Clinical Psychiatry News

Let us begin with a thought exercise. Close your eyes and picture the word, “hero.” What comes to mind? A relative, a teacher, a fictional character wielding a hammer or flying gracefully through the air?

© Maridav / iStockphoto.com

Several months ago, our country was introduced to a foe that brought us to our knees. Before that time, the idea of a hero had fluctuated with circumstance and had been guided by aging and maturity; however, since the moment COVID-19 struck, a new image has emerged. Not all heroes wear capes, but some wield stethoscopes.

Over these past months the phrase, “Health Care Heroes” has spread throughout our collective consciousness, highlighted everywhere from talk shows and news media to billboards and journals. Doctors, nurses, and other health care professionals are lauded for their strength, dedication, resilience, and compassion. Citizens line up to clap, honk horns, and shower praise in recognition of those who have risked their health, sacrificed their personal lives, and committed themselves to the greater good. Yet, what does it mean to be a hero, and what is the cost of hero worship?

The focus of medical training has gradually shifted to include the physical as well as mental well-being of future physicians, but the remnants of traditional doctrine linger. Hours of focused training through study and direct clinical interaction reinforce dedication to patient care. Rewards are given for time spent and compassion lent, and research is lauded, but family time is rarely applauded. We are encouraged to do our greatest, work our hardest, be the best, rise and defeat every test. Failure (or the perception thereof) is not an option.

According to Rikinkumar S. Patel, MD, MPH, and associates, physicians have nearly twice the burnout rate of other professionals (Behav Sci. [Basel]. 2018 Nov;8[11]:98). The dedication to our craft propels excellence as well as sacrifice. When COVID-19 entered our lives, many of my colleagues did not hesitate to heed to the call for action. They immersed themselves in the ICU, led triage units, and extended work hours in the service of the sick and dying. Several were years removed from emergency/intensive care, while others were allocated from their chosen residency programs and voluntarily thrust into an environment they had never before traversed.

These individuals are praised as “brave,” “dedicated,” “selfless.” A few even provided insight into their experiences through various publications highlighting their appreciation and gratitude toward such a treacherous, albeit, tremendous experience. Even though their words are an honest perspective of life through one of the worst health care crises in 100 years, in effect, they perpetuate the noble hero; the myth of the super doctor.

In a profession that has borne witness to multiple suicides over the past few months, why do we not encourage open dialogue of our victories as well as our defeats? Our wins as much as our losses? Why does an esteemed veteran physician feel guilt over declining to provide emergency services to patients whom they have long forgotten how to manage? What drives the guilt and the self-doubt? Are we ashamed of what others will think? Is it that the fear of not living up to our cherished medical oath outweighs our own boundaries and acknowledgment of our limitations?

A hero is an entity, a person encompassing a state of being, yet health care professionals are bestowed this title and this burden on a near-daily basis. Physicians are people. We love, we fear, we hesitate, we fight, we deem to overcome. We are perfectly imperfect. The more in tune we are to vulnerability, the more honest we can become with ourselves and one another.
 

Dr. Thomas is a board-certified adult psychiatrist with an interest in chronic illness, women’s behavioral health, and minority mental health. She currently practices in North Kingstown and East Providence, R.I. She has no conflicts of interest.

Let us begin with a thought exercise. Close your eyes and picture the word, “hero.” What comes to mind? A relative, a teacher, a fictional character wielding a hammer or flying gracefully through the air?

© Maridav / iStockphoto.com

Several months ago, our country was introduced to a foe that brought us to our knees. Before that time, the idea of a hero had fluctuated with circumstance and had been guided by aging and maturity; however, since the moment COVID-19 struck, a new image has emerged. Not all heroes wear capes, but some wield stethoscopes.

Over these past months the phrase, “Health Care Heroes” has spread throughout our collective consciousness, highlighted everywhere from talk shows and news media to billboards and journals. Doctors, nurses, and other health care professionals are lauded for their strength, dedication, resilience, and compassion. Citizens line up to clap, honk horns, and shower praise in recognition of those who have risked their health, sacrificed their personal lives, and committed themselves to the greater good. Yet, what does it mean to be a hero, and what is the cost of hero worship?

The focus of medical training has gradually shifted to include the physical as well as mental well-being of future physicians, but the remnants of traditional doctrine linger. Hours of focused training through study and direct clinical interaction reinforce dedication to patient care. Rewards are given for time spent and compassion lent, and research is lauded, but family time is rarely applauded. We are encouraged to do our greatest, work our hardest, be the best, rise and defeat every test. Failure (or the perception thereof) is not an option.

According to Rikinkumar S. Patel, MD, MPH, and associates, physicians have nearly twice the burnout rate of other professionals (Behav Sci. [Basel]. 2018 Nov;8[11]:98). The dedication to our craft propels excellence as well as sacrifice. When COVID-19 entered our lives, many of my colleagues did not hesitate to heed to the call for action. They immersed themselves in the ICU, led triage units, and extended work hours in the service of the sick and dying. Several were years removed from emergency/intensive care, while others were allocated from their chosen residency programs and voluntarily thrust into an environment they had never before traversed.

These individuals are praised as “brave,” “dedicated,” “selfless.” A few even provided insight into their experiences through various publications highlighting their appreciation and gratitude toward such a treacherous, albeit, tremendous experience. Even though their words are an honest perspective of life through one of the worst health care crises in 100 years, in effect, they perpetuate the noble hero; the myth of the super doctor.

In a profession that has borne witness to multiple suicides over the past few months, why do we not encourage open dialogue of our victories as well as our defeats? Our wins as much as our losses? Why does an esteemed veteran physician feel guilt over declining to provide emergency services to patients whom they have long forgotten how to manage? What drives the guilt and the self-doubt? Are we ashamed of what others will think? Is it that the fear of not living up to our cherished medical oath outweighs our own boundaries and acknowledgment of our limitations?

A hero is an entity, a person encompassing a state of being, yet health care professionals are bestowed this title and this burden on a near-daily basis. Physicians are people. We love, we fear, we hesitate, we fight, we deem to overcome. We are perfectly imperfect. The more in tune we are to vulnerability, the more honest we can become with ourselves and one another.
 

Dr. Thomas is a board-certified adult psychiatrist with an interest in chronic illness, women’s behavioral health, and minority mental health. She currently practices in North Kingstown and East Providence, R.I. She has no conflicts of interest.

Let us begin with a thought exercise. Close your eyes and picture the word, “hero.” What comes to mind? A relative, a teacher, a fictional character wielding a hammer or flying gracefully through the air?

© Maridav / iStockphoto.com

Several months ago, our country was introduced to a foe that brought us to our knees. Before that time, the idea of a hero had fluctuated with circumstance and had been guided by aging and maturity; however, since the moment COVID-19 struck, a new image has emerged. Not all heroes wear capes, but some wield stethoscopes.

Over these past months the phrase, “Health Care Heroes” has spread throughout our collective consciousness, highlighted everywhere from talk shows and news media to billboards and journals. Doctors, nurses, and other health care professionals are lauded for their strength, dedication, resilience, and compassion. Citizens line up to clap, honk horns, and shower praise in recognition of those who have risked their health, sacrificed their personal lives, and committed themselves to the greater good. Yet, what does it mean to be a hero, and what is the cost of hero worship?

The focus of medical training has gradually shifted to include the physical as well as mental well-being of future physicians, but the remnants of traditional doctrine linger. Hours of focused training through study and direct clinical interaction reinforce dedication to patient care. Rewards are given for time spent and compassion lent, and research is lauded, but family time is rarely applauded. We are encouraged to do our greatest, work our hardest, be the best, rise and defeat every test. Failure (or the perception thereof) is not an option.

According to Rikinkumar S. Patel, MD, MPH, and associates, physicians have nearly twice the burnout rate of other professionals (Behav Sci. [Basel]. 2018 Nov;8[11]:98). The dedication to our craft propels excellence as well as sacrifice. When COVID-19 entered our lives, many of my colleagues did not hesitate to heed to the call for action. They immersed themselves in the ICU, led triage units, and extended work hours in the service of the sick and dying. Several were years removed from emergency/intensive care, while others were allocated from their chosen residency programs and voluntarily thrust into an environment they had never before traversed.

These individuals are praised as “brave,” “dedicated,” “selfless.” A few even provided insight into their experiences through various publications highlighting their appreciation and gratitude toward such a treacherous, albeit, tremendous experience. Even though their words are an honest perspective of life through one of the worst health care crises in 100 years, in effect, they perpetuate the noble hero; the myth of the super doctor.

In a profession that has borne witness to multiple suicides over the past few months, why do we not encourage open dialogue of our victories as well as our defeats? Our wins as much as our losses? Why does an esteemed veteran physician feel guilt over declining to provide emergency services to patients whom they have long forgotten how to manage? What drives the guilt and the self-doubt? Are we ashamed of what others will think? Is it that the fear of not living up to our cherished medical oath outweighs our own boundaries and acknowledgment of our limitations?

A hero is an entity, a person encompassing a state of being, yet health care professionals are bestowed this title and this burden on a near-daily basis. Physicians are people. We love, we fear, we hesitate, we fight, we deem to overcome. We are perfectly imperfect. The more in tune we are to vulnerability, the more honest we can become with ourselves and one another.
 

Dr. Thomas is a board-certified adult psychiatrist with an interest in chronic illness, women’s behavioral health, and minority mental health. She currently practices in North Kingstown and East Providence, R.I. She has no conflicts of interest.

The ongoing COVID-19 pandemic continues to exact a huge toll on mental health in the United States, according to results of a survey released Aug. 13 by the Centers for Disease Control and Prevention.

During late June, about two in five U.S. adults surveyed said they were struggling with mental health or substance use. Younger adults, racial/ethnic minorities, essential workers, and those with preexisting psychiatric conditions were suffering the most.

“Addressing mental health disparities and preparing support systems to mitigate mental health consequences as the pandemic evolves will continue to be needed urgently,” write Rashon Lane, with the CDC COVID-19 Response Team, and colleagues in an article published online in the CDC’s Morbidity and Mortality Weekly Report.

During the period of June 24-30, 2020, 5,412 U.S. adults aged 18 and older completed online surveys that gauged mental health, substance use, and suicidal ideation.

Overall, 40.9% of respondents reported having at least one adverse mental or behavioral health condition; 31% reported symptoms of anxiety or depressive disorder; and 26% reported symptoms of a trauma- and stressor-related disorder related to the pandemic.

The prevalence of symptoms of anxiety disorder alone was roughly three times that reported in the second quarter of 2019, the authors noted.

In addition, roughly 13% of respondents said that they started using substances or increased substance use to cope with stress or emotions related to COVID-19, and nearly 11% reported having seriously considered suicide in the preceding 30 days.

Approximately twice as many respondents reported seriously considering suicide in the prior month compared with adults in the United States in 2018 (referring to the previous 12 months), the authors noted.

Suicidal ideation was significantly higher among younger respondents (aged 18-24 years, 26%), Hispanic persons (19%), non-Hispanic Black persons (15%), unpaid caregivers for adults (31%), and essential workers (22%).

The survey results are in line with recent data from Mental Health America, which indicate dramatic increases in depression, anxiety, and suicidality since the start of the COVID-19 pandemic.

The “markedly elevated” prevalence of adverse mental and behavioral health conditions associated with the COVID-19 pandemic highlights the “broad impact of the pandemic and the need to prevent and treat these conditions,” the researchers wrote.

The survey also highlights populations at increased risk for psychological distress and unhealthy coping.

“Future studies should identify drivers of adverse mental and behavioral health during the COVID-19 pandemic and whether factors such as social isolation, absence of school structure, unemployment and other financial worries, and various forms of violence (e.g., physical, emotional, mental, or sexual abuse) serve as additional stressors,” they suggested.

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

The ongoing COVID-19 pandemic continues to exact a huge toll on mental health in the United States, according to results of a survey released Aug. 13 by the Centers for Disease Control and Prevention.

During late June, about two in five U.S. adults surveyed said they were struggling with mental health or substance use. Younger adults, racial/ethnic minorities, essential workers, and those with preexisting psychiatric conditions were suffering the most.

“Addressing mental health disparities and preparing support systems to mitigate mental health consequences as the pandemic evolves will continue to be needed urgently,” write Rashon Lane, with the CDC COVID-19 Response Team, and colleagues in an article published online in the CDC’s Morbidity and Mortality Weekly Report.

During the period of June 24-30, 2020, 5,412 U.S. adults aged 18 and older completed online surveys that gauged mental health, substance use, and suicidal ideation.

Overall, 40.9% of respondents reported having at least one adverse mental or behavioral health condition; 31% reported symptoms of anxiety or depressive disorder; and 26% reported symptoms of a trauma- and stressor-related disorder related to the pandemic.

The prevalence of symptoms of anxiety disorder alone was roughly three times that reported in the second quarter of 2019, the authors noted.

In addition, roughly 13% of respondents said that they started using substances or increased substance use to cope with stress or emotions related to COVID-19, and nearly 11% reported having seriously considered suicide in the preceding 30 days.

Approximately twice as many respondents reported seriously considering suicide in the prior month compared with adults in the United States in 2018 (referring to the previous 12 months), the authors noted.

Suicidal ideation was significantly higher among younger respondents (aged 18-24 years, 26%), Hispanic persons (19%), non-Hispanic Black persons (15%), unpaid caregivers for adults (31%), and essential workers (22%).

The survey results are in line with recent data from Mental Health America, which indicate dramatic increases in depression, anxiety, and suicidality since the start of the COVID-19 pandemic.

The “markedly elevated” prevalence of adverse mental and behavioral health conditions associated with the COVID-19 pandemic highlights the “broad impact of the pandemic and the need to prevent and treat these conditions,” the researchers wrote.

The survey also highlights populations at increased risk for psychological distress and unhealthy coping.

“Future studies should identify drivers of adverse mental and behavioral health during the COVID-19 pandemic and whether factors such as social isolation, absence of school structure, unemployment and other financial worries, and various forms of violence (e.g., physical, emotional, mental, or sexual abuse) serve as additional stressors,” they suggested.

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

The ongoing COVID-19 pandemic continues to exact a huge toll on mental health in the United States, according to results of a survey released Aug. 13 by the Centers for Disease Control and Prevention.

During late June, about two in five U.S. adults surveyed said they were struggling with mental health or substance use. Younger adults, racial/ethnic minorities, essential workers, and those with preexisting psychiatric conditions were suffering the most.

“Addressing mental health disparities and preparing support systems to mitigate mental health consequences as the pandemic evolves will continue to be needed urgently,” write Rashon Lane, with the CDC COVID-19 Response Team, and colleagues in an article published online in the CDC’s Morbidity and Mortality Weekly Report.

During the period of June 24-30, 2020, 5,412 U.S. adults aged 18 and older completed online surveys that gauged mental health, substance use, and suicidal ideation.

Overall, 40.9% of respondents reported having at least one adverse mental or behavioral health condition; 31% reported symptoms of anxiety or depressive disorder; and 26% reported symptoms of a trauma- and stressor-related disorder related to the pandemic.

The prevalence of symptoms of anxiety disorder alone was roughly three times that reported in the second quarter of 2019, the authors noted.

In addition, roughly 13% of respondents said that they started using substances or increased substance use to cope with stress or emotions related to COVID-19, and nearly 11% reported having seriously considered suicide in the preceding 30 days.

Approximately twice as many respondents reported seriously considering suicide in the prior month compared with adults in the United States in 2018 (referring to the previous 12 months), the authors noted.

Suicidal ideation was significantly higher among younger respondents (aged 18-24 years, 26%), Hispanic persons (19%), non-Hispanic Black persons (15%), unpaid caregivers for adults (31%), and essential workers (22%).

The survey results are in line with recent data from Mental Health America, which indicate dramatic increases in depression, anxiety, and suicidality since the start of the COVID-19 pandemic.

The “markedly elevated” prevalence of adverse mental and behavioral health conditions associated with the COVID-19 pandemic highlights the “broad impact of the pandemic and the need to prevent and treat these conditions,” the researchers wrote.

The survey also highlights populations at increased risk for psychological distress and unhealthy coping.

“Future studies should identify drivers of adverse mental and behavioral health during the COVID-19 pandemic and whether factors such as social isolation, absence of school structure, unemployment and other financial worries, and various forms of violence (e.g., physical, emotional, mental, or sexual abuse) serve as additional stressors,” they suggested.

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

Accumulating observational data suggest that metformin use in patients with type 2 diabetes might reduce the risk for death from COVID-19, but the randomized trials needed to prove this are unlikely to be carried out, according to experts.

The latest results, which are not yet peer reviewed, were published online July 31. The study was conducted by Andrew B. Crouse, PhD, of the Hugh Kaul Precision Medicine Institute, University of Alabama at Birmingham, and colleagues.

The researchers found that among more than 600 patients with diabetes and COVID-19, use of metformin was associated with a nearly 70% reduction in mortality after adjustment for multiple confounders.

