The human monoclonal antibody golimumab (Simponi) preserved endogenous insulin secretion in patients with new-onset type 1 diabetes and reduced their exogenous insulin requirements at 1 year, newly published phase 2 data indicate.

Results from the multicenter, double-blind, placebo-controlled trial were first reported as a poster at the virtual American Diabetes Association 80th Scientific Sessions in June. They were published online Nov. 18 in the New England Journal of Medicine.

In the 52-week study of 84 children and adults with new-onset type 1 diabetes, those given golimumab injections every 2 weeks had significantly higher levels of C-peptide, a marker of insulin secretion, and required less injected or infused insulin than did those who received placebo injections. There were no treatment-associated serious adverse events.

Golimumab is a human monoclonal antibody specific for tumor necrosis factor–alpha. It is approved for the treatment of several autoimmune diseases, including rheumatoid arthritis and ulcerative colitis, in the United States, Europe, and elsewhere.
 

An intermediate step toward a cure

Although none of the patients were able to stop taking insulin entirely, the results have important clinical implications, lead author Teresa Quattrin, MD, said in an interview.

“People want a cure, but the fact is, a cure is not available yet. So, this is an intermediate step towards a cure.... There are advantages to being on a small insulin dose,” including lower rates of hypoglycemia and maintenance of intraportal insulin, said Dr. Quattrin, of the State University of New York at Buffalo.

But in an accompanying editorial, Domenico Accili, MD, points to potential risks from immunotherapy and from attempting additional interventions at an “emotionally fraught” time when patients and families are coping with the new diabetes diagnosis.

He said of golimumab, “the effect is actually very small. ... There’s nothing wrong in and of itself with improving those outcomes. I just wouldn’t assign them as game changers.”

If this or a similar immunotherapeutic intervention were approved for this indication, “I would tell patients it exists and let them make the decision whether they want to try it. I wouldn’t say you must try it,” said Dr. Accili, of the Columbia University Diabetes and Endocrinology Research Center, New York.
 

With golimumab, higher C-peptide, lower insulin requirement

Of the 84 patients, who ranged in age from 6 to 21 years, 56 were randomly assigned within 100 days of being diagnosed with type 1 diabetes to receive golimumab, and 28 were assigned to receive placebo injections, given every 2 weeks.

The drug resulted in lower insulin use (0.51U/Kg per day vs. 0.69 U/kg per day), and the increase in insulin use over 52 weeks was less with golimumab than with placebo (0.07 vs. 0.24 U/kg per day; P = .001).

The mean percent decrease of C-peptide production from baseline was 12% with golimumab versus 56% with placebo.

Although the mean number of overall hypoglycemic events was similar, the mean number of level 2 hypoglycemic events (<54 mg/dL) was 36% lower with golimumab (11.5 vs. 17.6). There were no severe cases of hypoglycemia in either group.

No severe or serious infections occurred in either group, although mild to moderate infections were reported in 71% with golimumab versus 61% with placebo. More patients in the golimumab group experienced a decrease in neutrophils (29% vs. 19%).
 

Immunotherapy: Which one, and when should it start?

These findings come on the heels of the 2019 landmark results with another monoclonal antibody, the investigational anti-CD3 teplizumab (PRV-031). Among patients at risk, a diagnosis of type 1 diabetes was delayed by 2 years, and continued benefit was seen at 3 years.

However, Dr. Quattrin said teplizumab is limited by the fact that it must be administered via a 14-day infusion, whereas golimumab can be injected by patients themselves at home.

Moreover, the phase 2 teplizumab study was conducted in people who had antibodies that placed them at high risk for type 1 diabetes, but those patients did not yet have the condition. They were identified because they had close relatives with type 1 diabetes and were enrolled in the federally funded TrialNet screening program.

Dr. Quattrin is now participating in an ongoing phase 3 study of teplizumab that involves patients newly diagnosed with type 1 diabetes.

A Janssen spokesperson said in an interview that the company isn’t planning to further develop golimumab for use in type 1 diabetes.

“Our focus is to apply insights from the phase 2 ... proof-of-concept study to progress what we believe are novel, immunologically targeted pipeline candidates in stage 2 disease or presymptomatic stages of type 1 diabetes, which is consistent with our mission to intercept and prevent type 1 diabetes,” the spokesperson said.

To identify more individuals at risk for type 1 diabetes beyond the close relatives of those who already have it, so as to be able to intervene at a presymptomatic stage, Janssen is organizing a public-private effort to advocate for routine population screening for type 1 diabetes–related autoantibodies.

Dr. Quattrin said: “Preserving some insulin is key. Having somebody with beta cell functioning still is an intermediate step to a cure and will make their life easier, and that’s what people should care about.”

Dr. Accili, who cofounded and leads a company working on a novel approach to type 1 diabetes treatment, writes in his editorial: “We should also be mindful that this treatment debate is first world–centric.

“Current treatments for type 1 diabetes require resources not readily available in most parts of the world, where something as simple as refrigeration of insulin can become a logistic nightmare. While combinations of [approaches] tailored to individual risk and potential benefits are likely to make inroads in clinical practice, the need for a simpler, safer, and equally effective alternative to insulin remains,” he wrote.

Dr. Quattrin is a researcher and consultant for Janssen and conducts clinical trials for Provention Bio, Opko, and Ascendis. Dr. Accili is founder and director of Forkhead Therapeutics.

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

The human monoclonal antibody golimumab (Simponi) preserved endogenous insulin secretion in patients with new-onset type 1 diabetes and reduced their exogenous insulin requirements at 1 year, newly published phase 2 data indicate.

Results from the multicenter, double-blind, placebo-controlled trial were first reported as a poster at the virtual American Diabetes Association 80th Scientific Sessions in June. They were published online Nov. 18 in the New England Journal of Medicine.

In the 52-week study of 84 children and adults with new-onset type 1 diabetes, those given golimumab injections every 2 weeks had significantly higher levels of C-peptide, a marker of insulin secretion, and required less injected or infused insulin than did those who received placebo injections. There were no treatment-associated serious adverse events.

Golimumab is a human monoclonal antibody specific for tumor necrosis factor–alpha. It is approved for the treatment of several autoimmune diseases, including rheumatoid arthritis and ulcerative colitis, in the United States, Europe, and elsewhere.
 

An intermediate step toward a cure

Although none of the patients were able to stop taking insulin entirely, the results have important clinical implications, lead author Teresa Quattrin, MD, said in an interview.

“People want a cure, but the fact is, a cure is not available yet. So, this is an intermediate step towards a cure.... There are advantages to being on a small insulin dose,” including lower rates of hypoglycemia and maintenance of intraportal insulin, said Dr. Quattrin, of the State University of New York at Buffalo.

But in an accompanying editorial, Domenico Accili, MD, points to potential risks from immunotherapy and from attempting additional interventions at an “emotionally fraught” time when patients and families are coping with the new diabetes diagnosis.

He said of golimumab, “the effect is actually very small. ... There’s nothing wrong in and of itself with improving those outcomes. I just wouldn’t assign them as game changers.”

If this or a similar immunotherapeutic intervention were approved for this indication, “I would tell patients it exists and let them make the decision whether they want to try it. I wouldn’t say you must try it,” said Dr. Accili, of the Columbia University Diabetes and Endocrinology Research Center, New York.
 

With golimumab, higher C-peptide, lower insulin requirement

Of the 84 patients, who ranged in age from 6 to 21 years, 56 were randomly assigned within 100 days of being diagnosed with type 1 diabetes to receive golimumab, and 28 were assigned to receive placebo injections, given every 2 weeks.

The drug resulted in lower insulin use (0.51U/Kg per day vs. 0.69 U/kg per day), and the increase in insulin use over 52 weeks was less with golimumab than with placebo (0.07 vs. 0.24 U/kg per day; P = .001).

The mean percent decrease of C-peptide production from baseline was 12% with golimumab versus 56% with placebo.

Although the mean number of overall hypoglycemic events was similar, the mean number of level 2 hypoglycemic events (<54 mg/dL) was 36% lower with golimumab (11.5 vs. 17.6). There were no severe cases of hypoglycemia in either group.

No severe or serious infections occurred in either group, although mild to moderate infections were reported in 71% with golimumab versus 61% with placebo. More patients in the golimumab group experienced a decrease in neutrophils (29% vs. 19%).
 

Immunotherapy: Which one, and when should it start?

These findings come on the heels of the 2019 landmark results with another monoclonal antibody, the investigational anti-CD3 teplizumab (PRV-031). Among patients at risk, a diagnosis of type 1 diabetes was delayed by 2 years, and continued benefit was seen at 3 years.

However, Dr. Quattrin said teplizumab is limited by the fact that it must be administered via a 14-day infusion, whereas golimumab can be injected by patients themselves at home.

Moreover, the phase 2 teplizumab study was conducted in people who had antibodies that placed them at high risk for type 1 diabetes, but those patients did not yet have the condition. They were identified because they had close relatives with type 1 diabetes and were enrolled in the federally funded TrialNet screening program.

Dr. Quattrin is now participating in an ongoing phase 3 study of teplizumab that involves patients newly diagnosed with type 1 diabetes.

A Janssen spokesperson said in an interview that the company isn’t planning to further develop golimumab for use in type 1 diabetes.

“Our focus is to apply insights from the phase 2 ... proof-of-concept study to progress what we believe are novel, immunologically targeted pipeline candidates in stage 2 disease or presymptomatic stages of type 1 diabetes, which is consistent with our mission to intercept and prevent type 1 diabetes,” the spokesperson said.

To identify more individuals at risk for type 1 diabetes beyond the close relatives of those who already have it, so as to be able to intervene at a presymptomatic stage, Janssen is organizing a public-private effort to advocate for routine population screening for type 1 diabetes–related autoantibodies.

Dr. Quattrin said: “Preserving some insulin is key. Having somebody with beta cell functioning still is an intermediate step to a cure and will make their life easier, and that’s what people should care about.”

Dr. Accili, who cofounded and leads a company working on a novel approach to type 1 diabetes treatment, writes in his editorial: “We should also be mindful that this treatment debate is first world–centric.

“Current treatments for type 1 diabetes require resources not readily available in most parts of the world, where something as simple as refrigeration of insulin can become a logistic nightmare. While combinations of [approaches] tailored to individual risk and potential benefits are likely to make inroads in clinical practice, the need for a simpler, safer, and equally effective alternative to insulin remains,” he wrote.

Dr. Quattrin is a researcher and consultant for Janssen and conducts clinical trials for Provention Bio, Opko, and Ascendis. Dr. Accili is founder and director of Forkhead Therapeutics.

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

The human monoclonal antibody golimumab (Simponi) preserved endogenous insulin secretion in patients with new-onset type 1 diabetes and reduced their exogenous insulin requirements at 1 year, newly published phase 2 data indicate.

Results from the multicenter, double-blind, placebo-controlled trial were first reported as a poster at the virtual American Diabetes Association 80th Scientific Sessions in June. They were published online Nov. 18 in the New England Journal of Medicine.

In the 52-week study of 84 children and adults with new-onset type 1 diabetes, those given golimumab injections every 2 weeks had significantly higher levels of C-peptide, a marker of insulin secretion, and required less injected or infused insulin than did those who received placebo injections. There were no treatment-associated serious adverse events.

Golimumab is a human monoclonal antibody specific for tumor necrosis factor–alpha. It is approved for the treatment of several autoimmune diseases, including rheumatoid arthritis and ulcerative colitis, in the United States, Europe, and elsewhere.
 

An intermediate step toward a cure

Although none of the patients were able to stop taking insulin entirely, the results have important clinical implications, lead author Teresa Quattrin, MD, said in an interview.

“People want a cure, but the fact is, a cure is not available yet. So, this is an intermediate step towards a cure.... There are advantages to being on a small insulin dose,” including lower rates of hypoglycemia and maintenance of intraportal insulin, said Dr. Quattrin, of the State University of New York at Buffalo.

But in an accompanying editorial, Domenico Accili, MD, points to potential risks from immunotherapy and from attempting additional interventions at an “emotionally fraught” time when patients and families are coping with the new diabetes diagnosis.

He said of golimumab, “the effect is actually very small. ... There’s nothing wrong in and of itself with improving those outcomes. I just wouldn’t assign them as game changers.”

If this or a similar immunotherapeutic intervention were approved for this indication, “I would tell patients it exists and let them make the decision whether they want to try it. I wouldn’t say you must try it,” said Dr. Accili, of the Columbia University Diabetes and Endocrinology Research Center, New York.
 

With golimumab, higher C-peptide, lower insulin requirement

Of the 84 patients, who ranged in age from 6 to 21 years, 56 were randomly assigned within 100 days of being diagnosed with type 1 diabetes to receive golimumab, and 28 were assigned to receive placebo injections, given every 2 weeks.

The drug resulted in lower insulin use (0.51U/Kg per day vs. 0.69 U/kg per day), and the increase in insulin use over 52 weeks was less with golimumab than with placebo (0.07 vs. 0.24 U/kg per day; P = .001).

The mean percent decrease of C-peptide production from baseline was 12% with golimumab versus 56% with placebo.

Although the mean number of overall hypoglycemic events was similar, the mean number of level 2 hypoglycemic events (<54 mg/dL) was 36% lower with golimumab (11.5 vs. 17.6). There were no severe cases of hypoglycemia in either group.

No severe or serious infections occurred in either group, although mild to moderate infections were reported in 71% with golimumab versus 61% with placebo. More patients in the golimumab group experienced a decrease in neutrophils (29% vs. 19%).
 

Immunotherapy: Which one, and when should it start?

These findings come on the heels of the 2019 landmark results with another monoclonal antibody, the investigational anti-CD3 teplizumab (PRV-031). Among patients at risk, a diagnosis of type 1 diabetes was delayed by 2 years, and continued benefit was seen at 3 years.

However, Dr. Quattrin said teplizumab is limited by the fact that it must be administered via a 14-day infusion, whereas golimumab can be injected by patients themselves at home.

Moreover, the phase 2 teplizumab study was conducted in people who had antibodies that placed them at high risk for type 1 diabetes, but those patients did not yet have the condition. They were identified because they had close relatives with type 1 diabetes and were enrolled in the federally funded TrialNet screening program.

Dr. Quattrin is now participating in an ongoing phase 3 study of teplizumab that involves patients newly diagnosed with type 1 diabetes.

A Janssen spokesperson said in an interview that the company isn’t planning to further develop golimumab for use in type 1 diabetes.

“Our focus is to apply insights from the phase 2 ... proof-of-concept study to progress what we believe are novel, immunologically targeted pipeline candidates in stage 2 disease or presymptomatic stages of type 1 diabetes, which is consistent with our mission to intercept and prevent type 1 diabetes,” the spokesperson said.

To identify more individuals at risk for type 1 diabetes beyond the close relatives of those who already have it, so as to be able to intervene at a presymptomatic stage, Janssen is organizing a public-private effort to advocate for routine population screening for type 1 diabetes–related autoantibodies.

Dr. Quattrin said: “Preserving some insulin is key. Having somebody with beta cell functioning still is an intermediate step to a cure and will make their life easier, and that’s what people should care about.”

Dr. Accili, who cofounded and leads a company working on a novel approach to type 1 diabetes treatment, writes in his editorial: “We should also be mindful that this treatment debate is first world–centric.

“Current treatments for type 1 diabetes require resources not readily available in most parts of the world, where something as simple as refrigeration of insulin can become a logistic nightmare. While combinations of [approaches] tailored to individual risk and potential benefits are likely to make inroads in clinical practice, the need for a simpler, safer, and equally effective alternative to insulin remains,” he wrote.

Dr. Quattrin is a researcher and consultant for Janssen and conducts clinical trials for Provention Bio, Opko, and Ascendis. Dr. Accili is founder and director of Forkhead Therapeutics.

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

Delirium should be included on checklists of the presenting signs and symptoms of COVID-19, particularly in elderly adults, according to a multicenter study of seniors visiting emergency departments.

Overall, 28% of the 817 older adults who presented to the emergency department and were diagnosed with COVID-19 had delirium, according to a study published online November 19 in JAMA Network Open. Moreover, 16% of these patients had delirium that was not accompanied by typical symptoms or signs of SARS-CoV-2 infection.

Among patients with delirium, there was a greater probability of admission to the intensive care unit compared with patients who presented without delirium (adjusted relative risk [aRR], 1.67; 95% CI, 1.30 – 2.15), as well as a greater probability of death (aRR, 1.24; 95% CI, 1.00 – 1.55).

“These findings suggest the clinical importance of including delirium on checklists of presenting signs and symptoms of COVID-19 that guide screening, testing, and evaluation,” write Maura Kennedy, MD, MPH, and colleagues.

“I was absolutely seeing cases of delirium where there were no other symptoms of COVID-19, but we didn’t have lot of data on the frequency of this,” explained Kennedy, an emergency department physician at Massachusetts General Hospital and an assistant professor of emergency medicine at Harvard Medical School, Boston.

“And the rate was somewhat surprising compared with that seen in non-COVID studies of delirium, but then our study population was more at risk, coming from long-term care facilities and having prior stroke or dementia,” she said. The most common form of delirium was hypoactive sleepiness and nonresponsiveness, although hyperactivity and agitation were also seen.

