of an era of nearly 50 years of publication. The Journal of Family Practice has left a lasting mark, providing generations of clinicians with evidence-based, practical guidance to help care for patients as well as serving as an important venue for scholarly work by the family medicine community. Although I have had the privilege of serving the discipline as an editor-in-chief for only a brief time, I am grateful I had the opportunity. Most of all, I appreciate being on the journey of family medicine with you, renewing the dream together.

The references for this Editorial are available in the online version of the article at www.mdedge.com/familymedicine.

The dream of family practice began more than 6 decades ago with a movement toward personal physicians who have “… the feeling of warm personal regard and concern of doctor for patient, the feeling that the doctor treats people, not illnesses ….” The personal family physician helps patients “… not because of the interesting medical problems they may present but because they are human beings in need of help.”¹ One of the most influential founders of family medicine, Dr. Gayle Stephens, expounded on this idea in a series of essays that tapped into the intellectual, philosophical, historical, and moral underpinnings of our discipline.²

Following the dream and the birth of family medicine—like any organization—its lifecycle can be envisioned as proceeding through the rest of the 7 stages of organizational life (TABLE).³ Now allow me to give you some numbers. There are more than 118,000 family physicians in the United States, 784 family medicine residencies filled by 4530 medical school graduates, more than 150 departments of family medicine, multiple national family medicine organizations, and even a World Organization of Family Doctors.^4,5 The American Board of Family Medicine is the second largest medical specialty board in the country. Family doctors make up nearly 40% of our total primary care workforce.⁶ We launched the venture, got organized, made it. We are an institution.

This final issue of The Journal of Family Practice marks the end of an era of nearly 50 years of publication.

The threat at the institution stage is that we are on the precipice of “closing in.” Many factors are driving this stage: commoditization in health care, market influences and competition for patients, alternative primary care models, erosion of the patient-physician relationship (partly driven by technology), narrowing scope of care, clinician burnout, and the challenges of implementing value-based care, to name a few. You see what comes next in the TABLE.³ The good news is that there is an alternative to the “natural” progression to the ending stage: the path of renewal.³

In the lifecycle of an organization, the path of renewal starts the cycle anew, with dreaming the dream. I recently had the opportunity to visit Singapore to learn about their health system. Singapore is one of the wealthiest countries in the world. I was impressed with their many innovations, including technological ones, as well as new models of care. However, I was most impressed that the country is betting big on family medicine. Their Ministry of Health has launched an initiative they are calling Healthier SG.⁷ The goal is for “all Singaporeans to have a trusted and lifelong relationship with [their] family doctor.” Their dream is to bring personal doctoring to everyone in the country to make Singapore healthier.

While their path of renewal is occurring halfway around the world, here at home, our path of renewal has been ignited over the past several years by the work of the Robert Graham Center; the Keystone Conferences; the American Board of Family Medicine; and the National Academies of Science, Engineering, and Medicine, among others.^8-11 These organizations are aligning around re-centering on ­patient-clinician relationships, measuring what is important, care by interprofessional teams, payment reform, professionalism, health equity, improved information technology, and adherence to the best available evidence. We are working toward the solution shop as opposed to the production line.¹² We are indeed dreaming a new dream.

While I write about this renewal, I close with an ending. This is the final issue of The Journal of Family Practice. It marks the end of an era of nearly 50 years of publication. The Journal of Family Practice has left a lasting mark, providing generations of clinicians with evidence-based, practical guidance to help care for patients as well as serving as an important venue for scholarly work by the family medicine community. Although I have had the privilege of serving the discipline as an editor-in-chief for only a brief time, I am grateful I had the opportunity. Most of all, I appreciate being on the journey of family medicine with you, renewing the dream together.

The references for this Editorial are available in the online version of the article at www.mdedge.com/familymedicine.

THE CASE

A 55-year-old woman developed subacute progression of myalgias and subjective weakness in her proximal extremities after starting a new exercise regimen. The patient had a history of unilateral renal agenesis, type 2 diabetes, and hyperlipidemia, for which she had taken atorvastatin 40 mg/d for several years before discontinuing it 2 years earlier for unknown reasons. She had been evaluated multiple times in the primary care clinic and emergency department over the previous month. Each time, her strength was minimally reduced in the upper extremities on examination, her renal function and electrolytes were normal, and her creatine kinase (CK) level was elevated (16,000-20,000 U/L; normal range, 26-192 U/L). She was managed conservatively with fluids and given return precautions each time.

After her myalgias and weakness increased in severity, she presented to the emergency department with a muscle strength score of 4/5 in both shoulders, triceps, hip flexors, hip extensors, abductors, and adductors. Her laboratory results were significant for the presence of blood without red blood cells on her urine dipstick test and a CK level of 25,070 U/L. She was admitted for further evaluation of progressive myopathy and given aggressive IV fluid hydration to prevent renal injury based on her history of unilateral renal agenesis.

Infectious disease testing, which included a respiratory virus panel, acute hepatitis panel, HIV screening, Lyme antibody testing, cytomegalovirus DNA detection by polymerase chain reaction, Epstein-Barr virus capsid immunoglobulin M, and anti-­streptolysin O, were negative. Electrolytes, inflammatory markers, and kidney function were normal. However, high-­sensitivity troponin-T levels were elevated, with a peak value of 216.3 ng/L (normal range, 0-19 ng/L). The patient denied having any chest pain, and her electrocardiogram and transthoracic echocardiogram were normal. By hospital Day 4, her myalgias and weakness had improved, CK had stabilized (19,000-21,000 U/L), cardiac enzymes had improved, and urinalysis had normalized. She was discharged with a referral to a rheumatologist.

However, 10 days later—before she could see a rheumatologist—she was readmitted to a community hospital for recurrence of severe myalgias, progressive weakness, positive blood on urine dipstick testing, and a rising CK level (to 24,580 U/L) found during a follow-up appointment with her primary care physician. At this point, Neurology and Rheumatology were consulted and myositis-specific and ­myositis-associated autoantibody tests were sent out. Magnetic resonance imaging (MRI) of her thighs was performed and showed diffusely increased T2 signal and short tau inversion recovery in multiple proximal muscles (FIGURE).

DIAGNOSIS

Given her symmetrical proximal muscle weakness (which was refractory to IV fluid resuscitation), MRI findings, and the exclusion of infection and metabolic derangements, the patient was given a working diagnosis of myositis and treated with 1-g IV methylprednisolone followed by a 4-month steroid taper, methotrexate 20 mg weekly, and physical therapy. This working diagnosis was later confirmed with the results of her autoantibody tests.

At her 1-month follow-up visit, the ­patient reported minimal improvement in her strength, new neck weakness, and ­dysphagia with solids. Testing revealed ­anti–3-hydroxy-3-methylglutaryl-coenzyme A reductase ­(anti-HMGCR) antibody levels of more than 200 U/L (negative < 20 U/L; positive > 59 U/L), which pointed to a more refined diagnosis of anti-HMGCR immune-mediated necrotizing myositis.

DISCUSSION

Myositis should be in the differential diagnosis for patients with symmetrical proximal muscle weakness. Bohan and Peter devised a 5-part set of criteria to help diagnose myositis, shown in the TABLE.^1,2 This simple framework broadens the differential and guides diagnostic testing. Our patient’s presentation was fairly typical for anti-HMGCR myositis, a subset of immune-mediated necrotizing myositis,³ with a pretest probability of 62% per the European League Against Rheumatism/American College of Rheumatology classification criteria.² Probability of this diagnosis was further increased by the high-titer anti-HMGCR, so biopsy and electromyography (EMG), as noted by Bohan and Peter, were not pursued.

Continue to: Autoimmune myopathies...

Two-thirds of patients with anti-HMGCR myositis report current or prior statin use, and this increases to more than 90% in those age 50 years or older.

Autoimmune myopathies occur in 9 to 14 per 100,000 people,⁴ with6% of patients having anti-HMGCR auto-antibodies.⁵ Anti-HMGCR myositis is more prevalent in older women, patients with type 2 diabetes, and those with a history of atorvastatin use.^3,6 Two-thirds of patients with anti-HMGCR myositis report current or prior statin use, and this increases to more than 90% in those age 50 years or older.⁵ Anti-HMGCR myositis causes significant muscle weakness that does not resolve with discontinuation of the statin and can occur years after the initiation or discontinuation of statin treatment.⁶ Cardiac involvement is rare⁴ but dysphagia is relatively common.^7,8 Anti-HMGCR myositis also has a weak association with cancer, most commonly gastrointestinal and lung cancers.^4,7

Distinguishing statin-induced myalgias from statin-induced myositis guides management. Statin-induced myalgias are associated with normal or slightly increased CK levels (typically < 1000 U/L) and resolve with discontinuation of the statin; the patient can often tolerate re-challenge with a statin.⁶ In contrast, CK elevation in patients with statin-induced myositis is typically more than 10,000 U/L⁶ and requires aggressive treatment with immunomodulatory medications to prevent permanent muscle damage.

Treatment recommendations are supported only by case series, observational studies, and expert opinion. Typical first-line treatment includes induction with high-dose corticosteroids followed by prolonged taper plus a conventional synthetic disease-­modifying antirheumatic drug (csDMARD) such as methotrexate, azathioprine, or mycophenolate.⁴ Maintenance therapy often is achieved with csDMARD therapy for 2 years.⁴ Severe cases frequently are treated with combination csDMARD therapy (eg, methotrexate and azathioprine or methotrexate and mycophenolate).⁴ Rituximab and IV immunoglobulin (IVIG) are typically reserved for refractory cases.⁶ Usual monitoring for relapse includes muscle strength testing on examination and evaluation of trending CK levels.⁸

Our patient received monthly 2-g/kg IVIG infusions, which led to slow, consistent improvement in her strength and normalization of her CK levels to 181 U/L after 6 months.

THE TAKEAWAY

Anti-HMGCR myositis should be suspected in any patient currently or previously treated with a statin who presents with proximal muscle weakness, myalgias, or an elevated CK level. We suggest early subspecialty consultation to discuss whether antibody testing, EMG, or muscle biopsy are warranted. If anti-HMGCR myositis is confirmed, it is advisable to rule out comorbid malignancy and initiate early combination treatment to minimize relapses and permanent muscle damage.

CORRESPONDENCE
Daniel T. Schoenherr, MD, Family Medicine Residency, National Capital Consortium–Alexander T. Augusta Military Medical Center, 9300 DeWitt Loop, Fort Belvoir, VA 22060; [email protected]

THE CASE

A 55-year-old woman developed subacute progression of myalgias and subjective weakness in her proximal extremities after starting a new exercise regimen. The patient had a history of unilateral renal agenesis, type 2 diabetes, and hyperlipidemia, for which she had taken atorvastatin 40 mg/d for several years before discontinuing it 2 years earlier for unknown reasons. She had been evaluated multiple times in the primary care clinic and emergency department over the previous month. Each time, her strength was minimally reduced in the upper extremities on examination, her renal function and electrolytes were normal, and her creatine kinase (CK) level was elevated (16,000-20,000 U/L; normal range, 26-192 U/L). She was managed conservatively with fluids and given return precautions each time.

After her myalgias and weakness increased in severity, she presented to the emergency department with a muscle strength score of 4/5 in both shoulders, triceps, hip flexors, hip extensors, abductors, and adductors. Her laboratory results were significant for the presence of blood without red blood cells on her urine dipstick test and a CK level of 25,070 U/L. She was admitted for further evaluation of progressive myopathy and given aggressive IV fluid hydration to prevent renal injury based on her history of unilateral renal agenesis.

Infectious disease testing, which included a respiratory virus panel, acute hepatitis panel, HIV screening, Lyme antibody testing, cytomegalovirus DNA detection by polymerase chain reaction, Epstein-Barr virus capsid immunoglobulin M, and anti-­streptolysin O, were negative. Electrolytes, inflammatory markers, and kidney function were normal. However, high-­sensitivity troponin-T levels were elevated, with a peak value of 216.3 ng/L (normal range, 0-19 ng/L). The patient denied having any chest pain, and her electrocardiogram and transthoracic echocardiogram were normal. By hospital Day 4, her myalgias and weakness had improved, CK had stabilized (19,000-21,000 U/L), cardiac enzymes had improved, and urinalysis had normalized. She was discharged with a referral to a rheumatologist.

However, 10 days later—before she could see a rheumatologist—she was readmitted to a community hospital for recurrence of severe myalgias, progressive weakness, positive blood on urine dipstick testing, and a rising CK level (to 24,580 U/L) found during a follow-up appointment with her primary care physician. At this point, Neurology and Rheumatology were consulted and myositis-specific and ­myositis-associated autoantibody tests were sent out. Magnetic resonance imaging (MRI) of her thighs was performed and showed diffusely increased T2 signal and short tau inversion recovery in multiple proximal muscles (FIGURE).

DIAGNOSIS

Given her symmetrical proximal muscle weakness (which was refractory to IV fluid resuscitation), MRI findings, and the exclusion of infection and metabolic derangements, the patient was given a working diagnosis of myositis and treated with 1-g IV methylprednisolone followed by a 4-month steroid taper, methotrexate 20 mg weekly, and physical therapy. This working diagnosis was later confirmed with the results of her autoantibody tests.

At her 1-month follow-up visit, the ­patient reported minimal improvement in her strength, new neck weakness, and ­dysphagia with solids. Testing revealed ­anti–3-hydroxy-3-methylglutaryl-coenzyme A reductase ­(anti-HMGCR) antibody levels of more than 200 U/L (negative < 20 U/L; positive > 59 U/L), which pointed to a more refined diagnosis of anti-HMGCR immune-mediated necrotizing myositis.