Data from four previous studies that also show a reduction in mortality among metformin users compared to nonusers were summarized in a “mini review” by André J. Scheen, MD, PhD, published Aug. 1 in Diabetes and Metabolism.

Dr. Scheen, of the division of diabetes, nutrition, and metabolic disorders and the division of clinical pharmacology at Liège (Belgium) University, discussed possible mechanisms behind this observation.

“Because metformin exerts various effects beyond its glucose-lowering action, among which are anti-inflammatory effects, it may be speculated that this biguanide might positively influence the prognosis of patients with [type 2 diabetes] hospitalized for COVID-19,” he said.

“However, given the potential confounders inherently found in observational studies, caution is required before drawing any firm conclusions in the absence of randomized controlled trials,” Dr. Scheen wrote.

Indeed, when asked to comment, endocrinologist Kasia Lipska, MD, of Yale University, New Haven, Conn., said in an interview: “Metformin users tend to do better in many different settings with respect to many different outcomes. To me, it is still unclear whether metformin is truly a miracle drug or whether it is simply used more often among people who are healthier and who do not have contraindications to its use.”

She added, “I don’t think we have enough data to suggest metformin use for COVID-19 mitigation at this point.”

Alabama authors say confounding effects ‘unlikely’

In the retrospective analysis of electronic health records from their institution, Dr. Crouse and colleagues reviewed data from 604 patients who were confirmed to have tested positive for COVID-19 between Feb. 25 and June 22, 2020. Of those individuals, 40% had diabetes.

Death occurred in 11% (n = 67); the odds ratio (OR) for death among those with, vs. without, diabetes was 3.62 (P < .0001).

Individuals with diabetes accounted for >60% of all deaths. In multiple logistic regression, age 50-70 vs. <50, male sex, and diabetes emerged as independent predictors of death.

Of the 42 patients with diabetes who died, 8 (19%) had used metformin, and 34 (81%) had not*, a significant difference (OR, 0.38; P = .0221). Insulin use, on the other hand, had no effect on mortality (P = .5728).

“In fact, with 11% [being] the mortality of metformin users, [this] was comparable to that of the general COVID-19-positive population and dramatically lower than the 23% mortality observed in subjects with diabetes and not on metformin,” the authors said.

The survival benefit observed with metformin remained after exclusion of patients with classic metformin contraindications, such as chronic kidney disease and heart failure (OR, 0.17; P = .0231).

“This makes any potential confounding effects from skewing metformin users toward healthier subjects without these additional comorbidities very unlikely,” Dr. Crouse and colleagues contended.

After further analysis that controlled for other covariates (age, sex, obesity status, and hypertension), age, sex, and metformin use remained independent predictors of mortality.

For metformin, the odds ratio was 0.33 (P = .0210).

But, Dr. Lipska pointed out, “Observational studies can take into account confounders that are measured. However, unmeasured confounders may still affect the conclusions of these studies ... Propensity score matching to account for the likelihood of use of metformin could be used to better account for differences between metformin users and nonusers.”

If metformin does reduce COVID-19 deaths, multiple mechanisms likely

In his article, Dr. Scheen noted that several mechanisms have been proposed for the possible beneficial effect of metformin on COVID-19 outcomes, including direct improvements in glucose control, body weight, and insulin resistance; reduction in inflammation; inhibition of virus penetration via phosphorylation of ACE2; inhibition of an immune hyperactivation pathway; and neutrophil reduction. All remain theoretical, he emphasized.

He noted that some authors have raised concerns about possible harms from the use of metformin by patients with type 2 diabetes who are hospitalized for COVID-19, particularly because of the potential risk for lactic acidosis in cases of multiple organ failure.

In totality, four studies suggest 25% death reduction with metformin

Taken together, the four observational studies that Dr. Scheen reviewed showed that metformin had a positive effect, with an overall 25% reduction in death (P < .00001), albeit with relatively high heterogeneity (I² = 61%).

The largest of these, from the United States, included 6,256 patients hospitalized with COVID-19 and involved propensity matching. A significant reduction in mortality with metformin use was seen in women but not men (odds ratio, 0.759).

The French Coronavirus-SARS-CoV-2 and Diabetes Outcomes (CORONADO) study of 1,317 patients with diabetes and confirmed COVID-19 who were admitted to 53 French hospitals also showed a significant survival benefit for metformin, although the study wasn’t designed to address that issue.

In that study, the odds ratio for death on day 7 in prior metformin users compared to nonusers was 0.59. This finding lost significance but remained a trend after full adjustments (0.80).

Two smaller observational studies produced similar trends toward survival benefit with metformin.

Nonetheless, Dr. Scheen cautioned: “Firm conclusions about the impact of metformin therapy can only be drawn from double-blind randomized controlled trials (RCTs), and such trials are almost impossible in the context of COVID-19.”

He added: “Because metformin is out of patent and very inexpensive, no pharmaceutical company is likely to be interested in planning a study to demonstrate the benefits of metformin on COVID-19-related clinical outcomes.”

Dr. Lipska agreed: “RCTs are unlikely to be conducted to settle these issues. In their absence, metformin use should be based on its safety and effectiveness profile.”

Dr. Scheen concluded, however, that “there are at least no negative safety indications, so there is no reason to stop metformin therapy during COVID-19 infection except in cases of severe gastrointestinal symptoms, hypoxia and/or multiple organ failure.”

Dr. Lipska has received grants from the National Institutes of Health and works under contract for the Centers for Medicare & Medicaid Services to develop publicly reported quality measures. Dr. Scheen has disclosed no relevant financial relationships.
 

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

*A previous version reversed these two outcomes in error. 

Accumulating observational data suggest that metformin use in patients with type 2 diabetes might reduce the risk for death from COVID-19, but the randomized trials needed to prove this are unlikely to be carried out, according to experts.

The latest results, which are not yet peer reviewed, were published online July 31. The study was conducted by Andrew B. Crouse, PhD, of the Hugh Kaul Precision Medicine Institute, University of Alabama at Birmingham, and colleagues.

The researchers found that among more than 600 patients with diabetes and COVID-19, use of metformin was associated with a nearly 70% reduction in mortality after adjustment for multiple confounders.

Data from four previous studies that also show a reduction in mortality among metformin users compared to nonusers were summarized in a “mini review” by André J. Scheen, MD, PhD, published Aug. 1 in Diabetes and Metabolism.

Dr. Scheen, of the division of diabetes, nutrition, and metabolic disorders and the division of clinical pharmacology at Liège (Belgium) University, discussed possible mechanisms behind this observation.

“Because metformin exerts various effects beyond its glucose-lowering action, among which are anti-inflammatory effects, it may be speculated that this biguanide might positively influence the prognosis of patients with [type 2 diabetes] hospitalized for COVID-19,” he said.

“However, given the potential confounders inherently found in observational studies, caution is required before drawing any firm conclusions in the absence of randomized controlled trials,” Dr. Scheen wrote.

Indeed, when asked to comment, endocrinologist Kasia Lipska, MD, of Yale University, New Haven, Conn., said in an interview: “Metformin users tend to do better in many different settings with respect to many different outcomes. To me, it is still unclear whether metformin is truly a miracle drug or whether it is simply used more often among people who are healthier and who do not have contraindications to its use.”

She added, “I don’t think we have enough data to suggest metformin use for COVID-19 mitigation at this point.”

Alabama authors say confounding effects ‘unlikely’

In the retrospective analysis of electronic health records from their institution, Dr. Crouse and colleagues reviewed data from 604 patients who were confirmed to have tested positive for COVID-19 between Feb. 25 and June 22, 2020. Of those individuals, 40% had diabetes.

Death occurred in 11% (n = 67); the odds ratio (OR) for death among those with, vs. without, diabetes was 3.62 (P < .0001).

Individuals with diabetes accounted for >60% of all deaths. In multiple logistic regression, age 50-70 vs. <50, male sex, and diabetes emerged as independent predictors of death.

Of the 42 patients with diabetes who died, 8 (19%) had used metformin, and 34 (81%) had not*, a significant difference (OR, 0.38; P = .0221). Insulin use, on the other hand, had no effect on mortality (P = .5728).

“In fact, with 11% [being] the mortality of metformin users, [this] was comparable to that of the general COVID-19-positive population and dramatically lower than the 23% mortality observed in subjects with diabetes and not on metformin,” the authors said.

The survival benefit observed with metformin remained after exclusion of patients with classic metformin contraindications, such as chronic kidney disease and heart failure (OR, 0.17; P = .0231).

“This makes any potential confounding effects from skewing metformin users toward healthier subjects without these additional comorbidities very unlikely,” Dr. Crouse and colleagues contended.

After further analysis that controlled for other covariates (age, sex, obesity status, and hypertension), age, sex, and metformin use remained independent predictors of mortality.

For metformin, the odds ratio was 0.33 (P = .0210).

But, Dr. Lipska pointed out, “Observational studies can take into account confounders that are measured. However, unmeasured confounders may still affect the conclusions of these studies ... Propensity score matching to account for the likelihood of use of metformin could be used to better account for differences between metformin users and nonusers.”

If metformin does reduce COVID-19 deaths, multiple mechanisms likely

In his article, Dr. Scheen noted that several mechanisms have been proposed for the possible beneficial effect of metformin on COVID-19 outcomes, including direct improvements in glucose control, body weight, and insulin resistance; reduction in inflammation; inhibition of virus penetration via phosphorylation of ACE2; inhibition of an immune hyperactivation pathway; and neutrophil reduction. All remain theoretical, he emphasized.

He noted that some authors have raised concerns about possible harms from the use of metformin by patients with type 2 diabetes who are hospitalized for COVID-19, particularly because of the potential risk for lactic acidosis in cases of multiple organ failure.

In totality, four studies suggest 25% death reduction with metformin

Taken together, the four observational studies that Dr. Scheen reviewed showed that metformin had a positive effect, with an overall 25% reduction in death (P < .00001), albeit with relatively high heterogeneity (I² = 61%).

The largest of these, from the United States, included 6,256 patients hospitalized with COVID-19 and involved propensity matching. A significant reduction in mortality with metformin use was seen in women but not men (odds ratio, 0.759).

The French Coronavirus-SARS-CoV-2 and Diabetes Outcomes (CORONADO) study of 1,317 patients with diabetes and confirmed COVID-19 who were admitted to 53 French hospitals also showed a significant survival benefit for metformin, although the study wasn’t designed to address that issue.

In that study, the odds ratio for death on day 7 in prior metformin users compared to nonusers was 0.59. This finding lost significance but remained a trend after full adjustments (0.80).

Two smaller observational studies produced similar trends toward survival benefit with metformin.

Nonetheless, Dr. Scheen cautioned: “Firm conclusions about the impact of metformin therapy can only be drawn from double-blind randomized controlled trials (RCTs), and such trials are almost impossible in the context of COVID-19.”

He added: “Because metformin is out of patent and very inexpensive, no pharmaceutical company is likely to be interested in planning a study to demonstrate the benefits of metformin on COVID-19-related clinical outcomes.”

Dr. Lipska agreed: “RCTs are unlikely to be conducted to settle these issues. In their absence, metformin use should be based on its safety and effectiveness profile.”

Dr. Scheen concluded, however, that “there are at least no negative safety indications, so there is no reason to stop metformin therapy during COVID-19 infection except in cases of severe gastrointestinal symptoms, hypoxia and/or multiple organ failure.”

Dr. Lipska has received grants from the National Institutes of Health and works under contract for the Centers for Medicare & Medicaid Services to develop publicly reported quality measures. Dr. Scheen has disclosed no relevant financial relationships.
 

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

*A previous version reversed these two outcomes in error. 

Accumulating observational data suggest that metformin use in patients with type 2 diabetes might reduce the risk for death from COVID-19, but the randomized trials needed to prove this are unlikely to be carried out, according to experts.

The latest results, which are not yet peer reviewed, were published online July 31. The study was conducted by Andrew B. Crouse, PhD, of the Hugh Kaul Precision Medicine Institute, University of Alabama at Birmingham, and colleagues.

The researchers found that among more than 600 patients with diabetes and COVID-19, use of metformin was associated with a nearly 70% reduction in mortality after adjustment for multiple confounders.

Data from four previous studies that also show a reduction in mortality among metformin users compared to nonusers were summarized in a “mini review” by André J. Scheen, MD, PhD, published Aug. 1 in Diabetes and Metabolism.

Dr. Scheen, of the division of diabetes, nutrition, and metabolic disorders and the division of clinical pharmacology at Liège (Belgium) University, discussed possible mechanisms behind this observation.

“Because metformin exerts various effects beyond its glucose-lowering action, among which are anti-inflammatory effects, it may be speculated that this biguanide might positively influence the prognosis of patients with [type 2 diabetes] hospitalized for COVID-19,” he said.

“However, given the potential confounders inherently found in observational studies, caution is required before drawing any firm conclusions in the absence of randomized controlled trials,” Dr. Scheen wrote.

Indeed, when asked to comment, endocrinologist Kasia Lipska, MD, of Yale University, New Haven, Conn., said in an interview: “Metformin users tend to do better in many different settings with respect to many different outcomes. To me, it is still unclear whether metformin is truly a miracle drug or whether it is simply used more often among people who are healthier and who do not have contraindications to its use.”

She added, “I don’t think we have enough data to suggest metformin use for COVID-19 mitigation at this point.”

Alabama authors say confounding effects ‘unlikely’

In the retrospective analysis of electronic health records from their institution, Dr. Crouse and colleagues reviewed data from 604 patients who were confirmed to have tested positive for COVID-19 between Feb. 25 and June 22, 2020. Of those individuals, 40% had diabetes.

Death occurred in 11% (n = 67); the odds ratio (OR) for death among those with, vs. without, diabetes was 3.62 (P < .0001).

Individuals with diabetes accounted for >60% of all deaths. In multiple logistic regression, age 50-70 vs. <50, male sex, and diabetes emerged as independent predictors of death.

Of the 42 patients with diabetes who died, 8 (19%) had used metformin, and 34 (81%) had not*, a significant difference (OR, 0.38; P = .0221). Insulin use, on the other hand, had no effect on mortality (P = .5728).

“In fact, with 11% [being] the mortality of metformin users, [this] was comparable to that of the general COVID-19-positive population and dramatically lower than the 23% mortality observed in subjects with diabetes and not on metformin,” the authors said.

The survival benefit observed with metformin remained after exclusion of patients with classic metformin contraindications, such as chronic kidney disease and heart failure (OR, 0.17; P = .0231).

“This makes any potential confounding effects from skewing metformin users toward healthier subjects without these additional comorbidities very unlikely,” Dr. Crouse and colleagues contended.

After further analysis that controlled for other covariates (age, sex, obesity status, and hypertension), age, sex, and metformin use remained independent predictors of mortality.

For metformin, the odds ratio was 0.33 (P = .0210).

But, Dr. Lipska pointed out, “Observational studies can take into account confounders that are measured. However, unmeasured confounders may still affect the conclusions of these studies ... Propensity score matching to account for the likelihood of use of metformin could be used to better account for differences between metformin users and nonusers.”

If metformin does reduce COVID-19 deaths, multiple mechanisms likely

In his article, Dr. Scheen noted that several mechanisms have been proposed for the possible beneficial effect of metformin on COVID-19 outcomes, including direct improvements in glucose control, body weight, and insulin resistance; reduction in inflammation; inhibition of virus penetration via phosphorylation of ACE2; inhibition of an immune hyperactivation pathway; and neutrophil reduction. All remain theoretical, he emphasized.

He noted that some authors have raised concerns about possible harms from the use of metformin by patients with type 2 diabetes who are hospitalized for COVID-19, particularly because of the potential risk for lactic acidosis in cases of multiple organ failure.

In totality, four studies suggest 25% death reduction with metformin

Taken together, the four observational studies that Dr. Scheen reviewed showed that metformin had a positive effect, with an overall 25% reduction in death (P < .00001), albeit with relatively high heterogeneity (I² = 61%).

The largest of these, from the United States, included 6,256 patients hospitalized with COVID-19 and involved propensity matching. A significant reduction in mortality with metformin use was seen in women but not men (odds ratio, 0.759).

The French Coronavirus-SARS-CoV-2 and Diabetes Outcomes (CORONADO) study of 1,317 patients with diabetes and confirmed COVID-19 who were admitted to 53 French hospitals also showed a significant survival benefit for metformin, although the study wasn’t designed to address that issue.

In that study, the odds ratio for death on day 7 in prior metformin users compared to nonusers was 0.59. This finding lost significance but remained a trend after full adjustments (0.80).

Two smaller observational studies produced similar trends toward survival benefit with metformin.

Nonetheless, Dr. Scheen cautioned: “Firm conclusions about the impact of metformin therapy can only be drawn from double-blind randomized controlled trials (RCTs), and such trials are almost impossible in the context of COVID-19.”