Kennedy thinks the addition of delirium as a common presenting symptom to diagnostic checklists would prevent some cases from being missed and allow earlier identification and management of COVID-19 patients at high risk for poor outcomes. “We certainly don’t want to send them back undiagnosed to a long-term care facility or promote transmission within the hospital,” she told Medscape Medical News.

That step has already been implemented in some US centers. “Delirium is something we’ve been looking at since the early summer,” said geriatrician Angela Catic, MD, an assistant professor at Baylor College of Medicine’s Huffington Center on Aging and the Michael E. DeBakey VA Medical Center, Houston, Texas.

“If we see delirium, we’re looking for COVID-19,” said Catic, who was not involved in the study.

In Catic’s experience, it is “not at all atypical” to see patients whose only symptom of COVID-19 is delirium. As with other infections and diseases, “the aging brain is incredibly vulnerable,” she said.

According to William W. Hung, MD, MPH, an assistant professor of geriatrics and palliative medicine at the Icahn School of Medicine at Mount Sinai, New York City, delirium is “generally a common sign of something seriously wrong” in older adults. “In the case of COVID-19, low oxygenation caused by the infection may play a role,” he told Medscape Medical News. Although he agreed that delirium should be included in the differential diagnosis of COVID-19, how frequently it is the only symptom at presentation would need to be determined in a considerably larger population, he said.

Joining the company of those observing this COVID-19 manifestation is Christopher R. Carpenter, MD, a professor of emergency medicine at Washington University in St. Louis, St. Louis, Missouri. He was not a participant in the current study.

“I have absolutely seen and documented delirium as the presenting complaint in older adult patients who were ultimately diagnosed with SARS-CoV-2, and since March, I contemplate SARS-CoV-2 each time I identify delirium,” Carpenter told Medscape Medical News. “Honestly, I ― and most of my colleagues ― are considering SARS-CoV-2 for a range of symptoms and complaints these days, because of the odd presentations we’ve all encountered.”
 

Study details

For the study, Kennedy and colleagues enrolled consecutive adults aged 65 years and older who were diagnosed with active COVID-19 and who presented to emergency departments at seven centers in Massachusetts, Maine, Connecticut, Michigan, and North Carolina on or after March 13, 2020. Active infection with SARS-CoV-2 was determined on the basis of results of nasal swab polymerase chain reaction tests (99% of cases) or the appearance and distribution of ground-glass opacities on chest radiography or CT (1%).

Of the 817 patients enrolled, 386 (47%) were men, 493 (62%) were White, 215 (27%) were Black, and 54 (7%) were Hispanic or Latinx. The mean age of patients was 77.7 years (standard deviation, 8.2). Their age placed them at risk for chronic comorbidities and cognitive problems; indeed, 15% had at least four chronic conditions, and 30% had existing cognitive impairment.

The authors note that among the 226 patients (28%) who had delirium at presentation, 60 (27%) had experienced delirium for a duration of 2 to 7 days.

Additionally, of the 226 patients who exhibited delirium as a primary symptom, 84 (37%) showed no typical COVID-19 symptoms or signs, such as cough, fever, or shortness of breath.

The presence of delirium did not correlate with any of the typical COVID-19 symptoms in particular; Kennedy noted that only 56% of patients in the cohort had a fever at presentation.

Delirium at presentation was significantly associated with a median hospital stay of more than 8 days (aRR, 1.14; 95% CI, .97 – 1.35) and a greater risk for discharge to a rehabilitation facility (aRR, 1.55; 95% CI, 1.07 – 2.26). Factors associated with delirium included age older than 75 years, residence in a nursing home or assisted-living facility, previous use of psychoactive medications, vision impairment, hearing impairment, stroke, and Parkinson’s disease.

Kennedy noted that the rate of delirium observed in this study is much higher than that generally reported in emergency department studies conducted before the COVID-19 pandemic. In those studies, the delirium rate ranged from 7% to 20%. The associated risk factors, however, are comparable.

“Mounting evidence supports the high occurrence of delirium and other neuropsychiatric manifestations with COVID-19, with previously reported rates of 22% to 33% among hospitalized patients,” Kennedy and associates write.

In Carpenter’s opinion, the development of incident delirium while receiving care in the emergency department, as opposed to delirium at the time of presentation, has been exacerbated by the no-visitor policies mandated by the pandemic, which have prevented visits even from personal caregivers of patients with moderate to severe dementia. “Although healthcare systems need to be cognizant of the risk of spread to uninfected caregivers, there’s a risk-benefit balance that must be found, because having one caregiver at the bedside can prevent delirium in cognitively impaired patients,” said Carpenter, who was not involved in the current study.

Among the barriers to improving the situation, Carpenter cited the lack of routine delirium screening and the absence of high-quality evidence to support emergency department interventions to mitigate delirium.

“Layer those challenges on top of COVID-19’s rapidly evolving diagnostic landscape, frequent atypical presentations, and asymptomatic carriers across all age groups and the negative impact of delirium is magnified,” Carpenter said.

Once elderly patients are hospitalized, Kennedy recommends the nonpharmacologic guidelines of the Hospital Elder Life Program for reducing delirium risk. Recommendations include the providing of adequate sleep, hydration, and nutrition, as well as function restoration, precipitant avoidance, and reorientation.

The study was supported in part by the National Institute on Aging and the Massachusetts Medical School. The authors, Carpenter, Hung, and Catic have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Delirium should be included on checklists of the presenting signs and symptoms of COVID-19, particularly in elderly adults, according to a multicenter study of seniors visiting emergency departments.

Overall, 28% of the 817 older adults who presented to the emergency department and were diagnosed with COVID-19 had delirium, according to a study published online November 19 in JAMA Network Open. Moreover, 16% of these patients had delirium that was not accompanied by typical symptoms or signs of SARS-CoV-2 infection.

Among patients with delirium, there was a greater probability of admission to the intensive care unit compared with patients who presented without delirium (adjusted relative risk [aRR], 1.67; 95% CI, 1.30 – 2.15), as well as a greater probability of death (aRR, 1.24; 95% CI, 1.00 – 1.55).

“These findings suggest the clinical importance of including delirium on checklists of presenting signs and symptoms of COVID-19 that guide screening, testing, and evaluation,” write Maura Kennedy, MD, MPH, and colleagues.

“I was absolutely seeing cases of delirium where there were no other symptoms of COVID-19, but we didn’t have lot of data on the frequency of this,” explained Kennedy, an emergency department physician at Massachusetts General Hospital and an assistant professor of emergency medicine at Harvard Medical School, Boston.

“And the rate was somewhat surprising compared with that seen in non-COVID studies of delirium, but then our study population was more at risk, coming from long-term care facilities and having prior stroke or dementia,” she said. The most common form of delirium was hypoactive sleepiness and nonresponsiveness, although hyperactivity and agitation were also seen.

Kennedy thinks the addition of delirium as a common presenting symptom to diagnostic checklists would prevent some cases from being missed and allow earlier identification and management of COVID-19 patients at high risk for poor outcomes. “We certainly don’t want to send them back undiagnosed to a long-term care facility or promote transmission within the hospital,” she told Medscape Medical News.

That step has already been implemented in some US centers. “Delirium is something we’ve been looking at since the early summer,” said geriatrician Angela Catic, MD, an assistant professor at Baylor College of Medicine’s Huffington Center on Aging and the Michael E. DeBakey VA Medical Center, Houston, Texas.

“If we see delirium, we’re looking for COVID-19,” said Catic, who was not involved in the study.

In Catic’s experience, it is “not at all atypical” to see patients whose only symptom of COVID-19 is delirium. As with other infections and diseases, “the aging brain is incredibly vulnerable,” she said.

According to William W. Hung, MD, MPH, an assistant professor of geriatrics and palliative medicine at the Icahn School of Medicine at Mount Sinai, New York City, delirium is “generally a common sign of something seriously wrong” in older adults. “In the case of COVID-19, low oxygenation caused by the infection may play a role,” he told Medscape Medical News. Although he agreed that delirium should be included in the differential diagnosis of COVID-19, how frequently it is the only symptom at presentation would need to be determined in a considerably larger population, he said.

Joining the company of those observing this COVID-19 manifestation is Christopher R. Carpenter, MD, a professor of emergency medicine at Washington University in St. Louis, St. Louis, Missouri. He was not a participant in the current study.

“I have absolutely seen and documented delirium as the presenting complaint in older adult patients who were ultimately diagnosed with SARS-CoV-2, and since March, I contemplate SARS-CoV-2 each time I identify delirium,” Carpenter told Medscape Medical News. “Honestly, I ― and most of my colleagues ― are considering SARS-CoV-2 for a range of symptoms and complaints these days, because of the odd presentations we’ve all encountered.”
 

Study details

For the study, Kennedy and colleagues enrolled consecutive adults aged 65 years and older who were diagnosed with active COVID-19 and who presented to emergency departments at seven centers in Massachusetts, Maine, Connecticut, Michigan, and North Carolina on or after March 13, 2020. Active infection with SARS-CoV-2 was determined on the basis of results of nasal swab polymerase chain reaction tests (99% of cases) or the appearance and distribution of ground-glass opacities on chest radiography or CT (1%).

Of the 817 patients enrolled, 386 (47%) were men, 493 (62%) were White, 215 (27%) were Black, and 54 (7%) were Hispanic or Latinx. The mean age of patients was 77.7 years (standard deviation, 8.2). Their age placed them at risk for chronic comorbidities and cognitive problems; indeed, 15% had at least four chronic conditions, and 30% had existing cognitive impairment.

The authors note that among the 226 patients (28%) who had delirium at presentation, 60 (27%) had experienced delirium for a duration of 2 to 7 days.

Additionally, of the 226 patients who exhibited delirium as a primary symptom, 84 (37%) showed no typical COVID-19 symptoms or signs, such as cough, fever, or shortness of breath.

The presence of delirium did not correlate with any of the typical COVID-19 symptoms in particular; Kennedy noted that only 56% of patients in the cohort had a fever at presentation.

Delirium at presentation was significantly associated with a median hospital stay of more than 8 days (aRR, 1.14; 95% CI, .97 – 1.35) and a greater risk for discharge to a rehabilitation facility (aRR, 1.55; 95% CI, 1.07 – 2.26). Factors associated with delirium included age older than 75 years, residence in a nursing home or assisted-living facility, previous use of psychoactive medications, vision impairment, hearing impairment, stroke, and Parkinson’s disease.

Kennedy noted that the rate of delirium observed in this study is much higher than that generally reported in emergency department studies conducted before the COVID-19 pandemic. In those studies, the delirium rate ranged from 7% to 20%. The associated risk factors, however, are comparable.

“Mounting evidence supports the high occurrence of delirium and other neuropsychiatric manifestations with COVID-19, with previously reported rates of 22% to 33% among hospitalized patients,” Kennedy and associates write.

In Carpenter’s opinion, the development of incident delirium while receiving care in the emergency department, as opposed to delirium at the time of presentation, has been exacerbated by the no-visitor policies mandated by the pandemic, which have prevented visits even from personal caregivers of patients with moderate to severe dementia. “Although healthcare systems need to be cognizant of the risk of spread to uninfected caregivers, there’s a risk-benefit balance that must be found, because having one caregiver at the bedside can prevent delirium in cognitively impaired patients,” said Carpenter, who was not involved in the current study.

Among the barriers to improving the situation, Carpenter cited the lack of routine delirium screening and the absence of high-quality evidence to support emergency department interventions to mitigate delirium.

“Layer those challenges on top of COVID-19’s rapidly evolving diagnostic landscape, frequent atypical presentations, and asymptomatic carriers across all age groups and the negative impact of delirium is magnified,” Carpenter said.

Once elderly patients are hospitalized, Kennedy recommends the nonpharmacologic guidelines of the Hospital Elder Life Program for reducing delirium risk. Recommendations include the providing of adequate sleep, hydration, and nutrition, as well as function restoration, precipitant avoidance, and reorientation.

The study was supported in part by the National Institute on Aging and the Massachusetts Medical School. The authors, Carpenter, Hung, and Catic have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Delirium should be included on checklists of the presenting signs and symptoms of COVID-19, particularly in elderly adults, according to a multicenter study of seniors visiting emergency departments.

Overall, 28% of the 817 older adults who presented to the emergency department and were diagnosed with COVID-19 had delirium, according to a study published online November 19 in JAMA Network Open. Moreover, 16% of these patients had delirium that was not accompanied by typical symptoms or signs of SARS-CoV-2 infection.

Among patients with delirium, there was a greater probability of admission to the intensive care unit compared with patients who presented without delirium (adjusted relative risk [aRR], 1.67; 95% CI, 1.30 – 2.15), as well as a greater probability of death (aRR, 1.24; 95% CI, 1.00 – 1.55).

“These findings suggest the clinical importance of including delirium on checklists of presenting signs and symptoms of COVID-19 that guide screening, testing, and evaluation,” write Maura Kennedy, MD, MPH, and colleagues.

“I was absolutely seeing cases of delirium where there were no other symptoms of COVID-19, but we didn’t have lot of data on the frequency of this,” explained Kennedy, an emergency department physician at Massachusetts General Hospital and an assistant professor of emergency medicine at Harvard Medical School, Boston.

“And the rate was somewhat surprising compared with that seen in non-COVID studies of delirium, but then our study population was more at risk, coming from long-term care facilities and having prior stroke or dementia,” she said. The most common form of delirium was hypoactive sleepiness and nonresponsiveness, although hyperactivity and agitation were also seen.

Kennedy thinks the addition of delirium as a common presenting symptom to diagnostic checklists would prevent some cases from being missed and allow earlier identification and management of COVID-19 patients at high risk for poor outcomes. “We certainly don’t want to send them back undiagnosed to a long-term care facility or promote transmission within the hospital,” she told Medscape Medical News.

That step has already been implemented in some US centers. “Delirium is something we’ve been looking at since the early summer,” said geriatrician Angela Catic, MD, an assistant professor at Baylor College of Medicine’s Huffington Center on Aging and the Michael E. DeBakey VA Medical Center, Houston, Texas.

“If we see delirium, we’re looking for COVID-19,” said Catic, who was not involved in the study.

In Catic’s experience, it is “not at all atypical” to see patients whose only symptom of COVID-19 is delirium. As with other infections and diseases, “the aging brain is incredibly vulnerable,” she said.

According to William W. Hung, MD, MPH, an assistant professor of geriatrics and palliative medicine at the Icahn School of Medicine at Mount Sinai, New York City, delirium is “generally a common sign of something seriously wrong” in older adults. “In the case of COVID-19, low oxygenation caused by the infection may play a role,” he told Medscape Medical News. Although he agreed that delirium should be included in the differential diagnosis of COVID-19, how frequently it is the only symptom at presentation would need to be determined in a considerably larger population, he said.

Joining the company of those observing this COVID-19 manifestation is Christopher R. Carpenter, MD, a professor of emergency medicine at Washington University in St. Louis, St. Louis, Missouri. He was not a participant in the current study.

“I have absolutely seen and documented delirium as the presenting complaint in older adult patients who were ultimately diagnosed with SARS-CoV-2, and since March, I contemplate SARS-CoV-2 each time I identify delirium,” Carpenter told Medscape Medical News. “Honestly, I ― and most of my colleagues ― are considering SARS-CoV-2 for a range of symptoms and complaints these days, because of the odd presentations we’ve all encountered.”
 

Study details

For the study, Kennedy and colleagues enrolled consecutive adults aged 65 years and older who were diagnosed with active COVID-19 and who presented to emergency departments at seven centers in Massachusetts, Maine, Connecticut, Michigan, and North Carolina on or after March 13, 2020. Active infection with SARS-CoV-2 was determined on the basis of results of nasal swab polymerase chain reaction tests (99% of cases) or the appearance and distribution of ground-glass opacities on chest radiography or CT (1%).

Of the 817 patients enrolled, 386 (47%) were men, 493 (62%) were White, 215 (27%) were Black, and 54 (7%) were Hispanic or Latinx. The mean age of patients was 77.7 years (standard deviation, 8.2). Their age placed them at risk for chronic comorbidities and cognitive problems; indeed, 15% had at least four chronic conditions, and 30% had existing cognitive impairment.

The authors note that among the 226 patients (28%) who had delirium at presentation, 60 (27%) had experienced delirium for a duration of 2 to 7 days.

Additionally, of the 226 patients who exhibited delirium as a primary symptom, 84 (37%) showed no typical COVID-19 symptoms or signs, such as cough, fever, or shortness of breath.

The presence of delirium did not correlate with any of the typical COVID-19 symptoms in particular; Kennedy noted that only 56% of patients in the cohort had a fever at presentation.

Delirium at presentation was significantly associated with a median hospital stay of more than 8 days (aRR, 1.14; 95% CI, .97 – 1.35) and a greater risk for discharge to a rehabilitation facility (aRR, 1.55; 95% CI, 1.07 – 2.26). Factors associated with delirium included age older than 75 years, residence in a nursing home or assisted-living facility, previous use of psychoactive medications, vision impairment, hearing impairment, stroke, and Parkinson’s disease.

Kennedy noted that the rate of delirium observed in this study is much higher than that generally reported in emergency department studies conducted before the COVID-19 pandemic. In those studies, the delirium rate ranged from 7% to 20%. The associated risk factors, however, are comparable.