DISCUSSION

Myositis should be in the differential diagnosis for patients with symmetrical proximal muscle weakness. Bohan and Peter devised a 5-part set of criteria to help diagnose myositis, shown in the TABLE.^1,2 This simple framework broadens the differential and guides diagnostic testing. Our patient’s presentation was fairly typical for anti-HMGCR myositis, a subset of immune-mediated necrotizing myositis,³ with a pretest probability of 62% per the European League Against Rheumatism/American College of Rheumatology classification criteria.² Probability of this diagnosis was further increased by the high-titer anti-HMGCR, so biopsy and electromyography (EMG), as noted by Bohan and Peter, were not pursued.

Continue to: Autoimmune myopathies...

Two-thirds of patients with anti-HMGCR myositis report current or prior statin use, and this increases to more than 90% in those age 50 years or older.

Autoimmune myopathies occur in 9 to 14 per 100,000 people,⁴ with6% of patients having anti-HMGCR auto-antibodies.⁵ Anti-HMGCR myositis is more prevalent in older women, patients with type 2 diabetes, and those with a history of atorvastatin use.^3,6 Two-thirds of patients with anti-HMGCR myositis report current or prior statin use, and this increases to more than 90% in those age 50 years or older.⁵ Anti-HMGCR myositis causes significant muscle weakness that does not resolve with discontinuation of the statin and can occur years after the initiation or discontinuation of statin treatment.⁶ Cardiac involvement is rare⁴ but dysphagia is relatively common.^7,8 Anti-HMGCR myositis also has a weak association with cancer, most commonly gastrointestinal and lung cancers.^4,7

Distinguishing statin-induced myalgias from statin-induced myositis guides management. Statin-induced myalgias are associated with normal or slightly increased CK levels (typically < 1000 U/L) and resolve with discontinuation of the statin; the patient can often tolerate re-challenge with a statin.⁶ In contrast, CK elevation in patients with statin-induced myositis is typically more than 10,000 U/L⁶ and requires aggressive treatment with immunomodulatory medications to prevent permanent muscle damage.

Treatment recommendations are supported only by case series, observational studies, and expert opinion. Typical first-line treatment includes induction with high-dose corticosteroids followed by prolonged taper plus a conventional synthetic disease-­modifying antirheumatic drug (csDMARD) such as methotrexate, azathioprine, or mycophenolate.⁴ Maintenance therapy often is achieved with csDMARD therapy for 2 years.⁴ Severe cases frequently are treated with combination csDMARD therapy (eg, methotrexate and azathioprine or methotrexate and mycophenolate).⁴ Rituximab and IV immunoglobulin (IVIG) are typically reserved for refractory cases.⁶ Usual monitoring for relapse includes muscle strength testing on examination and evaluation of trending CK levels.⁸

Our patient received monthly 2-g/kg IVIG infusions, which led to slow, consistent improvement in her strength and normalization of her CK levels to 181 U/L after 6 months.

THE TAKEAWAY

Anti-HMGCR myositis should be suspected in any patient currently or previously treated with a statin who presents with proximal muscle weakness, myalgias, or an elevated CK level. We suggest early subspecialty consultation to discuss whether antibody testing, EMG, or muscle biopsy are warranted. If anti-HMGCR myositis is confirmed, it is advisable to rule out comorbid malignancy and initiate early combination treatment to minimize relapses and permanent muscle damage.

CORRESPONDENCE
Daniel T. Schoenherr, MD, Family Medicine Residency, National Capital Consortium–Alexander T. Augusta Military Medical Center, 9300 DeWitt Loop, Fort Belvoir, VA 22060; [email protected]

THE CASE

A 55-year-old woman developed subacute progression of myalgias and subjective weakness in her proximal extremities after starting a new exercise regimen. The patient had a history of unilateral renal agenesis, type 2 diabetes, and hyperlipidemia, for which she had taken atorvastatin 40 mg/d for several years before discontinuing it 2 years earlier for unknown reasons. She had been evaluated multiple times in the primary care clinic and emergency department over the previous month. Each time, her strength was minimally reduced in the upper extremities on examination, her renal function and electrolytes were normal, and her creatine kinase (CK) level was elevated (16,000-20,000 U/L; normal range, 26-192 U/L). She was managed conservatively with fluids and given return precautions each time.

After her myalgias and weakness increased in severity, she presented to the emergency department with a muscle strength score of 4/5 in both shoulders, triceps, hip flexors, hip extensors, abductors, and adductors. Her laboratory results were significant for the presence of blood without red blood cells on her urine dipstick test and a CK level of 25,070 U/L. She was admitted for further evaluation of progressive myopathy and given aggressive IV fluid hydration to prevent renal injury based on her history of unilateral renal agenesis.

Infectious disease testing, which included a respiratory virus panel, acute hepatitis panel, HIV screening, Lyme antibody testing, cytomegalovirus DNA detection by polymerase chain reaction, Epstein-Barr virus capsid immunoglobulin M, and anti-­streptolysin O, were negative. Electrolytes, inflammatory markers, and kidney function were normal. However, high-­sensitivity troponin-T levels were elevated, with a peak value of 216.3 ng/L (normal range, 0-19 ng/L). The patient denied having any chest pain, and her electrocardiogram and transthoracic echocardiogram were normal. By hospital Day 4, her myalgias and weakness had improved, CK had stabilized (19,000-21,000 U/L), cardiac enzymes had improved, and urinalysis had normalized. She was discharged with a referral to a rheumatologist.

However, 10 days later—before she could see a rheumatologist—she was readmitted to a community hospital for recurrence of severe myalgias, progressive weakness, positive blood on urine dipstick testing, and a rising CK level (to 24,580 U/L) found during a follow-up appointment with her primary care physician. At this point, Neurology and Rheumatology were consulted and myositis-specific and ­myositis-associated autoantibody tests were sent out. Magnetic resonance imaging (MRI) of her thighs was performed and showed diffusely increased T2 signal and short tau inversion recovery in multiple proximal muscles (FIGURE).

DIAGNOSIS

Given her symmetrical proximal muscle weakness (which was refractory to IV fluid resuscitation), MRI findings, and the exclusion of infection and metabolic derangements, the patient was given a working diagnosis of myositis and treated with 1-g IV methylprednisolone followed by a 4-month steroid taper, methotrexate 20 mg weekly, and physical therapy. This working diagnosis was later confirmed with the results of her autoantibody tests.

At her 1-month follow-up visit, the ­patient reported minimal improvement in her strength, new neck weakness, and ­dysphagia with solids. Testing revealed ­anti–3-hydroxy-3-methylglutaryl-coenzyme A reductase ­(anti-HMGCR) antibody levels of more than 200 U/L (negative < 20 U/L; positive > 59 U/L), which pointed to a more refined diagnosis of anti-HMGCR immune-mediated necrotizing myositis.

DISCUSSION

Myositis should be in the differential diagnosis for patients with symmetrical proximal muscle weakness. Bohan and Peter devised a 5-part set of criteria to help diagnose myositis, shown in the TABLE.^1,2 This simple framework broadens the differential and guides diagnostic testing. Our patient’s presentation was fairly typical for anti-HMGCR myositis, a subset of immune-mediated necrotizing myositis,³ with a pretest probability of 62% per the European League Against Rheumatism/American College of Rheumatology classification criteria.² Probability of this diagnosis was further increased by the high-titer anti-HMGCR, so biopsy and electromyography (EMG), as noted by Bohan and Peter, were not pursued.

Continue to: Autoimmune myopathies...

Two-thirds of patients with anti-HMGCR myositis report current or prior statin use, and this increases to more than 90% in those age 50 years or older.

Autoimmune myopathies occur in 9 to 14 per 100,000 people,⁴ with6% of patients having anti-HMGCR auto-antibodies.⁵ Anti-HMGCR myositis is more prevalent in older women, patients with type 2 diabetes, and those with a history of atorvastatin use.^3,6 Two-thirds of patients with anti-HMGCR myositis report current or prior statin use, and this increases to more than 90% in those age 50 years or older.⁵ Anti-HMGCR myositis causes significant muscle weakness that does not resolve with discontinuation of the statin and can occur years after the initiation or discontinuation of statin treatment.⁶ Cardiac involvement is rare⁴ but dysphagia is relatively common.^7,8 Anti-HMGCR myositis also has a weak association with cancer, most commonly gastrointestinal and lung cancers.^4,7

Distinguishing statin-induced myalgias from statin-induced myositis guides management. Statin-induced myalgias are associated with normal or slightly increased CK levels (typically < 1000 U/L) and resolve with discontinuation of the statin; the patient can often tolerate re-challenge with a statin.⁶ In contrast, CK elevation in patients with statin-induced myositis is typically more than 10,000 U/L⁶ and requires aggressive treatment with immunomodulatory medications to prevent permanent muscle damage.

Treatment recommendations are supported only by case series, observational studies, and expert opinion. Typical first-line treatment includes induction with high-dose corticosteroids followed by prolonged taper plus a conventional synthetic disease-­modifying antirheumatic drug (csDMARD) such as methotrexate, azathioprine, or mycophenolate.⁴ Maintenance therapy often is achieved with csDMARD therapy for 2 years.⁴ Severe cases frequently are treated with combination csDMARD therapy (eg, methotrexate and azathioprine or methotrexate and mycophenolate).⁴ Rituximab and IV immunoglobulin (IVIG) are typically reserved for refractory cases.⁶ Usual monitoring for relapse includes muscle strength testing on examination and evaluation of trending CK levels.⁸

Our patient received monthly 2-g/kg IVIG infusions, which led to slow, consistent improvement in her strength and normalization of her CK levels to 181 U/L after 6 months.

THE TAKEAWAY

Anti-HMGCR myositis should be suspected in any patient currently or previously treated with a statin who presents with proximal muscle weakness, myalgias, or an elevated CK level. We suggest early subspecialty consultation to discuss whether antibody testing, EMG, or muscle biopsy are warranted. If anti-HMGCR myositis is confirmed, it is advisable to rule out comorbid malignancy and initiate early combination treatment to minimize relapses and permanent muscle damage.

CORRESPONDENCE
Daniel T. Schoenherr, MD, Family Medicine Residency, National Capital Consortium–Alexander T. Augusta Military Medical Center, 9300 DeWitt Loop, Fort Belvoir, VA 22060; [email protected]

Pharmaceutical-grade cannabidiol (CBD) relieved symptoms in patients with idiopathic and diabetic gastroparesis and increased tolerance of liquid nutrient intake after 4 weeks of treatment in a phase 2 randomized double-blinded, placebo-controlled study recently published in Clinical Gastroenterology and Hepatology.

There is “significant unmet medical need in gastroparesis,” and compared with cannabis, which has been used to relieve nausea and pain in patients with the condition, CBD has limited psychic effects with the added potential to reduce gut sensation and inflammation, wrote Ting Zheng, MD, and colleagues at Mayo Clinic in Rochester, Minn.

The researchers assessed the symptoms of 44 patients (21 randomized to receive CBD and 23 to receive placebo) – each of whom had nonsurgical gastroparesis with documented delayed gastric emptying of solids (GES) by scintigraphy for at least 3 months – with the American Neurogastroenterology and Motility Society’s Gastroparesis Cardinal Symptom Index (GCSI) Daily Diary.

They measured GES at baseline, and at 4 weeks, they measured GES again as well as fasting and postprandial gastric volumes and satiation using a validated Ensure drink test. (Patients ingested Ensure [Abbott Laboratories] at a rate of 30 mL/min and recorded their sensations every 5 minutes.) The two treatment arms were compared via 2-way analysis of covariance that included body mass index and, when applicable, baseline measurements.

Patients in the CBD group received twice-daily oral Epidiolex (Jazz Pharmaceuticals, Dublin), which is Food and Drug Administration–approved for the treatment of seizures associated with two rare forms of epilepsy and with another rare genetic disease in patients 1 year of age and older.

The researchers documented significant improvements in the CBD group in total GCSI score (P = .0008) and in scores measuring the inability to finish a normal-sized meal (P = .029), number of vomiting episodes/24 hours (P = .006), and overall perceived severity of symptoms (P = .034).

CBD treatment was also associated with greater tolerated volume of Ensure – “without increases in scores for nausea, fullness, bloating, and pain” – and, in another component of the GCSI, there was “a borderline reduction in upper abdominal pain,” Dr. Zheng and coauthors wrote.

There was a significant slowing of GES in the CBD group, however, and no significant differences were seen at 4 weeks in the fasting or accommodation gastric volumes between the two treatment groups. That beneficial effects of CBD were seen despite slowing of GES “raises the question of the contribution of the delayed GE of solids to development of symptoms in patients with gastroparesis, which is supported by some but not all meta-analyses on this topic,” they noted.

Patients had a mean age of 44 and most were female. Of the 44 patients, 32 had idiopathic gastroparesis, 6 had type 1 diabetes, and 6 had type 2 diabetes. Four patients in the study did not tolerate the FDA-recommended full-dose escalation of CBD to 20 mg/kg per day, but completed the study on the highest tolerated dose.

Adverse effects (fatigue, headache, nausea) were distributed equally between the two groups, but diarrhea was more common in the CBD group. Diarrhea was the most common adverse event in a recently published analysis of 892 pediatric patients receiving Epidiolex over an estimated 1,755.7 patient-years of CBD exposure, the researchers noted.