He added: “Because metformin is out of patent and very inexpensive, no pharmaceutical company is likely to be interested in planning a study to demonstrate the benefits of metformin on COVID-19-related clinical outcomes.”

Dr. Lipska agreed: “RCTs are unlikely to be conducted to settle these issues. In their absence, metformin use should be based on its safety and effectiveness profile.”

Dr. Scheen concluded, however, that “there are at least no negative safety indications, so there is no reason to stop metformin therapy during COVID-19 infection except in cases of severe gastrointestinal symptoms, hypoxia and/or multiple organ failure.”

Dr. Lipska has received grants from the National Institutes of Health and works under contract for the Centers for Medicare & Medicaid Services to develop publicly reported quality measures. Dr. Scheen has disclosed no relevant financial relationships.
 

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

*A previous version reversed these two outcomes in error. 

As mask mandates have increased, some people are looking for a way around the rules by asking doctors for medical excuses to opt out of wearing one.

filadendron/E+

In the last 2 months, at least 10 patients have asked Constantine George, MD, for a written medical exemption so they won’t have to wear a mask in public. Dr. George, the chief medical officer of Vedius, an app for a travelers’ concierge medical service in Las Vegas, turned them all down.

Elena Christofides, MD, an endocrinologist in Columbus, Ohio, has also refused patients’ requests for exemptions.

“It’s very rare for someone to need an exemption,” says Albert Rizzo, MD, chief medical officer for the American Lung Association and a lung specialist at ChristianaCare Health System in Newark, Del.

The opposition is sometimes strong. Recently, a video of Lenka Koloma of Laguna Niguel, Calif., who founded the antimask Freedom to Breathe Agency, went viral. She was in a California supermarket, maskless, telling an employee she was breaking the law by requiring patrons to wear masks.

“People need oxygen,” she said. “That alone is a medical condition.” Her webpage has a “Face Mask Exempt Card” that cites the Americans with Disabilities Act and posts a Department of Justice ADA violation reporting number. The DOJ issued a statement calling the cards fraudulent.

Figuring out if a patient’s request to opt out of wearing a mask is legitimate is a ‘’new frontier” for doctors, says Mical Raz, MD, a professor in public policy and health at the University of Rochester (N.Y.), and a hospitalist at the university medical center.
 

Should some people skip masks?

Experts say there are very few medical reasons for people to skip masks. “If you look at the research, patients with COPD [chronic obstructive pulmonary disorder], those with reactive airway, even those can breathe through a mask,” Dr. George said. Requests for exemptions due to medical reasons are usually without basis. “Obviously, if someone is incapacitated, for example, with mental health issues, that’s case by case.”

Dr. Christofides said one of her patients cited anxiety and the other cited headaches as reasons not to wear a mask. “I told the one who asked for anxiety [reasons] that she could wear ones that were less tight.” The patient with headaches told Dr. Christofides that she had a buildup of carbon dioxide in the mask because of industrial exposure. Baloney, Dr. Christofides told her.

Dr. Rizzo says one rare example of someone who can’t wear a mask might be a patient with an advanced lung condition so severe, they need extra oxygen. “These are the extreme patients where any change in oxygen and carbon dioxide could make a difference,” he said. But “that’s also the population that shouldn’t be going out in the first place.”

Dr. Raz cowrote a commentary about mask exemptions, saying doctors are faced with difficult decisions and must keep a delicate balance between public health and individual disability needs. “Inappropriate medical exemptions may inadvertently hasten viral spread and threaten public health,” she wrote.

In an interview, she says that some people do have a hard time tolerating a mask. “Probably the most common reasons are mental health issues, such as anxiety, panic and PTSD, and children with sensory processing disorders (making them oversensitive to their environment). I think there are very few pulmonary reasons.”
 

CDC, professional organization guidelines

The CDC says people should wear masks in public and when around people who don’t live in the same household. Beyond that, it simply says masks should not be worn by children under age 2, “or anyone who has trouble breathing, is unconscious, incapacitated, or otherwise unable to remove the mask without assistance.”

In mid-July, four professional organizations released a statement in response to the CDC recommendation for facial coverings. Jointly issued by the American College of Chest Physicians, the American Lung Association, the American Thoracic Society and the COPD Foundation, it states in part that people with normal lungs and “even many individuals with underlying chronic lung disease should be able to wear a non-N95 facial covering without affecting their oxygen or carbon dioxide levels.”

It acknowledges that some people will seek an exemption and doctors must weigh the patient’s concerns against the need to stop the spread of the virus. “In some instances, physician reassurance regarding the safety of the facial coverings may be all that is needed,” it states.
 

Addressing the excuses

Here are some of the common medical reasons people give for not being able to tolerate a mask:

Claustrophobia or anxiety. Dr. Raz and others suggests a “desensitizing” period, wearing the mask for longer and longer periods of time to get used to it. Parents could suggest kids wear a mask when doing something they like, such as watching television, so they equate it with something pleasant. Switching to a different kind of mask or one that fits better could also help.

Masks cause Legionnaires’ disease. Not true, experts say. Legionnaires’ is a severe form of pneumonia, the result of inhaling tiny water droplets with legionella bacteria.

It’s difficult to read lips. People can buy masks with a clear window that makes their mouth and lips visible.

Trouble breathing. Brief periods of mask use won’t have a bad effect on oxygen levels for most people.

“There is not an inherent right to be out in a pandemic with an unmasked face,” Dr. Raz says. But “you are entitled to an accommodation.” That might be using curbside pickup for food and medication. That requires much less time wearing a mask than entering a store would.

There are no “boilerplate” cards or letters to excuse people provided by the four organizations that addressed the issue, Dr. Rizzo said. If he were to write a letter asking for an exemption, he would personalize it for an individual patient’s medical condition. As to whether a state would honor it, he cannot say. The states have a patchwork of recommendations, making it difficult to say.

Dr. Rizzo tells lung disease patients who are able to go out that wearing a mask for 15-20 minutes to do an errand won’t harm their oxygen levels. And he reminds them that having an exemption, in the form of a doctor’s letter, may bring more problems. “Even with an exemption, someone may confront them” for their lack of a face covering. People with COPD have a higher risk of getting a severe illness from COVID-19, according to the CDC.

This article first appeared on WebMD.com.

As mask mandates have increased, some people are looking for a way around the rules by asking doctors for medical excuses to opt out of wearing one.

filadendron/E+

In the last 2 months, at least 10 patients have asked Constantine George, MD, for a written medical exemption so they won’t have to wear a mask in public. Dr. George, the chief medical officer of Vedius, an app for a travelers’ concierge medical service in Las Vegas, turned them all down.

Elena Christofides, MD, an endocrinologist in Columbus, Ohio, has also refused patients’ requests for exemptions.

“It’s very rare for someone to need an exemption,” says Albert Rizzo, MD, chief medical officer for the American Lung Association and a lung specialist at ChristianaCare Health System in Newark, Del.

The opposition is sometimes strong. Recently, a video of Lenka Koloma of Laguna Niguel, Calif., who founded the antimask Freedom to Breathe Agency, went viral. She was in a California supermarket, maskless, telling an employee she was breaking the law by requiring patrons to wear masks.

“People need oxygen,” she said. “That alone is a medical condition.” Her webpage has a “Face Mask Exempt Card” that cites the Americans with Disabilities Act and posts a Department of Justice ADA violation reporting number. The DOJ issued a statement calling the cards fraudulent.

Figuring out if a patient’s request to opt out of wearing a mask is legitimate is a ‘’new frontier” for doctors, says Mical Raz, MD, a professor in public policy and health at the University of Rochester (N.Y.), and a hospitalist at the university medical center.
 

Should some people skip masks?

Experts say there are very few medical reasons for people to skip masks. “If you look at the research, patients with COPD [chronic obstructive pulmonary disorder], those with reactive airway, even those can breathe through a mask,” Dr. George said. Requests for exemptions due to medical reasons are usually without basis. “Obviously, if someone is incapacitated, for example, with mental health issues, that’s case by case.”

Dr. Christofides said one of her patients cited anxiety and the other cited headaches as reasons not to wear a mask. “I told the one who asked for anxiety [reasons] that she could wear ones that were less tight.” The patient with headaches told Dr. Christofides that she had a buildup of carbon dioxide in the mask because of industrial exposure. Baloney, Dr. Christofides told her.

Dr. Rizzo says one rare example of someone who can’t wear a mask might be a patient with an advanced lung condition so severe, they need extra oxygen. “These are the extreme patients where any change in oxygen and carbon dioxide could make a difference,” he said. But “that’s also the population that shouldn’t be going out in the first place.”

Dr. Raz cowrote a commentary about mask exemptions, saying doctors are faced with difficult decisions and must keep a delicate balance between public health and individual disability needs. “Inappropriate medical exemptions may inadvertently hasten viral spread and threaten public health,” she wrote.

In an interview, she says that some people do have a hard time tolerating a mask. “Probably the most common reasons are mental health issues, such as anxiety, panic and PTSD, and children with sensory processing disorders (making them oversensitive to their environment). I think there are very few pulmonary reasons.”
 

CDC, professional organization guidelines

The CDC says people should wear masks in public and when around people who don’t live in the same household. Beyond that, it simply says masks should not be worn by children under age 2, “or anyone who has trouble breathing, is unconscious, incapacitated, or otherwise unable to remove the mask without assistance.”

In mid-July, four professional organizations released a statement in response to the CDC recommendation for facial coverings. Jointly issued by the American College of Chest Physicians, the American Lung Association, the American Thoracic Society and the COPD Foundation, it states in part that people with normal lungs and “even many individuals with underlying chronic lung disease should be able to wear a non-N95 facial covering without affecting their oxygen or carbon dioxide levels.”

It acknowledges that some people will seek an exemption and doctors must weigh the patient’s concerns against the need to stop the spread of the virus. “In some instances, physician reassurance regarding the safety of the facial coverings may be all that is needed,” it states.
 

Addressing the excuses

Here are some of the common medical reasons people give for not being able to tolerate a mask:

Claustrophobia or anxiety. Dr. Raz and others suggests a “desensitizing” period, wearing the mask for longer and longer periods of time to get used to it. Parents could suggest kids wear a mask when doing something they like, such as watching television, so they equate it with something pleasant. Switching to a different kind of mask or one that fits better could also help.

Masks cause Legionnaires’ disease. Not true, experts say. Legionnaires’ is a severe form of pneumonia, the result of inhaling tiny water droplets with legionella bacteria.

It’s difficult to read lips. People can buy masks with a clear window that makes their mouth and lips visible.

Trouble breathing. Brief periods of mask use won’t have a bad effect on oxygen levels for most people.

“There is not an inherent right to be out in a pandemic with an unmasked face,” Dr. Raz says. But “you are entitled to an accommodation.” That might be using curbside pickup for food and medication. That requires much less time wearing a mask than entering a store would.

There are no “boilerplate” cards or letters to excuse people provided by the four organizations that addressed the issue, Dr. Rizzo said. If he were to write a letter asking for an exemption, he would personalize it for an individual patient’s medical condition. As to whether a state would honor it, he cannot say. The states have a patchwork of recommendations, making it difficult to say.

Dr. Rizzo tells lung disease patients who are able to go out that wearing a mask for 15-20 minutes to do an errand won’t harm their oxygen levels. And he reminds them that having an exemption, in the form of a doctor’s letter, may bring more problems. “Even with an exemption, someone may confront them” for their lack of a face covering. People with COPD have a higher risk of getting a severe illness from COVID-19, according to the CDC.

This article first appeared on WebMD.com.

As mask mandates have increased, some people are looking for a way around the rules by asking doctors for medical excuses to opt out of wearing one.

filadendron/E+

In the last 2 months, at least 10 patients have asked Constantine George, MD, for a written medical exemption so they won’t have to wear a mask in public. Dr. George, the chief medical officer of Vedius, an app for a travelers’ concierge medical service in Las Vegas, turned them all down.

Elena Christofides, MD, an endocrinologist in Columbus, Ohio, has also refused patients’ requests for exemptions.

“It’s very rare for someone to need an exemption,” says Albert Rizzo, MD, chief medical officer for the American Lung Association and a lung specialist at ChristianaCare Health System in Newark, Del.

The opposition is sometimes strong. Recently, a video of Lenka Koloma of Laguna Niguel, Calif., who founded the antimask Freedom to Breathe Agency, went viral. She was in a California supermarket, maskless, telling an employee she was breaking the law by requiring patrons to wear masks.

“People need oxygen,” she said. “That alone is a medical condition.” Her webpage has a “Face Mask Exempt Card” that cites the Americans with Disabilities Act and posts a Department of Justice ADA violation reporting number. The DOJ issued a statement calling the cards fraudulent.

Figuring out if a patient’s request to opt out of wearing a mask is legitimate is a ‘’new frontier” for doctors, says Mical Raz, MD, a professor in public policy and health at the University of Rochester (N.Y.), and a hospitalist at the university medical center.
 

Should some people skip masks?

Experts say there are very few medical reasons for people to skip masks. “If you look at the research, patients with COPD [chronic obstructive pulmonary disorder], those with reactive airway, even those can breathe through a mask,” Dr. George said. Requests for exemptions due to medical reasons are usually without basis. “Obviously, if someone is incapacitated, for example, with mental health issues, that’s case by case.”

Dr. Christofides said one of her patients cited anxiety and the other cited headaches as reasons not to wear a mask. “I told the one who asked for anxiety [reasons] that she could wear ones that were less tight.” The patient with headaches told Dr. Christofides that she had a buildup of carbon dioxide in the mask because of industrial exposure. Baloney, Dr. Christofides told her.

Dr. Rizzo says one rare example of someone who can’t wear a mask might be a patient with an advanced lung condition so severe, they need extra oxygen. “These are the extreme patients where any change in oxygen and carbon dioxide could make a difference,” he said. But “that’s also the population that shouldn’t be going out in the first place.”

Dr. Raz cowrote a commentary about mask exemptions, saying doctors are faced with difficult decisions and must keep a delicate balance between public health and individual disability needs. “Inappropriate medical exemptions may inadvertently hasten viral spread and threaten public health,” she wrote.

In an interview, she says that some people do have a hard time tolerating a mask. “Probably the most common reasons are mental health issues, such as anxiety, panic and PTSD, and children with sensory processing disorders (making them oversensitive to their environment). I think there are very few pulmonary reasons.”
 

CDC, professional organization guidelines

The CDC says people should wear masks in public and when around people who don’t live in the same household. Beyond that, it simply says masks should not be worn by children under age 2, “or anyone who has trouble breathing, is unconscious, incapacitated, or otherwise unable to remove the mask without assistance.”

In mid-July, four professional organizations released a statement in response to the CDC recommendation for facial coverings. Jointly issued by the American College of Chest Physicians, the American Lung Association, the American Thoracic Society and the COPD Foundation, it states in part that people with normal lungs and “even many individuals with underlying chronic lung disease should be able to wear a non-N95 facial covering without affecting their oxygen or carbon dioxide levels.”

It acknowledges that some people will seek an exemption and doctors must weigh the patient’s concerns against the need to stop the spread of the virus. “In some instances, physician reassurance regarding the safety of the facial coverings may be all that is needed,” it states.
 

Addressing the excuses

Here are some of the common medical reasons people give for not being able to tolerate a mask:

Claustrophobia or anxiety. Dr. Raz and others suggests a “desensitizing” period, wearing the mask for longer and longer periods of time to get used to it. Parents could suggest kids wear a mask when doing something they like, such as watching television, so they equate it with something pleasant. Switching to a different kind of mask or one that fits better could also help.

Masks cause Legionnaires’ disease. Not true, experts say. Legionnaires’ is a severe form of pneumonia, the result of inhaling tiny water droplets with legionella bacteria.

It’s difficult to read lips. People can buy masks with a clear window that makes their mouth and lips visible.

Trouble breathing. Brief periods of mask use won’t have a bad effect on oxygen levels for most people.

“There is not an inherent right to be out in a pandemic with an unmasked face,” Dr. Raz says. But “you are entitled to an accommodation.” That might be using curbside pickup for food and medication. That requires much less time wearing a mask than entering a store would.

There are no “boilerplate” cards or letters to excuse people provided by the four organizations that addressed the issue, Dr. Rizzo said. If he were to write a letter asking for an exemption, he would personalize it for an individual patient’s medical condition. As to whether a state would honor it, he cannot say. The states have a patchwork of recommendations, making it difficult to say.

Dr. Rizzo tells lung disease patients who are able to go out that wearing a mask for 15-20 minutes to do an errand won’t harm their oxygen levels. And he reminds them that having an exemption, in the form of a doctor’s letter, may bring more problems. “Even with an exemption, someone may confront them” for their lack of a face covering. People with COPD have a higher risk of getting a severe illness from COVID-19, according to the CDC.

This article first appeared on WebMD.com.