“Mounting evidence supports the high occurrence of delirium and other neuropsychiatric manifestations with COVID-19, with previously reported rates of 22% to 33% among hospitalized patients,” Kennedy and associates write.

In Carpenter’s opinion, the development of incident delirium while receiving care in the emergency department, as opposed to delirium at the time of presentation, has been exacerbated by the no-visitor policies mandated by the pandemic, which have prevented visits even from personal caregivers of patients with moderate to severe dementia. “Although healthcare systems need to be cognizant of the risk of spread to uninfected caregivers, there’s a risk-benefit balance that must be found, because having one caregiver at the bedside can prevent delirium in cognitively impaired patients,” said Carpenter, who was not involved in the current study.

Among the barriers to improving the situation, Carpenter cited the lack of routine delirium screening and the absence of high-quality evidence to support emergency department interventions to mitigate delirium.

“Layer those challenges on top of COVID-19’s rapidly evolving diagnostic landscape, frequent atypical presentations, and asymptomatic carriers across all age groups and the negative impact of delirium is magnified,” Carpenter said.

Once elderly patients are hospitalized, Kennedy recommends the nonpharmacologic guidelines of the Hospital Elder Life Program for reducing delirium risk. Recommendations include the providing of adequate sleep, hydration, and nutrition, as well as function restoration, precipitant avoidance, and reorientation.

The study was supported in part by the National Institute on Aging and the Massachusetts Medical School. The authors, Carpenter, Hung, and Catic have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Lowering blood pressure for patients with intracerebral hemorrhage (ICH) does not improve functional recovery, a systematic review and meta-analysis shows, although it does reduce hematoma growth in these patients.

Despite the negative finding, the investigators observed broad variation in treatment effect among the studies they reviewed. They also found that target-based blood pressure treatment tended to improve function more than fixed-dose treatment.

“These data provide a strong message that early blood pressure–lowering treatment can control bleeding. This was not clear beforehand,” Craig Anderson, PhD, professor of neurology and epidemiology at the University of New South Wales, Sydney, said in an interview.

“But these data also indicate that the management of blood pressure in ICH is complex,” he added. Timing, type of drug, and type of patient must be considered, he said. “We need more data to allow better individualizing of such therapy.”

The results were presented at the European Stroke Organisation–World Stroke Organisation (ESO-WSO) Conference 2020.

Controversy about the efficacy of blood pressure reduction for patients with ICH continues, despite studies that have examined this question. In this analysis, Dr. Anderson and colleagues sought to examine the evidence from randomized controlled trials in this area and identify potentially overlooked heterogeneity among trials.

The investigators conducted a systematic review and meta-analysis of studies in the Cochrane Central Register of Controlled Trials, EMBASE, and MEDLINE databases. They searched for randomized controlled trials of blood pressure management for adults with acute ICH, focusing on studies in which patients were enrolled within 7 days of ICH onset. These studies compared intensive blood pressure management with guideline-based management.

Investigators chose function, defined as Modified Rankin Scale (mRS) score at 90 days, as their primary outcome. Radiologic outcomes included absolute (>6 mL) and proportional (>33%) hematoma growth at 24 hours. They used the intention to treat dataset from each trial in their statistical analyses and created generalized linear mixed models with prespecified covariables using a one-stage approach.
 

Variation by drug

A total of 7,094 studies were identified, of which 50 were eligible for inclusion. Their analysis encompassed 16 studies for which the respective investigators were willing to share patient-level data. The analysis included data on 6,221 patients. The mean age of the patients was 64.2 years, 36.4% were women, and the median time from symptom onset to randomization was 3.8 hours.

Mean National Institutes of Health Stroke Scale score was approximately 11. Mean systolic blood pressure at baseline was 177 mm Hg, and mean hematoma volume was approximately 10.6 mL.

The difference in blood pressure between the intensive and guideline groups was approximately 8 mm Hg at 1 hour and 12 mm Hg at 24 hours.

Intensive blood pressure management did not affect function at 90 days. The adjusted odds ratio for unfavorable shift in mRS scores was 0.97 (95% CI, 0.88-1.06; P = .503). Intensive blood pressure management did, however, reduce hematoma growth (absolute aOR, 0.75; 95% CI, 0.60-0.92; P = .007; relative aOR, 0.82; 95% CI, 0.68-0.99; P = .034).

In prespecified subgroup analyses, they found a trend toward adverse outcomes among patients who received renin-angiotensin blockers and a trend toward benefit for patients who received alpha- or beta-receptor antagonists or calcium channel blockers. They did not observe a clear association between time of treatment and outcome.

In addition to hematoma growth, other factors influence prognosis after ICH, such as the patient’s status before ICH (for example, cardiovascular risk factors, age, and hypertensive effects on the brain, kidneys, and heart), the location of ICH and its effects on surrounding structures, and complications of care in hospitals, such as infection and bleeding, said Dr. Anderson.

They are conducting two ongoing clinical trials in patients with ICH. One, INTERACT3, is evaluating a “care bundle” quality control package that includes early intensive blood pressure lowering for patients with large ICH who undergo surgery.

The other, INTERACT4, is evaluating early blood pressure control in the ambulance for patients with suspected acute stroke. At least one-fifth of those patients will have ICH, said Dr. Anderson.
 

Prevention is essential

Among patients with ICH, much of the bleeding occurs before presentation at the hospital, Louis R. Caplan, MD, a neurologist at Beth Israel Deaconess Medical Center, Boston, said in an interview. Furthermore, the bleeding mainly occurs in the deep part of the brain where most of the important motor tracts are. “If those tracts are already hit, a little extra blood isn’t going to change things,” said Dr. Caplan, who was not involved in the research.

In addition, blood is pushed from inside the brain to the periphery until the pressure outside the brain is equal to the pressure inside it. “You can decrease the amount of bleeding significantly, but it probably doesn’t affect the outcome,” said Dr. Caplan.

One factor in patients’ apparent lack of functional improvement is that the mRS is not sensitive to minor changes in disability, he said. “You have to show a pretty important change for it to make a difference,” said Dr. Caplan.

In addition, recovery from a hemorrhage takes much longer than recovery from an infarct. Examining the population at 6 months would have been preferable to examining them at 90 days, but the investigators might not have 6-month data, said Dr. Caplan.

“The main thing is really prevention,” he concluded.

The study was conducted with funding from Takeda. Dr. Anderson reported receiving funding from the National Health and Medical Research Council of Australia and speaker fees from Takeda. Dr. Caplan has disclosed no relevant financial relationships.

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

Lowering blood pressure for patients with intracerebral hemorrhage (ICH) does not improve functional recovery, a systematic review and meta-analysis shows, although it does reduce hematoma growth in these patients.

Despite the negative finding, the investigators observed broad variation in treatment effect among the studies they reviewed. They also found that target-based blood pressure treatment tended to improve function more than fixed-dose treatment.

“These data provide a strong message that early blood pressure–lowering treatment can control bleeding. This was not clear beforehand,” Craig Anderson, PhD, professor of neurology and epidemiology at the University of New South Wales, Sydney, said in an interview.

“But these data also indicate that the management of blood pressure in ICH is complex,” he added. Timing, type of drug, and type of patient must be considered, he said. “We need more data to allow better individualizing of such therapy.”

The results were presented at the European Stroke Organisation–World Stroke Organisation (ESO-WSO) Conference 2020.

Controversy about the efficacy of blood pressure reduction for patients with ICH continues, despite studies that have examined this question. In this analysis, Dr. Anderson and colleagues sought to examine the evidence from randomized controlled trials in this area and identify potentially overlooked heterogeneity among trials.

The investigators conducted a systematic review and meta-analysis of studies in the Cochrane Central Register of Controlled Trials, EMBASE, and MEDLINE databases. They searched for randomized controlled trials of blood pressure management for adults with acute ICH, focusing on studies in which patients were enrolled within 7 days of ICH onset. These studies compared intensive blood pressure management with guideline-based management.

Investigators chose function, defined as Modified Rankin Scale (mRS) score at 90 days, as their primary outcome. Radiologic outcomes included absolute (>6 mL) and proportional (>33%) hematoma growth at 24 hours. They used the intention to treat dataset from each trial in their statistical analyses and created generalized linear mixed models with prespecified covariables using a one-stage approach.
 

Variation by drug

A total of 7,094 studies were identified, of which 50 were eligible for inclusion. Their analysis encompassed 16 studies for which the respective investigators were willing to share patient-level data. The analysis included data on 6,221 patients. The mean age of the patients was 64.2 years, 36.4% were women, and the median time from symptom onset to randomization was 3.8 hours.

Mean National Institutes of Health Stroke Scale score was approximately 11. Mean systolic blood pressure at baseline was 177 mm Hg, and mean hematoma volume was approximately 10.6 mL.

The difference in blood pressure between the intensive and guideline groups was approximately 8 mm Hg at 1 hour and 12 mm Hg at 24 hours.

Intensive blood pressure management did not affect function at 90 days. The adjusted odds ratio for unfavorable shift in mRS scores was 0.97 (95% CI, 0.88-1.06; P = .503). Intensive blood pressure management did, however, reduce hematoma growth (absolute aOR, 0.75; 95% CI, 0.60-0.92; P = .007; relative aOR, 0.82; 95% CI, 0.68-0.99; P = .034).

In prespecified subgroup analyses, they found a trend toward adverse outcomes among patients who received renin-angiotensin blockers and a trend toward benefit for patients who received alpha- or beta-receptor antagonists or calcium channel blockers. They did not observe a clear association between time of treatment and outcome.

In addition to hematoma growth, other factors influence prognosis after ICH, such as the patient’s status before ICH (for example, cardiovascular risk factors, age, and hypertensive effects on the brain, kidneys, and heart), the location of ICH and its effects on surrounding structures, and complications of care in hospitals, such as infection and bleeding, said Dr. Anderson.

They are conducting two ongoing clinical trials in patients with ICH. One, INTERACT3, is evaluating a “care bundle” quality control package that includes early intensive blood pressure lowering for patients with large ICH who undergo surgery.

The other, INTERACT4, is evaluating early blood pressure control in the ambulance for patients with suspected acute stroke. At least one-fifth of those patients will have ICH, said Dr. Anderson.
 

Prevention is essential

Among patients with ICH, much of the bleeding occurs before presentation at the hospital, Louis R. Caplan, MD, a neurologist at Beth Israel Deaconess Medical Center, Boston, said in an interview. Furthermore, the bleeding mainly occurs in the deep part of the brain where most of the important motor tracts are. “If those tracts are already hit, a little extra blood isn’t going to change things,” said Dr. Caplan, who was not involved in the research.

In addition, blood is pushed from inside the brain to the periphery until the pressure outside the brain is equal to the pressure inside it. “You can decrease the amount of bleeding significantly, but it probably doesn’t affect the outcome,” said Dr. Caplan.

One factor in patients’ apparent lack of functional improvement is that the mRS is not sensitive to minor changes in disability, he said. “You have to show a pretty important change for it to make a difference,” said Dr. Caplan.

In addition, recovery from a hemorrhage takes much longer than recovery from an infarct. Examining the population at 6 months would have been preferable to examining them at 90 days, but the investigators might not have 6-month data, said Dr. Caplan.

“The main thing is really prevention,” he concluded.

The study was conducted with funding from Takeda. Dr. Anderson reported receiving funding from the National Health and Medical Research Council of Australia and speaker fees from Takeda. Dr. Caplan has disclosed no relevant financial relationships.

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

Lowering blood pressure for patients with intracerebral hemorrhage (ICH) does not improve functional recovery, a systematic review and meta-analysis shows, although it does reduce hematoma growth in these patients.

Despite the negative finding, the investigators observed broad variation in treatment effect among the studies they reviewed. They also found that target-based blood pressure treatment tended to improve function more than fixed-dose treatment.

“These data provide a strong message that early blood pressure–lowering treatment can control bleeding. This was not clear beforehand,” Craig Anderson, PhD, professor of neurology and epidemiology at the University of New South Wales, Sydney, said in an interview.

“But these data also indicate that the management of blood pressure in ICH is complex,” he added. Timing, type of drug, and type of patient must be considered, he said. “We need more data to allow better individualizing of such therapy.”

The results were presented at the European Stroke Organisation–World Stroke Organisation (ESO-WSO) Conference 2020.

Controversy about the efficacy of blood pressure reduction for patients with ICH continues, despite studies that have examined this question. In this analysis, Dr. Anderson and colleagues sought to examine the evidence from randomized controlled trials in this area and identify potentially overlooked heterogeneity among trials.

The investigators conducted a systematic review and meta-analysis of studies in the Cochrane Central Register of Controlled Trials, EMBASE, and MEDLINE databases. They searched for randomized controlled trials of blood pressure management for adults with acute ICH, focusing on studies in which patients were enrolled within 7 days of ICH onset. These studies compared intensive blood pressure management with guideline-based management.

Investigators chose function, defined as Modified Rankin Scale (mRS) score at 90 days, as their primary outcome. Radiologic outcomes included absolute (>6 mL) and proportional (>33%) hematoma growth at 24 hours. They used the intention to treat dataset from each trial in their statistical analyses and created generalized linear mixed models with prespecified covariables using a one-stage approach.
 

Variation by drug

A total of 7,094 studies were identified, of which 50 were eligible for inclusion. Their analysis encompassed 16 studies for which the respective investigators were willing to share patient-level data. The analysis included data on 6,221 patients. The mean age of the patients was 64.2 years, 36.4% were women, and the median time from symptom onset to randomization was 3.8 hours.

Mean National Institutes of Health Stroke Scale score was approximately 11. Mean systolic blood pressure at baseline was 177 mm Hg, and mean hematoma volume was approximately 10.6 mL.

The difference in blood pressure between the intensive and guideline groups was approximately 8 mm Hg at 1 hour and 12 mm Hg at 24 hours.

Intensive blood pressure management did not affect function at 90 days. The adjusted odds ratio for unfavorable shift in mRS scores was 0.97 (95% CI, 0.88-1.06; P = .503). Intensive blood pressure management did, however, reduce hematoma growth (absolute aOR, 0.75; 95% CI, 0.60-0.92; P = .007; relative aOR, 0.82; 95% CI, 0.68-0.99; P = .034).

In prespecified subgroup analyses, they found a trend toward adverse outcomes among patients who received renin-angiotensin blockers and a trend toward benefit for patients who received alpha- or beta-receptor antagonists or calcium channel blockers. They did not observe a clear association between time of treatment and outcome.

In addition to hematoma growth, other factors influence prognosis after ICH, such as the patient’s status before ICH (for example, cardiovascular risk factors, age, and hypertensive effects on the brain, kidneys, and heart), the location of ICH and its effects on surrounding structures, and complications of care in hospitals, such as infection and bleeding, said Dr. Anderson.

They are conducting two ongoing clinical trials in patients with ICH. One, INTERACT3, is evaluating a “care bundle” quality control package that includes early intensive blood pressure lowering for patients with large ICH who undergo surgery.

The other, INTERACT4, is evaluating early blood pressure control in the ambulance for patients with suspected acute stroke. At least one-fifth of those patients will have ICH, said Dr. Anderson.
 

Prevention is essential

Among patients with ICH, much of the bleeding occurs before presentation at the hospital, Louis R. Caplan, MD, a neurologist at Beth Israel Deaconess Medical Center, Boston, said in an interview. Furthermore, the bleeding mainly occurs in the deep part of the brain where most of the important motor tracts are. “If those tracts are already hit, a little extra blood isn’t going to change things,” said Dr. Caplan, who was not involved in the research.

In addition, blood is pushed from inside the brain to the periphery until the pressure outside the brain is equal to the pressure inside it. “You can decrease the amount of bleeding significantly, but it probably doesn’t affect the outcome,” said Dr. Caplan.

One factor in patients’ apparent lack of functional improvement is that the mRS is not sensitive to minor changes in disability, he said. “You have to show a pretty important change for it to make a difference,” said Dr. Caplan.

In addition, recovery from a hemorrhage takes much longer than recovery from an infarct. Examining the population at 6 months would have been preferable to examining them at 90 days, but the investigators might not have 6-month data, said Dr. Caplan.

“The main thing is really prevention,” he concluded.

The study was conducted with funding from Takeda. Dr. Anderson reported receiving funding from the National Health and Medical Research Council of Australia and speaker fees from Takeda. Dr. Caplan has disclosed no relevant financial relationships.

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

Contrary to historical evidence, among older people, elevated LDL cholesterol levels increase risk for heart attack and cardiovascular disease, and older patients benefit as much, if not more, from statins and other cholesterol-lowering drugs than do younger people, two new studies show.

“By contrast with previous historical studies, our data show that LDL cholesterol is an important risk factor for myocardial infarction and atherosclerotic cardiovascular disease in a contemporary primary prevention cohort of individuals aged 70 to 100 years,” Borge Nordestgaard, MD, of the University of Copenhagen, and colleagues noted in the first of the two studies, published this week in the Lancet.

“By lowering LDL cholesterol in healthy individuals aged 70-100 years, the potential for preventing myocardial infarctions and atherosclerotic cardiovascular disease is huge, and at a substantially lower number needed to treat when compared with those aged 20-69 years,” they added.