CBD is a cannabinoid receptor 2 inverse agonist with central nervous system effects, but it also affects visceral or somatic sensation peripherally, the authors noted. The beneficial effects of CBD in gastroparesis are “presumed to reflect effects on sensory mechanisms or anti-inflammatory effects mediated via CBR2 (cannabinoid receptor type 2) reversing the hypersensitivity and intrinsic inflammatory pathogenesis recorded in idiopathic and diabetic gastroparesis,” Dr. Zheng and colleagues wrote. CBD may also, in a mechanism unrelated to CB receptors, inhibit smooth muscle contractile activity, they said.

Larger randomized controlled trials of longer-term administration of CBD in both idiopathic and diabetic gastroparesis are warranted, the investigators said.

The researchers disclosed no conflicts. The study was supported by a grant from the National Institutes of Health.

Pharmaceutical-grade cannabidiol (CBD) relieved symptoms in patients with idiopathic and diabetic gastroparesis and increased tolerance of liquid nutrient intake after 4 weeks of treatment in a phase 2 randomized double-blinded, placebo-controlled study recently published in Clinical Gastroenterology and Hepatology.

There is “significant unmet medical need in gastroparesis,” and compared with cannabis, which has been used to relieve nausea and pain in patients with the condition, CBD has limited psychic effects with the added potential to reduce gut sensation and inflammation, wrote Ting Zheng, MD, and colleagues at Mayo Clinic in Rochester, Minn.

The researchers assessed the symptoms of 44 patients (21 randomized to receive CBD and 23 to receive placebo) – each of whom had nonsurgical gastroparesis with documented delayed gastric emptying of solids (GES) by scintigraphy for at least 3 months – with the American Neurogastroenterology and Motility Society’s Gastroparesis Cardinal Symptom Index (GCSI) Daily Diary.

They measured GES at baseline, and at 4 weeks, they measured GES again as well as fasting and postprandial gastric volumes and satiation using a validated Ensure drink test. (Patients ingested Ensure [Abbott Laboratories] at a rate of 30 mL/min and recorded their sensations every 5 minutes.) The two treatment arms were compared via 2-way analysis of covariance that included body mass index and, when applicable, baseline measurements.

Patients in the CBD group received twice-daily oral Epidiolex (Jazz Pharmaceuticals, Dublin), which is Food and Drug Administration–approved for the treatment of seizures associated with two rare forms of epilepsy and with another rare genetic disease in patients 1 year of age and older.

The researchers documented significant improvements in the CBD group in total GCSI score (P = .0008) and in scores measuring the inability to finish a normal-sized meal (P = .029), number of vomiting episodes/24 hours (P = .006), and overall perceived severity of symptoms (P = .034).

CBD treatment was also associated with greater tolerated volume of Ensure – “without increases in scores for nausea, fullness, bloating, and pain” – and, in another component of the GCSI, there was “a borderline reduction in upper abdominal pain,” Dr. Zheng and coauthors wrote.

There was a significant slowing of GES in the CBD group, however, and no significant differences were seen at 4 weeks in the fasting or accommodation gastric volumes between the two treatment groups. That beneficial effects of CBD were seen despite slowing of GES “raises the question of the contribution of the delayed GE of solids to development of symptoms in patients with gastroparesis, which is supported by some but not all meta-analyses on this topic,” they noted.

Patients had a mean age of 44 and most were female. Of the 44 patients, 32 had idiopathic gastroparesis, 6 had type 1 diabetes, and 6 had type 2 diabetes. Four patients in the study did not tolerate the FDA-recommended full-dose escalation of CBD to 20 mg/kg per day, but completed the study on the highest tolerated dose.

Adverse effects (fatigue, headache, nausea) were distributed equally between the two groups, but diarrhea was more common in the CBD group. Diarrhea was the most common adverse event in a recently published analysis of 892 pediatric patients receiving Epidiolex over an estimated 1,755.7 patient-years of CBD exposure, the researchers noted.

CBD is a cannabinoid receptor 2 inverse agonist with central nervous system effects, but it also affects visceral or somatic sensation peripherally, the authors noted. The beneficial effects of CBD in gastroparesis are “presumed to reflect effects on sensory mechanisms or anti-inflammatory effects mediated via CBR2 (cannabinoid receptor type 2) reversing the hypersensitivity and intrinsic inflammatory pathogenesis recorded in idiopathic and diabetic gastroparesis,” Dr. Zheng and colleagues wrote. CBD may also, in a mechanism unrelated to CB receptors, inhibit smooth muscle contractile activity, they said.

Larger randomized controlled trials of longer-term administration of CBD in both idiopathic and diabetic gastroparesis are warranted, the investigators said.

The researchers disclosed no conflicts. The study was supported by a grant from the National Institutes of Health.

Pharmaceutical-grade cannabidiol (CBD) relieved symptoms in patients with idiopathic and diabetic gastroparesis and increased tolerance of liquid nutrient intake after 4 weeks of treatment in a phase 2 randomized double-blinded, placebo-controlled study recently published in Clinical Gastroenterology and Hepatology.

There is “significant unmet medical need in gastroparesis,” and compared with cannabis, which has been used to relieve nausea and pain in patients with the condition, CBD has limited psychic effects with the added potential to reduce gut sensation and inflammation, wrote Ting Zheng, MD, and colleagues at Mayo Clinic in Rochester, Minn.

The researchers assessed the symptoms of 44 patients (21 randomized to receive CBD and 23 to receive placebo) – each of whom had nonsurgical gastroparesis with documented delayed gastric emptying of solids (GES) by scintigraphy for at least 3 months – with the American Neurogastroenterology and Motility Society’s Gastroparesis Cardinal Symptom Index (GCSI) Daily Diary.

They measured GES at baseline, and at 4 weeks, they measured GES again as well as fasting and postprandial gastric volumes and satiation using a validated Ensure drink test. (Patients ingested Ensure [Abbott Laboratories] at a rate of 30 mL/min and recorded their sensations every 5 minutes.) The two treatment arms were compared via 2-way analysis of covariance that included body mass index and, when applicable, baseline measurements.

Patients in the CBD group received twice-daily oral Epidiolex (Jazz Pharmaceuticals, Dublin), which is Food and Drug Administration–approved for the treatment of seizures associated with two rare forms of epilepsy and with another rare genetic disease in patients 1 year of age and older.

The researchers documented significant improvements in the CBD group in total GCSI score (P = .0008) and in scores measuring the inability to finish a normal-sized meal (P = .029), number of vomiting episodes/24 hours (P = .006), and overall perceived severity of symptoms (P = .034).

CBD treatment was also associated with greater tolerated volume of Ensure – “without increases in scores for nausea, fullness, bloating, and pain” – and, in another component of the GCSI, there was “a borderline reduction in upper abdominal pain,” Dr. Zheng and coauthors wrote.

There was a significant slowing of GES in the CBD group, however, and no significant differences were seen at 4 weeks in the fasting or accommodation gastric volumes between the two treatment groups. That beneficial effects of CBD were seen despite slowing of GES “raises the question of the contribution of the delayed GE of solids to development of symptoms in patients with gastroparesis, which is supported by some but not all meta-analyses on this topic,” they noted.

Patients had a mean age of 44 and most were female. Of the 44 patients, 32 had idiopathic gastroparesis, 6 had type 1 diabetes, and 6 had type 2 diabetes. Four patients in the study did not tolerate the FDA-recommended full-dose escalation of CBD to 20 mg/kg per day, but completed the study on the highest tolerated dose.

Adverse effects (fatigue, headache, nausea) were distributed equally between the two groups, but diarrhea was more common in the CBD group. Diarrhea was the most common adverse event in a recently published analysis of 892 pediatric patients receiving Epidiolex over an estimated 1,755.7 patient-years of CBD exposure, the researchers noted.

CBD is a cannabinoid receptor 2 inverse agonist with central nervous system effects, but it also affects visceral or somatic sensation peripherally, the authors noted. The beneficial effects of CBD in gastroparesis are “presumed to reflect effects on sensory mechanisms or anti-inflammatory effects mediated via CBR2 (cannabinoid receptor type 2) reversing the hypersensitivity and intrinsic inflammatory pathogenesis recorded in idiopathic and diabetic gastroparesis,” Dr. Zheng and colleagues wrote. CBD may also, in a mechanism unrelated to CB receptors, inhibit smooth muscle contractile activity, they said.

Larger randomized controlled trials of longer-term administration of CBD in both idiopathic and diabetic gastroparesis are warranted, the investigators said.

The researchers disclosed no conflicts. The study was supported by a grant from the National Institutes of Health.

Dermatopathologists tend to render “more severe diagnoses for skin biopsy cases of melanocytic lesions” more often than general pathologists, results from an exploratory study showed.

The findings “could in part play a role in the rising incidence of early-stage melanoma with low risk of progression or patient morbidity, thereby contributing to increasing rates of overdiagnosis,” researchers led by co–senior authors Joann G. Elmore, MD, MPH, of the University of California, Los Angeles, and Raymond L. Barnhill, MD, MBA, of the Institut Curie, Paris, wrote in their study, published online in JAMA Dermatology.

To investigate the characteristics associated with rendering higher-grade diagnoses, including invasive melanoma, the researchers drew from two national data sets: the Melanoma Pathology (M-Path) study, conducted from July 2013 to May 2016, and the Reducing Errors in Melanocytic Interpretations (REMI) study, conducted from August 2018 to March 2021. In both studies, pathologists who interpreted melanocytic lesions in their clinical practices interpreted study cases in glass slide format. For the current study, researchers used logistic regression to examine the association of pathologist characteristics with diagnosis of a study case as higher grade (including severely dysplastic and melanoma in situ) vs. lower grade (including mild to moderately dysplastic nevi) and diagnosis of invasive melanoma vs. any less severe diagnosis.

A total of 338 pathologists were included in the analysis. Of these, 113 were general pathologists and 225 were dermatopathologists (those who were board certified and/or fellowship trained in dermatopathology).

The researchers found that, compared with general pathologists, dermatopathologists were 2.63 times more likely to render higher-grade diagnoses and 1.95 times more likely to diagnose invasive melanoma (P < .001 for both associations). Diagnoses of stage pT1a melanomas with no mitotic activity completely accounted for the difference between dermatopathologists and general pathologists in diagnosing invasive melanoma.

For the analysis limited to the 225 dermatopathologists, those with a higher practice caseload of melanocytic lesions were more likely to assign higher-grade diagnoses (odds ratio for trend, 1.27; P = .02), while those affiliated with an academic center had lower odds of diagnosing invasive melanoma (OR, 0.61; P = .049).

The researchers acknowledged limitations of their analysis, including the lack of data on patient outcomes, “so we could not make conclusions about the clinical outcome of any particular diagnosis by a study participant,” they wrote. “While our analyses revealed pathologist characteristics associated with assigning more vs. less severe diagnoses of melanocytic lesions, we could not conclude that any particular diagnosis by a study participant was overcalling or undercalling. However, the epidemiologic evidence that melanoma is overdiagnosed suggests that overcalling by some pathologists may be contributing to increasing rates of low-risk melanoma diagnoses.”

In an accompanying editorial, authors Klaus J. Busam, MD, of the department of pathology and laboratory medicine at Memorial Sloan Kettering Cancer Center, New York, Pedram Gerami, MD, of the department of dermatology at Northwestern University, Chicago, and Richard A. Scolyer, MD, of the Melanoma Institute, Wollstonecraft, Australia, wrote that the study findings “raise the question of whether subspecialization in dermatopathology may be a factor contributing to the epidemiologic phenomenon of overdiagnosis – that is, the discordance in the rise of melanoma incidence and relatively constant annual mortality rates over many decades. The findings also invite a discussion about strategies to minimize harm from overdiagnosis for both patients and the health care system.”

To minimize misdiagnoses, they continued, efforts to facilitate diagnostic accuracy should be encouraged. “Excisional (rather than partial) biopsies and provision of relevant clinical information would facilitate rendering of the correct histopathologic diagnosis,” they wrote. “When the diagnosis is uncertain, this is best acknowledged. If felt necessary, a reexcision of a lesion with an uncertain diagnosis can be recommended without upgrading the diagnosis.”

In addition, “improvements in prognosis are needed beyond American Joint Committee on Cancer staging,” they noted. “This will likely require a multimodal approach with novel methods, including artificial intelligence and biomarkers that help distinguish low-risk melanomas, for which a conservative approach may be appropriate, from those that require surgical intervention.”

The study was supported by the National Center for Advancing Translational Sciences and by the National Institutes of Health. One author disclosed receiving grants from the National Cancer Institute during the conduct of the study, and another disclosed serving as editor in chief of Primary Care topics at UpToDate; other authors had no disclosures. Dr. Busam reported receiving nonfinancial support from the American Society of Dermatopathology. Dr. Gerami reported receiving consulting fees from Castle Biosciences. Dr. Scolyer reported receiving an investigator grant from the National Health and Medical Research Council of Australia during the conduct of the study and personal fees from several pharmaceutical companies outside the submitted work.

Dermatopathologists tend to render “more severe diagnoses for skin biopsy cases of melanocytic lesions” more often than general pathologists, results from an exploratory study showed.

The findings “could in part play a role in the rising incidence of early-stage melanoma with low risk of progression or patient morbidity, thereby contributing to increasing rates of overdiagnosis,” researchers led by co–senior authors Joann G. Elmore, MD, MPH, of the University of California, Los Angeles, and Raymond L. Barnhill, MD, MBA, of the Institut Curie, Paris, wrote in their study, published online in JAMA Dermatology.