The Centers for Disease Control and Prevention reported recently that opioid overdose deaths will increase to a new U.S. record, and more are expected as pandemic-related overdose deaths are yet to be counted.¹

Specifically, according to the CDC, 70,980 people died from fatal overdoses in 2019,² which is record high. Experts such as Bruce A. Goldberger, PhD, fear that the 2020 numbers could rise even higher, exacerbated by the coronavirus pandemic.

Deaths from drug overdoses remain higher than the peak yearly death totals ever recorded for car accidents, guns, or AIDS. Overdose deaths have accelerated further – pushing down overall life expectancy in the United States.³ Headlines purporting to identify good news in drug death figures don’t always get below top-level data. Deaths and despair tied to drug dependence are indeed accelerating. I am concerned about these alarmingly dangerous trends.

Synthetic opioids such as fentanyl accounted for about 3,000 deaths in 2013. By 2019, they accounted for more than 37,137.⁴ In addition, 16,539 deaths involved stimulants such as methamphetamine, and 16,196 deaths involved cocaine, the most recent CDC reporting shows. Opioids continue to play a role in U.S. “deaths of despair,” or rising fatalities from drugs, suicides, and alcohol among Americans without employment, hope of job opportunities, or college degrees.⁵ As the American Medical Association has warned,⁶ more people are dying from overdoses amid the COVID-19 pandemic. Clinicians need to be aware of trends so that we can help our patients navigate these challenges.
 

Fentanyl presents dangers

Experts had predicted that the pandemic, by limiting access to treatment, rescue, or overdose services, and increasing time at home and in the neighborhood, would result in more tragedy. In addition, the shift from prescription opioids to heroin and now to fentanyl has made deaths more common.

Fentanyls – synthetic opioids – are involved in more than half of overdose deaths, and in many of the cocaine and methamphetamine-related deaths, which also are on the rise. Fentanyl is about 100 times more potent than morphine and 50 times more potent than heroin. Breathing can stop after use of just 2 mg of fentanyl, which is about as much as trace amounts of table salt. Fentanyl has replaced heroin in many cities as the pandemic changed the relative ease of importing raw drugs such as heroin.

Another important trend is that fentanyl production and distribution throughout the United States have expanded. The ease of manufacture in unregulated sectors of the Chinese and Mexican economies is difficult for U.S. authorities to curb or eliminate. The Internet promotes novel strategies for synthesizing the substance, spreading its production across many labs; suppliers use the U.S. Postal Service for distribution, and e-commerce helps to get the drug from manufacturers to U.S. consumers for fentanyl transactions.

A recent RAND report observes that, for only $10 through the postal service, suppliers can ship a 1-kg parcel from China to the United States, and private shipments cost about $100.⁷ And with large volumes of legal trade between the two countries making rigorous scrutiny of products difficult, especially given the light weight of fentanyl, suppliers find it relatively easy to hide illicit substances in licit shipments. Opioid users have made the switch to fentanyl, and have seen fentanyl added to cocaine and methamphetamine they buy on the streets.
 

OUD and buprenorphine

Fentanyl is one part of the overdose crisis. Opioid use disorder (OUD) is the other. Both need to be addressed if we are to make any progress in this epidemic of death and dependency.

The OUD crisis continues amid the pandemic – and isn’t going away.⁸ Slips, relapses, and overdoses are all too common. Medication-assisted treatment (MAT) and OUD treatment programs are essential parts of our response to overdose initiatives. After naloxone rescue, the best anti-overdose response is to get the OUD patient into treatment with MATs. Patients with OUD have continuously high risks of overdose. The best outcomes appear to be related to treatment duration of greater than 2 years. But it is common to see patients with OUDs who have been in treatment multiple times, taking MATs, dropping out, overdosing, and dying. Some have been described as treatment resistant.⁹ It is clear that treatment can work, but also that even evidence-based treatments often fail.¹⁰

A recent study compared OUD patients who continued treatment for 6-9 months to those patients who had continued MAT treatment for 15-18 months. The longer the treatment, the fewer emergencies, prescriptions, or hospitalizations.¹¹

But this study reminds us that all OUD patients, whether they are currently buprenorphine treated or not, experience overdoses and emergency department interventions. Short and longer treatment groups have a similar nonfatal overdose rate, about 6%, and went to the emergency department at a high rate, above 40%. Discontinuation of buprenorphine treatment is a major risk factor in opioid relapse, emergency department visits, and overdose. Cures are not common. Whether an OUD patient is being treated or has been treated in the past, carrying naloxone (brand name Narcan), makes sense and can save lives.
 

Methadone still considered most effective

Methadone is a synthetic opioid first studied as a treatment for OUD at Rockefeller University in New York City in the 1960s. Methadone may be the most effective treatment for OUD in promoting treatment retention for years, decreasing intravenous drug use, and decreasing deaths.¹² It has been studied and safely used in treatment programs for decades. Methadone is typically administered in a clinic, daily, and with observation. In addition, methadone patients periodically take urine drug tests, which can distinguish methadone from substances of abuse. They also receive counseling. But methadone can be prescribed and administered only in methadone clinics in the United States. It is available for prescription in primary care clinics in Great Britain, Canada, and Australia.¹³ Numerous experts have suggested passing new legislation aimed at changing how methadone can be prescribed. Allowing primary care to administer methadone, just like buprenorphine, can improve access and benefit OUD patients.¹²

Availability of Narcan is critical

A comprehensive treatment model for OUDs includes prescribing naloxone, encouraging those patients with an OUD and their loved ones to have naloxone with them, and providing MATs and appropriate therapies, such as counseling.

As described by Allison L. Pitt and colleagues at Stanford (Calif.) University,¹⁴ the United States might be on track to have up to 500,000 deaths tied to opioid overdoses that might occur over the next 5 years. They modeled the effect on overdose of a long list of interventions, but only a few had an impact. At the top of the list was naloxone availability. We need to focus on saving lives by increasing naloxone availability, improving initiation, and expanding access to MAT, and increasing psychosocial treatment to improve outcomes, increase life-years and quality-adjusted life-years, and reduce opioid-related deaths. When Ms. Pitt and colleagues looked at what would make the most impact in reducing OUD deaths, it was naloxone. Pain patients on higher doses of opioids, nonprescription opioid users, OUD patients should be given naloxone prescriptions. While many can give a Heimlich to a choking person or CPR, few have naloxone to rescue a person who has overdosed on opioids. If an overdose is suspected, it should be administered by anyone who has it, as soon as possible. Then, the person who is intervening should call 911.
 

What we can do today

At this moment, clinicians can follow the Surgeon General’s advice,¹⁵ and prescribe naloxone.

We should give naloxone to OUD patients and their families, to pain patients at dosages of greater than or equal to 50 MME. Our top priorities should be patients with comorbid pain syndromes, those being treated with benzodiazepines and sleeping medications, and patients with alcohol use disorders. This is also an important intervention for those who binge drink, and have sleep apnea, and heart and respiratory diseases.

Naloxone is available without a prescription in at least 43 states. Naloxone is available in harm reduction programs and in hospitals, and is carried by emergency medical staff, law enforcement, and EMTs. It also is available on the streets, though it does not appear to have a dollar value like opioids or even buprenorphine. Also, the availability of naloxone in pharmacies has made it easier for family members and caregivers of pain patients or those with OUD to have it to administer in an emergency.

An excellent place for MDs to start is to do more to encourage all patients with OUD to carry naloxone, for their loved ones to carry naloxone, and for their homes to have naloxone nearby in the bedroom or bathroom. It is not logical to expect a person with an OUD to rescue themselves. Current and past OUD patients, as well as their loved ones, are at high risk – and should have naloxone nearby at all times.

Naloxone reverses an opioid overdose, but it should be thought about like cardioversion or CPR rather than a treatment for an underlying disease. Increasing access to buprenorphine, buprenorphine + naloxone, and naltrexone treatment for OUDs is an important organizing principle. Initiation of MAT treatment in the emergency setting or most anywhere and any place a patient with an OUD can begin treatment is necessary. Treatment with buprenorphine or methadone reduces opioid overdose and opioid-related acute care use.¹⁶

Reducing racial disparities in OUD treatment is necessary, because buprenorphine treatment is concentrated among White patients who either use private insurance or are self-pay.¹⁷ Reducing barriers to methadone program licenses, expanding sites for distribution,¹⁸ prescribing methadone in an office setting might help. Clinicians can do a better job of explaining the risks associated with opioid prescriptions, including diversion and overdose, and the benefits of OUD treatment. So, while naloxone saves lives and is a wonder drug, it does not replace an intervention such as MAT, a counselor, a good treatment program, and a treatment plan. To reduce opioid overdoses, we must increase physician competencies in addiction medicine.
 

Dr. Gold is professor of psychiatry (adjunct) at Washington University, St. Louis. He is the 17th Distinguished Alumni Professor at the University of Florida, Gainesville. For more than 40 years, Dr. Gold has worked on developing models for understanding the effects of opioid, tobacco, cocaine, and other drugs, as well as food, on the brain and behavior. He disclosed financial ties with ADAPT Pharma and Magstim Ltd.

References

1. Kamp J. Overdose deaths rise, may reach record level, federal data show. Wall Street Journal. 2020 Jul 15.

2. 12 month–ending provisional number of drug overdose drugs. Centers for Disease Control and Prevention. 2020 Jul 5.

3. Katz J et al. In shadow of pandemic, U.S. drug overdose deaths resurge to record. New York Times. 2020 Jul 15.

4. Gold MS. The fentanyl crisis is only getting worse. Addiction Policy Forum. Updated 2020 Mar 12.

5. Gold MS. Mo Med. 2020-Mar-Apr;117(2):99-101.

6. Reports of increases in opioid-related overdoses and other concerns during the COVID-19 pandemic. American Medical Association. Issue brief. Updated 2020 Jul 20.

7. Pardo B et al. The future of fentanyl and other synthetic opioids. RAND report.

8. Gold MS. New challenges in the opioid epidemic. Addiction Policy Forum. 2020 Jun 4.

9. Patterson Silver Wolf DA and Gold MS. J Neurol Sci. 2020;411:116718.

10. Oesterle TS et al. Mayo Clin Proc. 2019;94(10):2072-86.

11. Connery HS and Weiss RD. Am J Psychiatry. 2020;177(2):104-6.

12. Kleber HD. JAMA. 2008;300(19):2303-5.

13. Samet JH et al. N Engl J Med. 2018;379(1):7-8.

14. Pitt AL et al. Am J Public Health. 2018;108(10):1394-1400.

15. U.S. Surgeon General’s Advisory on Naloxone and Opioid Overdose. hhs.gov.

16. Wakeman SE et al. JAMA Netw Open. 2020;3(2):e1920622.

17. Lagisetty PA et al. JAMA Psychiatry. 2019;76(9):979-81.

18. Kleinman RA. JAMA Psychiatry. 2020 Jul 15. doi: 10.1001/jamapsychiatry.2020.1624.

The Centers for Disease Control and Prevention reported recently that opioid overdose deaths will increase to a new U.S. record, and more are expected as pandemic-related overdose deaths are yet to be counted.¹

Specifically, according to the CDC, 70,980 people died from fatal overdoses in 2019,² which is record high. Experts such as Bruce A. Goldberger, PhD, fear that the 2020 numbers could rise even higher, exacerbated by the coronavirus pandemic.

Deaths from drug overdoses remain higher than the peak yearly death totals ever recorded for car accidents, guns, or AIDS. Overdose deaths have accelerated further – pushing down overall life expectancy in the United States.³ Headlines purporting to identify good news in drug death figures don’t always get below top-level data. Deaths and despair tied to drug dependence are indeed accelerating. I am concerned about these alarmingly dangerous trends.

Synthetic opioids such as fentanyl accounted for about 3,000 deaths in 2013. By 2019, they accounted for more than 37,137.⁴ In addition, 16,539 deaths involved stimulants such as methamphetamine, and 16,196 deaths involved cocaine, the most recent CDC reporting shows. Opioids continue to play a role in U.S. “deaths of despair,” or rising fatalities from drugs, suicides, and alcohol among Americans without employment, hope of job opportunities, or college degrees.⁵ As the American Medical Association has warned,⁶ more people are dying from overdoses amid the COVID-19 pandemic. Clinicians need to be aware of trends so that we can help our patients navigate these challenges.
 

Fentanyl presents dangers

Experts had predicted that the pandemic, by limiting access to treatment, rescue, or overdose services, and increasing time at home and in the neighborhood, would result in more tragedy. In addition, the shift from prescription opioids to heroin and now to fentanyl has made deaths more common.

Fentanyls – synthetic opioids – are involved in more than half of overdose deaths, and in many of the cocaine and methamphetamine-related deaths, which also are on the rise. Fentanyl is about 100 times more potent than morphine and 50 times more potent than heroin. Breathing can stop after use of just 2 mg of fentanyl, which is about as much as trace amounts of table salt. Fentanyl has replaced heroin in many cities as the pandemic changed the relative ease of importing raw drugs such as heroin.

Another important trend is that fentanyl production and distribution throughout the United States have expanded. The ease of manufacture in unregulated sectors of the Chinese and Mexican economies is difficult for U.S. authorities to curb or eliminate. The Internet promotes novel strategies for synthesizing the substance, spreading its production across many labs; suppliers use the U.S. Postal Service for distribution, and e-commerce helps to get the drug from manufacturers to U.S. consumers for fentanyl transactions.

A recent RAND report observes that, for only $10 through the postal service, suppliers can ship a 1-kg parcel from China to the United States, and private shipments cost about $100.⁷ And with large volumes of legal trade between the two countries making rigorous scrutiny of products difficult, especially given the light weight of fentanyl, suppliers find it relatively easy to hide illicit substances in licit shipments. Opioid users have made the switch to fentanyl, and have seen fentanyl added to cocaine and methamphetamine they buy on the streets.
 

OUD and buprenorphine

Fentanyl is one part of the overdose crisis. Opioid use disorder (OUD) is the other. Both need to be addressed if we are to make any progress in this epidemic of death and dependency.

The OUD crisis continues amid the pandemic – and isn’t going away.⁸ Slips, relapses, and overdoses are all too common. Medication-assisted treatment (MAT) and OUD treatment programs are essential parts of our response to overdose initiatives. After naloxone rescue, the best anti-overdose response is to get the OUD patient into treatment with MATs. Patients with OUD have continuously high risks of overdose. The best outcomes appear to be related to treatment duration of greater than 2 years. But it is common to see patients with OUDs who have been in treatment multiple times, taking MATs, dropping out, overdosing, and dying. Some have been described as treatment resistant.⁹ It is clear that treatment can work, but also that even evidence-based treatments often fail.¹⁰

A recent study compared OUD patients who continued treatment for 6-9 months to those patients who had continued MAT treatment for 15-18 months. The longer the treatment, the fewer emergencies, prescriptions, or hospitalizations.¹¹

But this study reminds us that all OUD patients, whether they are currently buprenorphine treated or not, experience overdoses and emergency department interventions. Short and longer treatment groups have a similar nonfatal overdose rate, about 6%, and went to the emergency department at a high rate, above 40%. Discontinuation of buprenorphine treatment is a major risk factor in opioid relapse, emergency department visits, and overdose. Cures are not common. Whether an OUD patient is being treated or has been treated in the past, carrying naloxone (brand name Narcan), makes sense and can save lives.
 

Methadone still considered most effective

Methadone is a synthetic opioid first studied as a treatment for OUD at Rockefeller University in New York City in the 1960s. Methadone may be the most effective treatment for OUD in promoting treatment retention for years, decreasing intravenous drug use, and decreasing deaths.¹² It has been studied and safely used in treatment programs for decades. Methadone is typically administered in a clinic, daily, and with observation. In addition, methadone patients periodically take urine drug tests, which can distinguish methadone from substances of abuse. They also receive counseling. But methadone can be prescribed and administered only in methadone clinics in the United States. It is available for prescription in primary care clinics in Great Britain, Canada, and Australia.¹³ Numerous experts have suggested passing new legislation aimed at changing how methadone can be prescribed. Allowing primary care to administer methadone, just like buprenorphine, can improve access and benefit OUD patients.¹²

Availability of Narcan is critical

A comprehensive treatment model for OUDs includes prescribing naloxone, encouraging those patients with an OUD and their loved ones to have naloxone with them, and providing MATs and appropriate therapies, such as counseling.

As described by Allison L. Pitt and colleagues at Stanford (Calif.) University,¹⁴ the United States might be on track to have up to 500,000 deaths tied to opioid overdoses that might occur over the next 5 years. They modeled the effect on overdose of a long list of interventions, but only a few had an impact. At the top of the list was naloxone availability. We need to focus on saving lives by increasing naloxone availability, improving initiation, and expanding access to MAT, and increasing psychosocial treatment to improve outcomes, increase life-years and quality-adjusted life-years, and reduce opioid-related deaths. When Ms. Pitt and colleagues looked at what would make the most impact in reducing OUD deaths, it was naloxone. Pain patients on higher doses of opioids, nonprescription opioid users, OUD patients should be given naloxone prescriptions. While many can give a Heimlich to a choking person or CPR, few have naloxone to rescue a person who has overdosed on opioids. If an overdose is suspected, it should be administered by anyone who has it, as soon as possible. Then, the person who is intervening should call 911.
 