“These findings support the concept of the cumulative burden of LDL cholesterol over one’s lifetime and the progressive increase in risk for atherosclerotic cardiovascular disease, including myocardial infarction, with age,” added Frederick J. Raal, PhD, and Farzahna Mohamed, MB BCh, of the University of the Witwatersrand, Johannesburg, South Africa, in an editorial published with both new studies in the Lancet (2020 Nov 10. doi: 10.1016/S0140-6736[20]32333-3).

The studies underscore the need for clinicians to consider continued risks associated with elevated LDL cholesterol in older age, they stressed, adding that statins are also beneficial for younger persons at risk to prevent conditions from worsening.

“The average age of patients in all the trials analyzed was older than 60 years, an age when atherosclerotic cardiovascular disease is already well established,” the editorialists wrote.

“Lipid-lowering therapy should be initiated at a younger age, preferably before age 40 years, in those at risk to delay the onset of atherosclerosis, rather than try to manage the condition once fully established or advanced,” they stressed.
 

No RCTs have included patients older than 70

For persons aged 40-75 years, elevated LDL cholesterol levels are a known risk factor for MI and atherosclerotic cardiovascular disease, and there is consensus in guidelines regarding treatment with statins.

However, the risk for people older than 70 is controversial. Some studies show little or no association between elevated LDL cholesterol levels and an increased risk for MI.

Contributing to the uncertainty is that few of the randomized, controlled trials that have investigated the question have included patients aged older than 70 years.

As a consequence, many practice guidelines have noted that the level of evidence in older patients is low, and some organizations have lowered the strength of recommendations regarding the treatment for older patients in comparison with younger patients.
 

Primary prevention: CV events increase with elevated LDL cholesterol in older age

Dr. Nordestgaard and colleagues studied data on 91,131 people living in Copenhagen who did not have atherosclerotic cardiovascular disease or diabetes at baseline and were not taking statins.

Of the participants, 10,592 were aged 70-79 years, and 3,188 participants were aged 80-100 years.

Over an average follow-up period of 7.7 years, 1,515 participants had a first MI, and 3,389 developed atherosclerotic cardiovascular disease.

In the primary-prevention cohort, after multivariate adjustment, the risk of having a heart attack per 1.0 mmol/L increase in LDL cholesterol was increased in the group overall (hazard ratio, 1.34). The increased risk was observed for all age groups, including those aged 80-100 years (HR, 1.28), 70-79 (HR, 1.25), 60-69 (HR, 1.29), 50-59 (HR, 1.28), and 20-49 (HR, 1.68).

Risk for atherosclerotic cardiovascular disease was also raised per 1.0 mmol/L increase in LDL cholesterol overall (HR, 1.16) and in all age groups, particularly those aged 70-100 years.

Greater elevations in LDL cholesterol (5.0 mmol/L or higher, indicative of possible familial hypercholesterolemia) were associated with a notably higher risk for heart attack after multivariate adjustment in people aged 80-100 (HR, 2.99). Risk was also higher among those aged 70-79 (HR, 1.82).

The highest incidence was in those older than 70. The rate was 8.5 heart attacks per 1,000 people per year among those aged 80-100 and 5.2 heart attacks per 1,000 in those aged 70-79. The rates were 2.5 per 1,000 among those 60-69, 1.8 for those aged 50-59, and 0.8 for those aged 20-49.

“The absolute risk [of cardiovascular events] is of course much higher in the elderly than those under the age of 75, but what was a surprise was how clear our results were on a relative risk scale, that the risk associated with elevated LDL [cholesterol] was as high in people aged 80-100 as the younger patients,” Dr. Nordestgaard said in an interview.

With regard to the benefits of cholesterol-lowering drugs, the study showed that the number needed to prevent one heart attack over 5 years was 80 among those aged 80-100; the number was 439 for people aged 50-59.

With regard to stronger statins, when moderate-intensity statins were used, the number needed to treat to prevent one cardiovascular disease event of any type dropped to 42 for patients aged 80-100. It was 88 for those aged 70-79, 164 for those aged 60-69, 345 for those aged 50-59, and 769 for those aged 20-49.

“The clinical significance of this is that it appears those in older age groups indeed benefit from cholesterol-lowering therapy,” Dr. Nordestgaard said. “I think many people have this idea that LDL [cholesterol] is not important over the age of about 70-75, but that’s not the case.”

“These robust findings are novel,” he and his colleagues stressed.

Despite these observational findings, the South African editorialists noted that “whether lipid-lowering therapy should be initiated for primary prevention in people aged 75 years or older is unclear,” owing to the host of risks and benefits that need to be balanced.

The findings of an ongoing randomized, placebo-controlled trial (STAREE) may answer this question, they wrote. It is investigating primary prevention in 18,000 older patients (≥70 years) who are being randomly assigned to receive atorvastatin 40 mg/d or placebo. The study is seeking to determine whether statin treatment extends the length of a disability-free life, which will be assessed on the basis of survival outside permanent residential care. Results are expected in 2022-2023.
 

Unequivocal reductions in events in elderly, comparable with younger patients

In the second study (Lancet. 2020 Nov 10. doi: 10.1016/S0140-6736[20]32332-1), Baris Gencer, MD, of Brigham and Women’s Hospital, Boston, =and colleagues evaluated the effects of statins and other cholesterol-lowering drugs, including ezetimibe and proprotein convertase subtilisin/kexin type 9 inhibitors, in older versus younger patients.

The systematic review and meta-analysis of 29 randomized controlled trials, also published in the Lancet, were presented virtually as a poster as part of the 2020 American Heart Association scientific session. It included data on 244,090 patients, including 21,492 aged 75 years and older.

The meta-analysis included studies of cardiovascular outcomes of a guideline-recommended LDL cholesterol–lowering drug, with a median follow-up of at least 2 years and inclusion of data on patients aged 75 years and older.

The results showed that over a median follow-up of 2.2 to 6 years, statin use by older patients was associated with a relative risk reduction of major vascular events of 26% per 1 mmol/L reduction in LDL cholesterol (P = .0019), which was comparable with a risk reduction of 15% per 1 mmol/L reduction in LDL cholesterol for patients younger than 75 years (P = .37, compared with older patients).

Treatment of older patients with LDL cholesterol–lowering drugs was also associated with significantly improved outcomes in cardiovascular death (risk ratio, 0.85), MI (RR, 0.80), stroke (RR, 0.73), and coronary revascularization (RR, 0.80).

“We found an unequivocal reduction in the risk of major vascular events with both statin and nonstatin LDL cholesterol-lowering treatments, which was similar to that seen in younger patients,” the authors wrote.

“Cholesterol-lowering medications are affordable drugs that have reduced risk of heart disease for millions of people worldwide, but until now, their benefits for older people have remained less certain,” said lead author Marc Sabatine, MD, also of Brigham and Women’s Hospital, in a Lancet press release.

“Our analysis indicates that these therapies are as effective in reducing cardiovascular events and deaths in people aged 75 years and over as they are in younger people. We found no offsetting safety concerns, and together, these results should strengthen guideline recommendations for the use of cholesterol-lowering medications, including statin and nonstatin therapy, in elderly people.”

The editorialists agreed: “More than 80% of fatal cardiovascular events occur in individuals older than 65 years, and the incidence of cardiovascular events is increasing in those older than 80 years; therefore, the findings of Gencer and colleagues’ study should encourage the use of lipid-lowering therapy in older patients.”

The authors of the two studies have disclosed no relevant financial relationships. Dr. Raal has received research grants, honoraria, or consulting fees for advisory board membership, professional input, and lectures on lipid-lowering drug therapy from Amgen, Regeneron, Sanofi, Novartis, and the Medicines Company.

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

Contrary to historical evidence, among older people, elevated LDL cholesterol levels increase risk for heart attack and cardiovascular disease, and older patients benefit as much, if not more, from statins and other cholesterol-lowering drugs than do younger people, two new studies show.

“By contrast with previous historical studies, our data show that LDL cholesterol is an important risk factor for myocardial infarction and atherosclerotic cardiovascular disease in a contemporary primary prevention cohort of individuals aged 70 to 100 years,” Borge Nordestgaard, MD, of the University of Copenhagen, and colleagues noted in the first of the two studies, published this week in the Lancet.

“By lowering LDL cholesterol in healthy individuals aged 70-100 years, the potential for preventing myocardial infarctions and atherosclerotic cardiovascular disease is huge, and at a substantially lower number needed to treat when compared with those aged 20-69 years,” they added.

“These findings support the concept of the cumulative burden of LDL cholesterol over one’s lifetime and the progressive increase in risk for atherosclerotic cardiovascular disease, including myocardial infarction, with age,” added Frederick J. Raal, PhD, and Farzahna Mohamed, MB BCh, of the University of the Witwatersrand, Johannesburg, South Africa, in an editorial published with both new studies in the Lancet (2020 Nov 10. doi: 10.1016/S0140-6736[20]32333-3).

The studies underscore the need for clinicians to consider continued risks associated with elevated LDL cholesterol in older age, they stressed, adding that statins are also beneficial for younger persons at risk to prevent conditions from worsening.

“The average age of patients in all the trials analyzed was older than 60 years, an age when atherosclerotic cardiovascular disease is already well established,” the editorialists wrote.

“Lipid-lowering therapy should be initiated at a younger age, preferably before age 40 years, in those at risk to delay the onset of atherosclerosis, rather than try to manage the condition once fully established or advanced,” they stressed.
 

No RCTs have included patients older than 70

For persons aged 40-75 years, elevated LDL cholesterol levels are a known risk factor for MI and atherosclerotic cardiovascular disease, and there is consensus in guidelines regarding treatment with statins.

However, the risk for people older than 70 is controversial. Some studies show little or no association between elevated LDL cholesterol levels and an increased risk for MI.

Contributing to the uncertainty is that few of the randomized, controlled trials that have investigated the question have included patients aged older than 70 years.

As a consequence, many practice guidelines have noted that the level of evidence in older patients is low, and some organizations have lowered the strength of recommendations regarding the treatment for older patients in comparison with younger patients.
 

Primary prevention: CV events increase with elevated LDL cholesterol in older age

Dr. Nordestgaard and colleagues studied data on 91,131 people living in Copenhagen who did not have atherosclerotic cardiovascular disease or diabetes at baseline and were not taking statins.

Of the participants, 10,592 were aged 70-79 years, and 3,188 participants were aged 80-100 years.

Over an average follow-up period of 7.7 years, 1,515 participants had a first MI, and 3,389 developed atherosclerotic cardiovascular disease.

In the primary-prevention cohort, after multivariate adjustment, the risk of having a heart attack per 1.0 mmol/L increase in LDL cholesterol was increased in the group overall (hazard ratio, 1.34). The increased risk was observed for all age groups, including those aged 80-100 years (HR, 1.28), 70-79 (HR, 1.25), 60-69 (HR, 1.29), 50-59 (HR, 1.28), and 20-49 (HR, 1.68).

Risk for atherosclerotic cardiovascular disease was also raised per 1.0 mmol/L increase in LDL cholesterol overall (HR, 1.16) and in all age groups, particularly those aged 70-100 years.

Greater elevations in LDL cholesterol (5.0 mmol/L or higher, indicative of possible familial hypercholesterolemia) were associated with a notably higher risk for heart attack after multivariate adjustment in people aged 80-100 (HR, 2.99). Risk was also higher among those aged 70-79 (HR, 1.82).

The highest incidence was in those older than 70. The rate was 8.5 heart attacks per 1,000 people per year among those aged 80-100 and 5.2 heart attacks per 1,000 in those aged 70-79. The rates were 2.5 per 1,000 among those 60-69, 1.8 for those aged 50-59, and 0.8 for those aged 20-49.

“The absolute risk [of cardiovascular events] is of course much higher in the elderly than those under the age of 75, but what was a surprise was how clear our results were on a relative risk scale, that the risk associated with elevated LDL [cholesterol] was as high in people aged 80-100 as the younger patients,” Dr. Nordestgaard said in an interview.

With regard to the benefits of cholesterol-lowering drugs, the study showed that the number needed to prevent one heart attack over 5 years was 80 among those aged 80-100; the number was 439 for people aged 50-59.

With regard to stronger statins, when moderate-intensity statins were used, the number needed to treat to prevent one cardiovascular disease event of any type dropped to 42 for patients aged 80-100. It was 88 for those aged 70-79, 164 for those aged 60-69, 345 for those aged 50-59, and 769 for those aged 20-49.

“The clinical significance of this is that it appears those in older age groups indeed benefit from cholesterol-lowering therapy,” Dr. Nordestgaard said. “I think many people have this idea that LDL [cholesterol] is not important over the age of about 70-75, but that’s not the case.”

“These robust findings are novel,” he and his colleagues stressed.

Despite these observational findings, the South African editorialists noted that “whether lipid-lowering therapy should be initiated for primary prevention in people aged 75 years or older is unclear,” owing to the host of risks and benefits that need to be balanced.

The findings of an ongoing randomized, placebo-controlled trial (STAREE) may answer this question, they wrote. It is investigating primary prevention in 18,000 older patients (≥70 years) who are being randomly assigned to receive atorvastatin 40 mg/d or placebo. The study is seeking to determine whether statin treatment extends the length of a disability-free life, which will be assessed on the basis of survival outside permanent residential care. Results are expected in 2022-2023.
 

Unequivocal reductions in events in elderly, comparable with younger patients

In the second study (Lancet. 2020 Nov 10. doi: 10.1016/S0140-6736[20]32332-1), Baris Gencer, MD, of Brigham and Women’s Hospital, Boston, =and colleagues evaluated the effects of statins and other cholesterol-lowering drugs, including ezetimibe and proprotein convertase subtilisin/kexin type 9 inhibitors, in older versus younger patients.

The systematic review and meta-analysis of 29 randomized controlled trials, also published in the Lancet, were presented virtually as a poster as part of the 2020 American Heart Association scientific session. It included data on 244,090 patients, including 21,492 aged 75 years and older.

The meta-analysis included studies of cardiovascular outcomes of a guideline-recommended LDL cholesterol–lowering drug, with a median follow-up of at least 2 years and inclusion of data on patients aged 75 years and older.

The results showed that over a median follow-up of 2.2 to 6 years, statin use by older patients was associated with a relative risk reduction of major vascular events of 26% per 1 mmol/L reduction in LDL cholesterol (P = .0019), which was comparable with a risk reduction of 15% per 1 mmol/L reduction in LDL cholesterol for patients younger than 75 years (P = .37, compared with older patients).

Treatment of older patients with LDL cholesterol–lowering drugs was also associated with significantly improved outcomes in cardiovascular death (risk ratio, 0.85), MI (RR, 0.80), stroke (RR, 0.73), and coronary revascularization (RR, 0.80).

“We found an unequivocal reduction in the risk of major vascular events with both statin and nonstatin LDL cholesterol-lowering treatments, which was similar to that seen in younger patients,” the authors wrote.

“Cholesterol-lowering medications are affordable drugs that have reduced risk of heart disease for millions of people worldwide, but until now, their benefits for older people have remained less certain,” said lead author Marc Sabatine, MD, also of Brigham and Women’s Hospital, in a Lancet press release.

“Our analysis indicates that these therapies are as effective in reducing cardiovascular events and deaths in people aged 75 years and over as they are in younger people. We found no offsetting safety concerns, and together, these results should strengthen guideline recommendations for the use of cholesterol-lowering medications, including statin and nonstatin therapy, in elderly people.”

The editorialists agreed: “More than 80% of fatal cardiovascular events occur in individuals older than 65 years, and the incidence of cardiovascular events is increasing in those older than 80 years; therefore, the findings of Gencer and colleagues’ study should encourage the use of lipid-lowering therapy in older patients.”

The authors of the two studies have disclosed no relevant financial relationships. Dr. Raal has received research grants, honoraria, or consulting fees for advisory board membership, professional input, and lectures on lipid-lowering drug therapy from Amgen, Regeneron, Sanofi, Novartis, and the Medicines Company.

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

Contrary to historical evidence, among older people, elevated LDL cholesterol levels increase risk for heart attack and cardiovascular disease, and older patients benefit as much, if not more, from statins and other cholesterol-lowering drugs than do younger people, two new studies show.

“By contrast with previous historical studies, our data show that LDL cholesterol is an important risk factor for myocardial infarction and atherosclerotic cardiovascular disease in a contemporary primary prevention cohort of individuals aged 70 to 100 years,” Borge Nordestgaard, MD, of the University of Copenhagen, and colleagues noted in the first of the two studies, published this week in the Lancet.

“By lowering LDL cholesterol in healthy individuals aged 70-100 years, the potential for preventing myocardial infarctions and atherosclerotic cardiovascular disease is huge, and at a substantially lower number needed to treat when compared with those aged 20-69 years,” they added.

“These findings support the concept of the cumulative burden of LDL cholesterol over one’s lifetime and the progressive increase in risk for atherosclerotic cardiovascular disease, including myocardial infarction, with age,” added Frederick J. Raal, PhD, and Farzahna Mohamed, MB BCh, of the University of the Witwatersrand, Johannesburg, South Africa, in an editorial published with both new studies in the Lancet (2020 Nov 10. doi: 10.1016/S0140-6736[20]32333-3).