To investigate the characteristics associated with rendering higher-grade diagnoses, including invasive melanoma, the researchers drew from two national data sets: the Melanoma Pathology (M-Path) study, conducted from July 2013 to May 2016, and the Reducing Errors in Melanocytic Interpretations (REMI) study, conducted from August 2018 to March 2021. In both studies, pathologists who interpreted melanocytic lesions in their clinical practices interpreted study cases in glass slide format. For the current study, researchers used logistic regression to examine the association of pathologist characteristics with diagnosis of a study case as higher grade (including severely dysplastic and melanoma in situ) vs. lower grade (including mild to moderately dysplastic nevi) and diagnosis of invasive melanoma vs. any less severe diagnosis.

A total of 338 pathologists were included in the analysis. Of these, 113 were general pathologists and 225 were dermatopathologists (those who were board certified and/or fellowship trained in dermatopathology).

The researchers found that, compared with general pathologists, dermatopathologists were 2.63 times more likely to render higher-grade diagnoses and 1.95 times more likely to diagnose invasive melanoma (P < .001 for both associations). Diagnoses of stage pT1a melanomas with no mitotic activity completely accounted for the difference between dermatopathologists and general pathologists in diagnosing invasive melanoma.

For the analysis limited to the 225 dermatopathologists, those with a higher practice caseload of melanocytic lesions were more likely to assign higher-grade diagnoses (odds ratio for trend, 1.27; P = .02), while those affiliated with an academic center had lower odds of diagnosing invasive melanoma (OR, 0.61; P = .049).

The researchers acknowledged limitations of their analysis, including the lack of data on patient outcomes, “so we could not make conclusions about the clinical outcome of any particular diagnosis by a study participant,” they wrote. “While our analyses revealed pathologist characteristics associated with assigning more vs. less severe diagnoses of melanocytic lesions, we could not conclude that any particular diagnosis by a study participant was overcalling or undercalling. However, the epidemiologic evidence that melanoma is overdiagnosed suggests that overcalling by some pathologists may be contributing to increasing rates of low-risk melanoma diagnoses.”

In an accompanying editorial, authors Klaus J. Busam, MD, of the department of pathology and laboratory medicine at Memorial Sloan Kettering Cancer Center, New York, Pedram Gerami, MD, of the department of dermatology at Northwestern University, Chicago, and Richard A. Scolyer, MD, of the Melanoma Institute, Wollstonecraft, Australia, wrote that the study findings “raise the question of whether subspecialization in dermatopathology may be a factor contributing to the epidemiologic phenomenon of overdiagnosis – that is, the discordance in the rise of melanoma incidence and relatively constant annual mortality rates over many decades. The findings also invite a discussion about strategies to minimize harm from overdiagnosis for both patients and the health care system.”

To minimize misdiagnoses, they continued, efforts to facilitate diagnostic accuracy should be encouraged. “Excisional (rather than partial) biopsies and provision of relevant clinical information would facilitate rendering of the correct histopathologic diagnosis,” they wrote. “When the diagnosis is uncertain, this is best acknowledged. If felt necessary, a reexcision of a lesion with an uncertain diagnosis can be recommended without upgrading the diagnosis.”

In addition, “improvements in prognosis are needed beyond American Joint Committee on Cancer staging,” they noted. “This will likely require a multimodal approach with novel methods, including artificial intelligence and biomarkers that help distinguish low-risk melanomas, for which a conservative approach may be appropriate, from those that require surgical intervention.”

The study was supported by the National Center for Advancing Translational Sciences and by the National Institutes of Health. One author disclosed receiving grants from the National Cancer Institute during the conduct of the study, and another disclosed serving as editor in chief of Primary Care topics at UpToDate; other authors had no disclosures. Dr. Busam reported receiving nonfinancial support from the American Society of Dermatopathology. Dr. Gerami reported receiving consulting fees from Castle Biosciences. Dr. Scolyer reported receiving an investigator grant from the National Health and Medical Research Council of Australia during the conduct of the study and personal fees from several pharmaceutical companies outside the submitted work.

Dermatopathologists tend to render “more severe diagnoses for skin biopsy cases of melanocytic lesions” more often than general pathologists, results from an exploratory study showed.

The findings “could in part play a role in the rising incidence of early-stage melanoma with low risk of progression or patient morbidity, thereby contributing to increasing rates of overdiagnosis,” researchers led by co–senior authors Joann G. Elmore, MD, MPH, of the University of California, Los Angeles, and Raymond L. Barnhill, MD, MBA, of the Institut Curie, Paris, wrote in their study, published online in JAMA Dermatology.

To investigate the characteristics associated with rendering higher-grade diagnoses, including invasive melanoma, the researchers drew from two national data sets: the Melanoma Pathology (M-Path) study, conducted from July 2013 to May 2016, and the Reducing Errors in Melanocytic Interpretations (REMI) study, conducted from August 2018 to March 2021. In both studies, pathologists who interpreted melanocytic lesions in their clinical practices interpreted study cases in glass slide format. For the current study, researchers used logistic regression to examine the association of pathologist characteristics with diagnosis of a study case as higher grade (including severely dysplastic and melanoma in situ) vs. lower grade (including mild to moderately dysplastic nevi) and diagnosis of invasive melanoma vs. any less severe diagnosis.

A total of 338 pathologists were included in the analysis. Of these, 113 were general pathologists and 225 were dermatopathologists (those who were board certified and/or fellowship trained in dermatopathology).

The researchers found that, compared with general pathologists, dermatopathologists were 2.63 times more likely to render higher-grade diagnoses and 1.95 times more likely to diagnose invasive melanoma (P < .001 for both associations). Diagnoses of stage pT1a melanomas with no mitotic activity completely accounted for the difference between dermatopathologists and general pathologists in diagnosing invasive melanoma.

For the analysis limited to the 225 dermatopathologists, those with a higher practice caseload of melanocytic lesions were more likely to assign higher-grade diagnoses (odds ratio for trend, 1.27; P = .02), while those affiliated with an academic center had lower odds of diagnosing invasive melanoma (OR, 0.61; P = .049).

The researchers acknowledged limitations of their analysis, including the lack of data on patient outcomes, “so we could not make conclusions about the clinical outcome of any particular diagnosis by a study participant,” they wrote. “While our analyses revealed pathologist characteristics associated with assigning more vs. less severe diagnoses of melanocytic lesions, we could not conclude that any particular diagnosis by a study participant was overcalling or undercalling. However, the epidemiologic evidence that melanoma is overdiagnosed suggests that overcalling by some pathologists may be contributing to increasing rates of low-risk melanoma diagnoses.”

In an accompanying editorial, authors Klaus J. Busam, MD, of the department of pathology and laboratory medicine at Memorial Sloan Kettering Cancer Center, New York, Pedram Gerami, MD, of the department of dermatology at Northwestern University, Chicago, and Richard A. Scolyer, MD, of the Melanoma Institute, Wollstonecraft, Australia, wrote that the study findings “raise the question of whether subspecialization in dermatopathology may be a factor contributing to the epidemiologic phenomenon of overdiagnosis – that is, the discordance in the rise of melanoma incidence and relatively constant annual mortality rates over many decades. The findings also invite a discussion about strategies to minimize harm from overdiagnosis for both patients and the health care system.”

To minimize misdiagnoses, they continued, efforts to facilitate diagnostic accuracy should be encouraged. “Excisional (rather than partial) biopsies and provision of relevant clinical information would facilitate rendering of the correct histopathologic diagnosis,” they wrote. “When the diagnosis is uncertain, this is best acknowledged. If felt necessary, a reexcision of a lesion with an uncertain diagnosis can be recommended without upgrading the diagnosis.”

In addition, “improvements in prognosis are needed beyond American Joint Committee on Cancer staging,” they noted. “This will likely require a multimodal approach with novel methods, including artificial intelligence and biomarkers that help distinguish low-risk melanomas, for which a conservative approach may be appropriate, from those that require surgical intervention.”

The study was supported by the National Center for Advancing Translational Sciences and by the National Institutes of Health. One author disclosed receiving grants from the National Cancer Institute during the conduct of the study, and another disclosed serving as editor in chief of Primary Care topics at UpToDate; other authors had no disclosures. Dr. Busam reported receiving nonfinancial support from the American Society of Dermatopathology. Dr. Gerami reported receiving consulting fees from Castle Biosciences. Dr. Scolyer reported receiving an investigator grant from the National Health and Medical Research Council of Australia during the conduct of the study and personal fees from several pharmaceutical companies outside the submitted work.

Two biomarkers – pregnancy-associated plasma protein A2 (PAPP-A2) and activin A – when added to relevant clinical information have a better positive predictive value than and a comparable negative predictive value to the currently used ratio of soluble fms-like tyrosine kinase 1 (sFlt-1) to placental growth factor (PlGF), new research suggests.

The third-trimester sFlt-1:PlGF ratio can predict short-term absence of preeclampsia. By contrast, PAPP-A2 and activin A could serve as biomarkers to predict the occurrence as well as the absence of preeclampsia, according to the authors.

Preeclampsia has “potentially devastating maternal and fetal complications, [including] significantly increased cardiovascular risk for affected women later in life,” study author Stella S. Daskalopoulou, MD, PhD, associate professor of medicine at McGill University Health Centre in Montreal, said in an interview.

“A more accurate prediction of preeclampsia is expected to improve risk stratification and clinical care and shape clinical practice guidelines,” she said.

The study was published online in the Canadian Journal of Cardiology.
 

Better predictive value

For a prospective cohort study, the investigators recruited 192 women with first-trimester high-risk singleton pregnancies from tertiary obstetric clinics in Montreal.

At baseline, they collected clinical information, including height, prepregnancy weight, personal and family medical history, and medication use.

At each trimester, blood pressure was measured, and blood samples were collected to quantify sFlt-1, PlGF, PAPP-A2, PAPP-A, activin A, inhibin A, follistatin, and glycosylated fibronectin. For the sFlt-1:PlGF ratio, the researchers used a cutoff point of 38, based on prior evidence. Because there are no agreed-upon cutoff points for the other biomarkers, they chose cutoff points that maximized sensitivity and specificity.

Pregnancies were considered high risk if the mother had any of the following conditions: prepregnancy BMI ≥ 25, maternal age ≥ 35 years, chronic hypertension, diabetes, renal disease, conception via in vitro fertilization, or maternal or first-degree family history of preeclampsia.

The primary outcome was preeclampsia, which was defined according to the Society of Obstetrics and Gynecology guidelines as systolic blood pressure ≥ 140 mm Hg or diastolic blood pressure of ≥ mm Hg together with either proteinuria or maternal end-organ dysfunction.

A total of 18 women (9.38%) developed preeclampsia. Those women had higher blood pressure at baseline (although it was within normal limits) and were more likely to have preexisting diabetes or a previous pregnancy with preeclampsia. They were also more likely to report Black race. Serum levels of PAPP-A, PAPP-A2, activin A, and inhibin A were significantly different between patients who developed preeclampsia and those who did not. These levels were increased throughout pregnancy.

Alongside the sFlt-1:PlGF ratio, two biomarkers, PAPP-A2 (odds ratio, 1.78) and activin A (OR, 1.84), were significantly associated with the primary outcome after adjustment for age, prepregnancy BMI, race, and mean arterial pressure.

When added to a model that included those clinical factors, a positive third-trimester result for both PAPP-A2 and activin A had a better positive predictive value than the sFlt-1:PlGF ratio added to the clinical model (91.67% vs. 66.67%). The two biomarkers also had a negative predictive value that was comparable to that of the sFlt-1:PlGF ratio (97.69% vs. 96%).

Study limitations include the small sample size and missing covariates for some participants. Furthermore, the findings cannot be generalized to low-risk populations.

“Whereas the third-trimester sFlt-1:PlGF ratio can predict short-term absence of preeclampsia, PAPP-A2 and activin A had both high positive and negative predictive values and thus could serve as biomarkers to predict the occurrence (and absence) of preeclampsia; these findings will be validated in future studies,” the authors concluded.

Dr. Daskalopoulou said that her group is currently performing a large multinational study, PULSE, “which will be the ideal platform to validate and extend our findings. The aim of the study is to predict preeclampsia using a multimodal approach that includes arterial stiffness measurements and blood biomarkers.”

She expanded on the potential benefits of this research. “Finding an accurate predictive tool would not only help design appropriate early care plans for truly high-risk pregnant women, including monitoring and delivery planning, but also facilitate the development of novel strategies for the prevention and treatment of preeclampsia, improving the life of millions of young mothers and their offspring around the world.”
 

Promising biomarkers

Commenting on the study, Nieca Goldberg, MD, clinical associate professor of medicine at NYU Langone Health and medical director of Atria, both in New York, said, “These biomarkers are promising, as the current biomarker, sFlt-1:PlGF, is good at ruling out preeclampsia in the short term, while the new biomarkers show that they are better at ruling in preeclampsia” as well as ruling it out. Dr. Goldberg was not involved in the research.

“The current study is small, some participant data points are missing, and the researchers only studied high-risk pregnancies,” she added. “We need larger studies of all the risk markers, in both high- and low-risk pregnancies that are followed throughout pregnancy.”

This work was supported by the Fonds de recherche du Québec Santé (FRQS), Heart and Stroke Foundation of Canada, McGill University Department of Obstetrics and Gynecology Academic Enrichment Fund, and Canadian Foundation for Women›s Health. Dr. Daskalopoulou is a senior clinician-scientist supported by a FRQS Clinician Scientist-Senior salary award. Dr. Daskalopoulou and Dr. Goldberg disclosed no conflicts of interest.