What we can do today

At this moment, clinicians can follow the Surgeon General’s advice,¹⁵ and prescribe naloxone.

We should give naloxone to OUD patients and their families, to pain patients at dosages of greater than or equal to 50 MME. Our top priorities should be patients with comorbid pain syndromes, those being treated with benzodiazepines and sleeping medications, and patients with alcohol use disorders. This is also an important intervention for those who binge drink, and have sleep apnea, and heart and respiratory diseases.

Naloxone is available without a prescription in at least 43 states. Naloxone is available in harm reduction programs and in hospitals, and is carried by emergency medical staff, law enforcement, and EMTs. It also is available on the streets, though it does not appear to have a dollar value like opioids or even buprenorphine. Also, the availability of naloxone in pharmacies has made it easier for family members and caregivers of pain patients or those with OUD to have it to administer in an emergency.

An excellent place for MDs to start is to do more to encourage all patients with OUD to carry naloxone, for their loved ones to carry naloxone, and for their homes to have naloxone nearby in the bedroom or bathroom. It is not logical to expect a person with an OUD to rescue themselves. Current and past OUD patients, as well as their loved ones, are at high risk – and should have naloxone nearby at all times.

Naloxone reverses an opioid overdose, but it should be thought about like cardioversion or CPR rather than a treatment for an underlying disease. Increasing access to buprenorphine, buprenorphine + naloxone, and naltrexone treatment for OUDs is an important organizing principle. Initiation of MAT treatment in the emergency setting or most anywhere and any place a patient with an OUD can begin treatment is necessary. Treatment with buprenorphine or methadone reduces opioid overdose and opioid-related acute care use.¹⁶

Reducing racial disparities in OUD treatment is necessary, because buprenorphine treatment is concentrated among White patients who either use private insurance or are self-pay.¹⁷ Reducing barriers to methadone program licenses, expanding sites for distribution,¹⁸ prescribing methadone in an office setting might help. Clinicians can do a better job of explaining the risks associated with opioid prescriptions, including diversion and overdose, and the benefits of OUD treatment. So, while naloxone saves lives and is a wonder drug, it does not replace an intervention such as MAT, a counselor, a good treatment program, and a treatment plan. To reduce opioid overdoses, we must increase physician competencies in addiction medicine.
 

Dr. Gold is professor of psychiatry (adjunct) at Washington University, St. Louis. He is the 17th Distinguished Alumni Professor at the University of Florida, Gainesville. For more than 40 years, Dr. Gold has worked on developing models for understanding the effects of opioid, tobacco, cocaine, and other drugs, as well as food, on the brain and behavior. He disclosed financial ties with ADAPT Pharma and Magstim Ltd.

References

1. Kamp J. Overdose deaths rise, may reach record level, federal data show. Wall Street Journal. 2020 Jul 15.

2. 12 month–ending provisional number of drug overdose drugs. Centers for Disease Control and Prevention. 2020 Jul 5.

3. Katz J et al. In shadow of pandemic, U.S. drug overdose deaths resurge to record. New York Times. 2020 Jul 15.

4. Gold MS. The fentanyl crisis is only getting worse. Addiction Policy Forum. Updated 2020 Mar 12.

5. Gold MS. Mo Med. 2020-Mar-Apr;117(2):99-101.

6. Reports of increases in opioid-related overdoses and other concerns during the COVID-19 pandemic. American Medical Association. Issue brief. Updated 2020 Jul 20.

7. Pardo B et al. The future of fentanyl and other synthetic opioids. RAND report.

8. Gold MS. New challenges in the opioid epidemic. Addiction Policy Forum. 2020 Jun 4.

9. Patterson Silver Wolf DA and Gold MS. J Neurol Sci. 2020;411:116718.

10. Oesterle TS et al. Mayo Clin Proc. 2019;94(10):2072-86.

11. Connery HS and Weiss RD. Am J Psychiatry. 2020;177(2):104-6.

12. Kleber HD. JAMA. 2008;300(19):2303-5.

13. Samet JH et al. N Engl J Med. 2018;379(1):7-8.

14. Pitt AL et al. Am J Public Health. 2018;108(10):1394-1400.

15. U.S. Surgeon General’s Advisory on Naloxone and Opioid Overdose. hhs.gov.

16. Wakeman SE et al. JAMA Netw Open. 2020;3(2):e1920622.

17. Lagisetty PA et al. JAMA Psychiatry. 2019;76(9):979-81.

18. Kleinman RA. JAMA Psychiatry. 2020 Jul 15. doi: 10.1001/jamapsychiatry.2020.1624.

The Centers for Disease Control and Prevention reported recently that opioid overdose deaths will increase to a new U.S. record, and more are expected as pandemic-related overdose deaths are yet to be counted.¹

Specifically, according to the CDC, 70,980 people died from fatal overdoses in 2019,² which is record high. Experts such as Bruce A. Goldberger, PhD, fear that the 2020 numbers could rise even higher, exacerbated by the coronavirus pandemic.

Deaths from drug overdoses remain higher than the peak yearly death totals ever recorded for car accidents, guns, or AIDS. Overdose deaths have accelerated further – pushing down overall life expectancy in the United States.³ Headlines purporting to identify good news in drug death figures don’t always get below top-level data. Deaths and despair tied to drug dependence are indeed accelerating. I am concerned about these alarmingly dangerous trends.

Synthetic opioids such as fentanyl accounted for about 3,000 deaths in 2013. By 2019, they accounted for more than 37,137.⁴ In addition, 16,539 deaths involved stimulants such as methamphetamine, and 16,196 deaths involved cocaine, the most recent CDC reporting shows. Opioids continue to play a role in U.S. “deaths of despair,” or rising fatalities from drugs, suicides, and alcohol among Americans without employment, hope of job opportunities, or college degrees.⁵ As the American Medical Association has warned,⁶ more people are dying from overdoses amid the COVID-19 pandemic. Clinicians need to be aware of trends so that we can help our patients navigate these challenges.
 

Fentanyl presents dangers

Experts had predicted that the pandemic, by limiting access to treatment, rescue, or overdose services, and increasing time at home and in the neighborhood, would result in more tragedy. In addition, the shift from prescription opioids to heroin and now to fentanyl has made deaths more common.

Fentanyls – synthetic opioids – are involved in more than half of overdose deaths, and in many of the cocaine and methamphetamine-related deaths, which also are on the rise. Fentanyl is about 100 times more potent than morphine and 50 times more potent than heroin. Breathing can stop after use of just 2 mg of fentanyl, which is about as much as trace amounts of table salt. Fentanyl has replaced heroin in many cities as the pandemic changed the relative ease of importing raw drugs such as heroin.

Another important trend is that fentanyl production and distribution throughout the United States have expanded. The ease of manufacture in unregulated sectors of the Chinese and Mexican economies is difficult for U.S. authorities to curb or eliminate. The Internet promotes novel strategies for synthesizing the substance, spreading its production across many labs; suppliers use the U.S. Postal Service for distribution, and e-commerce helps to get the drug from manufacturers to U.S. consumers for fentanyl transactions.

A recent RAND report observes that, for only $10 through the postal service, suppliers can ship a 1-kg parcel from China to the United States, and private shipments cost about $100.⁷ And with large volumes of legal trade between the two countries making rigorous scrutiny of products difficult, especially given the light weight of fentanyl, suppliers find it relatively easy to hide illicit substances in licit shipments. Opioid users have made the switch to fentanyl, and have seen fentanyl added to cocaine and methamphetamine they buy on the streets.
 

OUD and buprenorphine

Fentanyl is one part of the overdose crisis. Opioid use disorder (OUD) is the other. Both need to be addressed if we are to make any progress in this epidemic of death and dependency.

The OUD crisis continues amid the pandemic – and isn’t going away.⁸ Slips, relapses, and overdoses are all too common. Medication-assisted treatment (MAT) and OUD treatment programs are essential parts of our response to overdose initiatives. After naloxone rescue, the best anti-overdose response is to get the OUD patient into treatment with MATs. Patients with OUD have continuously high risks of overdose. The best outcomes appear to be related to treatment duration of greater than 2 years. But it is common to see patients with OUDs who have been in treatment multiple times, taking MATs, dropping out, overdosing, and dying. Some have been described as treatment resistant.⁹ It is clear that treatment can work, but also that even evidence-based treatments often fail.¹⁰

A recent study compared OUD patients who continued treatment for 6-9 months to those patients who had continued MAT treatment for 15-18 months. The longer the treatment, the fewer emergencies, prescriptions, or hospitalizations.¹¹

But this study reminds us that all OUD patients, whether they are currently buprenorphine treated or not, experience overdoses and emergency department interventions. Short and longer treatment groups have a similar nonfatal overdose rate, about 6%, and went to the emergency department at a high rate, above 40%. Discontinuation of buprenorphine treatment is a major risk factor in opioid relapse, emergency department visits, and overdose. Cures are not common. Whether an OUD patient is being treated or has been treated in the past, carrying naloxone (brand name Narcan), makes sense and can save lives.
 

Methadone still considered most effective

Methadone is a synthetic opioid first studied as a treatment for OUD at Rockefeller University in New York City in the 1960s. Methadone may be the most effective treatment for OUD in promoting treatment retention for years, decreasing intravenous drug use, and decreasing deaths.¹² It has been studied and safely used in treatment programs for decades. Methadone is typically administered in a clinic, daily, and with observation. In addition, methadone patients periodically take urine drug tests, which can distinguish methadone from substances of abuse. They also receive counseling. But methadone can be prescribed and administered only in methadone clinics in the United States. It is available for prescription in primary care clinics in Great Britain, Canada, and Australia.¹³ Numerous experts have suggested passing new legislation aimed at changing how methadone can be prescribed. Allowing primary care to administer methadone, just like buprenorphine, can improve access and benefit OUD patients.¹²

Availability of Narcan is critical

A comprehensive treatment model for OUDs includes prescribing naloxone, encouraging those patients with an OUD and their loved ones to have naloxone with them, and providing MATs and appropriate therapies, such as counseling.

As described by Allison L. Pitt and colleagues at Stanford (Calif.) University,¹⁴ the United States might be on track to have up to 500,000 deaths tied to opioid overdoses that might occur over the next 5 years. They modeled the effect on overdose of a long list of interventions, but only a few had an impact. At the top of the list was naloxone availability. We need to focus on saving lives by increasing naloxone availability, improving initiation, and expanding access to MAT, and increasing psychosocial treatment to improve outcomes, increase life-years and quality-adjusted life-years, and reduce opioid-related deaths. When Ms. Pitt and colleagues looked at what would make the most impact in reducing OUD deaths, it was naloxone. Pain patients on higher doses of opioids, nonprescription opioid users, OUD patients should be given naloxone prescriptions. While many can give a Heimlich to a choking person or CPR, few have naloxone to rescue a person who has overdosed on opioids. If an overdose is suspected, it should be administered by anyone who has it, as soon as possible. Then, the person who is intervening should call 911.
 

What we can do today

At this moment, clinicians can follow the Surgeon General’s advice,¹⁵ and prescribe naloxone.

We should give naloxone to OUD patients and their families, to pain patients at dosages of greater than or equal to 50 MME. Our top priorities should be patients with comorbid pain syndromes, those being treated with benzodiazepines and sleeping medications, and patients with alcohol use disorders. This is also an important intervention for those who binge drink, and have sleep apnea, and heart and respiratory diseases.

Naloxone is available without a prescription in at least 43 states. Naloxone is available in harm reduction programs and in hospitals, and is carried by emergency medical staff, law enforcement, and EMTs. It also is available on the streets, though it does not appear to have a dollar value like opioids or even buprenorphine. Also, the availability of naloxone in pharmacies has made it easier for family members and caregivers of pain patients or those with OUD to have it to administer in an emergency.

An excellent place for MDs to start is to do more to encourage all patients with OUD to carry naloxone, for their loved ones to carry naloxone, and for their homes to have naloxone nearby in the bedroom or bathroom. It is not logical to expect a person with an OUD to rescue themselves. Current and past OUD patients, as well as their loved ones, are at high risk – and should have naloxone nearby at all times.

Naloxone reverses an opioid overdose, but it should be thought about like cardioversion or CPR rather than a treatment for an underlying disease. Increasing access to buprenorphine, buprenorphine + naloxone, and naltrexone treatment for OUDs is an important organizing principle. Initiation of MAT treatment in the emergency setting or most anywhere and any place a patient with an OUD can begin treatment is necessary. Treatment with buprenorphine or methadone reduces opioid overdose and opioid-related acute care use.¹⁶

Reducing racial disparities in OUD treatment is necessary, because buprenorphine treatment is concentrated among White patients who either use private insurance or are self-pay.¹⁷ Reducing barriers to methadone program licenses, expanding sites for distribution,¹⁸ prescribing methadone in an office setting might help. Clinicians can do a better job of explaining the risks associated with opioid prescriptions, including diversion and overdose, and the benefits of OUD treatment. So, while naloxone saves lives and is a wonder drug, it does not replace an intervention such as MAT, a counselor, a good treatment program, and a treatment plan. To reduce opioid overdoses, we must increase physician competencies in addiction medicine.
 

Dr. Gold is professor of psychiatry (adjunct) at Washington University, St. Louis. He is the 17th Distinguished Alumni Professor at the University of Florida, Gainesville. For more than 40 years, Dr. Gold has worked on developing models for understanding the effects of opioid, tobacco, cocaine, and other drugs, as well as food, on the brain and behavior. He disclosed financial ties with ADAPT Pharma and Magstim Ltd.

References

1. Kamp J. Overdose deaths rise, may reach record level, federal data show. Wall Street Journal. 2020 Jul 15.

2. 12 month–ending provisional number of drug overdose drugs. Centers for Disease Control and Prevention. 2020 Jul 5.

3. Katz J et al. In shadow of pandemic, U.S. drug overdose deaths resurge to record. New York Times. 2020 Jul 15.

4. Gold MS. The fentanyl crisis is only getting worse. Addiction Policy Forum. Updated 2020 Mar 12.

5. Gold MS. Mo Med. 2020-Mar-Apr;117(2):99-101.

6. Reports of increases in opioid-related overdoses and other concerns during the COVID-19 pandemic. American Medical Association. Issue brief. Updated 2020 Jul 20.

7. Pardo B et al. The future of fentanyl and other synthetic opioids. RAND report.

8. Gold MS. New challenges in the opioid epidemic. Addiction Policy Forum. 2020 Jun 4.

9. Patterson Silver Wolf DA and Gold MS. J Neurol Sci. 2020;411:116718.

10. Oesterle TS et al. Mayo Clin Proc. 2019;94(10):2072-86.

11. Connery HS and Weiss RD. Am J Psychiatry. 2020;177(2):104-6.

12. Kleber HD. JAMA. 2008;300(19):2303-5.

13. Samet JH et al. N Engl J Med. 2018;379(1):7-8.

14. Pitt AL et al. Am J Public Health. 2018;108(10):1394-1400.

15. U.S. Surgeon General’s Advisory on Naloxone and Opioid Overdose. hhs.gov.

16. Wakeman SE et al. JAMA Netw Open. 2020;3(2):e1920622.

17. Lagisetty PA et al. JAMA Psychiatry. 2019;76(9):979-81.

18. Kleinman RA. JAMA Psychiatry. 2020 Jul 15. doi: 10.1001/jamapsychiatry.2020.1624.

A poor combined score on tests of hearing, vision, smell, and touch is associated with a higher risk for dementia and cognitive decline among older adults, new research suggests. The study, which included almost 1,800 participants, adds to emerging evidence that even mild levels of multisensory impairment are associated with accelerated cognitive aging, the researchers noted.

Clinicians should be aware of this link between sensory impairment and dementia risk, said lead author Willa Brenowitz, PhD, assistant professor, department of psychiatry and behavioral sciences, University of California, San Francisco. “Many of these impairments are treatable, or at least physicians can monitor them; and this can improve quality of life, even if it doesn’t improve dementia risk.”

The findings were published online July 12 in Alzheimer’s and Dementia.
 

Additive effects

Previous research has focused on the link between dementia and individual senses, but this new work is unique in that it focuses on the additive effects of multiple impairments in sensory function, said Dr. Brenowitz. The study included 1,794 dementia-free participants in their 70s from the Health, Aging and Body Composition study, a prospective cohort study of healthy Black and White men and women.

Researchers tested participants’ hearing using a pure tone average without hearing aids and vision using contrast sensitivity with glasses permitted. They also measured vibrations in the big toe to assess touch and had participants identify distinctive odors such as paint thinner, roses, lemons, and onions to assess smell.