The studies underscore the need for clinicians to consider continued risks associated with elevated LDL cholesterol in older age, they stressed, adding that statins are also beneficial for younger persons at risk to prevent conditions from worsening.

“The average age of patients in all the trials analyzed was older than 60 years, an age when atherosclerotic cardiovascular disease is already well established,” the editorialists wrote.

“Lipid-lowering therapy should be initiated at a younger age, preferably before age 40 years, in those at risk to delay the onset of atherosclerosis, rather than try to manage the condition once fully established or advanced,” they stressed.
 

No RCTs have included patients older than 70

For persons aged 40-75 years, elevated LDL cholesterol levels are a known risk factor for MI and atherosclerotic cardiovascular disease, and there is consensus in guidelines regarding treatment with statins.

However, the risk for people older than 70 is controversial. Some studies show little or no association between elevated LDL cholesterol levels and an increased risk for MI.

Contributing to the uncertainty is that few of the randomized, controlled trials that have investigated the question have included patients aged older than 70 years.

As a consequence, many practice guidelines have noted that the level of evidence in older patients is low, and some organizations have lowered the strength of recommendations regarding the treatment for older patients in comparison with younger patients.
 

Primary prevention: CV events increase with elevated LDL cholesterol in older age

Dr. Nordestgaard and colleagues studied data on 91,131 people living in Copenhagen who did not have atherosclerotic cardiovascular disease or diabetes at baseline and were not taking statins.

Of the participants, 10,592 were aged 70-79 years, and 3,188 participants were aged 80-100 years.

Over an average follow-up period of 7.7 years, 1,515 participants had a first MI, and 3,389 developed atherosclerotic cardiovascular disease.

In the primary-prevention cohort, after multivariate adjustment, the risk of having a heart attack per 1.0 mmol/L increase in LDL cholesterol was increased in the group overall (hazard ratio, 1.34). The increased risk was observed for all age groups, including those aged 80-100 years (HR, 1.28), 70-79 (HR, 1.25), 60-69 (HR, 1.29), 50-59 (HR, 1.28), and 20-49 (HR, 1.68).

Risk for atherosclerotic cardiovascular disease was also raised per 1.0 mmol/L increase in LDL cholesterol overall (HR, 1.16) and in all age groups, particularly those aged 70-100 years.

Greater elevations in LDL cholesterol (5.0 mmol/L or higher, indicative of possible familial hypercholesterolemia) were associated with a notably higher risk for heart attack after multivariate adjustment in people aged 80-100 (HR, 2.99). Risk was also higher among those aged 70-79 (HR, 1.82).

The highest incidence was in those older than 70. The rate was 8.5 heart attacks per 1,000 people per year among those aged 80-100 and 5.2 heart attacks per 1,000 in those aged 70-79. The rates were 2.5 per 1,000 among those 60-69, 1.8 for those aged 50-59, and 0.8 for those aged 20-49.

“The absolute risk [of cardiovascular events] is of course much higher in the elderly than those under the age of 75, but what was a surprise was how clear our results were on a relative risk scale, that the risk associated with elevated LDL [cholesterol] was as high in people aged 80-100 as the younger patients,” Dr. Nordestgaard said in an interview.

With regard to the benefits of cholesterol-lowering drugs, the study showed that the number needed to prevent one heart attack over 5 years was 80 among those aged 80-100; the number was 439 for people aged 50-59.

With regard to stronger statins, when moderate-intensity statins were used, the number needed to treat to prevent one cardiovascular disease event of any type dropped to 42 for patients aged 80-100. It was 88 for those aged 70-79, 164 for those aged 60-69, 345 for those aged 50-59, and 769 for those aged 20-49.

“The clinical significance of this is that it appears those in older age groups indeed benefit from cholesterol-lowering therapy,” Dr. Nordestgaard said. “I think many people have this idea that LDL [cholesterol] is not important over the age of about 70-75, but that’s not the case.”

“These robust findings are novel,” he and his colleagues stressed.

Despite these observational findings, the South African editorialists noted that “whether lipid-lowering therapy should be initiated for primary prevention in people aged 75 years or older is unclear,” owing to the host of risks and benefits that need to be balanced.

The findings of an ongoing randomized, placebo-controlled trial (STAREE) may answer this question, they wrote. It is investigating primary prevention in 18,000 older patients (≥70 years) who are being randomly assigned to receive atorvastatin 40 mg/d or placebo. The study is seeking to determine whether statin treatment extends the length of a disability-free life, which will be assessed on the basis of survival outside permanent residential care. Results are expected in 2022-2023.
 

Unequivocal reductions in events in elderly, comparable with younger patients

In the second study (Lancet. 2020 Nov 10. doi: 10.1016/S0140-6736[20]32332-1), Baris Gencer, MD, of Brigham and Women’s Hospital, Boston, =and colleagues evaluated the effects of statins and other cholesterol-lowering drugs, including ezetimibe and proprotein convertase subtilisin/kexin type 9 inhibitors, in older versus younger patients.

The systematic review and meta-analysis of 29 randomized controlled trials, also published in the Lancet, were presented virtually as a poster as part of the 2020 American Heart Association scientific session. It included data on 244,090 patients, including 21,492 aged 75 years and older.

The meta-analysis included studies of cardiovascular outcomes of a guideline-recommended LDL cholesterol–lowering drug, with a median follow-up of at least 2 years and inclusion of data on patients aged 75 years and older.

The results showed that over a median follow-up of 2.2 to 6 years, statin use by older patients was associated with a relative risk reduction of major vascular events of 26% per 1 mmol/L reduction in LDL cholesterol (P = .0019), which was comparable with a risk reduction of 15% per 1 mmol/L reduction in LDL cholesterol for patients younger than 75 years (P = .37, compared with older patients).

Treatment of older patients with LDL cholesterol–lowering drugs was also associated with significantly improved outcomes in cardiovascular death (risk ratio, 0.85), MI (RR, 0.80), stroke (RR, 0.73), and coronary revascularization (RR, 0.80).

“We found an unequivocal reduction in the risk of major vascular events with both statin and nonstatin LDL cholesterol-lowering treatments, which was similar to that seen in younger patients,” the authors wrote.

“Cholesterol-lowering medications are affordable drugs that have reduced risk of heart disease for millions of people worldwide, but until now, their benefits for older people have remained less certain,” said lead author Marc Sabatine, MD, also of Brigham and Women’s Hospital, in a Lancet press release.

“Our analysis indicates that these therapies are as effective in reducing cardiovascular events and deaths in people aged 75 years and over as they are in younger people. We found no offsetting safety concerns, and together, these results should strengthen guideline recommendations for the use of cholesterol-lowering medications, including statin and nonstatin therapy, in elderly people.”

The editorialists agreed: “More than 80% of fatal cardiovascular events occur in individuals older than 65 years, and the incidence of cardiovascular events is increasing in those older than 80 years; therefore, the findings of Gencer and colleagues’ study should encourage the use of lipid-lowering therapy in older patients.”

The authors of the two studies have disclosed no relevant financial relationships. Dr. Raal has received research grants, honoraria, or consulting fees for advisory board membership, professional input, and lectures on lipid-lowering drug therapy from Amgen, Regeneron, Sanofi, Novartis, and the Medicines Company.

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

• Survey reveals special impact of COVID-19 on persons with rare disorders
• Topical treatment tackles oral ulcers in Behçet’s syndrome
• Managing the risk of congenital heart block in anti-Ro/SSA-positive women
• Newly described lung disorder strikes children with systemic juvenile idiopathic arthritis

Read the report here.

• Survey reveals special impact of COVID-19 on persons with rare disorders
• Topical treatment tackles oral ulcers in Behçet’s syndrome
• Managing the risk of congenital heart block in anti-Ro/SSA-positive women
• Newly described lung disorder strikes children with systemic juvenile idiopathic arthritis

Read the report here.

• Survey reveals special impact of COVID-19 on persons with rare disorders
• Topical treatment tackles oral ulcers in Behçet’s syndrome
• Managing the risk of congenital heart block in anti-Ro/SSA-positive women
• Newly described lung disorder strikes children with systemic juvenile idiopathic arthritis

Read the report here.

As far as the pandemic is concerned, it seems like a pretty small thing. A difference of just 0.3%. Children now represent 11.8% of all COVID-19 cases that have occurred since the beginning of the pandemic, compared with 11.5% 1 week ago, according to the American Academy of Pediatrics and the Children’s Hospital Association.

Hiding behind that 0.3%, however, is a much larger number: 144,145. That is the number of new child cases that occurred during the week that ended Nov. 19, and it’s the highest weekly figure yet, eclipsing the previous high of 111,946 from the week of Nov. 12, the AAP and the CHA said in their latest COVID-19 report. For the week ending Nov. 19, children represented 14.1% of all new cases, up from 14.0% the week before.

In the United States, more than 1.18 million children have been infected by the coronavirus since the beginning of the pandemic, with the total among all ages topping 10 million in 49 states (New York is not providing age distribution), the District of Columbia, New York City, Puerto Rico, and Guam, the AAP/CHA data show. That works out to 11.8% of all cases.

The overall rate of child COVID-19 cases is now up to 1,573 per 100,000 children nationally, with considerable variation seen among the states. The lowest rates can be found in Vermont (344 per 100,000), Maine (452), and Hawaii (675), and the highest in North Dakota (5,589), South Dakota (3,993), and Wisconsin (3,727), the AAP and CHA said in the report.

Comparisons between states are somewhat problematic, though, because “each state makes different decisions about how to report the age distribution of COVID-19 cases, and as a result the age range for reported cases varies by state. … It is not possible to standardize more detailed age ranges for children based on what is publicly available from the states at this time,” the two organizations noted.

Five more COVID-19–related deaths in children were reported during the week of Nov. 19, bringing the count to 138 and holding at just 0.06% of the total for all ages, based on data from 43 states and New York City. Children’s share of hospitalizations increased slightly in the last week, rising from 1.7% to 1.8% in the 24 states (and NYC) that are reporting such data. The total number of child hospitalizations in those jurisdictions is just over 6,700, the AAP and CHA said.

[email protected]

As far as the pandemic is concerned, it seems like a pretty small thing. A difference of just 0.3%. Children now represent 11.8% of all COVID-19 cases that have occurred since the beginning of the pandemic, compared with 11.5% 1 week ago, according to the American Academy of Pediatrics and the Children’s Hospital Association.

Hiding behind that 0.3%, however, is a much larger number: 144,145. That is the number of new child cases that occurred during the week that ended Nov. 19, and it’s the highest weekly figure yet, eclipsing the previous high of 111,946 from the week of Nov. 12, the AAP and the CHA said in their latest COVID-19 report. For the week ending Nov. 19, children represented 14.1% of all new cases, up from 14.0% the week before.

In the United States, more than 1.18 million children have been infected by the coronavirus since the beginning of the pandemic, with the total among all ages topping 10 million in 49 states (New York is not providing age distribution), the District of Columbia, New York City, Puerto Rico, and Guam, the AAP/CHA data show. That works out to 11.8% of all cases.

The overall rate of child COVID-19 cases is now up to 1,573 per 100,000 children nationally, with considerable variation seen among the states. The lowest rates can be found in Vermont (344 per 100,000), Maine (452), and Hawaii (675), and the highest in North Dakota (5,589), South Dakota (3,993), and Wisconsin (3,727), the AAP and CHA said in the report.

Comparisons between states are somewhat problematic, though, because “each state makes different decisions about how to report the age distribution of COVID-19 cases, and as a result the age range for reported cases varies by state. … It is not possible to standardize more detailed age ranges for children based on what is publicly available from the states at this time,” the two organizations noted.

Five more COVID-19–related deaths in children were reported during the week of Nov. 19, bringing the count to 138 and holding at just 0.06% of the total for all ages, based on data from 43 states and New York City. Children’s share of hospitalizations increased slightly in the last week, rising from 1.7% to 1.8% in the 24 states (and NYC) that are reporting such data. The total number of child hospitalizations in those jurisdictions is just over 6,700, the AAP and CHA said.

[email protected]

As far as the pandemic is concerned, it seems like a pretty small thing. A difference of just 0.3%. Children now represent 11.8% of all COVID-19 cases that have occurred since the beginning of the pandemic, compared with 11.5% 1 week ago, according to the American Academy of Pediatrics and the Children’s Hospital Association.

Hiding behind that 0.3%, however, is a much larger number: 144,145. That is the number of new child cases that occurred during the week that ended Nov. 19, and it’s the highest weekly figure yet, eclipsing the previous high of 111,946 from the week of Nov. 12, the AAP and the CHA said in their latest COVID-19 report. For the week ending Nov. 19, children represented 14.1% of all new cases, up from 14.0% the week before.

In the United States, more than 1.18 million children have been infected by the coronavirus since the beginning of the pandemic, with the total among all ages topping 10 million in 49 states (New York is not providing age distribution), the District of Columbia, New York City, Puerto Rico, and Guam, the AAP/CHA data show. That works out to 11.8% of all cases.

The overall rate of child COVID-19 cases is now up to 1,573 per 100,000 children nationally, with considerable variation seen among the states. The lowest rates can be found in Vermont (344 per 100,000), Maine (452), and Hawaii (675), and the highest in North Dakota (5,589), South Dakota (3,993), and Wisconsin (3,727), the AAP and CHA said in the report.

Comparisons between states are somewhat problematic, though, because “each state makes different decisions about how to report the age distribution of COVID-19 cases, and as a result the age range for reported cases varies by state. … It is not possible to standardize more detailed age ranges for children based on what is publicly available from the states at this time,” the two organizations noted.

Five more COVID-19–related deaths in children were reported during the week of Nov. 19, bringing the count to 138 and holding at just 0.06% of the total for all ages, based on data from 43 states and New York City. Children’s share of hospitalizations increased slightly in the last week, rising from 1.7% to 1.8% in the 24 states (and NYC) that are reporting such data. The total number of child hospitalizations in those jurisdictions is just over 6,700, the AAP and CHA said.

[email protected]

Concussion is associated with increased risk for subsequent development of attention-deficit/hyperactivity disorder (ADHD), as well as dementia and Parkinson’s disease, new research suggests. Results from a retrospective, population-based cohort study showed that controlling for socioeconomic status and overall health did not significantly affect this association.

The link between concussion and risk for ADHD and for mood and anxiety disorder was stronger in the women than in the men. In addition, having a history of multiple concussions strengthened the association between concussion and subsequent mood and anxiety disorder, dementia, and Parkinson’s disease compared with experiencing just one concussion.

The findings are similar to those of previous studies, noted lead author Marc P. Morissette, PhD, research assistant at the Pan Am Clinic Foundation in Winnipeg, Manitoba, Canada. “The main methodological differences separating our study from previous studies in this area is a focus on concussion-specific injuries identified from medical records and the potential for study participants to have up to 25 years of follow-up data,” said Dr. Morissette.

The findings were published online July 27 in Family Medicine and Community Health, a BMJ journal.
 

Almost 190,000 participants

Several studies have shown associations between head injury and increased risk for ADHD, depression, anxiety, Alzheimer’s disease, and Parkinson’s disease. However, many of these studies relied on self-reported medical history, included all forms of traumatic brain injury, and failed to adjust for preexisting health conditions.

An improved understanding of concussion and the risks associated with it could help physicians manage their patients’ long-term needs, the investigators noted.

In the current study, the researchers examined anonymized administrative health data collected between the periods of 1990–1991 and 2014–2015 in the Manitoba Population Research Data Repository at the Manitoba Center for Health Policy.

Eligible patients had been diagnosed with concussion in accordance with standard criteria. Participants were excluded if they had been diagnosed with dementia or Parkinson’s disease before the incident concussion during the study period. The investigators matched three control participants to each included patient on the basis of age, sex, and location.

Study outcome was time from index date (date of first concussion) to diagnosis of ADHD, mood and anxiety disorder, dementia, or Parkinson’s disease. The researchers controlled for socioeconomic status using the Socioeconomic Factor Index, version 2 (SEFI2), and for preexisting medical conditions using the Charlson Comorbidity Index (CCI).

The study included 28,021 men (mean age, 25 years) and 19,462 women (mean age, 30 years) in the concussion group and 81,871 men (mean age, 25 years) and 57,159 women (mean age, 30 years) in the control group. Mean SEFI2 score was approximately −0.05, and mean CCI score was approximately 0.2.
 

Dose effect?

Results showed that concussion was associated with an increased risk for ADHD (hazard ratio [HR], 1.39), mood and anxiety disorder (HR, 1.72), dementia (HR, 1.72), and Parkinson’s disease (HR, 1.57).

After a concussion, the risk of developing ADHD was 28% higher and the risk of developing mood and anxiety disorder was 7% higher among women than among men. Gender was not associated with risk for dementia or Parkinson’s disease after concussion.

Sustaining a second concussion increased the strength of the association with risk for dementia compared with sustaining a single concussion (HR, 1.62). Similarly, sustaining more than three concussions increased the strength of the association with the risk for mood and anxiety disorders (HR for more than three vs one concussion, 1.22) and Parkinson›s disease (HR, 3.27).

A sensitivity analysis found similar associations between concussion and risk for mood and anxiety disorder among all age groups. Younger participants were at greater risk for ADHD, however, and older participants were at greater risk for dementia and Parkinson’s disease.