A version of this article appeared on Medscape.com.

Two biomarkers – pregnancy-associated plasma protein A2 (PAPP-A2) and activin A – when added to relevant clinical information have a better positive predictive value than and a comparable negative predictive value to the currently used ratio of soluble fms-like tyrosine kinase 1 (sFlt-1) to placental growth factor (PlGF), new research suggests.

The third-trimester sFlt-1:PlGF ratio can predict short-term absence of preeclampsia. By contrast, PAPP-A2 and activin A could serve as biomarkers to predict the occurrence as well as the absence of preeclampsia, according to the authors.

Preeclampsia has “potentially devastating maternal and fetal complications, [including] significantly increased cardiovascular risk for affected women later in life,” study author Stella S. Daskalopoulou, MD, PhD, associate professor of medicine at McGill University Health Centre in Montreal, said in an interview.

“A more accurate prediction of preeclampsia is expected to improve risk stratification and clinical care and shape clinical practice guidelines,” she said.

The study was published online in the Canadian Journal of Cardiology.
 

Better predictive value

For a prospective cohort study, the investigators recruited 192 women with first-trimester high-risk singleton pregnancies from tertiary obstetric clinics in Montreal.

At baseline, they collected clinical information, including height, prepregnancy weight, personal and family medical history, and medication use.

At each trimester, blood pressure was measured, and blood samples were collected to quantify sFlt-1, PlGF, PAPP-A2, PAPP-A, activin A, inhibin A, follistatin, and glycosylated fibronectin. For the sFlt-1:PlGF ratio, the researchers used a cutoff point of 38, based on prior evidence. Because there are no agreed-upon cutoff points for the other biomarkers, they chose cutoff points that maximized sensitivity and specificity.

Pregnancies were considered high risk if the mother had any of the following conditions: prepregnancy BMI ≥ 25, maternal age ≥ 35 years, chronic hypertension, diabetes, renal disease, conception via in vitro fertilization, or maternal or first-degree family history of preeclampsia.

The primary outcome was preeclampsia, which was defined according to the Society of Obstetrics and Gynecology guidelines as systolic blood pressure ≥ 140 mm Hg or diastolic blood pressure of ≥ mm Hg together with either proteinuria or maternal end-organ dysfunction.

A total of 18 women (9.38%) developed preeclampsia. Those women had higher blood pressure at baseline (although it was within normal limits) and were more likely to have preexisting diabetes or a previous pregnancy with preeclampsia. They were also more likely to report Black race. Serum levels of PAPP-A, PAPP-A2, activin A, and inhibin A were significantly different between patients who developed preeclampsia and those who did not. These levels were increased throughout pregnancy.

Alongside the sFlt-1:PlGF ratio, two biomarkers, PAPP-A2 (odds ratio, 1.78) and activin A (OR, 1.84), were significantly associated with the primary outcome after adjustment for age, prepregnancy BMI, race, and mean arterial pressure.

When added to a model that included those clinical factors, a positive third-trimester result for both PAPP-A2 and activin A had a better positive predictive value than the sFlt-1:PlGF ratio added to the clinical model (91.67% vs. 66.67%). The two biomarkers also had a negative predictive value that was comparable to that of the sFlt-1:PlGF ratio (97.69% vs. 96%).

Study limitations include the small sample size and missing covariates for some participants. Furthermore, the findings cannot be generalized to low-risk populations.

“Whereas the third-trimester sFlt-1:PlGF ratio can predict short-term absence of preeclampsia, PAPP-A2 and activin A had both high positive and negative predictive values and thus could serve as biomarkers to predict the occurrence (and absence) of preeclampsia; these findings will be validated in future studies,” the authors concluded.

Dr. Daskalopoulou said that her group is currently performing a large multinational study, PULSE, “which will be the ideal platform to validate and extend our findings. The aim of the study is to predict preeclampsia using a multimodal approach that includes arterial stiffness measurements and blood biomarkers.”

She expanded on the potential benefits of this research. “Finding an accurate predictive tool would not only help design appropriate early care plans for truly high-risk pregnant women, including monitoring and delivery planning, but also facilitate the development of novel strategies for the prevention and treatment of preeclampsia, improving the life of millions of young mothers and their offspring around the world.”
 

Promising biomarkers

Commenting on the study, Nieca Goldberg, MD, clinical associate professor of medicine at NYU Langone Health and medical director of Atria, both in New York, said, “These biomarkers are promising, as the current biomarker, sFlt-1:PlGF, is good at ruling out preeclampsia in the short term, while the new biomarkers show that they are better at ruling in preeclampsia” as well as ruling it out. Dr. Goldberg was not involved in the research.

“The current study is small, some participant data points are missing, and the researchers only studied high-risk pregnancies,” she added. “We need larger studies of all the risk markers, in both high- and low-risk pregnancies that are followed throughout pregnancy.”

This work was supported by the Fonds de recherche du Québec Santé (FRQS), Heart and Stroke Foundation of Canada, McGill University Department of Obstetrics and Gynecology Academic Enrichment Fund, and Canadian Foundation for Women›s Health. Dr. Daskalopoulou is a senior clinician-scientist supported by a FRQS Clinician Scientist-Senior salary award. Dr. Daskalopoulou and Dr. Goldberg disclosed no conflicts of interest.

A version of this article appeared on Medscape.com.

Two biomarkers – pregnancy-associated plasma protein A2 (PAPP-A2) and activin A – when added to relevant clinical information have a better positive predictive value than and a comparable negative predictive value to the currently used ratio of soluble fms-like tyrosine kinase 1 (sFlt-1) to placental growth factor (PlGF), new research suggests.

The third-trimester sFlt-1:PlGF ratio can predict short-term absence of preeclampsia. By contrast, PAPP-A2 and activin A could serve as biomarkers to predict the occurrence as well as the absence of preeclampsia, according to the authors.

Preeclampsia has “potentially devastating maternal and fetal complications, [including] significantly increased cardiovascular risk for affected women later in life,” study author Stella S. Daskalopoulou, MD, PhD, associate professor of medicine at McGill University Health Centre in Montreal, said in an interview.

“A more accurate prediction of preeclampsia is expected to improve risk stratification and clinical care and shape clinical practice guidelines,” she said.

The study was published online in the Canadian Journal of Cardiology.
 

Better predictive value

For a prospective cohort study, the investigators recruited 192 women with first-trimester high-risk singleton pregnancies from tertiary obstetric clinics in Montreal.

At baseline, they collected clinical information, including height, prepregnancy weight, personal and family medical history, and medication use.

At each trimester, blood pressure was measured, and blood samples were collected to quantify sFlt-1, PlGF, PAPP-A2, PAPP-A, activin A, inhibin A, follistatin, and glycosylated fibronectin. For the sFlt-1:PlGF ratio, the researchers used a cutoff point of 38, based on prior evidence. Because there are no agreed-upon cutoff points for the other biomarkers, they chose cutoff points that maximized sensitivity and specificity.

Pregnancies were considered high risk if the mother had any of the following conditions: prepregnancy BMI ≥ 25, maternal age ≥ 35 years, chronic hypertension, diabetes, renal disease, conception via in vitro fertilization, or maternal or first-degree family history of preeclampsia.

The primary outcome was preeclampsia, which was defined according to the Society of Obstetrics and Gynecology guidelines as systolic blood pressure ≥ 140 mm Hg or diastolic blood pressure of ≥ mm Hg together with either proteinuria or maternal end-organ dysfunction.

A total of 18 women (9.38%) developed preeclampsia. Those women had higher blood pressure at baseline (although it was within normal limits) and were more likely to have preexisting diabetes or a previous pregnancy with preeclampsia. They were also more likely to report Black race. Serum levels of PAPP-A, PAPP-A2, activin A, and inhibin A were significantly different between patients who developed preeclampsia and those who did not. These levels were increased throughout pregnancy.

Alongside the sFlt-1:PlGF ratio, two biomarkers, PAPP-A2 (odds ratio, 1.78) and activin A (OR, 1.84), were significantly associated with the primary outcome after adjustment for age, prepregnancy BMI, race, and mean arterial pressure.

When added to a model that included those clinical factors, a positive third-trimester result for both PAPP-A2 and activin A had a better positive predictive value than the sFlt-1:PlGF ratio added to the clinical model (91.67% vs. 66.67%). The two biomarkers also had a negative predictive value that was comparable to that of the sFlt-1:PlGF ratio (97.69% vs. 96%).

Study limitations include the small sample size and missing covariates for some participants. Furthermore, the findings cannot be generalized to low-risk populations.

“Whereas the third-trimester sFlt-1:PlGF ratio can predict short-term absence of preeclampsia, PAPP-A2 and activin A had both high positive and negative predictive values and thus could serve as biomarkers to predict the occurrence (and absence) of preeclampsia; these findings will be validated in future studies,” the authors concluded.

Dr. Daskalopoulou said that her group is currently performing a large multinational study, PULSE, “which will be the ideal platform to validate and extend our findings. The aim of the study is to predict preeclampsia using a multimodal approach that includes arterial stiffness measurements and blood biomarkers.”

She expanded on the potential benefits of this research. “Finding an accurate predictive tool would not only help design appropriate early care plans for truly high-risk pregnant women, including monitoring and delivery planning, but also facilitate the development of novel strategies for the prevention and treatment of preeclampsia, improving the life of millions of young mothers and their offspring around the world.”
 

Promising biomarkers

Commenting on the study, Nieca Goldberg, MD, clinical associate professor of medicine at NYU Langone Health and medical director of Atria, both in New York, said, “These biomarkers are promising, as the current biomarker, sFlt-1:PlGF, is good at ruling out preeclampsia in the short term, while the new biomarkers show that they are better at ruling in preeclampsia” as well as ruling it out. Dr. Goldberg was not involved in the research.

“The current study is small, some participant data points are missing, and the researchers only studied high-risk pregnancies,” she added. “We need larger studies of all the risk markers, in both high- and low-risk pregnancies that are followed throughout pregnancy.”

This work was supported by the Fonds de recherche du Québec Santé (FRQS), Heart and Stroke Foundation of Canada, McGill University Department of Obstetrics and Gynecology Academic Enrichment Fund, and Canadian Foundation for Women›s Health. Dr. Daskalopoulou is a senior clinician-scientist supported by a FRQS Clinician Scientist-Senior salary award. Dr. Daskalopoulou and Dr. Goldberg disclosed no conflicts of interest.

A version of this article appeared on Medscape.com.

Emergency department (ED) boarding in the United States has escalated to crisis levels, sparking significant concerns among adults, according to a poll conducted on behalf of the American College of Emergency Physicians in September 2023. This issue not only affects patient care but also has far-reaching consequences for the efficiency of emergency medical services (EMS).

The survey interviewed 2,164 adults and showed that an overwhelming majority (80%) expressed serious concerns about the boarding crisis. Moreover, 43% of respondents either delayed seeking medical care at an ED or avoided it altogether if they anticipated prolonged wait times before being admitted to the hospital or transferred to another facility.

Nearly half of adults (44%) experienced long wait times following initial care in an ED, and 16% of these adults reported 13 or more hours of waiting after receiving initial care.

“The boarding crisis is a predictable result of an acute care hospital system with insufficient capacity – we lack enough space and staff in our acute care hospitals, as we have not created the bed capacity needed for an aging and higher acuity patient population, and staffing shortages for inpatient beds have resulted in a longer hospital length of stay that we observe as boarding patients in the ED,” Arjun Venkatesh, MD, chief of emergency services at Yale New Haven Hospital, told this news organization, commenting on the factors contributing to this crisis.

One concerning side effect of boarding in EDs is the delayed response of ambulance services. When a hospital is unprepared to receive patients arriving in an ambulance, ambulance crews often wait with the patients for extended periods until the hospital can admit them. This situation can have critical implications, as parked ambulances are unable to respond to other emergencies in the community.

Adults who have endured long wait times in EDs voiced concerns about the negative impact such delays can have on their medical care. The experiences of patients and their families have underscored the urgency of addressing the boarding crisis.

“There are no low-hanging fruit solutions or simple communication strategies to alleviate these concerns,” said Dr. Venkatesh, adding that “the only way to change that perception is to change the care by addressing the lack of inpatient capacity and community care capacity to avoid back-up in the ED.”

The poll revealed that 93% of adults across different demographic groups considered EMS, including paramedics, essential. Older adults were more likely to emphasize the significance of these services than were younger adults.

“We all need a place for people to go when there is an emergency, whether it be trauma, a heart attack, a stroke, or similar conditions,” said Scott Weiner, MD, associate professor of emergency medicine at Harvard Medical School and attending emergency physician at Brigham and Women’s Hospital, Boston.

“However, the modern ED is much more than that. It has become the center for coordination of care across the health system where diagnostic tests can be completed promptly, where follow-up care is arranged, and where behavioral health emergencies come,” he added.

A vast majority, 89%, believed that additional or supplemental government funding should be directed toward these essential services, highlighting the public’s concern for the accessibility of EMS.

Dr. Weiner stressed the need for a complete realignment of the payment system: “It’s unfair that public insurance like Medicaid reimburses sometimes less than a quarter of the rate that commercial insurance pays for the exact same service. This exacerbates and perpetuates disparities in health.” According to him, the solution may involve transitioning to a single-payer model, but it could face significant challenges owing to people’s apprehensions about changes in their health care and negative perceptions of “socialized” medicine in other countries. Furthermore, the poll found that the largest share of adults (42%) believed that hospitals should take the lead in improving boarding and shortening ED wait times. These findings indicated the need for hospitals to reevaluate their processes and capabilities to reduce boarding and enhance the overall patient experience in EDs.