A score of 0-3 was assigned based on sample quartiles for each of the four sensory functions. Individuals with the best quartile were assigned a score of 0 and those with the worst were assigned a score of 3.

The investigators added scores across all senses to create a summary score of multisensory function (0-12) and classified the participants into tertiles of good, medium, and poor. Individuals with a score of 0 would have good function in all senses, whereas those with 12 would have poor function in all senses. Those with medium scores could have a mix of impairments.

Participants with good multisensory function were more likely to be healthier than those with poor function. They were also significantly more likely to have completed high school (85.0% vs. 72.1%), were significantly less likely to have diabetes (16.9% vs. 27.9%), and were marginally less likely to have cardiovascular disease, high blood pressure, and history of stroke.

Investigators measured cognition using the Modified Mini-Mental State (3MS) examination, a test of global cognitive function, and the Digit Symbol Substitution Test (DSST), a measure of cognitive processing speed. Cognitive testing was carried out at the beginning of the study and repeated every other year.

Dementia was defined as the use of dementia medication, being hospitalized with dementia as a primary or secondary diagnosis, or having a 3MS score 1.5 standard deviations lower than the race-stratified Health ABC study baseline mean.

Over an average follow-up of 6.3 years, 18% of participants developed dementia.
 

Dose-response increase

Results showed that, with worsening multisensory function score, the risk for dementia increased in a dose-response manner. In models adjusted for demographics and health conditions, participants with a poor multisensory function score were more than twice as likely to develop dementia than those with a good score (hazard ratio, 2.05; 95% confidence interval, 1.50-2.81; P < .001). Those with a middle multisensory function score were 1.45 times more likely to develop dementia (HR, 1.45; 95% CI, 1.09-1.91; P < .001).

Even a 1-point worse multisensory function score was associated with a 14% higher risk for dementia (95% CI, 8%-21%), while a 4-point worse score was associated with 71% higher risk for dementia (95% CI, 38%-211%).

Smell was the sensory function most strongly associated with dementia risk. Participants whose sense of smell declined by 10% had a 19% higher risk for dementia versus a 1%-3% higher risk for declines in vision, hearing, and touch.

It is not clear why smell was a stronger determinant of dementia risk. However, loss of this sense is often considered to be a marker for Alzheimer’s disease “because it is closely linked with brain regions that are affected” in that disease, said Dr. Brenowitz.

However, that does not necessarily mean smell is more important than vision or hearing, she added. “Even if hearing and vision have a smaller contribution to dementia, they have a stronger potential for intervention.” The findings suggest “some additive or cumulative” effects for loss of the different senses. “There’s an association above and beyond those which can be attributed to individual sensory domains,” she said.
 

Frailty link

After including mobility, which is a potential mediator, estimates for the multisensory function score were slightly lower. “Walking speed is pretty strongly associated with dementia risk,” Dr. Brenowitz noted. Physical frailty might help explain the link between sensory impairment and dementia risk. “It’s not clear if that’s because people with dementia are declining or because people with frailty are especially vulnerable to dementia,” she said.

The researchers also assessed the role of social support, another potential mechanism by which sensory decline, especially in hearing and vision, could influence dementia risk. Although the study did not find substantial differences in social support measures, the investigators noted that questions assessing social support were limited in scope.

Interactions between multisensory function score and race, APOE e4 allele status, and sex were not significant.

Worsening multisensory function was also linked to faster annual rates of cognitive decline as measured by both the 3MS and DSST. Each 1-point worse score was associated with faster decline (P < .05), even after adjustment for demographics and health conditions.
 

Possible mechanisms

A number of possible mechanisms may explain the link between poor sensory function and dementia. It could be that neurodegeneration underlying dementia affects the senses, or vision and/or hearing loss leads to social isolation and poor mental health, which in turn could affect dementia risk, the researchers wrote. It also is possible that cardiovascular disease or diabetes affect both dementia risk and sensory impairment.

Dr. Brenowitz noted that, because cognitive tests rely on a certain degree of vision and hearing, impairment of these senses may complicate such tests. Still to be determined is whether correcting sensory impairments, such as wearing corrective lenses or hearing aids, affects dementia risk.

Meanwhile, it might be a good idea to more regularly check sensory function, especially vision and hearing, the researchers suggested. These functions affect various aspects of health and can be assessed rather easily. However, because smell is so strongly associated with dementia risk, Dr. Brenowitz said she would like to see it also become “part of a screening tool.”

A possible study limitation cited was that the researchers checked sensory function only once. “Most likely, some of these would change over time, but at least it captured sensory function at one point,” Dr. Brenowitz said.
 

“Sheds further light”

Commenting on the study, Jo V. Rushworth, PhD, associate professor and national teaching fellow, De Montfort University Leicester (England), said it “sheds further light on the emerging links” between multisensory impairment and cognitive decline leading to dementia. “The authors show that people with even mild loss of function in various senses are more likely to develop cognitive impairment.”

Dr. Rushworth was not involved with the study but has done research in the area.

The current results suggest that measuring patients’ hearing, vision, sense of smell, and touch might “flag at-risk groups” who could be targeted for dementia prevention strategies, Dr. Rushworth noted. Such tests are noninvasive and potentially less distressing than other methods of diagnosing dementia. “Importantly, the relatively low cost and simplicity of sensory tests offer the potential for more frequent testing and the use of these methods in areas of the world where medical facilities and resources are limited.”

This new study raises the question of whether the observed sensory impairments are a cause or an effect of dementia, Dr. Rushworth noted. “As the authors suggest, decreased sensory function can lead to a decrease in social engagement, mobility, and other factors which would usually contribute to counteracting cognitive decline.”

The study raises other questions, too, said Dr. Rushworth. She noted that the participants who experienced more severe sensory impairments were, on average, 2 years older than those with the least impairments. “To what degree were the observed sensory deficits linked to normal aging rather than dementia?”

As well, Dr. Rushworth pointed out that the molecular mechanisms that “kick-start” dementia are believed to occur in midlife – so possibly at an age younger than the study participants. “Do younger people of a ‘predementia’ age range display multisensory impairments?”

Because study participants could wear glasses during vision tests but were not allowed to wear hearing aids for the hearing tests, further standardization of sensory impairment is required, Dr. Rushworth said.

“Future studies will be essential in determining the value of clinical measurement of multisensory impairment as a possible dementia indicator and prevention strategy,” she concluded.

The study was funded by the National Institute on Aging, the National Institute of Nursing Research, and the Alzheimer’s Association. Dr. Brenowitz and Dr. Rushworth have reported no relevant financial relationships.

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

A poor combined score on tests of hearing, vision, smell, and touch is associated with a higher risk for dementia and cognitive decline among older adults, new research suggests. The study, which included almost 1,800 participants, adds to emerging evidence that even mild levels of multisensory impairment are associated with accelerated cognitive aging, the researchers noted.

Clinicians should be aware of this link between sensory impairment and dementia risk, said lead author Willa Brenowitz, PhD, assistant professor, department of psychiatry and behavioral sciences, University of California, San Francisco. “Many of these impairments are treatable, or at least physicians can monitor them; and this can improve quality of life, even if it doesn’t improve dementia risk.”

The findings were published online July 12 in Alzheimer’s and Dementia.
 

Additive effects

Previous research has focused on the link between dementia and individual senses, but this new work is unique in that it focuses on the additive effects of multiple impairments in sensory function, said Dr. Brenowitz. The study included 1,794 dementia-free participants in their 70s from the Health, Aging and Body Composition study, a prospective cohort study of healthy Black and White men and women.

Researchers tested participants’ hearing using a pure tone average without hearing aids and vision using contrast sensitivity with glasses permitted. They also measured vibrations in the big toe to assess touch and had participants identify distinctive odors such as paint thinner, roses, lemons, and onions to assess smell.

A score of 0-3 was assigned based on sample quartiles for each of the four sensory functions. Individuals with the best quartile were assigned a score of 0 and those with the worst were assigned a score of 3.

The investigators added scores across all senses to create a summary score of multisensory function (0-12) and classified the participants into tertiles of good, medium, and poor. Individuals with a score of 0 would have good function in all senses, whereas those with 12 would have poor function in all senses. Those with medium scores could have a mix of impairments.

Participants with good multisensory function were more likely to be healthier than those with poor function. They were also significantly more likely to have completed high school (85.0% vs. 72.1%), were significantly less likely to have diabetes (16.9% vs. 27.9%), and were marginally less likely to have cardiovascular disease, high blood pressure, and history of stroke.

Investigators measured cognition using the Modified Mini-Mental State (3MS) examination, a test of global cognitive function, and the Digit Symbol Substitution Test (DSST), a measure of cognitive processing speed. Cognitive testing was carried out at the beginning of the study and repeated every other year.

Dementia was defined as the use of dementia medication, being hospitalized with dementia as a primary or secondary diagnosis, or having a 3MS score 1.5 standard deviations lower than the race-stratified Health ABC study baseline mean.

Over an average follow-up of 6.3 years, 18% of participants developed dementia.
 

Dose-response increase

Results showed that, with worsening multisensory function score, the risk for dementia increased in a dose-response manner. In models adjusted for demographics and health conditions, participants with a poor multisensory function score were more than twice as likely to develop dementia than those with a good score (hazard ratio, 2.05; 95% confidence interval, 1.50-2.81; P < .001). Those with a middle multisensory function score were 1.45 times more likely to develop dementia (HR, 1.45; 95% CI, 1.09-1.91; P < .001).

Even a 1-point worse multisensory function score was associated with a 14% higher risk for dementia (95% CI, 8%-21%), while a 4-point worse score was associated with 71% higher risk for dementia (95% CI, 38%-211%).

Smell was the sensory function most strongly associated with dementia risk. Participants whose sense of smell declined by 10% had a 19% higher risk for dementia versus a 1%-3% higher risk for declines in vision, hearing, and touch.

It is not clear why smell was a stronger determinant of dementia risk. However, loss of this sense is often considered to be a marker for Alzheimer’s disease “because it is closely linked with brain regions that are affected” in that disease, said Dr. Brenowitz.

However, that does not necessarily mean smell is more important than vision or hearing, she added. “Even if hearing and vision have a smaller contribution to dementia, they have a stronger potential for intervention.” The findings suggest “some additive or cumulative” effects for loss of the different senses. “There’s an association above and beyond those which can be attributed to individual sensory domains,” she said.
 

Frailty link

After including mobility, which is a potential mediator, estimates for the multisensory function score were slightly lower. “Walking speed is pretty strongly associated with dementia risk,” Dr. Brenowitz noted. Physical frailty might help explain the link between sensory impairment and dementia risk. “It’s not clear if that’s because people with dementia are declining or because people with frailty are especially vulnerable to dementia,” she said.

The researchers also assessed the role of social support, another potential mechanism by which sensory decline, especially in hearing and vision, could influence dementia risk. Although the study did not find substantial differences in social support measures, the investigators noted that questions assessing social support were limited in scope.

Interactions between multisensory function score and race, APOE e4 allele status, and sex were not significant.

Worsening multisensory function was also linked to faster annual rates of cognitive decline as measured by both the 3MS and DSST. Each 1-point worse score was associated with faster decline (P < .05), even after adjustment for demographics and health conditions.
 

Possible mechanisms

A number of possible mechanisms may explain the link between poor sensory function and dementia. It could be that neurodegeneration underlying dementia affects the senses, or vision and/or hearing loss leads to social isolation and poor mental health, which in turn could affect dementia risk, the researchers wrote. It also is possible that cardiovascular disease or diabetes affect both dementia risk and sensory impairment.

Dr. Brenowitz noted that, because cognitive tests rely on a certain degree of vision and hearing, impairment of these senses may complicate such tests. Still to be determined is whether correcting sensory impairments, such as wearing corrective lenses or hearing aids, affects dementia risk.

Meanwhile, it might be a good idea to more regularly check sensory function, especially vision and hearing, the researchers suggested. These functions affect various aspects of health and can be assessed rather easily. However, because smell is so strongly associated with dementia risk, Dr. Brenowitz said she would like to see it also become “part of a screening tool.”

A possible study limitation cited was that the researchers checked sensory function only once. “Most likely, some of these would change over time, but at least it captured sensory function at one point,” Dr. Brenowitz said.
 

“Sheds further light”

Commenting on the study, Jo V. Rushworth, PhD, associate professor and national teaching fellow, De Montfort University Leicester (England), said it “sheds further light on the emerging links” between multisensory impairment and cognitive decline leading to dementia. “The authors show that people with even mild loss of function in various senses are more likely to develop cognitive impairment.”

Dr. Rushworth was not involved with the study but has done research in the area.

The current results suggest that measuring patients’ hearing, vision, sense of smell, and touch might “flag at-risk groups” who could be targeted for dementia prevention strategies, Dr. Rushworth noted. Such tests are noninvasive and potentially less distressing than other methods of diagnosing dementia. “Importantly, the relatively low cost and simplicity of sensory tests offer the potential for more frequent testing and the use of these methods in areas of the world where medical facilities and resources are limited.”

This new study raises the question of whether the observed sensory impairments are a cause or an effect of dementia, Dr. Rushworth noted. “As the authors suggest, decreased sensory function can lead to a decrease in social engagement, mobility, and other factors which would usually contribute to counteracting cognitive decline.”

The study raises other questions, too, said Dr. Rushworth. She noted that the participants who experienced more severe sensory impairments were, on average, 2 years older than those with the least impairments. “To what degree were the observed sensory deficits linked to normal aging rather than dementia?”

As well, Dr. Rushworth pointed out that the molecular mechanisms that “kick-start” dementia are believed to occur in midlife – so possibly at an age younger than the study participants. “Do younger people of a ‘predementia’ age range display multisensory impairments?”

Because study participants could wear glasses during vision tests but were not allowed to wear hearing aids for the hearing tests, further standardization of sensory impairment is required, Dr. Rushworth said.

“Future studies will be essential in determining the value of clinical measurement of multisensory impairment as a possible dementia indicator and prevention strategy,” she concluded.

The study was funded by the National Institute on Aging, the National Institute of Nursing Research, and the Alzheimer’s Association. Dr. Brenowitz and Dr. Rushworth have reported no relevant financial relationships.

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

A poor combined score on tests of hearing, vision, smell, and touch is associated with a higher risk for dementia and cognitive decline among older adults, new research suggests. The study, which included almost 1,800 participants, adds to emerging evidence that even mild levels of multisensory impairment are associated with accelerated cognitive aging, the researchers noted.

Clinicians should be aware of this link between sensory impairment and dementia risk, said lead author Willa Brenowitz, PhD, assistant professor, department of psychiatry and behavioral sciences, University of California, San Francisco. “Many of these impairments are treatable, or at least physicians can monitor them; and this can improve quality of life, even if it doesn’t improve dementia risk.”

The findings were published online July 12 in Alzheimer’s and Dementia.
 

Additive effects

Previous research has focused on the link between dementia and individual senses, but this new work is unique in that it focuses on the additive effects of multiple impairments in sensory function, said Dr. Brenowitz. The study included 1,794 dementia-free participants in their 70s from the Health, Aging and Body Composition study, a prospective cohort study of healthy Black and White men and women.

Researchers tested participants’ hearing using a pure tone average without hearing aids and vision using contrast sensitivity with glasses permitted. They also measured vibrations in the big toe to assess touch and had participants identify distinctive odors such as paint thinner, roses, lemons, and onions to assess smell.

A score of 0-3 was assigned based on sample quartiles for each of the four sensory functions. Individuals with the best quartile were assigned a score of 0 and those with the worst were assigned a score of 3.

The investigators added scores across all senses to create a summary score of multisensory function (0-12) and classified the participants into tertiles of good, medium, and poor. Individuals with a score of 0 would have good function in all senses, whereas those with 12 would have poor function in all senses. Those with medium scores could have a mix of impairments.

Participants with good multisensory function were more likely to be healthier than those with poor function. They were also significantly more likely to have completed high school (85.0% vs. 72.1%), were significantly less likely to have diabetes (16.9% vs. 27.9%), and were marginally less likely to have cardiovascular disease, high blood pressure, and history of stroke.

Investigators measured cognition using the Modified Mini-Mental State (3MS) examination, a test of global cognitive function, and the Digit Symbol Substitution Test (DSST), a measure of cognitive processing speed. Cognitive testing was carried out at the beginning of the study and repeated every other year.

Dementia was defined as the use of dementia medication, being hospitalized with dementia as a primary or secondary diagnosis, or having a 3MS score 1.5 standard deviations lower than the race-stratified Health ABC study baseline mean.

Over an average follow-up of 6.3 years, 18% of participants developed dementia.
 

Dose-response increase

Results showed that, with worsening multisensory function score, the risk for dementia increased in a dose-response manner. In models adjusted for demographics and health conditions, participants with a poor multisensory function score were more than twice as likely to develop dementia than those with a good score (hazard ratio, 2.05; 95% confidence interval, 1.50-2.81; P < .001). Those with a middle multisensory function score were 1.45 times more likely to develop dementia (HR, 1.45; 95% CI, 1.09-1.91; P < .001).