Increased awareness of concussion and the outcomes of interest, along with improved diagnostic tools, may have influenced the study’s findings, Dr. Morissette noted. “The sex-based differences may be due to either pathophysiological differences in response to concussive injuries or potentially a difference in willingness to seek medical care or share symptoms, concussion-related or otherwise, with a medical professional,” he said.

“We are hopeful that our findings will encourage practitioners to be cognizant of various conditions that may present in individuals who have previously experienced a concussion,” Dr. Morissette added. “If physicians are aware of the various associations identified following a concussion, it may lead to more thorough clinical examination at initial presentation, along with more dedicated care throughout the patient’s life.”
 

Association versus causation

Commenting on the research, Steven Erickson, MD, sports medicine specialist at Banner–University Medicine Neuroscience Institute, Phoenix, Ariz., noted that although the study showed an association between concussion and subsequent diagnosis of ADHD, anxiety, and Parkinson’s disease, “this association should not be misconstrued as causation.” He added that the study’s conclusions “are just as likely to be due to labeling theory” or a self-fulfilling prophecy.

“Patients diagnosed with ADHD, anxiety, or Parkinson’s disease may recall concussion and associate the two diagnoses; but patients who have not previously been diagnosed with a concussion cannot draw that conclusion,” said Dr. Erickson, who was not involved with the research.

Citing the apparent gender difference in the strength of the association between concussion and the outcomes of interest, Dr. Erickson noted that women are more likely to report symptoms in general “and therefore are more likely to be diagnosed with ADHD and anxiety disorders” because of differences in reporting rather than incidence of disease.

“Further research needs to be done to definitively determine a causal relationship between concussion and any psychiatric or neurologic diagnosis,” Dr. Erickson concluded.

The study was funded by the Pan Am Clinic Foundation. Dr. Morissette and Dr. Erickson have disclosed no relevant financial relationships.

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

Concussion is associated with increased risk for subsequent development of attention-deficit/hyperactivity disorder (ADHD), as well as dementia and Parkinson’s disease, new research suggests. Results from a retrospective, population-based cohort study showed that controlling for socioeconomic status and overall health did not significantly affect this association.

The link between concussion and risk for ADHD and for mood and anxiety disorder was stronger in the women than in the men. In addition, having a history of multiple concussions strengthened the association between concussion and subsequent mood and anxiety disorder, dementia, and Parkinson’s disease compared with experiencing just one concussion.

The findings are similar to those of previous studies, noted lead author Marc P. Morissette, PhD, research assistant at the Pan Am Clinic Foundation in Winnipeg, Manitoba, Canada. “The main methodological differences separating our study from previous studies in this area is a focus on concussion-specific injuries identified from medical records and the potential for study participants to have up to 25 years of follow-up data,” said Dr. Morissette.

The findings were published online July 27 in Family Medicine and Community Health, a BMJ journal.
 

Almost 190,000 participants

Several studies have shown associations between head injury and increased risk for ADHD, depression, anxiety, Alzheimer’s disease, and Parkinson’s disease. However, many of these studies relied on self-reported medical history, included all forms of traumatic brain injury, and failed to adjust for preexisting health conditions.

An improved understanding of concussion and the risks associated with it could help physicians manage their patients’ long-term needs, the investigators noted.

In the current study, the researchers examined anonymized administrative health data collected between the periods of 1990–1991 and 2014–2015 in the Manitoba Population Research Data Repository at the Manitoba Center for Health Policy.

Eligible patients had been diagnosed with concussion in accordance with standard criteria. Participants were excluded if they had been diagnosed with dementia or Parkinson’s disease before the incident concussion during the study period. The investigators matched three control participants to each included patient on the basis of age, sex, and location.

Study outcome was time from index date (date of first concussion) to diagnosis of ADHD, mood and anxiety disorder, dementia, or Parkinson’s disease. The researchers controlled for socioeconomic status using the Socioeconomic Factor Index, version 2 (SEFI2), and for preexisting medical conditions using the Charlson Comorbidity Index (CCI).

The study included 28,021 men (mean age, 25 years) and 19,462 women (mean age, 30 years) in the concussion group and 81,871 men (mean age, 25 years) and 57,159 women (mean age, 30 years) in the control group. Mean SEFI2 score was approximately −0.05, and mean CCI score was approximately 0.2.
 

Dose effect?

Results showed that concussion was associated with an increased risk for ADHD (hazard ratio [HR], 1.39), mood and anxiety disorder (HR, 1.72), dementia (HR, 1.72), and Parkinson’s disease (HR, 1.57).

After a concussion, the risk of developing ADHD was 28% higher and the risk of developing mood and anxiety disorder was 7% higher among women than among men. Gender was not associated with risk for dementia or Parkinson’s disease after concussion.

Sustaining a second concussion increased the strength of the association with risk for dementia compared with sustaining a single concussion (HR, 1.62). Similarly, sustaining more than three concussions increased the strength of the association with the risk for mood and anxiety disorders (HR for more than three vs one concussion, 1.22) and Parkinson›s disease (HR, 3.27).

A sensitivity analysis found similar associations between concussion and risk for mood and anxiety disorder among all age groups. Younger participants were at greater risk for ADHD, however, and older participants were at greater risk for dementia and Parkinson’s disease.

Increased awareness of concussion and the outcomes of interest, along with improved diagnostic tools, may have influenced the study’s findings, Dr. Morissette noted. “The sex-based differences may be due to either pathophysiological differences in response to concussive injuries or potentially a difference in willingness to seek medical care or share symptoms, concussion-related or otherwise, with a medical professional,” he said.

“We are hopeful that our findings will encourage practitioners to be cognizant of various conditions that may present in individuals who have previously experienced a concussion,” Dr. Morissette added. “If physicians are aware of the various associations identified following a concussion, it may lead to more thorough clinical examination at initial presentation, along with more dedicated care throughout the patient’s life.”
 

Association versus causation

Commenting on the research, Steven Erickson, MD, sports medicine specialist at Banner–University Medicine Neuroscience Institute, Phoenix, Ariz., noted that although the study showed an association between concussion and subsequent diagnosis of ADHD, anxiety, and Parkinson’s disease, “this association should not be misconstrued as causation.” He added that the study’s conclusions “are just as likely to be due to labeling theory” or a self-fulfilling prophecy.

“Patients diagnosed with ADHD, anxiety, or Parkinson’s disease may recall concussion and associate the two diagnoses; but patients who have not previously been diagnosed with a concussion cannot draw that conclusion,” said Dr. Erickson, who was not involved with the research.

Citing the apparent gender difference in the strength of the association between concussion and the outcomes of interest, Dr. Erickson noted that women are more likely to report symptoms in general “and therefore are more likely to be diagnosed with ADHD and anxiety disorders” because of differences in reporting rather than incidence of disease.

“Further research needs to be done to definitively determine a causal relationship between concussion and any psychiatric or neurologic diagnosis,” Dr. Erickson concluded.

The study was funded by the Pan Am Clinic Foundation. Dr. Morissette and Dr. Erickson have disclosed no relevant financial relationships.

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

Concussion is associated with increased risk for subsequent development of attention-deficit/hyperactivity disorder (ADHD), as well as dementia and Parkinson’s disease, new research suggests. Results from a retrospective, population-based cohort study showed that controlling for socioeconomic status and overall health did not significantly affect this association.

The link between concussion and risk for ADHD and for mood and anxiety disorder was stronger in the women than in the men. In addition, having a history of multiple concussions strengthened the association between concussion and subsequent mood and anxiety disorder, dementia, and Parkinson’s disease compared with experiencing just one concussion.

The findings are similar to those of previous studies, noted lead author Marc P. Morissette, PhD, research assistant at the Pan Am Clinic Foundation in Winnipeg, Manitoba, Canada. “The main methodological differences separating our study from previous studies in this area is a focus on concussion-specific injuries identified from medical records and the potential for study participants to have up to 25 years of follow-up data,” said Dr. Morissette.

The findings were published online July 27 in Family Medicine and Community Health, a BMJ journal.
 

Almost 190,000 participants

Several studies have shown associations between head injury and increased risk for ADHD, depression, anxiety, Alzheimer’s disease, and Parkinson’s disease. However, many of these studies relied on self-reported medical history, included all forms of traumatic brain injury, and failed to adjust for preexisting health conditions.

An improved understanding of concussion and the risks associated with it could help physicians manage their patients’ long-term needs, the investigators noted.

In the current study, the researchers examined anonymized administrative health data collected between the periods of 1990–1991 and 2014–2015 in the Manitoba Population Research Data Repository at the Manitoba Center for Health Policy.

Eligible patients had been diagnosed with concussion in accordance with standard criteria. Participants were excluded if they had been diagnosed with dementia or Parkinson’s disease before the incident concussion during the study period. The investigators matched three control participants to each included patient on the basis of age, sex, and location.

Study outcome was time from index date (date of first concussion) to diagnosis of ADHD, mood and anxiety disorder, dementia, or Parkinson’s disease. The researchers controlled for socioeconomic status using the Socioeconomic Factor Index, version 2 (SEFI2), and for preexisting medical conditions using the Charlson Comorbidity Index (CCI).

The study included 28,021 men (mean age, 25 years) and 19,462 women (mean age, 30 years) in the concussion group and 81,871 men (mean age, 25 years) and 57,159 women (mean age, 30 years) in the control group. Mean SEFI2 score was approximately −0.05, and mean CCI score was approximately 0.2.
 

Dose effect?

Results showed that concussion was associated with an increased risk for ADHD (hazard ratio [HR], 1.39), mood and anxiety disorder (HR, 1.72), dementia (HR, 1.72), and Parkinson’s disease (HR, 1.57).

After a concussion, the risk of developing ADHD was 28% higher and the risk of developing mood and anxiety disorder was 7% higher among women than among men. Gender was not associated with risk for dementia or Parkinson’s disease after concussion.

Sustaining a second concussion increased the strength of the association with risk for dementia compared with sustaining a single concussion (HR, 1.62). Similarly, sustaining more than three concussions increased the strength of the association with the risk for mood and anxiety disorders (HR for more than three vs one concussion, 1.22) and Parkinson›s disease (HR, 3.27).

A sensitivity analysis found similar associations between concussion and risk for mood and anxiety disorder among all age groups. Younger participants were at greater risk for ADHD, however, and older participants were at greater risk for dementia and Parkinson’s disease.

Increased awareness of concussion and the outcomes of interest, along with improved diagnostic tools, may have influenced the study’s findings, Dr. Morissette noted. “The sex-based differences may be due to either pathophysiological differences in response to concussive injuries or potentially a difference in willingness to seek medical care or share symptoms, concussion-related or otherwise, with a medical professional,” he said.

“We are hopeful that our findings will encourage practitioners to be cognizant of various conditions that may present in individuals who have previously experienced a concussion,” Dr. Morissette added. “If physicians are aware of the various associations identified following a concussion, it may lead to more thorough clinical examination at initial presentation, along with more dedicated care throughout the patient’s life.”
 

Association versus causation

Commenting on the research, Steven Erickson, MD, sports medicine specialist at Banner–University Medicine Neuroscience Institute, Phoenix, Ariz., noted that although the study showed an association between concussion and subsequent diagnosis of ADHD, anxiety, and Parkinson’s disease, “this association should not be misconstrued as causation.” He added that the study’s conclusions “are just as likely to be due to labeling theory” or a self-fulfilling prophecy.

“Patients diagnosed with ADHD, anxiety, or Parkinson’s disease may recall concussion and associate the two diagnoses; but patients who have not previously been diagnosed with a concussion cannot draw that conclusion,” said Dr. Erickson, who was not involved with the research.

Citing the apparent gender difference in the strength of the association between concussion and the outcomes of interest, Dr. Erickson noted that women are more likely to report symptoms in general “and therefore are more likely to be diagnosed with ADHD and anxiety disorders” because of differences in reporting rather than incidence of disease.

“Further research needs to be done to definitively determine a causal relationship between concussion and any psychiatric or neurologic diagnosis,” Dr. Erickson concluded.

The study was funded by the Pan Am Clinic Foundation. Dr. Morissette and Dr. Erickson have disclosed no relevant financial relationships.

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

To the Editor:

Cutaneous reactions to implantable devices, such as dental implants, intracoronary stents, prosthetic valves, endovascular prostheses, gynecologic devices, and spinal cord stimulator devices, occur with varying frequency and include infectious, hypersensitivity, allergic, and foreign-body reactions. Manifestations have included contact dermatitis; urticarial, vasculitic, and bullous eruptions; extrusion; and granuloma formation.^1,2 Immune complex reactions around implants causing pain, inflammation, and loosening of hardwarealso have been reported.^3,4 Most reported cutaneous reactions typically occur within the first weeks or months after implantation; a reaction rarely presents several years after implantation. We report a cutaneous reaction to an orthopedic appliance almost 10 years after implantation.

A 67-year-old man presented with 2 painful nodules on the right clavicle that were present for several months. The patient denied fever, chills, weight loss, enlarged lymph nodes, or night sweats. Approximately 10 years prior to the appearance of the nodules, the patient fractured the right clavicle and underwent placement of a metal plate. His medical history included resection of the right tonsil and soft-palate carcinoma with radical neck dissection and postoperative radiation, which was completed approximately 4 years prior to placement of the metal plate. The patient recently completed 4 to 6 weeks of fluorouracil for shave biopsy–proven actinic keratosis overlying the entire irradiated area.

Physical examination revealed 2 pink friable nodules measuring 1.5 to 2.5 cm in diameter and leaking serous fluid within the irradiated area (Figure 1). The differential diagnosis included pyogenic granuloma, cutaneous recurrent metastasis, and atypical basal cell carcinoma. A skin biopsy specimen showed hemorrhagic ulcerated skin with acute and chronic inflammation and abscess.

To the Editor:

Cutaneous reactions to implantable devices, such as dental implants, intracoronary stents, prosthetic valves, endovascular prostheses, gynecologic devices, and spinal cord stimulator devices, occur with varying frequency and include infectious, hypersensitivity, allergic, and foreign-body reactions. Manifestations have included contact dermatitis; urticarial, vasculitic, and bullous eruptions; extrusion; and granuloma formation.^1,2 Immune complex reactions around implants causing pain, inflammation, and loosening of hardwarealso have been reported.^3,4 Most reported cutaneous reactions typically occur within the first weeks or months after implantation; a reaction rarely presents several years after implantation. We report a cutaneous reaction to an orthopedic appliance almost 10 years after implantation.

A 67-year-old man presented with 2 painful nodules on the right clavicle that were present for several months. The patient denied fever, chills, weight loss, enlarged lymph nodes, or night sweats. Approximately 10 years prior to the appearance of the nodules, the patient fractured the right clavicle and underwent placement of a metal plate. His medical history included resection of the right tonsil and soft-palate carcinoma with radical neck dissection and postoperative radiation, which was completed approximately 4 years prior to placement of the metal plate. The patient recently completed 4 to 6 weeks of fluorouracil for shave biopsy–proven actinic keratosis overlying the entire irradiated area.

Physical examination revealed 2 pink friable nodules measuring 1.5 to 2.5 cm in diameter and leaking serous fluid within the irradiated area (Figure 1). The differential diagnosis included pyogenic granuloma, cutaneous recurrent metastasis, and atypical basal cell carcinoma. A skin biopsy specimen showed hemorrhagic ulcerated skin with acute and chronic inflammation and abscess.

To the Editor:

Cutaneous reactions to implantable devices, such as dental implants, intracoronary stents, prosthetic valves, endovascular prostheses, gynecologic devices, and spinal cord stimulator devices, occur with varying frequency and include infectious, hypersensitivity, allergic, and foreign-body reactions. Manifestations have included contact dermatitis; urticarial, vasculitic, and bullous eruptions; extrusion; and granuloma formation.^1,2 Immune complex reactions around implants causing pain, inflammation, and loosening of hardwarealso have been reported.^3,4 Most reported cutaneous reactions typically occur within the first weeks or months after implantation; a reaction rarely presents several years after implantation. We report a cutaneous reaction to an orthopedic appliance almost 10 years after implantation.

A 67-year-old man presented with 2 painful nodules on the right clavicle that were present for several months. The patient denied fever, chills, weight loss, enlarged lymph nodes, or night sweats. Approximately 10 years prior to the appearance of the nodules, the patient fractured the right clavicle and underwent placement of a metal plate. His medical history included resection of the right tonsil and soft-palate carcinoma with radical neck dissection and postoperative radiation, which was completed approximately 4 years prior to placement of the metal plate. The patient recently completed 4 to 6 weeks of fluorouracil for shave biopsy–proven actinic keratosis overlying the entire irradiated area.

Physical examination revealed 2 pink friable nodules measuring 1.5 to 2.5 cm in diameter and leaking serous fluid within the irradiated area (Figure 1). The differential diagnosis included pyogenic granuloma, cutaneous recurrent metastasis, and atypical basal cell carcinoma. A skin biopsy specimen showed hemorrhagic ulcerated skin with acute and chronic inflammation and abscess.