“The top three entities that can fix the boarding crisis are hospitals, Congress, and insurance companies,” noted Dr. Wiener. “However, until there is parity at all levels, hospitals will continue to accept lucrative elective admissions but allow ED patients to linger without a bed,” he added.
 

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

Emergency department (ED) boarding in the United States has escalated to crisis levels, sparking significant concerns among adults, according to a poll conducted on behalf of the American College of Emergency Physicians in September 2023. This issue not only affects patient care but also has far-reaching consequences for the efficiency of emergency medical services (EMS).

The survey interviewed 2,164 adults and showed that an overwhelming majority (80%) expressed serious concerns about the boarding crisis. Moreover, 43% of respondents either delayed seeking medical care at an ED or avoided it altogether if they anticipated prolonged wait times before being admitted to the hospital or transferred to another facility.

Nearly half of adults (44%) experienced long wait times following initial care in an ED, and 16% of these adults reported 13 or more hours of waiting after receiving initial care.

“The boarding crisis is a predictable result of an acute care hospital system with insufficient capacity – we lack enough space and staff in our acute care hospitals, as we have not created the bed capacity needed for an aging and higher acuity patient population, and staffing shortages for inpatient beds have resulted in a longer hospital length of stay that we observe as boarding patients in the ED,” Arjun Venkatesh, MD, chief of emergency services at Yale New Haven Hospital, told this news organization, commenting on the factors contributing to this crisis.

One concerning side effect of boarding in EDs is the delayed response of ambulance services. When a hospital is unprepared to receive patients arriving in an ambulance, ambulance crews often wait with the patients for extended periods until the hospital can admit them. This situation can have critical implications, as parked ambulances are unable to respond to other emergencies in the community.

Adults who have endured long wait times in EDs voiced concerns about the negative impact such delays can have on their medical care. The experiences of patients and their families have underscored the urgency of addressing the boarding crisis.

“There are no low-hanging fruit solutions or simple communication strategies to alleviate these concerns,” said Dr. Venkatesh, adding that “the only way to change that perception is to change the care by addressing the lack of inpatient capacity and community care capacity to avoid back-up in the ED.”

The poll revealed that 93% of adults across different demographic groups considered EMS, including paramedics, essential. Older adults were more likely to emphasize the significance of these services than were younger adults.

“We all need a place for people to go when there is an emergency, whether it be trauma, a heart attack, a stroke, or similar conditions,” said Scott Weiner, MD, associate professor of emergency medicine at Harvard Medical School and attending emergency physician at Brigham and Women’s Hospital, Boston.

“However, the modern ED is much more than that. It has become the center for coordination of care across the health system where diagnostic tests can be completed promptly, where follow-up care is arranged, and where behavioral health emergencies come,” he added.

A vast majority, 89%, believed that additional or supplemental government funding should be directed toward these essential services, highlighting the public’s concern for the accessibility of EMS.

Dr. Weiner stressed the need for a complete realignment of the payment system: “It’s unfair that public insurance like Medicaid reimburses sometimes less than a quarter of the rate that commercial insurance pays for the exact same service. This exacerbates and perpetuates disparities in health.” According to him, the solution may involve transitioning to a single-payer model, but it could face significant challenges owing to people’s apprehensions about changes in their health care and negative perceptions of “socialized” medicine in other countries. Furthermore, the poll found that the largest share of adults (42%) believed that hospitals should take the lead in improving boarding and shortening ED wait times. These findings indicated the need for hospitals to reevaluate their processes and capabilities to reduce boarding and enhance the overall patient experience in EDs.

“The top three entities that can fix the boarding crisis are hospitals, Congress, and insurance companies,” noted Dr. Wiener. “However, until there is parity at all levels, hospitals will continue to accept lucrative elective admissions but allow ED patients to linger without a bed,” he added.
 

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

Emergency department (ED) boarding in the United States has escalated to crisis levels, sparking significant concerns among adults, according to a poll conducted on behalf of the American College of Emergency Physicians in September 2023. This issue not only affects patient care but also has far-reaching consequences for the efficiency of emergency medical services (EMS).

The survey interviewed 2,164 adults and showed that an overwhelming majority (80%) expressed serious concerns about the boarding crisis. Moreover, 43% of respondents either delayed seeking medical care at an ED or avoided it altogether if they anticipated prolonged wait times before being admitted to the hospital or transferred to another facility.

Nearly half of adults (44%) experienced long wait times following initial care in an ED, and 16% of these adults reported 13 or more hours of waiting after receiving initial care.

“The boarding crisis is a predictable result of an acute care hospital system with insufficient capacity – we lack enough space and staff in our acute care hospitals, as we have not created the bed capacity needed for an aging and higher acuity patient population, and staffing shortages for inpatient beds have resulted in a longer hospital length of stay that we observe as boarding patients in the ED,” Arjun Venkatesh, MD, chief of emergency services at Yale New Haven Hospital, told this news organization, commenting on the factors contributing to this crisis.

One concerning side effect of boarding in EDs is the delayed response of ambulance services. When a hospital is unprepared to receive patients arriving in an ambulance, ambulance crews often wait with the patients for extended periods until the hospital can admit them. This situation can have critical implications, as parked ambulances are unable to respond to other emergencies in the community.

Adults who have endured long wait times in EDs voiced concerns about the negative impact such delays can have on their medical care. The experiences of patients and their families have underscored the urgency of addressing the boarding crisis.

“There are no low-hanging fruit solutions or simple communication strategies to alleviate these concerns,” said Dr. Venkatesh, adding that “the only way to change that perception is to change the care by addressing the lack of inpatient capacity and community care capacity to avoid back-up in the ED.”

The poll revealed that 93% of adults across different demographic groups considered EMS, including paramedics, essential. Older adults were more likely to emphasize the significance of these services than were younger adults.

“We all need a place for people to go when there is an emergency, whether it be trauma, a heart attack, a stroke, or similar conditions,” said Scott Weiner, MD, associate professor of emergency medicine at Harvard Medical School and attending emergency physician at Brigham and Women’s Hospital, Boston.

“However, the modern ED is much more than that. It has become the center for coordination of care across the health system where diagnostic tests can be completed promptly, where follow-up care is arranged, and where behavioral health emergencies come,” he added.

A vast majority, 89%, believed that additional or supplemental government funding should be directed toward these essential services, highlighting the public’s concern for the accessibility of EMS.

Dr. Weiner stressed the need for a complete realignment of the payment system: “It’s unfair that public insurance like Medicaid reimburses sometimes less than a quarter of the rate that commercial insurance pays for the exact same service. This exacerbates and perpetuates disparities in health.” According to him, the solution may involve transitioning to a single-payer model, but it could face significant challenges owing to people’s apprehensions about changes in their health care and negative perceptions of “socialized” medicine in other countries. Furthermore, the poll found that the largest share of adults (42%) believed that hospitals should take the lead in improving boarding and shortening ED wait times. These findings indicated the need for hospitals to reevaluate their processes and capabilities to reduce boarding and enhance the overall patient experience in EDs.

“The top three entities that can fix the boarding crisis are hospitals, Congress, and insurance companies,” noted Dr. Wiener. “However, until there is parity at all levels, hospitals will continue to accept lucrative elective admissions but allow ED patients to linger without a bed,” he added.
 

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

Infant mortality rates rose in 2022 for the first time in more than 20 years, according to a new government report.

The overall mortality rate and the rate for neonatal infants, those younger than 28 days old, rose by 3% from 2021 to 2022, says the Centers for Disease Control and Prevention’s National Center for Health Statistics. The mortality rate for infants older than 28 days rose by 4%.

Meanwhile, infant deaths caused by maternal complications rose by 8% and those caused by bacterial sepsis rose by 14%, the report says.

“We live in a country with significant resources, so the infant mortality rate and the increase are shockingly high,” wrote Sandy Chung, MD, of the American Academy of Pediatrics, to CNN. “As pediatricians who help children grow into healthy adults, any death of any child is one too many. The infant mortality rate in this country in unacceptable.”

Experts say the increase could be a sign of an underlying health care issue, an unusual occurrence, or partly related to the COVID-19 pandemic.

The infant mortality rate rose among mothers aged 25-29 years; for preterm babies; for boys; and in Georgia, Iowa, Missouri, and Texas. The rate declined in Nevada.

“Mortality rates increased significantly among infants of American Indian and Alaska Native non-Hispanic ... and White non-Hispanic women,” the report says.

“Mortality rates for infants of Black women did not increase by much, the report found, but Black infants experienced the highest overall rates of infant mortality: nearly 11 deaths per 1,000 births, or over double the mortality rate of White infants,” CNN wrote.

“We know that for people who live in or near poverty and for certain racial and ethnic groups there are significant challenges with getting access to a doctor or getting treatments,” Dr. Chung wrote. “This can lead to moms and babies showing up for care when they are sicker and more likely have serious outcomes, even death.”

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

Infant mortality rates rose in 2022 for the first time in more than 20 years, according to a new government report.

The overall mortality rate and the rate for neonatal infants, those younger than 28 days old, rose by 3% from 2021 to 2022, says the Centers for Disease Control and Prevention’s National Center for Health Statistics. The mortality rate for infants older than 28 days rose by 4%.

Meanwhile, infant deaths caused by maternal complications rose by 8% and those caused by bacterial sepsis rose by 14%, the report says.

“We live in a country with significant resources, so the infant mortality rate and the increase are shockingly high,” wrote Sandy Chung, MD, of the American Academy of Pediatrics, to CNN. “As pediatricians who help children grow into healthy adults, any death of any child is one too many. The infant mortality rate in this country in unacceptable.”

Experts say the increase could be a sign of an underlying health care issue, an unusual occurrence, or partly related to the COVID-19 pandemic.

The infant mortality rate rose among mothers aged 25-29 years; for preterm babies; for boys; and in Georgia, Iowa, Missouri, and Texas. The rate declined in Nevada.

“Mortality rates increased significantly among infants of American Indian and Alaska Native non-Hispanic ... and White non-Hispanic women,” the report says.

“Mortality rates for infants of Black women did not increase by much, the report found, but Black infants experienced the highest overall rates of infant mortality: nearly 11 deaths per 1,000 births, or over double the mortality rate of White infants,” CNN wrote.

“We know that for people who live in or near poverty and for certain racial and ethnic groups there are significant challenges with getting access to a doctor or getting treatments,” Dr. Chung wrote. “This can lead to moms and babies showing up for care when they are sicker and more likely have serious outcomes, even death.”

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

Infant mortality rates rose in 2022 for the first time in more than 20 years, according to a new government report.

The overall mortality rate and the rate for neonatal infants, those younger than 28 days old, rose by 3% from 2021 to 2022, says the Centers for Disease Control and Prevention’s National Center for Health Statistics. The mortality rate for infants older than 28 days rose by 4%.

Meanwhile, infant deaths caused by maternal complications rose by 8% and those caused by bacterial sepsis rose by 14%, the report says.

“We live in a country with significant resources, so the infant mortality rate and the increase are shockingly high,” wrote Sandy Chung, MD, of the American Academy of Pediatrics, to CNN. “As pediatricians who help children grow into healthy adults, any death of any child is one too many. The infant mortality rate in this country in unacceptable.”

Experts say the increase could be a sign of an underlying health care issue, an unusual occurrence, or partly related to the COVID-19 pandemic.

The infant mortality rate rose among mothers aged 25-29 years; for preterm babies; for boys; and in Georgia, Iowa, Missouri, and Texas. The rate declined in Nevada.

“Mortality rates increased significantly among infants of American Indian and Alaska Native non-Hispanic ... and White non-Hispanic women,” the report says.

“Mortality rates for infants of Black women did not increase by much, the report found, but Black infants experienced the highest overall rates of infant mortality: nearly 11 deaths per 1,000 births, or over double the mortality rate of White infants,” CNN wrote.

“We know that for people who live in or near poverty and for certain racial and ethnic groups there are significant challenges with getting access to a doctor or getting treatments,” Dr. Chung wrote. “This can lead to moms and babies showing up for care when they are sicker and more likely have serious outcomes, even death.”

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

NEW YORK – As a result of recent progress in the control of prurigo nodularis, failure to recognize the differences in presentation across skin types threatens prolonged but preventable morbidity from a disease with a devastating clinical impact, according to an expert evaluating current approaches at the Skin of Color Update 2023.

“As dermatologists, prurigo nodularis is one of the most severe diseases we treat, said Shawn G. Kwatra, MD, director of the Johns Hopkins Itch Center, Baltimore. Now with one approved therapy and more coming, “it offers one of the most important opportunities we have to dramatically improve someone’s entire life.”

Ted Bosworth/MDedge News

Prior to the September 2022 approval of dupilumab for the treatment of prurigo nodularis (the first treatment approved for this indication), Dr. Kwatra said that the limited options for control of pruritus made him anxious. Prurigo nodularis is characterized by highly itchy nodules that can produce symptoms patients describe as unbearable.
 

Itch typically severe

On a scale for which 10 represents the worst itch imaginable, scores of 8 or greater are not unusual, according to Dr. Kwatra. Nodules on the trunk and the extensor surfaces of the arms and legs are characteristic, but the persistent itch is the immediate target of treatment once the diagnosis is made. For that reason, he urged clinicians to be familiar with the presentation in patients with darker skin types to reduce time to treatment.