Even a 1-point worse multisensory function score was associated with a 14% higher risk for dementia (95% CI, 8%-21%), while a 4-point worse score was associated with 71% higher risk for dementia (95% CI, 38%-211%).

Smell was the sensory function most strongly associated with dementia risk. Participants whose sense of smell declined by 10% had a 19% higher risk for dementia versus a 1%-3% higher risk for declines in vision, hearing, and touch.

It is not clear why smell was a stronger determinant of dementia risk. However, loss of this sense is often considered to be a marker for Alzheimer’s disease “because it is closely linked with brain regions that are affected” in that disease, said Dr. Brenowitz.

However, that does not necessarily mean smell is more important than vision or hearing, she added. “Even if hearing and vision have a smaller contribution to dementia, they have a stronger potential for intervention.” The findings suggest “some additive or cumulative” effects for loss of the different senses. “There’s an association above and beyond those which can be attributed to individual sensory domains,” she said.
 

Frailty link

After including mobility, which is a potential mediator, estimates for the multisensory function score were slightly lower. “Walking speed is pretty strongly associated with dementia risk,” Dr. Brenowitz noted. Physical frailty might help explain the link between sensory impairment and dementia risk. “It’s not clear if that’s because people with dementia are declining or because people with frailty are especially vulnerable to dementia,” she said.

The researchers also assessed the role of social support, another potential mechanism by which sensory decline, especially in hearing and vision, could influence dementia risk. Although the study did not find substantial differences in social support measures, the investigators noted that questions assessing social support were limited in scope.

Interactions between multisensory function score and race, APOE e4 allele status, and sex were not significant.

Worsening multisensory function was also linked to faster annual rates of cognitive decline as measured by both the 3MS and DSST. Each 1-point worse score was associated with faster decline (P < .05), even after adjustment for demographics and health conditions.
 

Possible mechanisms

A number of possible mechanisms may explain the link between poor sensory function and dementia. It could be that neurodegeneration underlying dementia affects the senses, or vision and/or hearing loss leads to social isolation and poor mental health, which in turn could affect dementia risk, the researchers wrote. It also is possible that cardiovascular disease or diabetes affect both dementia risk and sensory impairment.

Dr. Brenowitz noted that, because cognitive tests rely on a certain degree of vision and hearing, impairment of these senses may complicate such tests. Still to be determined is whether correcting sensory impairments, such as wearing corrective lenses or hearing aids, affects dementia risk.

Meanwhile, it might be a good idea to more regularly check sensory function, especially vision and hearing, the researchers suggested. These functions affect various aspects of health and can be assessed rather easily. However, because smell is so strongly associated with dementia risk, Dr. Brenowitz said she would like to see it also become “part of a screening tool.”

A possible study limitation cited was that the researchers checked sensory function only once. “Most likely, some of these would change over time, but at least it captured sensory function at one point,” Dr. Brenowitz said.
 

“Sheds further light”

Commenting on the study, Jo V. Rushworth, PhD, associate professor and national teaching fellow, De Montfort University Leicester (England), said it “sheds further light on the emerging links” between multisensory impairment and cognitive decline leading to dementia. “The authors show that people with even mild loss of function in various senses are more likely to develop cognitive impairment.”

Dr. Rushworth was not involved with the study but has done research in the area.

The current results suggest that measuring patients’ hearing, vision, sense of smell, and touch might “flag at-risk groups” who could be targeted for dementia prevention strategies, Dr. Rushworth noted. Such tests are noninvasive and potentially less distressing than other methods of diagnosing dementia. “Importantly, the relatively low cost and simplicity of sensory tests offer the potential for more frequent testing and the use of these methods in areas of the world where medical facilities and resources are limited.”

This new study raises the question of whether the observed sensory impairments are a cause or an effect of dementia, Dr. Rushworth noted. “As the authors suggest, decreased sensory function can lead to a decrease in social engagement, mobility, and other factors which would usually contribute to counteracting cognitive decline.”

The study raises other questions, too, said Dr. Rushworth. She noted that the participants who experienced more severe sensory impairments were, on average, 2 years older than those with the least impairments. “To what degree were the observed sensory deficits linked to normal aging rather than dementia?”

As well, Dr. Rushworth pointed out that the molecular mechanisms that “kick-start” dementia are believed to occur in midlife – so possibly at an age younger than the study participants. “Do younger people of a ‘predementia’ age range display multisensory impairments?”

Because study participants could wear glasses during vision tests but were not allowed to wear hearing aids for the hearing tests, further standardization of sensory impairment is required, Dr. Rushworth said.

“Future studies will be essential in determining the value of clinical measurement of multisensory impairment as a possible dementia indicator and prevention strategy,” she concluded.

The study was funded by the National Institute on Aging, the National Institute of Nursing Research, and the Alzheimer’s Association. Dr. Brenowitz and Dr. Rushworth have reported no relevant financial relationships.

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

August was National Immunization Awareness Month. ... just in time to address the precipitous drop in immunization delivered during the early months of the pandemic.

FatCamera/Getty Images

In May, the Centers for Disease Control and Prevention reported substantial reductions in vaccine doses ordered through the Vaccines for Children program after the declaration of national emergency because of COVID-19 on March 13. Approximately 2.5 million fewer doses of routine, noninfluenza vaccines were administered between Jan. 6 and April 2020, compared with a similar period last year (MMWR Morb Mortal Wkly Rep. 2020 May 15;69[19]:591-3). Declines in immunization rates were echoed by states and municipalities across the United States. Last month, the health system in which I work reported 40,000 children behind on at least one vaccine.

We all know that, when immunization rates drop, outbreaks of vaccine-preventable diseases follow. In order to avert another public health crisis, we need action as well as awareness to catch up with childhood immunizations, and that is going to take more than a single month.
 

Identify patients who’ve missed vaccinations

Simply being open and ready to vaccinate is not enough. The Centers for Disease Control and Prevention urges providers to identify patients who have missed vaccines, and call them to schedule in-person visits. Proactively let parents know about strategies implemented in your office to ensure a safe environment.

Pediatricians are accustomed to an influx of patients in the summer, as parents make sure their children have all of the vaccines required for school attendance. As noted in a Washington Post article from Aug. 4, 2020, schools have traditionally served as a backstop for immunization rates. But as many school districts opt to take education online this fall, the implications for vaccine requirements are unclear. District of Columbia public schools continue to require immunization for virtual school attendance, but it is not clear how easily this can be enforced. To read about how other school districts have chosen to address – or not address – immunization requirements for school, visit the the Immunization Action Coalition’s Repository of Resources for Maintaining Immunization during the COVID-19 Pandemic. The repository links to international, national, and state-level policies and guidance and advocacy materials, including talking points, webinars, press releases, media articles from around the United States and social media posts, as well as telehealth resources.
 

Get some inspiration to talk about vaccination

Need a little inspiration for talking to parents about vaccines? Check out the CDC’s #HowIRecommend video series. These are short videos, most under a minute in length, that explain the importance of vaccination, how to effectively address questions from parents about vaccine safety, and how clinicians routinely recommend same day vaccination to their patients. These videos are part of the CDC’s National Immunization Awareness Month (NIAM) toolkit for communication with health care professionals. A companion toolkit for communicating with parents and patients contains sample social media messages with graphics, along with educational resources to share with parents.

The “Comprehensive Vaccine Education Program – From Training to Practice,” a free online program offered by the Pediatric Infectious Diseases Society, takes a deeper dive into strategies to combat vaccine misinformation and address vaccine hesitancy. Available modules cover vaccine fundamentals, vaccine safety, clinical manifestations of vaccine-preventable diseases, and communication skills that lead to more effective conversations with patients and parents. The curriculum also includes the newest edition of The Vaccine Handbook app, a comprehensive source of practical information for vaccine providers.
 

Educate young children about vaccines

Don’t leave young children out of the conversation. Vax-Force is a children’s book that explores how vaccination works inside the human body. Dr. Vaxson the pediatrician explains how trusted doctors and scientists made Vicky the Vaccine. Her mission is to tell Willy the White Blood Cell and his Antibuddies how to find and fight bad-guy germs like measles, tetanus, and polio. The book was written by Kelsey Rowe, MD, while she was a medical student at Saint Louis University School of Medicine. Dr. Rowe, now a pediatric resident, notes, “In a world where anti-vaccination rhetoric threatens the health of our global community, this book’s mission is to teach children and adults alike that getting vaccinations is a safe, effective, and even exciting thing to do.” The book is available for purchase at https://www.vax-force.com/, and a small part of every sale is donated to Unicef USA.
 

Consider vaccination advocacy in your communities

Vaccinate Your Family, a national, nonprofit organization dedicated to protecting people of all ages from vaccine-preventable diseases, suggests that health care providers need to take an active role in raising immunization rates, not just in their own practices, but in their communities. One way to do this is to submit an opinion piece or letter to the editor to a local newspaper describing why it’s important for parents to make sure their child’s immunizations are current. Those who have never written an opinion-editorial should look at the guidance developed by Voices for Vaccines.
 

How are we doing?

Early data suggest a rebound in immunization rates in May and June, but that is unlikely to close the gap created by disruptions in health care delivery earlier in the year. Collectively, we need to set ambitious goals. Are we just trying to reach prepandemic immunization levels? In Kentucky, where I practice, only 71% of kids aged 19-45 months had received all doses of seven routinely recommended vaccines (≥4 DTaP doses, ≥3 polio doses, ≥1 MMR dose, Hib full series, ≥3 HepB doses, ≥1 varicella dose, and ≥4 PCV doses) based on 2017 National Immunization Survey data. The Healthy People 2020 target goal is 80%. Only 55% of Kentucky girls aged 13-17 years received at least one dose of HPV vaccine, and rates in boys were even lower. Flu vaccine coverage in children 6 months to 17 years also was 55%. The status quo sets the bar too low. To see how your state is doing, check out the interactive map developed by the American Academy of Pediatrics.

Are we attempting to avoid disaster or can we seize the opportunity to protect more children than ever from vaccine-preventable diseases? The latter would really be something to celebrate.
 

Dr. Bryant is a pediatrician specializing in infectious diseases at the University of Louisville (Ky.) and Norton Children’s Hospital, also in Louisville. She said she had no relevant financial disclosures. Email her at [email protected].

August was National Immunization Awareness Month. ... just in time to address the precipitous drop in immunization delivered during the early months of the pandemic.

FatCamera/Getty Images

In May, the Centers for Disease Control and Prevention reported substantial reductions in vaccine doses ordered through the Vaccines for Children program after the declaration of national emergency because of COVID-19 on March 13. Approximately 2.5 million fewer doses of routine, noninfluenza vaccines were administered between Jan. 6 and April 2020, compared with a similar period last year (MMWR Morb Mortal Wkly Rep. 2020 May 15;69[19]:591-3). Declines in immunization rates were echoed by states and municipalities across the United States. Last month, the health system in which I work reported 40,000 children behind on at least one vaccine.

We all know that, when immunization rates drop, outbreaks of vaccine-preventable diseases follow. In order to avert another public health crisis, we need action as well as awareness to catch up with childhood immunizations, and that is going to take more than a single month.
 

Identify patients who’ve missed vaccinations

Simply being open and ready to vaccinate is not enough. The Centers for Disease Control and Prevention urges providers to identify patients who have missed vaccines, and call them to schedule in-person visits. Proactively let parents know about strategies implemented in your office to ensure a safe environment.

Pediatricians are accustomed to an influx of patients in the summer, as parents make sure their children have all of the vaccines required for school attendance. As noted in a Washington Post article from Aug. 4, 2020, schools have traditionally served as a backstop for immunization rates. But as many school districts opt to take education online this fall, the implications for vaccine requirements are unclear. District of Columbia public schools continue to require immunization for virtual school attendance, but it is not clear how easily this can be enforced. To read about how other school districts have chosen to address – or not address – immunization requirements for school, visit the the Immunization Action Coalition’s Repository of Resources for Maintaining Immunization during the COVID-19 Pandemic. The repository links to international, national, and state-level policies and guidance and advocacy materials, including talking points, webinars, press releases, media articles from around the United States and social media posts, as well as telehealth resources.
 

Get some inspiration to talk about vaccination

Need a little inspiration for talking to parents about vaccines? Check out the CDC’s #HowIRecommend video series. These are short videos, most under a minute in length, that explain the importance of vaccination, how to effectively address questions from parents about vaccine safety, and how clinicians routinely recommend same day vaccination to their patients. These videos are part of the CDC’s National Immunization Awareness Month (NIAM) toolkit for communication with health care professionals. A companion toolkit for communicating with parents and patients contains sample social media messages with graphics, along with educational resources to share with parents.

The “Comprehensive Vaccine Education Program – From Training to Practice,” a free online program offered by the Pediatric Infectious Diseases Society, takes a deeper dive into strategies to combat vaccine misinformation and address vaccine hesitancy. Available modules cover vaccine fundamentals, vaccine safety, clinical manifestations of vaccine-preventable diseases, and communication skills that lead to more effective conversations with patients and parents. The curriculum also includes the newest edition of The Vaccine Handbook app, a comprehensive source of practical information for vaccine providers.
 

Educate young children about vaccines

Don’t leave young children out of the conversation. Vax-Force is a children’s book that explores how vaccination works inside the human body. Dr. Vaxson the pediatrician explains how trusted doctors and scientists made Vicky the Vaccine. Her mission is to tell Willy the White Blood Cell and his Antibuddies how to find and fight bad-guy germs like measles, tetanus, and polio. The book was written by Kelsey Rowe, MD, while she was a medical student at Saint Louis University School of Medicine. Dr. Rowe, now a pediatric resident, notes, “In a world where anti-vaccination rhetoric threatens the health of our global community, this book’s mission is to teach children and adults alike that getting vaccinations is a safe, effective, and even exciting thing to do.” The book is available for purchase at https://www.vax-force.com/, and a small part of every sale is donated to Unicef USA.
 

Consider vaccination advocacy in your communities

Vaccinate Your Family, a national, nonprofit organization dedicated to protecting people of all ages from vaccine-preventable diseases, suggests that health care providers need to take an active role in raising immunization rates, not just in their own practices, but in their communities. One way to do this is to submit an opinion piece or letter to the editor to a local newspaper describing why it’s important for parents to make sure their child’s immunizations are current. Those who have never written an opinion-editorial should look at the guidance developed by Voices for Vaccines.
 

How are we doing?

Early data suggest a rebound in immunization rates in May and June, but that is unlikely to close the gap created by disruptions in health care delivery earlier in the year. Collectively, we need to set ambitious goals. Are we just trying to reach prepandemic immunization levels? In Kentucky, where I practice, only 71% of kids aged 19-45 months had received all doses of seven routinely recommended vaccines (≥4 DTaP doses, ≥3 polio doses, ≥1 MMR dose, Hib full series, ≥3 HepB doses, ≥1 varicella dose, and ≥4 PCV doses) based on 2017 National Immunization Survey data. The Healthy People 2020 target goal is 80%. Only 55% of Kentucky girls aged 13-17 years received at least one dose of HPV vaccine, and rates in boys were even lower. Flu vaccine coverage in children 6 months to 17 years also was 55%. The status quo sets the bar too low. To see how your state is doing, check out the interactive map developed by the American Academy of Pediatrics.

Are we attempting to avoid disaster or can we seize the opportunity to protect more children than ever from vaccine-preventable diseases? The latter would really be something to celebrate.
 

Dr. Bryant is a pediatrician specializing in infectious diseases at the University of Louisville (Ky.) and Norton Children’s Hospital, also in Louisville. She said she had no relevant financial disclosures. Email her at [email protected].

August was National Immunization Awareness Month. ... just in time to address the precipitous drop in immunization delivered during the early months of the pandemic.

FatCamera/Getty Images

In May, the Centers for Disease Control and Prevention reported substantial reductions in vaccine doses ordered through the Vaccines for Children program after the declaration of national emergency because of COVID-19 on March 13. Approximately 2.5 million fewer doses of routine, noninfluenza vaccines were administered between Jan. 6 and April 2020, compared with a similar period last year (MMWR Morb Mortal Wkly Rep. 2020 May 15;69[19]:591-3). Declines in immunization rates were echoed by states and municipalities across the United States. Last month, the health system in which I work reported 40,000 children behind on at least one vaccine.

We all know that, when immunization rates drop, outbreaks of vaccine-preventable diseases follow. In order to avert another public health crisis, we need action as well as awareness to catch up with childhood immunizations, and that is going to take more than a single month.
 

Identify patients who’ve missed vaccinations

Simply being open and ready to vaccinate is not enough. The Centers for Disease Control and Prevention urges providers to identify patients who have missed vaccines, and call them to schedule in-person visits. Proactively let parents know about strategies implemented in your office to ensure a safe environment.