Prior to George Floyd’s death, Officer Thomas Lane reportedly said, “I am worried about excited delirium or whatever” to his colleague, Officer Derek Chauvin.¹ For those of us who frequently work with law enforcement and in correctional facilities, “excited delirium” is a common refrain. It would be too facile to dismiss the concept as an attempt by police officers to inappropriately use medically sounding jargon to justify violence. “Excited delirium” is a reminder of the complex situations faced by police officers and the need for better medical training, as well as the attention of research on this commonly used label.

Many law enforcement facilities, in particular jails that receive inmates directly from the community, will have large posters educating staff on the “signs of excited delirium.” The concept is not covered in residency training programs, or many of the leading textbooks of psychiatry. Yet, it has become common parlance in law enforcement. Officers in training receive education programs on excited delirium, although those are rarely conducted by clinicians.

In our practice and experience, “excited delirium” has been used by law enforcement officers to describe mood lability from the stress of arrest, acute agitation from stimulant or phencyclidine intoxication, actual delirium from a medical comorbidity, sociopathic aggression for the purpose of violence, and incoherence from psychosis, along with simply describing a person not following direction from a police officer.

Our differential diagnosis when informed that someone was described by a nonclinician as having so-called excited delirium is wider than the Diagnostic and Statistical Manual (DSM). In addition, the term comes at a cost. Its use has been implicated in police-related deaths and brutality.² There is also concern of its disproportionate application to Black people.^3,4

Nonetheless, the term “excited delirium” can sometimes accurately describe critical medical situations. We particularly remember a case of altered mental status from serotonin syndrome, a case of delirium tremens from alcohol withdrawal, and a case of life-threatening dehydration in the context of stimulant intoxication. Each of those cases was appropriately recognized as problematic by perceptive and caring police officers. It is important for police officers to recognize these life-threatening conditions, and they need the language to do so. Having a common label that can be used across professional fields and law enforcement departments to express medical concern in the context of aggressive behavior has value. The question is: can psychiatry help law enforcement describe situations more accurately?

As physicians, it would be overly simple to point out the limited understanding of medical information by police and correctional officers. Naming many behaviors poses significant challenges for psychiatrists and nonclinicians. Examples include the use of the word “agitation” to describe mild restlessness, “delusional” for uncooperative, and “irritable” for opinionated. We must also be cognizant of the infinite demands placed on police officers and that labels must be available to them to express complex situations without being forced to use medical diagnosis and terminology for which they do not have the license or expertise. It is possible that “excited delirium” serves an important role; the problem may not be as much “excited delirium,” the term itself, as the diversion of its use to justify poor policing.

It must be acknowledged that debates, concerns, poor nomenclature, confusing labels, and different interpretations of diagnoses and symptoms are not unusual things in psychiatry, even among professionals. In the 1970s, the famous American and British study of diagnostic criteria,showed that psychiatrists used the diagnosis of schizophrenia to describe vastly different patients.⁵ The findings of the study were a significant cause of the paradigm shift of the DSM in its 3rd edition. More recently, the DSM-5 field trials suggested that the field of psychiatry continues to struggle with this problem.⁶ Nonetheless, each edition of the DSM presents a new opportunity to discuss, refine, and improve our ability to communicate while emphasizing the importance of improving our common language.

Emergency physicians face delirious patients brought to them from the community on a regular basis. As such, it makes sense that they have been at the forefront of this issue and the American College of Emergency Physicians has recognized excited delirium as a condition since 2009.⁷ The emergency physician literature points out that death from excited delirium also happens in hospitals and is not a unique consequence of law enforcement. There is no accepted definition. Reported symptoms include agitation, bizarre behavior, tirelessness, unusual strength, pain tolerance, noncompliance, attraction to reflective surfaces, stupor, fear, panic, hyperthermia, inappropriate clothing, tachycardia, tachypnea, diaphoresis, seizure, and mydriasis. Etiology is suspected to be from catecholaminergic endogenous stress-related catecholamines and exogenous catecholaminergic drugs. In particular is the importance of dopamine through the use of stimulants, specifically cocaine. The literature makes some reference to management, including recommendations aimed at keeping patients on one of their sides, using de-escalation techniques, and performing evaluation in quiet rooms.

We certainly condone and commend efforts to understand and define this condition in the medical literature. The indiscriminate use of “excited delirium” to represent all sorts of behaviors by nonmedical personnel warrants intelligent, relevant, and researched commentary by physicians. There are several potentially appropriate ways forward. First, psychiatry may decide that excited delirium is not a useful diagnosis in the clinical setting and does not belong in the DSM. That distinction in itself would be potentially useful to law enforcement officers, who might welcome the opportunity to create their own nomenclature and classification. Second, psychiatry may decide that excited delirium is not a useful diagnosis in the clinical setting but warrants a definition nonetheless, akin to the ways homelessness and extreme poverty are defined in the DSM; this definition could take into account the wide use of the term by nonclinicians. Third, psychiatry may decide that excited delirium warrants a clinical diagnosis that warrants a distinction and clarification from the current delirium diagnosis with the hyperactive specifier.

At this time, the status quo doesn’t protect or help clinicians in their respective fields of work. “Excited delirium” is routinely used by law enforcement officers without clear meaning. Experts have difficulty pointing out the poor or ill-intended use of the term without a precise or accepted definition to rely on. Some of the proposed criteria, such as “unusual strength,” have unclear scientific legitimacy. Some, such as agitation or bizarre behavior, often have different meanings to nonphysicians. Some, such as poor clothing, may facilitate discrimination. The current state allows some professionals to hide their limited attempts at de-escalation by describing the person of interest as having excited delirium. On the other hand, the current state also prevents well-intended officers from using proper terminology that is understood by others as describing a concerning behavior reliably.

We wonder whether excited delirium is an important facet of the current dilemma of reconsidering the role of law enforcement in society. Frequent use of “excited delirium” by police officers is itself a testament to their desire to have assistance or delegation of certain duties to other social services, such as health care. In some ways, police officers face a difficult position: Admission that a behavior may be attributable to excited delirium should warrant a medical evaluation and, thus, render the person of interest a patient rather than a suspect. As such, this person interacting with police officers should be treated as someone in need of medical care, which makes many interventions – including neck compression – seemingly inappropriate. The frequent use of “excited delirium” suggests that law enforcement is ill-equipped in handling many situations and that an attempt to diversify the composition and funding of emergency response might be warranted. Psychiatry should be at the forefront of this research and effort.

References

1. State of Minnesota v. Derek Michael Chauvin (4th Judicial District, 2020 May 29).

2. J Forensic Leg Med. 2008 May 15(4):227-30.

3. “Excited delirium: Rare and deadly syndrome or a condition to excuse deaths by police?” Florida Today. 2020 Jan 20.

4. J Forensic Sci. 1997 Jan;42(1):25-31.

5. Arch Gen Psychiatry. 1971;25(2):123-30.

6. Am J Psychiatry. 2013 Jan;170(1):59-70.

7. White Paper Report on Excited Delirium Syndrome. ACEP Excited Delirium Task Force. 2009 Sep 10.
 

Dr. Amendolara is a first-year psychiatry resident at University of California, San Diego. He spent years advocating for survivors of rape and domestic violence at the Crime Victims Treatment Center in New York and conducted public health research at Lourdes Center for Public Health in Camden, N.J. Dr. Amendolara has no disclosures. Dr. Malik is a first-year psychiatry resident at the University of California, San Diego. She has a background in policy and grassroots organizing through her time working at the National Coalition for the Homeless and the Women’s Law Project. Dr. Malik has no disclosures. Dr. Abrams is a forensic psychiatrist and attorney in San Diego. He is an expert in addictionology, behavioral toxicology, psychopharmacology, and correctional mental health. He holds teaching positions at the University of California, San Diego. Among his writings are chapters about competency in national textbooks. Dr. Abrams has no disclosures. Dr. Badre is a forensic psychiatrist in San Diego and an expert in correctional mental health. He holds teaching positions at the University of California, San Diego, and the University of San Diego. He teaches medical education, psychopharmacology, ethics in psychiatry, and correctional care. Among his writings is chapter 7 in the book “Critical Psychiatry: Controversies and Clinical Implications” (Cham, Switzerland: Springer, 2019). He has no disclosures.

Prior to George Floyd’s death, Officer Thomas Lane reportedly said, “I am worried about excited delirium or whatever” to his colleague, Officer Derek Chauvin.¹ For those of us who frequently work with law enforcement and in correctional facilities, “excited delirium” is a common refrain. It would be too facile to dismiss the concept as an attempt by police officers to inappropriately use medically sounding jargon to justify violence. “Excited delirium” is a reminder of the complex situations faced by police officers and the need for better medical training, as well as the attention of research on this commonly used label.

Many law enforcement facilities, in particular jails that receive inmates directly from the community, will have large posters educating staff on the “signs of excited delirium.” The concept is not covered in residency training programs, or many of the leading textbooks of psychiatry. Yet, it has become common parlance in law enforcement. Officers in training receive education programs on excited delirium, although those are rarely conducted by clinicians.

In our practice and experience, “excited delirium” has been used by law enforcement officers to describe mood lability from the stress of arrest, acute agitation from stimulant or phencyclidine intoxication, actual delirium from a medical comorbidity, sociopathic aggression for the purpose of violence, and incoherence from psychosis, along with simply describing a person not following direction from a police officer.

Our differential diagnosis when informed that someone was described by a nonclinician as having so-called excited delirium is wider than the Diagnostic and Statistical Manual (DSM). In addition, the term comes at a cost. Its use has been implicated in police-related deaths and brutality.² There is also concern of its disproportionate application to Black people.^3,4

Nonetheless, the term “excited delirium” can sometimes accurately describe critical medical situations. We particularly remember a case of altered mental status from serotonin syndrome, a case of delirium tremens from alcohol withdrawal, and a case of life-threatening dehydration in the context of stimulant intoxication. Each of those cases was appropriately recognized as problematic by perceptive and caring police officers. It is important for police officers to recognize these life-threatening conditions, and they need the language to do so. Having a common label that can be used across professional fields and law enforcement departments to express medical concern in the context of aggressive behavior has value. The question is: can psychiatry help law enforcement describe situations more accurately?

As physicians, it would be overly simple to point out the limited understanding of medical information by police and correctional officers. Naming many behaviors poses significant challenges for psychiatrists and nonclinicians. Examples include the use of the word “agitation” to describe mild restlessness, “delusional” for uncooperative, and “irritable” for opinionated. We must also be cognizant of the infinite demands placed on police officers and that labels must be available to them to express complex situations without being forced to use medical diagnosis and terminology for which they do not have the license or expertise. It is possible that “excited delirium” serves an important role; the problem may not be as much “excited delirium,” the term itself, as the diversion of its use to justify poor policing.

It must be acknowledged that debates, concerns, poor nomenclature, confusing labels, and different interpretations of diagnoses and symptoms are not unusual things in psychiatry, even among professionals. In the 1970s, the famous American and British study of diagnostic criteria,showed that psychiatrists used the diagnosis of schizophrenia to describe vastly different patients.⁵ The findings of the study were a significant cause of the paradigm shift of the DSM in its 3rd edition. More recently, the DSM-5 field trials suggested that the field of psychiatry continues to struggle with this problem.⁶ Nonetheless, each edition of the DSM presents a new opportunity to discuss, refine, and improve our ability to communicate while emphasizing the importance of improving our common language.

Emergency physicians face delirious patients brought to them from the community on a regular basis. As such, it makes sense that they have been at the forefront of this issue and the American College of Emergency Physicians has recognized excited delirium as a condition since 2009.⁷ The emergency physician literature points out that death from excited delirium also happens in hospitals and is not a unique consequence of law enforcement. There is no accepted definition. Reported symptoms include agitation, bizarre behavior, tirelessness, unusual strength, pain tolerance, noncompliance, attraction to reflective surfaces, stupor, fear, panic, hyperthermia, inappropriate clothing, tachycardia, tachypnea, diaphoresis, seizure, and mydriasis. Etiology is suspected to be from catecholaminergic endogenous stress-related catecholamines and exogenous catecholaminergic drugs. In particular is the importance of dopamine through the use of stimulants, specifically cocaine. The literature makes some reference to management, including recommendations aimed at keeping patients on one of their sides, using de-escalation techniques, and performing evaluation in quiet rooms.

We certainly condone and commend efforts to understand and define this condition in the medical literature. The indiscriminate use of “excited delirium” to represent all sorts of behaviors by nonmedical personnel warrants intelligent, relevant, and researched commentary by physicians. There are several potentially appropriate ways forward. First, psychiatry may decide that excited delirium is not a useful diagnosis in the clinical setting and does not belong in the DSM. That distinction in itself would be potentially useful to law enforcement officers, who might welcome the opportunity to create their own nomenclature and classification. Second, psychiatry may decide that excited delirium is not a useful diagnosis in the clinical setting but warrants a definition nonetheless, akin to the ways homelessness and extreme poverty are defined in the DSM; this definition could take into account the wide use of the term by nonclinicians. Third, psychiatry may decide that excited delirium warrants a clinical diagnosis that warrants a distinction and clarification from the current delirium diagnosis with the hyperactive specifier.

At this time, the status quo doesn’t protect or help clinicians in their respective fields of work. “Excited delirium” is routinely used by law enforcement officers without clear meaning. Experts have difficulty pointing out the poor or ill-intended use of the term without a precise or accepted definition to rely on. Some of the proposed criteria, such as “unusual strength,” have unclear scientific legitimacy. Some, such as agitation or bizarre behavior, often have different meanings to nonphysicians. Some, such as poor clothing, may facilitate discrimination. The current state allows some professionals to hide their limited attempts at de-escalation by describing the person of interest as having excited delirium. On the other hand, the current state also prevents well-intended officers from using proper terminology that is understood by others as describing a concerning behavior reliably.

We wonder whether excited delirium is an important facet of the current dilemma of reconsidering the role of law enforcement in society. Frequent use of “excited delirium” by police officers is itself a testament to their desire to have assistance or delegation of certain duties to other social services, such as health care. In some ways, police officers face a difficult position: Admission that a behavior may be attributable to excited delirium should warrant a medical evaluation and, thus, render the person of interest a patient rather than a suspect. As such, this person interacting with police officers should be treated as someone in need of medical care, which makes many interventions – including neck compression – seemingly inappropriate. The frequent use of “excited delirium” suggests that law enforcement is ill-equipped in handling many situations and that an attempt to diversify the composition and funding of emergency response might be warranted. Psychiatry should be at the forefront of this research and effort.

References

1. State of Minnesota v. Derek Michael Chauvin (4th Judicial District, 2020 May 29).

2. J Forensic Leg Med. 2008 May 15(4):227-30.

3. “Excited delirium: Rare and deadly syndrome or a condition to excuse deaths by police?” Florida Today. 2020 Jan 20.

4. J Forensic Sci. 1997 Jan;42(1):25-31.

5. Arch Gen Psychiatry. 1971;25(2):123-30.

6. Am J Psychiatry. 2013 Jan;170(1):59-70.

7. White Paper Report on Excited Delirium Syndrome. ACEP Excited Delirium Task Force. 2009 Sep 10.
 

Dr. Amendolara is a first-year psychiatry resident at University of California, San Diego. He spent years advocating for survivors of rape and domestic violence at the Crime Victims Treatment Center in New York and conducted public health research at Lourdes Center for Public Health in Camden, N.J. Dr. Amendolara has no disclosures. Dr. Malik is a first-year psychiatry resident at the University of California, San Diego. She has a background in policy and grassroots organizing through her time working at the National Coalition for the Homeless and the Women’s Law Project. Dr. Malik has no disclosures. Dr. Abrams is a forensic psychiatrist and attorney in San Diego. He is an expert in addictionology, behavioral toxicology, psychopharmacology, and correctional mental health. He holds teaching positions at the University of California, San Diego. Among his writings are chapters about competency in national textbooks. Dr. Abrams has no disclosures. Dr. Badre is a forensic psychiatrist in San Diego and an expert in correctional mental health. He holds teaching positions at the University of California, San Diego, and the University of San Diego. He teaches medical education, psychopharmacology, ethics in psychiatry, and correctional care. Among his writings is chapter 7 in the book “Critical Psychiatry: Controversies and Clinical Implications” (Cham, Switzerland: Springer, 2019). He has no disclosures.

Prior to George Floyd’s death, Officer Thomas Lane reportedly said, “I am worried about excited delirium or whatever” to his colleague, Officer Derek Chauvin.¹ For those of us who frequently work with law enforcement and in correctional facilities, “excited delirium” is a common refrain. It would be too facile to dismiss the concept as an attempt by police officers to inappropriately use medically sounding jargon to justify violence. “Excited delirium” is a reminder of the complex situations faced by police officers and the need for better medical training, as well as the attention of research on this commonly used label.

Many law enforcement facilities, in particular jails that receive inmates directly from the community, will have large posters educating staff on the “signs of excited delirium.” The concept is not covered in residency training programs, or many of the leading textbooks of psychiatry. Yet, it has become common parlance in law enforcement. Officers in training receive education programs on excited delirium, although those are rarely conducted by clinicians.

In our practice and experience, “excited delirium” has been used by law enforcement officers to describe mood lability from the stress of arrest, acute agitation from stimulant or phencyclidine intoxication, actual delirium from a medical comorbidity, sociopathic aggression for the purpose of violence, and incoherence from psychosis, along with simply describing a person not following direction from a police officer.