In addition to the difficulty of seeing the characteristic red that is typical of erythema in lighter skin, patients with darker skin types tend to have larger nodules that might vary in shape relative to lighter skin types, Dr. Kwatra said. Given that the presentation of prurigo nodularis is highly heterogeneous even among the same skin types, the nuances in patients with darker skin can be that much more confusing for those without prior experience.

Among Blacks in particular, the nodules in some cases “can be huge,” he added. “They can almost look like keloids due to their thickened and fibrotic appearance.”
 

Phenotypes appear to be racially linked

In Black patients, the appearance can vary enough relative to lighter skin individuals, that “there seems to be something a little bit different going on,” he said, and this is, in fact, supported by a cluster analysis of circulating biomarkers reported by Dr. Kwatra and colleagues in 2022, in the Journal of Investigative Dermatology.

In that study, the biomarker profile distinguished two distinct groups. Whites were more common in a cluster with relatively low expression of inflammatory markers (cluster 1), while Blacks were more common in a cluster with an inflammatory plasma profile (cluster 2), with higher relative expression of multiple cytokines, C-reactive protein, eosinophils, and other markers of up-regulated inflammation.

In addition to a lower rate of myelopathy in cluster 2 than cluster 1 (18% vs. 67%; P = .028), patients in cluster 2 had a significantly worse itch than those in cluster 1 on the Numeric Rating Scale for itch and a significantly lower quality of life based on the Dermatology Life Quality Index score.

Other work at Dr. Kwatra’s center that is based on genetic sequencing has provided evidence that Blacks – and Asians to a lesser extent – are predisposed genetically to develop nodules, perhaps explaining why the nodules tend to be larger than those seen in Whites.

The significance of the evidence that prurigo nodularis is associated with a more up-regulated inflammatory profile in Blacks than in Whites is that they might be particularly likely to respond to dupilumab or other targeted immunomodulating therapies that are in development, according to Dr. Kwatra. Although he did not provide data on response by race, he did provide several case examples of complete itch control following dupilumab therapy in Black patients.

In his experience, high levels of blood eosinophils and other inflammatory markers are predictors of response to dupilumab regardless of skin type, but he expressed concern that time to diagnosis is sometimes longer in Black patients if the nuances of disease expression are not appreciated.

For treating prurigo nodularis in Blacks as well as Whites, Dr. Kwatra suggested that clinicians stay current with what he predicted will be a growing array of treatment options. He did not discuss nemolizumab, an interleukin-31 receptor alpha antagonist. Soon after the meeting, results of a phase 3 trial of nemolizumab in patients with moderate to severe prurigo nodularis were published in the New England Journal of Medicine. (Dr. Kwatra is the lead author of the study but did not specifically discuss this treatment at the meeting.)

In the international placebo-controlled trial, called OLYMPIA 2, treatment was associated with a significant reduction in the signs and symptoms of prurigo nodularis, including reductions in itch, at 16 weeks, although only 4% of patients in the study were Black.

Given the expanding array of therapies, the message of considering prurigo nodularis in Black patients in order to accelerate the time to diagnosis is timely, Andrew F. Alexis, MD, MPH, professor of clinical dermatology and vice-chair for diversity and inclusion for the department of dermatology, Weill Cornell Medicine, New York.

“Current studies suggest a higher prevalence and greater severity of prurigo nodularis among Black patients compared to White patients,” said Dr. Alexis, agreeing with Dr. Kwatra. Referring to evidence that Blacks might mount a greater inflammatory response to prurigo nodularis than Whites, Dr. Alexis called for “a better understanding of the pathomechanisms” of this disease in order “to address unmet needs and reduce disparities for our diverse population of patients who suffer from prurigo nodularis.’

Dr. Kwatra reported financial relationships with AbbVie, Amgen, Arcutis, ASLAN, Cara, Castle Biosciences, Celldex, Galderma, Incyte, Johnson & Johnson, LEO pharma, Novartis, Pfizer, Regeneron, and Sanofi.

NEW YORK – As a result of recent progress in the control of prurigo nodularis, failure to recognize the differences in presentation across skin types threatens prolonged but preventable morbidity from a disease with a devastating clinical impact, according to an expert evaluating current approaches at the Skin of Color Update 2023.

“As dermatologists, prurigo nodularis is one of the most severe diseases we treat, said Shawn G. Kwatra, MD, director of the Johns Hopkins Itch Center, Baltimore. Now with one approved therapy and more coming, “it offers one of the most important opportunities we have to dramatically improve someone’s entire life.”

Ted Bosworth/MDedge News

Prior to the September 2022 approval of dupilumab for the treatment of prurigo nodularis (the first treatment approved for this indication), Dr. Kwatra said that the limited options for control of pruritus made him anxious. Prurigo nodularis is characterized by highly itchy nodules that can produce symptoms patients describe as unbearable.
 

Itch typically severe

On a scale for which 10 represents the worst itch imaginable, scores of 8 or greater are not unusual, according to Dr. Kwatra. Nodules on the trunk and the extensor surfaces of the arms and legs are characteristic, but the persistent itch is the immediate target of treatment once the diagnosis is made. For that reason, he urged clinicians to be familiar with the presentation in patients with darker skin types to reduce time to treatment.

In addition to the difficulty of seeing the characteristic red that is typical of erythema in lighter skin, patients with darker skin types tend to have larger nodules that might vary in shape relative to lighter skin types, Dr. Kwatra said. Given that the presentation of prurigo nodularis is highly heterogeneous even among the same skin types, the nuances in patients with darker skin can be that much more confusing for those without prior experience.

Among Blacks in particular, the nodules in some cases “can be huge,” he added. “They can almost look like keloids due to their thickened and fibrotic appearance.”
 

Phenotypes appear to be racially linked

In Black patients, the appearance can vary enough relative to lighter skin individuals, that “there seems to be something a little bit different going on,” he said, and this is, in fact, supported by a cluster analysis of circulating biomarkers reported by Dr. Kwatra and colleagues in 2022, in the Journal of Investigative Dermatology.

In that study, the biomarker profile distinguished two distinct groups. Whites were more common in a cluster with relatively low expression of inflammatory markers (cluster 1), while Blacks were more common in a cluster with an inflammatory plasma profile (cluster 2), with higher relative expression of multiple cytokines, C-reactive protein, eosinophils, and other markers of up-regulated inflammation.

In addition to a lower rate of myelopathy in cluster 2 than cluster 1 (18% vs. 67%; P = .028), patients in cluster 2 had a significantly worse itch than those in cluster 1 on the Numeric Rating Scale for itch and a significantly lower quality of life based on the Dermatology Life Quality Index score.

Other work at Dr. Kwatra’s center that is based on genetic sequencing has provided evidence that Blacks – and Asians to a lesser extent – are predisposed genetically to develop nodules, perhaps explaining why the nodules tend to be larger than those seen in Whites.

The significance of the evidence that prurigo nodularis is associated with a more up-regulated inflammatory profile in Blacks than in Whites is that they might be particularly likely to respond to dupilumab or other targeted immunomodulating therapies that are in development, according to Dr. Kwatra. Although he did not provide data on response by race, he did provide several case examples of complete itch control following dupilumab therapy in Black patients.

In his experience, high levels of blood eosinophils and other inflammatory markers are predictors of response to dupilumab regardless of skin type, but he expressed concern that time to diagnosis is sometimes longer in Black patients if the nuances of disease expression are not appreciated.

For treating prurigo nodularis in Blacks as well as Whites, Dr. Kwatra suggested that clinicians stay current with what he predicted will be a growing array of treatment options. He did not discuss nemolizumab, an interleukin-31 receptor alpha antagonist. Soon after the meeting, results of a phase 3 trial of nemolizumab in patients with moderate to severe prurigo nodularis were published in the New England Journal of Medicine. (Dr. Kwatra is the lead author of the study but did not specifically discuss this treatment at the meeting.)

In the international placebo-controlled trial, called OLYMPIA 2, treatment was associated with a significant reduction in the signs and symptoms of prurigo nodularis, including reductions in itch, at 16 weeks, although only 4% of patients in the study were Black.

Given the expanding array of therapies, the message of considering prurigo nodularis in Black patients in order to accelerate the time to diagnosis is timely, Andrew F. Alexis, MD, MPH, professor of clinical dermatology and vice-chair for diversity and inclusion for the department of dermatology, Weill Cornell Medicine, New York.

“Current studies suggest a higher prevalence and greater severity of prurigo nodularis among Black patients compared to White patients,” said Dr. Alexis, agreeing with Dr. Kwatra. Referring to evidence that Blacks might mount a greater inflammatory response to prurigo nodularis than Whites, Dr. Alexis called for “a better understanding of the pathomechanisms” of this disease in order “to address unmet needs and reduce disparities for our diverse population of patients who suffer from prurigo nodularis.’

Dr. Kwatra reported financial relationships with AbbVie, Amgen, Arcutis, ASLAN, Cara, Castle Biosciences, Celldex, Galderma, Incyte, Johnson & Johnson, LEO pharma, Novartis, Pfizer, Regeneron, and Sanofi.

NEW YORK – As a result of recent progress in the control of prurigo nodularis, failure to recognize the differences in presentation across skin types threatens prolonged but preventable morbidity from a disease with a devastating clinical impact, according to an expert evaluating current approaches at the Skin of Color Update 2023.

“As dermatologists, prurigo nodularis is one of the most severe diseases we treat, said Shawn G. Kwatra, MD, director of the Johns Hopkins Itch Center, Baltimore. Now with one approved therapy and more coming, “it offers one of the most important opportunities we have to dramatically improve someone’s entire life.”

Ted Bosworth/MDedge News

Prior to the September 2022 approval of dupilumab for the treatment of prurigo nodularis (the first treatment approved for this indication), Dr. Kwatra said that the limited options for control of pruritus made him anxious. Prurigo nodularis is characterized by highly itchy nodules that can produce symptoms patients describe as unbearable.
 

Itch typically severe

On a scale for which 10 represents the worst itch imaginable, scores of 8 or greater are not unusual, according to Dr. Kwatra. Nodules on the trunk and the extensor surfaces of the arms and legs are characteristic, but the persistent itch is the immediate target of treatment once the diagnosis is made. For that reason, he urged clinicians to be familiar with the presentation in patients with darker skin types to reduce time to treatment.

In addition to the difficulty of seeing the characteristic red that is typical of erythema in lighter skin, patients with darker skin types tend to have larger nodules that might vary in shape relative to lighter skin types, Dr. Kwatra said. Given that the presentation of prurigo nodularis is highly heterogeneous even among the same skin types, the nuances in patients with darker skin can be that much more confusing for those without prior experience.

Among Blacks in particular, the nodules in some cases “can be huge,” he added. “They can almost look like keloids due to their thickened and fibrotic appearance.”
 

Phenotypes appear to be racially linked

In Black patients, the appearance can vary enough relative to lighter skin individuals, that “there seems to be something a little bit different going on,” he said, and this is, in fact, supported by a cluster analysis of circulating biomarkers reported by Dr. Kwatra and colleagues in 2022, in the Journal of Investigative Dermatology.

In that study, the biomarker profile distinguished two distinct groups. Whites were more common in a cluster with relatively low expression of inflammatory markers (cluster 1), while Blacks were more common in a cluster with an inflammatory plasma profile (cluster 2), with higher relative expression of multiple cytokines, C-reactive protein, eosinophils, and other markers of up-regulated inflammation.

In addition to a lower rate of myelopathy in cluster 2 than cluster 1 (18% vs. 67%; P = .028), patients in cluster 2 had a significantly worse itch than those in cluster 1 on the Numeric Rating Scale for itch and a significantly lower quality of life based on the Dermatology Life Quality Index score.

Other work at Dr. Kwatra’s center that is based on genetic sequencing has provided evidence that Blacks – and Asians to a lesser extent – are predisposed genetically to develop nodules, perhaps explaining why the nodules tend to be larger than those seen in Whites.

The significance of the evidence that prurigo nodularis is associated with a more up-regulated inflammatory profile in Blacks than in Whites is that they might be particularly likely to respond to dupilumab or other targeted immunomodulating therapies that are in development, according to Dr. Kwatra. Although he did not provide data on response by race, he did provide several case examples of complete itch control following dupilumab therapy in Black patients.

In his experience, high levels of blood eosinophils and other inflammatory markers are predictors of response to dupilumab regardless of skin type, but he expressed concern that time to diagnosis is sometimes longer in Black patients if the nuances of disease expression are not appreciated.

For treating prurigo nodularis in Blacks as well as Whites, Dr. Kwatra suggested that clinicians stay current with what he predicted will be a growing array of treatment options. He did not discuss nemolizumab, an interleukin-31 receptor alpha antagonist. Soon after the meeting, results of a phase 3 trial of nemolizumab in patients with moderate to severe prurigo nodularis were published in the New England Journal of Medicine. (Dr. Kwatra is the lead author of the study but did not specifically discuss this treatment at the meeting.)

In the international placebo-controlled trial, called OLYMPIA 2, treatment was associated with a significant reduction in the signs and symptoms of prurigo nodularis, including reductions in itch, at 16 weeks, although only 4% of patients in the study were Black.

Given the expanding array of therapies, the message of considering prurigo nodularis in Black patients in order to accelerate the time to diagnosis is timely, Andrew F. Alexis, MD, MPH, professor of clinical dermatology and vice-chair for diversity and inclusion for the department of dermatology, Weill Cornell Medicine, New York.