Our differential diagnosis when informed that someone was described by a nonclinician as having so-called excited delirium is wider than the Diagnostic and Statistical Manual (DSM). In addition, the term comes at a cost. Its use has been implicated in police-related deaths and brutality.² There is also concern of its disproportionate application to Black people.^3,4

Nonetheless, the term “excited delirium” can sometimes accurately describe critical medical situations. We particularly remember a case of altered mental status from serotonin syndrome, a case of delirium tremens from alcohol withdrawal, and a case of life-threatening dehydration in the context of stimulant intoxication. Each of those cases was appropriately recognized as problematic by perceptive and caring police officers. It is important for police officers to recognize these life-threatening conditions, and they need the language to do so. Having a common label that can be used across professional fields and law enforcement departments to express medical concern in the context of aggressive behavior has value. The question is: can psychiatry help law enforcement describe situations more accurately?

As physicians, it would be overly simple to point out the limited understanding of medical information by police and correctional officers. Naming many behaviors poses significant challenges for psychiatrists and nonclinicians. Examples include the use of the word “agitation” to describe mild restlessness, “delusional” for uncooperative, and “irritable” for opinionated. We must also be cognizant of the infinite demands placed on police officers and that labels must be available to them to express complex situations without being forced to use medical diagnosis and terminology for which they do not have the license or expertise. It is possible that “excited delirium” serves an important role; the problem may not be as much “excited delirium,” the term itself, as the diversion of its use to justify poor policing.

It must be acknowledged that debates, concerns, poor nomenclature, confusing labels, and different interpretations of diagnoses and symptoms are not unusual things in psychiatry, even among professionals. In the 1970s, the famous American and British study of diagnostic criteria,showed that psychiatrists used the diagnosis of schizophrenia to describe vastly different patients.⁵ The findings of the study were a significant cause of the paradigm shift of the DSM in its 3rd edition. More recently, the DSM-5 field trials suggested that the field of psychiatry continues to struggle with this problem.⁶ Nonetheless, each edition of the DSM presents a new opportunity to discuss, refine, and improve our ability to communicate while emphasizing the importance of improving our common language.

Emergency physicians face delirious patients brought to them from the community on a regular basis. As such, it makes sense that they have been at the forefront of this issue and the American College of Emergency Physicians has recognized excited delirium as a condition since 2009.⁷ The emergency physician literature points out that death from excited delirium also happens in hospitals and is not a unique consequence of law enforcement. There is no accepted definition. Reported symptoms include agitation, bizarre behavior, tirelessness, unusual strength, pain tolerance, noncompliance, attraction to reflective surfaces, stupor, fear, panic, hyperthermia, inappropriate clothing, tachycardia, tachypnea, diaphoresis, seizure, and mydriasis. Etiology is suspected to be from catecholaminergic endogenous stress-related catecholamines and exogenous catecholaminergic drugs. In particular is the importance of dopamine through the use of stimulants, specifically cocaine. The literature makes some reference to management, including recommendations aimed at keeping patients on one of their sides, using de-escalation techniques, and performing evaluation in quiet rooms.

We certainly condone and commend efforts to understand and define this condition in the medical literature. The indiscriminate use of “excited delirium” to represent all sorts of behaviors by nonmedical personnel warrants intelligent, relevant, and researched commentary by physicians. There are several potentially appropriate ways forward. First, psychiatry may decide that excited delirium is not a useful diagnosis in the clinical setting and does not belong in the DSM. That distinction in itself would be potentially useful to law enforcement officers, who might welcome the opportunity to create their own nomenclature and classification. Second, psychiatry may decide that excited delirium is not a useful diagnosis in the clinical setting but warrants a definition nonetheless, akin to the ways homelessness and extreme poverty are defined in the DSM; this definition could take into account the wide use of the term by nonclinicians. Third, psychiatry may decide that excited delirium warrants a clinical diagnosis that warrants a distinction and clarification from the current delirium diagnosis with the hyperactive specifier.

At this time, the status quo doesn’t protect or help clinicians in their respective fields of work. “Excited delirium” is routinely used by law enforcement officers without clear meaning. Experts have difficulty pointing out the poor or ill-intended use of the term without a precise or accepted definition to rely on. Some of the proposed criteria, such as “unusual strength,” have unclear scientific legitimacy. Some, such as agitation or bizarre behavior, often have different meanings to nonphysicians. Some, such as poor clothing, may facilitate discrimination. The current state allows some professionals to hide their limited attempts at de-escalation by describing the person of interest as having excited delirium. On the other hand, the current state also prevents well-intended officers from using proper terminology that is understood by others as describing a concerning behavior reliably.

We wonder whether excited delirium is an important facet of the current dilemma of reconsidering the role of law enforcement in society. Frequent use of “excited delirium” by police officers is itself a testament to their desire to have assistance or delegation of certain duties to other social services, such as health care. In some ways, police officers face a difficult position: Admission that a behavior may be attributable to excited delirium should warrant a medical evaluation and, thus, render the person of interest a patient rather than a suspect. As such, this person interacting with police officers should be treated as someone in need of medical care, which makes many interventions – including neck compression – seemingly inappropriate. The frequent use of “excited delirium” suggests that law enforcement is ill-equipped in handling many situations and that an attempt to diversify the composition and funding of emergency response might be warranted. Psychiatry should be at the forefront of this research and effort.

References

1. State of Minnesota v. Derek Michael Chauvin (4th Judicial District, 2020 May 29).

2. J Forensic Leg Med. 2008 May 15(4):227-30.

3. “Excited delirium: Rare and deadly syndrome or a condition to excuse deaths by police?” Florida Today. 2020 Jan 20.

4. J Forensic Sci. 1997 Jan;42(1):25-31.

5. Arch Gen Psychiatry. 1971;25(2):123-30.

6. Am J Psychiatry. 2013 Jan;170(1):59-70.

7. White Paper Report on Excited Delirium Syndrome. ACEP Excited Delirium Task Force. 2009 Sep 10.
 

Dr. Amendolara is a first-year psychiatry resident at University of California, San Diego. He spent years advocating for survivors of rape and domestic violence at the Crime Victims Treatment Center in New York and conducted public health research at Lourdes Center for Public Health in Camden, N.J. Dr. Amendolara has no disclosures. Dr. Malik is a first-year psychiatry resident at the University of California, San Diego. She has a background in policy and grassroots organizing through her time working at the National Coalition for the Homeless and the Women’s Law Project. Dr. Malik has no disclosures. Dr. Abrams is a forensic psychiatrist and attorney in San Diego. He is an expert in addictionology, behavioral toxicology, psychopharmacology, and correctional mental health. He holds teaching positions at the University of California, San Diego. Among his writings are chapters about competency in national textbooks. Dr. Abrams has no disclosures. Dr. Badre is a forensic psychiatrist in San Diego and an expert in correctional mental health. He holds teaching positions at the University of California, San Diego, and the University of San Diego. He teaches medical education, psychopharmacology, ethics in psychiatry, and correctional care. Among his writings is chapter 7 in the book “Critical Psychiatry: Controversies and Clinical Implications” (Cham, Switzerland: Springer, 2019). He has no disclosures.

Early in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, the World Health Organization issued guidance for coronavirus disease 2019 (COVID-19) management.¹ Based on a high intubation rate among 12 subjects with Middle Eastern respiratory syndrome, noninvasive ventilation (NIV) was discouraged.² While high-flow nasal oxygen (HFNO) was recognized as a reasonable strategy to avoid endotracheal intubation,¹ uncertainty regarding the potential of both therapies to aerosolize SARS-CoV-2 and reports of rapid, unexpected respiratory decompensations were deterrents to use.³ As hospitals prepared for a surge of patients, reports of SARS-CoV-2 transmission to healthcare personnel also emerged. Together, these issues led many institutions to recommend lower than usual thresholds for intubation. This well-intentioned guidance was based on limited historical data, a rapidly evolving literature that frequently appeared on preprint servers before peer review, or as anecdotes on social media.

As COVID-19 caseloads increased, clinicians were immediately faced with patients who rapidly reached the planned intubation threshold, but also looked very comfortable with minimal to no use of accessory muscles of respiration. In addition, the pace of respiratory decompensation among those who ultimately required intubation was slower than expected. Moreover, intensive care unit (ICU) capacity was stretched thin, raising concern for an imminent need for ventilator rationing. Lastly, the risk of SARS-CoV-2 transmission to healthcare workers appeared well-controlled with the use of personal protective equipment.⁴

In light of this accumulating experience, sites worldwide evolved quickly from their initial management strategies for COVID-19 respiratory failure. However, the deliberate process described by Soares et al in this issue of the Journal of Hospital Medicine is notable.⁵ Their transition towards the beginning of the pandemic from a conservative early intubation approach to a new strategy that encouraged use of NIV, HFNO, and self-proning is described. They were motivated by reports of good outcomes using these interventions, high mortality in intubated patients, and reassurance that aerosolization of respiratory secretions during NIV and HFNO was comparable to regular nasal cannula or face mask oxygen.³ The new protocol was defined and rapidly deployed over 4 days using multipronged communication from project and institutional leaders via in person and electronic means (email, Whatsapp, GoogleDrive). To facilitate implementation, COVID-19 patients requiring respiratory support were placed in dedicated units with bedside flowsheets for guidance. An immediate impact was demonstrated over the next 2 weeks by a significant decrease in use of mechanical ventilation in COVID-19 patients from 25.2% to 10.7%. In-hospital mortality, the primary outcome, did not change, ICU admissions decreased, as did hospital length of stay (10 vs 8.4 days, though not statistically significant), all providing supportive evidence for relative safety of the new protocol.

Soares et al exemplify a nimble system that recognized planned strategies to be problematic, and then achieved rapid implementation of a new protocol across a four-hospital system. Changes in medical practice are typically much slower, with some studies suggesting this process may take a decade or more. Implementation science focuses on translating research evidence into clinical practice using strategies tailored to particular contexts. The current study harnessed important implementation principles to quickly translate evidence into practice using effective engagement and education of key stakeholders across specialties (eg, emergency medicine, hospitalists, critical care, and respiratory therapy), the identification of pathways that mitigated barriers, frequent re-evaluation of a rapidly evolving literature, and an open-mindedness to the value of change.⁶ As the pandemic continues, traditional research and implementation science are critical not only to define optimal treatments and management strategies, but also to learn how best to implement successful interventions in an accelerated manner.⁷

The authors reported no conflicts of interest.

Dr Hochberg is supported by a National Institutes of Health training grant (T32HL007534).

Early in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, the World Health Organization issued guidance for coronavirus disease 2019 (COVID-19) management.¹ Based on a high intubation rate among 12 subjects with Middle Eastern respiratory syndrome, noninvasive ventilation (NIV) was discouraged.² While high-flow nasal oxygen (HFNO) was recognized as a reasonable strategy to avoid endotracheal intubation,¹ uncertainty regarding the potential of both therapies to aerosolize SARS-CoV-2 and reports of rapid, unexpected respiratory decompensations were deterrents to use.³ As hospitals prepared for a surge of patients, reports of SARS-CoV-2 transmission to healthcare personnel also emerged. Together, these issues led many institutions to recommend lower than usual thresholds for intubation. This well-intentioned guidance was based on limited historical data, a rapidly evolving literature that frequently appeared on preprint servers before peer review, or as anecdotes on social media.

As COVID-19 caseloads increased, clinicians were immediately faced with patients who rapidly reached the planned intubation threshold, but also looked very comfortable with minimal to no use of accessory muscles of respiration. In addition, the pace of respiratory decompensation among those who ultimately required intubation was slower than expected. Moreover, intensive care unit (ICU) capacity was stretched thin, raising concern for an imminent need for ventilator rationing. Lastly, the risk of SARS-CoV-2 transmission to healthcare workers appeared well-controlled with the use of personal protective equipment.⁴

In light of this accumulating experience, sites worldwide evolved quickly from their initial management strategies for COVID-19 respiratory failure. However, the deliberate process described by Soares et al in this issue of the Journal of Hospital Medicine is notable.⁵ Their transition towards the beginning of the pandemic from a conservative early intubation approach to a new strategy that encouraged use of NIV, HFNO, and self-proning is described. They were motivated by reports of good outcomes using these interventions, high mortality in intubated patients, and reassurance that aerosolization of respiratory secretions during NIV and HFNO was comparable to regular nasal cannula or face mask oxygen.³ The new protocol was defined and rapidly deployed over 4 days using multipronged communication from project and institutional leaders via in person and electronic means (email, Whatsapp, GoogleDrive). To facilitate implementation, COVID-19 patients requiring respiratory support were placed in dedicated units with bedside flowsheets for guidance. An immediate impact was demonstrated over the next 2 weeks by a significant decrease in use of mechanical ventilation in COVID-19 patients from 25.2% to 10.7%. In-hospital mortality, the primary outcome, did not change, ICU admissions decreased, as did hospital length of stay (10 vs 8.4 days, though not statistically significant), all providing supportive evidence for relative safety of the new protocol.

Soares et al exemplify a nimble system that recognized planned strategies to be problematic, and then achieved rapid implementation of a new protocol across a four-hospital system. Changes in medical practice are typically much slower, with some studies suggesting this process may take a decade or more. Implementation science focuses on translating research evidence into clinical practice using strategies tailored to particular contexts. The current study harnessed important implementation principles to quickly translate evidence into practice using effective engagement and education of key stakeholders across specialties (eg, emergency medicine, hospitalists, critical care, and respiratory therapy), the identification of pathways that mitigated barriers, frequent re-evaluation of a rapidly evolving literature, and an open-mindedness to the value of change.⁶ As the pandemic continues, traditional research and implementation science are critical not only to define optimal treatments and management strategies, but also to learn how best to implement successful interventions in an accelerated manner.⁷

The authors reported no conflicts of interest.

Dr Hochberg is supported by a National Institutes of Health training grant (T32HL007534).

Early in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, the World Health Organization issued guidance for coronavirus disease 2019 (COVID-19) management.¹ Based on a high intubation rate among 12 subjects with Middle Eastern respiratory syndrome, noninvasive ventilation (NIV) was discouraged.² While high-flow nasal oxygen (HFNO) was recognized as a reasonable strategy to avoid endotracheal intubation,¹ uncertainty regarding the potential of both therapies to aerosolize SARS-CoV-2 and reports of rapid, unexpected respiratory decompensations were deterrents to use.³ As hospitals prepared for a surge of patients, reports of SARS-CoV-2 transmission to healthcare personnel also emerged. Together, these issues led many institutions to recommend lower than usual thresholds for intubation. This well-intentioned guidance was based on limited historical data, a rapidly evolving literature that frequently appeared on preprint servers before peer review, or as anecdotes on social media.

As COVID-19 caseloads increased, clinicians were immediately faced with patients who rapidly reached the planned intubation threshold, but also looked very comfortable with minimal to no use of accessory muscles of respiration. In addition, the pace of respiratory decompensation among those who ultimately required intubation was slower than expected. Moreover, intensive care unit (ICU) capacity was stretched thin, raising concern for an imminent need for ventilator rationing. Lastly, the risk of SARS-CoV-2 transmission to healthcare workers appeared well-controlled with the use of personal protective equipment.⁴

In light of this accumulating experience, sites worldwide evolved quickly from their initial management strategies for COVID-19 respiratory failure. However, the deliberate process described by Soares et al in this issue of the Journal of Hospital Medicine is notable.⁵ Their transition towards the beginning of the pandemic from a conservative early intubation approach to a new strategy that encouraged use of NIV, HFNO, and self-proning is described. They were motivated by reports of good outcomes using these interventions, high mortality in intubated patients, and reassurance that aerosolization of respiratory secretions during NIV and HFNO was comparable to regular nasal cannula or face mask oxygen.³ The new protocol was defined and rapidly deployed over 4 days using multipronged communication from project and institutional leaders via in person and electronic means (email, Whatsapp, GoogleDrive). To facilitate implementation, COVID-19 patients requiring respiratory support were placed in dedicated units with bedside flowsheets for guidance. An immediate impact was demonstrated over the next 2 weeks by a significant decrease in use of mechanical ventilation in COVID-19 patients from 25.2% to 10.7%. In-hospital mortality, the primary outcome, did not change, ICU admissions decreased, as did hospital length of stay (10 vs 8.4 days, though not statistically significant), all providing supportive evidence for relative safety of the new protocol.

Soares et al exemplify a nimble system that recognized planned strategies to be problematic, and then achieved rapid implementation of a new protocol across a four-hospital system. Changes in medical practice are typically much slower, with some studies suggesting this process may take a decade or more. Implementation science focuses on translating research evidence into clinical practice using strategies tailored to particular contexts. The current study harnessed important implementation principles to quickly translate evidence into practice using effective engagement and education of key stakeholders across specialties (eg, emergency medicine, hospitalists, critical care, and respiratory therapy), the identification of pathways that mitigated barriers, frequent re-evaluation of a rapidly evolving literature, and an open-mindedness to the value of change.⁶ As the pandemic continues, traditional research and implementation science are critical not only to define optimal treatments and management strategies, but also to learn how best to implement successful interventions in an accelerated manner.⁷

The authors reported no conflicts of interest.

Dr Hochberg is supported by a National Institutes of Health training grant (T32HL007534).