“Current studies suggest a higher prevalence and greater severity of prurigo nodularis among Black patients compared to White patients,” said Dr. Alexis, agreeing with Dr. Kwatra. Referring to evidence that Blacks might mount a greater inflammatory response to prurigo nodularis than Whites, Dr. Alexis called for “a better understanding of the pathomechanisms” of this disease in order “to address unmet needs and reduce disparities for our diverse population of patients who suffer from prurigo nodularis.’

Dr. Kwatra reported financial relationships with AbbVie, Amgen, Arcutis, ASLAN, Cara, Castle Biosciences, Celldex, Galderma, Incyte, Johnson & Johnson, LEO pharma, Novartis, Pfizer, Regeneron, and Sanofi.

LA JOLLA, Calif. – A new analysis suggests that it may not be necessary to delay urate-lowering therapy (ULT) in gout flares, and a study warns of the potential heightened risk of peripheral arterial disease (PAD) in gout.

The reports were released at the annual research symposium of the Gout, Hyperuricemia, and Crystal Associated Disease Network (G-CAN).

The urate-lowering report, a systematic review and meta-analysis, suggests that the use of ULT during a gout flare “does not affect flare severity nor the duration of the flare or risk of recurrence in the subsequent month,” lead author Vicky Tai, MBChB, of the University of Auckland (New Zealand), said in a presentation.

She noted that there’s ongoing debate about whether ULT should be delayed until a week or two after gout flares subside to avoid their return. “This is reflected in guidelines on gout management, which have provided inconsistent recommendations on the issue,” Dr. Tai said.

As she noted, the American College of Rheumatology’s 2020 gout guidelines conditionally recommended starting ULT during gout flares – and not afterward – if it’s indicated. (The guidelines also conditionally recommend against ULT in a first gout flare, however, with a few exceptions.)

The British Society for Rheumatology’s 2017 gout guidelines suggested waiting until flares have settled down and “the patient was no longer in pain,” although ULT may be started in patients with frequent attacks. The European Alliance of Associations for Rheumatology’s gout guidelines from 2016 didn’t address timing, Dr. Tai said.

For the new analysis, Dr. Tai and colleagues examined six randomized studies from the United States (two), China (two), Taiwan (one), and Thailand (one) that examined the use of allopurinol (three studies), febuxostat (two studies), and probenecid (one). The studies, dated from 2012 to 2023, randomized 226 subjects with gout to early initiation of ULT vs. 219 who received placebo or delayed ULT. Subjects were tracked for a median of 28 days (15 days to 12 weeks).

Three of the studies were deemed to have high risk of bias.

There were no differences in patient-rated pain scores at various time points, duration of gout flares (examined in three studies), or recurrence of gout flares (examined in four studies).

“Other outcomes of interest, including long-term adherence, time to achieve target serum urate, and patient satisfaction with treatment, were not examined,” Dr. Tai said. “Adverse events were similar between groups.”

She cautioned that the sample sizes are small, and the findings may not be applicable to patients with tophaceous gout or comorbid renal disease.

A similar meta-analysis published in 2022 examined five studies (including three of those in the new analysis); among the five was one study from 1987 that examined azapropazone and indomethacin plus allopurinol. The review found “that initiation of ULT during an acute gout flare did not prolong the duration of acute flares.”
 

Risk for PAD

In the other study, researchers raised an alarm after finding a high rate of PAD in patients with gout regardless of whether they also had diabetes, which is a known risk factor for PAD. “Our data suggest that gout is an underrecognized risk factor for PAD and indicates the importance of assessing for PAD in gout patients,” lead author Nicole Leung, MD, of NYU Langone Health, said in a presentation.

According to Dr. Leung, there’s little known about links between PAD and gout, although she highlighted a 2018 study that found that patients with obstructive coronary artery disease were more likely to have poor outcomes if they also developed gout after catheterization. She highlighted a 2022 study that found higher rates of lower-extremity amputations in patients with gout independent of cardiovascular disease and diabetes. However, she noted that a link to PAD is unclear, and the study found a link between gout and amputations that was independent of PAD.

Patients with gout, she added, are not routinely screened for PAD.

For the new retrospective, cross-sectional analysis, Dr. Leung and colleagues examined Veterans Administration data from 2014 to 2018 for 7.2 million patients. The population was largely male.

Of those, 140,862 (2.52%) – the control group – had no gout or diabetes. In comparison, 11,449 (5.56%) of 205,904 with gout but not diabetes had PAD, for a rate 2.2 times greater than the control group). PAD occurred in 101,582 (8.70%) of 1,168,138 with diabetes but not gout, giving a rate 3.2 times greater than the control group. The rate was highest among people with both gout and diabetes, at 9.97% (9,905 of 99,377), which is about four times greater than the control group.

The link between gout and PAD remained after adjustment for creatinine levels, age, gender, and body mass index. Diabetes was linked to a higher risk for PAD than was gout, and the effect of both conditions combined was “less than additive.” This “may suggest an overlap and pathophysiology between the two,” she said.

Disclosure information was not provided. The Rheumatology Research Foundation funded the PAD study; funding information for the ULT/gout flare analysis was not provided.

LA JOLLA, Calif. – A new analysis suggests that it may not be necessary to delay urate-lowering therapy (ULT) in gout flares, and a study warns of the potential heightened risk of peripheral arterial disease (PAD) in gout.

The reports were released at the annual research symposium of the Gout, Hyperuricemia, and Crystal Associated Disease Network (G-CAN).

The urate-lowering report, a systematic review and meta-analysis, suggests that the use of ULT during a gout flare “does not affect flare severity nor the duration of the flare or risk of recurrence in the subsequent month,” lead author Vicky Tai, MBChB, of the University of Auckland (New Zealand), said in a presentation.

She noted that there’s ongoing debate about whether ULT should be delayed until a week or two after gout flares subside to avoid their return. “This is reflected in guidelines on gout management, which have provided inconsistent recommendations on the issue,” Dr. Tai said.

As she noted, the American College of Rheumatology’s 2020 gout guidelines conditionally recommended starting ULT during gout flares – and not afterward – if it’s indicated. (The guidelines also conditionally recommend against ULT in a first gout flare, however, with a few exceptions.)

The British Society for Rheumatology’s 2017 gout guidelines suggested waiting until flares have settled down and “the patient was no longer in pain,” although ULT may be started in patients with frequent attacks. The European Alliance of Associations for Rheumatology’s gout guidelines from 2016 didn’t address timing, Dr. Tai said.

For the new analysis, Dr. Tai and colleagues examined six randomized studies from the United States (two), China (two), Taiwan (one), and Thailand (one) that examined the use of allopurinol (three studies), febuxostat (two studies), and probenecid (one). The studies, dated from 2012 to 2023, randomized 226 subjects with gout to early initiation of ULT vs. 219 who received placebo or delayed ULT. Subjects were tracked for a median of 28 days (15 days to 12 weeks).

Three of the studies were deemed to have high risk of bias.

There were no differences in patient-rated pain scores at various time points, duration of gout flares (examined in three studies), or recurrence of gout flares (examined in four studies).

“Other outcomes of interest, including long-term adherence, time to achieve target serum urate, and patient satisfaction with treatment, were not examined,” Dr. Tai said. “Adverse events were similar between groups.”

She cautioned that the sample sizes are small, and the findings may not be applicable to patients with tophaceous gout or comorbid renal disease.

A similar meta-analysis published in 2022 examined five studies (including three of those in the new analysis); among the five was one study from 1987 that examined azapropazone and indomethacin plus allopurinol. The review found “that initiation of ULT during an acute gout flare did not prolong the duration of acute flares.”
 

Risk for PAD

In the other study, researchers raised an alarm after finding a high rate of PAD in patients with gout regardless of whether they also had diabetes, which is a known risk factor for PAD. “Our data suggest that gout is an underrecognized risk factor for PAD and indicates the importance of assessing for PAD in gout patients,” lead author Nicole Leung, MD, of NYU Langone Health, said in a presentation.

According to Dr. Leung, there’s little known about links between PAD and gout, although she highlighted a 2018 study that found that patients with obstructive coronary artery disease were more likely to have poor outcomes if they also developed gout after catheterization. She highlighted a 2022 study that found higher rates of lower-extremity amputations in patients with gout independent of cardiovascular disease and diabetes. However, she noted that a link to PAD is unclear, and the study found a link between gout and amputations that was independent of PAD.

Patients with gout, she added, are not routinely screened for PAD.

For the new retrospective, cross-sectional analysis, Dr. Leung and colleagues examined Veterans Administration data from 2014 to 2018 for 7.2 million patients. The population was largely male.

Of those, 140,862 (2.52%) – the control group – had no gout or diabetes. In comparison, 11,449 (5.56%) of 205,904 with gout but not diabetes had PAD, for a rate 2.2 times greater than the control group). PAD occurred in 101,582 (8.70%) of 1,168,138 with diabetes but not gout, giving a rate 3.2 times greater than the control group. The rate was highest among people with both gout and diabetes, at 9.97% (9,905 of 99,377), which is about four times greater than the control group.

The link between gout and PAD remained after adjustment for creatinine levels, age, gender, and body mass index. Diabetes was linked to a higher risk for PAD than was gout, and the effect of both conditions combined was “less than additive.” This “may suggest an overlap and pathophysiology between the two,” she said.

Disclosure information was not provided. The Rheumatology Research Foundation funded the PAD study; funding information for the ULT/gout flare analysis was not provided.

LA JOLLA, Calif. – A new analysis suggests that it may not be necessary to delay urate-lowering therapy (ULT) in gout flares, and a study warns of the potential heightened risk of peripheral arterial disease (PAD) in gout.

The reports were released at the annual research symposium of the Gout, Hyperuricemia, and Crystal Associated Disease Network (G-CAN).

The urate-lowering report, a systematic review and meta-analysis, suggests that the use of ULT during a gout flare “does not affect flare severity nor the duration of the flare or risk of recurrence in the subsequent month,” lead author Vicky Tai, MBChB, of the University of Auckland (New Zealand), said in a presentation.

She noted that there’s ongoing debate about whether ULT should be delayed until a week or two after gout flares subside to avoid their return. “This is reflected in guidelines on gout management, which have provided inconsistent recommendations on the issue,” Dr. Tai said.

As she noted, the American College of Rheumatology’s 2020 gout guidelines conditionally recommended starting ULT during gout flares – and not afterward – if it’s indicated. (The guidelines also conditionally recommend against ULT in a first gout flare, however, with a few exceptions.)

The British Society for Rheumatology’s 2017 gout guidelines suggested waiting until flares have settled down and “the patient was no longer in pain,” although ULT may be started in patients with frequent attacks. The European Alliance of Associations for Rheumatology’s gout guidelines from 2016 didn’t address timing, Dr. Tai said.

For the new analysis, Dr. Tai and colleagues examined six randomized studies from the United States (two), China (two), Taiwan (one), and Thailand (one) that examined the use of allopurinol (three studies), febuxostat (two studies), and probenecid (one). The studies, dated from 2012 to 2023, randomized 226 subjects with gout to early initiation of ULT vs. 219 who received placebo or delayed ULT. Subjects were tracked for a median of 28 days (15 days to 12 weeks).

Three of the studies were deemed to have high risk of bias.

There were no differences in patient-rated pain scores at various time points, duration of gout flares (examined in three studies), or recurrence of gout flares (examined in four studies).

“Other outcomes of interest, including long-term adherence, time to achieve target serum urate, and patient satisfaction with treatment, were not examined,” Dr. Tai said. “Adverse events were similar between groups.”

She cautioned that the sample sizes are small, and the findings may not be applicable to patients with tophaceous gout or comorbid renal disease.

A similar meta-analysis published in 2022 examined five studies (including three of those in the new analysis); among the five was one study from 1987 that examined azapropazone and indomethacin plus allopurinol. The review found “that initiation of ULT during an acute gout flare did not prolong the duration of acute flares.”
 

Risk for PAD

In the other study, researchers raised an alarm after finding a high rate of PAD in patients with gout regardless of whether they also had diabetes, which is a known risk factor for PAD. “Our data suggest that gout is an underrecognized risk factor for PAD and indicates the importance of assessing for PAD in gout patients,” lead author Nicole Leung, MD, of NYU Langone Health, said in a presentation.

According to Dr. Leung, there’s little known about links between PAD and gout, although she highlighted a 2018 study that found that patients with obstructive coronary artery disease were more likely to have poor outcomes if they also developed gout after catheterization. She highlighted a 2022 study that found higher rates of lower-extremity amputations in patients with gout independent of cardiovascular disease and diabetes. However, she noted that a link to PAD is unclear, and the study found a link between gout and amputations that was independent of PAD.

Patients with gout, she added, are not routinely screened for PAD.

For the new retrospective, cross-sectional analysis, Dr. Leung and colleagues examined Veterans Administration data from 2014 to 2018 for 7.2 million patients. The population was largely male.

Of those, 140,862 (2.52%) – the control group – had no gout or diabetes. In comparison, 11,449 (5.56%) of 205,904 with gout but not diabetes had PAD, for a rate 2.2 times greater than the control group). PAD occurred in 101,582 (8.70%) of 1,168,138 with diabetes but not gout, giving a rate 3.2 times greater than the control group. The rate was highest among people with both gout and diabetes, at 9.97% (9,905 of 99,377), which is about four times greater than the control group.

The link between gout and PAD remained after adjustment for creatinine levels, age, gender, and body mass index. Diabetes was linked to a higher risk for PAD than was gout, and the effect of both conditions combined was “less than additive.” This “may suggest an overlap and pathophysiology between the two,” she said.

Disclosure information was not provided. The Rheumatology Research Foundation funded the PAD study; funding information for the ULT/gout flare analysis was not provided.