Pediatricians are accustomed to an influx of patients in the summer, as parents make sure their children have all of the vaccines required for school attendance. As noted in a Washington Post article from Aug. 4, 2020, schools have traditionally served as a backstop for immunization rates. But as many school districts opt to take education online this fall, the implications for vaccine requirements are unclear. District of Columbia public schools continue to require immunization for virtual school attendance, but it is not clear how easily this can be enforced. To read about how other school districts have chosen to address – or not address – immunization requirements for school, visit the the Immunization Action Coalition’s Repository of Resources for Maintaining Immunization during the COVID-19 Pandemic. The repository links to international, national, and state-level policies and guidance and advocacy materials, including talking points, webinars, press releases, media articles from around the United States and social media posts, as well as telehealth resources.
 

Get some inspiration to talk about vaccination

Need a little inspiration for talking to parents about vaccines? Check out the CDC’s #HowIRecommend video series. These are short videos, most under a minute in length, that explain the importance of vaccination, how to effectively address questions from parents about vaccine safety, and how clinicians routinely recommend same day vaccination to their patients. These videos are part of the CDC’s National Immunization Awareness Month (NIAM) toolkit for communication with health care professionals. A companion toolkit for communicating with parents and patients contains sample social media messages with graphics, along with educational resources to share with parents.

The “Comprehensive Vaccine Education Program – From Training to Practice,” a free online program offered by the Pediatric Infectious Diseases Society, takes a deeper dive into strategies to combat vaccine misinformation and address vaccine hesitancy. Available modules cover vaccine fundamentals, vaccine safety, clinical manifestations of vaccine-preventable diseases, and communication skills that lead to more effective conversations with patients and parents. The curriculum also includes the newest edition of The Vaccine Handbook app, a comprehensive source of practical information for vaccine providers.
 

Educate young children about vaccines

Don’t leave young children out of the conversation. Vax-Force is a children’s book that explores how vaccination works inside the human body. Dr. Vaxson the pediatrician explains how trusted doctors and scientists made Vicky the Vaccine. Her mission is to tell Willy the White Blood Cell and his Antibuddies how to find and fight bad-guy germs like measles, tetanus, and polio. The book was written by Kelsey Rowe, MD, while she was a medical student at Saint Louis University School of Medicine. Dr. Rowe, now a pediatric resident, notes, “In a world where anti-vaccination rhetoric threatens the health of our global community, this book’s mission is to teach children and adults alike that getting vaccinations is a safe, effective, and even exciting thing to do.” The book is available for purchase at https://www.vax-force.com/, and a small part of every sale is donated to Unicef USA.
 

Consider vaccination advocacy in your communities

Vaccinate Your Family, a national, nonprofit organization dedicated to protecting people of all ages from vaccine-preventable diseases, suggests that health care providers need to take an active role in raising immunization rates, not just in their own practices, but in their communities. One way to do this is to submit an opinion piece or letter to the editor to a local newspaper describing why it’s important for parents to make sure their child’s immunizations are current. Those who have never written an opinion-editorial should look at the guidance developed by Voices for Vaccines.
 

How are we doing?

Early data suggest a rebound in immunization rates in May and June, but that is unlikely to close the gap created by disruptions in health care delivery earlier in the year. Collectively, we need to set ambitious goals. Are we just trying to reach prepandemic immunization levels? In Kentucky, where I practice, only 71% of kids aged 19-45 months had received all doses of seven routinely recommended vaccines (≥4 DTaP doses, ≥3 polio doses, ≥1 MMR dose, Hib full series, ≥3 HepB doses, ≥1 varicella dose, and ≥4 PCV doses) based on 2017 National Immunization Survey data. The Healthy People 2020 target goal is 80%. Only 55% of Kentucky girls aged 13-17 years received at least one dose of HPV vaccine, and rates in boys were even lower. Flu vaccine coverage in children 6 months to 17 years also was 55%. The status quo sets the bar too low. To see how your state is doing, check out the interactive map developed by the American Academy of Pediatrics.

Are we attempting to avoid disaster or can we seize the opportunity to protect more children than ever from vaccine-preventable diseases? The latter would really be something to celebrate.
 

Dr. Bryant is a pediatrician specializing in infectious diseases at the University of Louisville (Ky.) and Norton Children’s Hospital, also in Louisville. She said she had no relevant financial disclosures. Email her at [email protected].

Many COVID-19 treatments, in addition to the infection, may be associated with adverse skin reactions and should be considered in a differential diagnosis, according to a review published in the Journal of the American Academy of Dermatology.

SARS-CoV-2 infection has been associated with a range of skin conditions, wrote Antonio Martinez-Lopez, MD, of Virgen de las Nieves University Hospital, Granada, Spain, and colleagues, who provided an overview of the cutaneous side effects associated with drugs used to treat COVID-19 infection.

“Cutaneous manifestations have recently been described in patients with the new coronavirus infection, similar to cutaneous involvement occurring in common viral infections,” they said. Infected individuals have experienced maculopapular eruption, pseudo-chilblain lesions, urticaria, monomorphic disseminated vesicular lesions, acral vesicular-pustulous lesions, and livedo or necrosis, they noted.

Diagnosing skin manifestations in patients with COVID-19 remains a challenge, because it is unclear whether the skin lesions are related to the virus, the authors said. “Skin diseases not related to coronavirus, other seasonal viral infections, and drug reactions should be considered in the differential diagnosis, especially in those patients suffering from nonspecific manifestations such as urticaria or maculopapular eruptions,” they wrote.

However, “urticarial lesions and maculopapular eruptions in SARS-CoV-2 infections usually appear at the same time as the systemic symptoms, while drug adverse reactions are likely to arise hours to days after the start of the treatment,” they said.

The reviewers noted several cutaneous side effects associated with several of the often-prescribed drugs for COVID-19 infection. The antimalarials hydroxychloroquine and chloroquine had been authorized for COVID-19 treatment by the Food and Drug Administration, but this emergency authorization was rescinded in June. They noted that up to 11.5% of patients on these drugs may experience cutaneous adverse effects, including some that “can be mistaken for skin manifestations of SARS-CoV-2, especially those with maculopapular rash or exanthematous reactions.” Another side effect is exacerbation of psoriasis, which has been described in patients with COVID-19, the authors said.

The oral antiretroviral combination lopinavir/ritonavir, under investigation in clinical trials for COVID-19, has been associated with skin rashes in as many as 5% of adults in HIV studies. Usually appearing after treatment is started, the maculopapular pruritic rash is “usually well tolerated,” they said, although there have been reports of Stevens-Johnson syndrome. Alopecia areata is among the other side effects reported.

Remdesivir also has been authorized for emergency treatment of COVID-19, and the small amount of data available suggest that cutaneous manifestations may be infrequent, the reviewers said. In a recent study of 53 patients treated with remdesivir for 10 days, approximately 8% developed a rash, but the study did not include any information “about rash morphology, distribution, or timeline in relation to remdesivir that may help clinicians differentiate from cutaneous manifestations of COVID-19,” they said.

Other potential treatments for complications of COVID-19 include imatinib, tocilizumab, anakinra, immunoglobulins, corticosteroids, colchicine, and low molecular weight heparins; all have the potential for association with skin reactions, but data on skin manifestations associated with COVID-19 are limited, the authors wrote.

Notably, data on the use of systemic corticosteroids for COVID-19 patients are controversial, although preliminary data showed some reduced mortality in COVID-19 patients who were on respiratory support, they noted. “With regard to differential diagnosis of cutaneous manifestations of COVID-19, the vascular fragility associated with corticosteroid use, especially in elderly patients, may be similar to the thrombotic complications of COVID-19 infection.”

Knowledge about the virology of COVID-19 continues to evolve rapidly, and the number of drugs being studied as treatments continues to expand, the authors pointed out.

“By considering adverse drug reactions in the differential diagnosis, dermatologists can be useful in assisting in the care of these patients,” they wrote. Drugs, rather than the infection, may be the cause of skin reactions in some COVID-19 patients, and “management is often symptomatic, but it is sometimes necessary to modify or discontinue the treatment, and some conditions can even be life-threatening,” they concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose.

SOURCE: Martinez-Lopez A et al. J Am Acad Dermatol. 2020 doi: 10.1016/j.jaad.2020.08.006.

Many COVID-19 treatments, in addition to the infection, may be associated with adverse skin reactions and should be considered in a differential diagnosis, according to a review published in the Journal of the American Academy of Dermatology.

SARS-CoV-2 infection has been associated with a range of skin conditions, wrote Antonio Martinez-Lopez, MD, of Virgen de las Nieves University Hospital, Granada, Spain, and colleagues, who provided an overview of the cutaneous side effects associated with drugs used to treat COVID-19 infection.

“Cutaneous manifestations have recently been described in patients with the new coronavirus infection, similar to cutaneous involvement occurring in common viral infections,” they said. Infected individuals have experienced maculopapular eruption, pseudo-chilblain lesions, urticaria, monomorphic disseminated vesicular lesions, acral vesicular-pustulous lesions, and livedo or necrosis, they noted.

Diagnosing skin manifestations in patients with COVID-19 remains a challenge, because it is unclear whether the skin lesions are related to the virus, the authors said. “Skin diseases not related to coronavirus, other seasonal viral infections, and drug reactions should be considered in the differential diagnosis, especially in those patients suffering from nonspecific manifestations such as urticaria or maculopapular eruptions,” they wrote.

However, “urticarial lesions and maculopapular eruptions in SARS-CoV-2 infections usually appear at the same time as the systemic symptoms, while drug adverse reactions are likely to arise hours to days after the start of the treatment,” they said.

The reviewers noted several cutaneous side effects associated with several of the often-prescribed drugs for COVID-19 infection. The antimalarials hydroxychloroquine and chloroquine had been authorized for COVID-19 treatment by the Food and Drug Administration, but this emergency authorization was rescinded in June. They noted that up to 11.5% of patients on these drugs may experience cutaneous adverse effects, including some that “can be mistaken for skin manifestations of SARS-CoV-2, especially those with maculopapular rash or exanthematous reactions.” Another side effect is exacerbation of psoriasis, which has been described in patients with COVID-19, the authors said.

The oral antiretroviral combination lopinavir/ritonavir, under investigation in clinical trials for COVID-19, has been associated with skin rashes in as many as 5% of adults in HIV studies. Usually appearing after treatment is started, the maculopapular pruritic rash is “usually well tolerated,” they said, although there have been reports of Stevens-Johnson syndrome. Alopecia areata is among the other side effects reported.

Remdesivir also has been authorized for emergency treatment of COVID-19, and the small amount of data available suggest that cutaneous manifestations may be infrequent, the reviewers said. In a recent study of 53 patients treated with remdesivir for 10 days, approximately 8% developed a rash, but the study did not include any information “about rash morphology, distribution, or timeline in relation to remdesivir that may help clinicians differentiate from cutaneous manifestations of COVID-19,” they said.

Other potential treatments for complications of COVID-19 include imatinib, tocilizumab, anakinra, immunoglobulins, corticosteroids, colchicine, and low molecular weight heparins; all have the potential for association with skin reactions, but data on skin manifestations associated with COVID-19 are limited, the authors wrote.

Notably, data on the use of systemic corticosteroids for COVID-19 patients are controversial, although preliminary data showed some reduced mortality in COVID-19 patients who were on respiratory support, they noted. “With regard to differential diagnosis of cutaneous manifestations of COVID-19, the vascular fragility associated with corticosteroid use, especially in elderly patients, may be similar to the thrombotic complications of COVID-19 infection.”

Knowledge about the virology of COVID-19 continues to evolve rapidly, and the number of drugs being studied as treatments continues to expand, the authors pointed out.

“By considering adverse drug reactions in the differential diagnosis, dermatologists can be useful in assisting in the care of these patients,” they wrote. Drugs, rather than the infection, may be the cause of skin reactions in some COVID-19 patients, and “management is often symptomatic, but it is sometimes necessary to modify or discontinue the treatment, and some conditions can even be life-threatening,” they concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose.

SOURCE: Martinez-Lopez A et al. J Am Acad Dermatol. 2020 doi: 10.1016/j.jaad.2020.08.006.

Many COVID-19 treatments, in addition to the infection, may be associated with adverse skin reactions and should be considered in a differential diagnosis, according to a review published in the Journal of the American Academy of Dermatology.

SARS-CoV-2 infection has been associated with a range of skin conditions, wrote Antonio Martinez-Lopez, MD, of Virgen de las Nieves University Hospital, Granada, Spain, and colleagues, who provided an overview of the cutaneous side effects associated with drugs used to treat COVID-19 infection.

“Cutaneous manifestations have recently been described in patients with the new coronavirus infection, similar to cutaneous involvement occurring in common viral infections,” they said. Infected individuals have experienced maculopapular eruption, pseudo-chilblain lesions, urticaria, monomorphic disseminated vesicular lesions, acral vesicular-pustulous lesions, and livedo or necrosis, they noted.

Diagnosing skin manifestations in patients with COVID-19 remains a challenge, because it is unclear whether the skin lesions are related to the virus, the authors said. “Skin diseases not related to coronavirus, other seasonal viral infections, and drug reactions should be considered in the differential diagnosis, especially in those patients suffering from nonspecific manifestations such as urticaria or maculopapular eruptions,” they wrote.

However, “urticarial lesions and maculopapular eruptions in SARS-CoV-2 infections usually appear at the same time as the systemic symptoms, while drug adverse reactions are likely to arise hours to days after the start of the treatment,” they said.

The reviewers noted several cutaneous side effects associated with several of the often-prescribed drugs for COVID-19 infection. The antimalarials hydroxychloroquine and chloroquine had been authorized for COVID-19 treatment by the Food and Drug Administration, but this emergency authorization was rescinded in June. They noted that up to 11.5% of patients on these drugs may experience cutaneous adverse effects, including some that “can be mistaken for skin manifestations of SARS-CoV-2, especially those with maculopapular rash or exanthematous reactions.” Another side effect is exacerbation of psoriasis, which has been described in patients with COVID-19, the authors said.

The oral antiretroviral combination lopinavir/ritonavir, under investigation in clinical trials for COVID-19, has been associated with skin rashes in as many as 5% of adults in HIV studies. Usually appearing after treatment is started, the maculopapular pruritic rash is “usually well tolerated,” they said, although there have been reports of Stevens-Johnson syndrome. Alopecia areata is among the other side effects reported.

Remdesivir also has been authorized for emergency treatment of COVID-19, and the small amount of data available suggest that cutaneous manifestations may be infrequent, the reviewers said. In a recent study of 53 patients treated with remdesivir for 10 days, approximately 8% developed a rash, but the study did not include any information “about rash morphology, distribution, or timeline in relation to remdesivir that may help clinicians differentiate from cutaneous manifestations of COVID-19,” they said.

Other potential treatments for complications of COVID-19 include imatinib, tocilizumab, anakinra, immunoglobulins, corticosteroids, colchicine, and low molecular weight heparins; all have the potential for association with skin reactions, but data on skin manifestations associated with COVID-19 are limited, the authors wrote.

Notably, data on the use of systemic corticosteroids for COVID-19 patients are controversial, although preliminary data showed some reduced mortality in COVID-19 patients who were on respiratory support, they noted. “With regard to differential diagnosis of cutaneous manifestations of COVID-19, the vascular fragility associated with corticosteroid use, especially in elderly patients, may be similar to the thrombotic complications of COVID-19 infection.”

Knowledge about the virology of COVID-19 continues to evolve rapidly, and the number of drugs being studied as treatments continues to expand, the authors pointed out.

“By considering adverse drug reactions in the differential diagnosis, dermatologists can be useful in assisting in the care of these patients,” they wrote. Drugs, rather than the infection, may be the cause of skin reactions in some COVID-19 patients, and “management is often symptomatic, but it is sometimes necessary to modify or discontinue the treatment, and some conditions can even be life-threatening,” they concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose.

SOURCE: Martinez-Lopez A et al. J Am Acad Dermatol. 2020 doi: 10.1016/j.jaad.2020.08.006.

Compared with their counterparts who get more relief, patients with difficult-to-treat migraine are more likely to delay acute treatment and take over-the-counter and opioid painkillers. They are also more likely to have depression and impairment. Overall, insufficient responders—patients less likely to get relief shortly after acute treatment—are “more medically and psychosocially complex,” wrote the authors of the study, which appeared in the July/August issue of Headache.

Common characteristics of insufficient responders

The researchers, led by Louise Lombard, M Nutr, of Eli Lilly and Company, analyzed data from a 2014 cross-sectional survey. They tracked 583 patients with migraine, including 200 (34%) who were considered insufficient responders because they failed to achieve freedom from pain within 2 hours of acute treatment in at least four of five attacks.

The insufficient and sufficient responder groups were similar in age (mean = 40 for both) and gender (80% and 75% female, respectively, P = .170) and race (72% and 77% white, P = .279).

However, insufficient responders were clearly more affected by headaches, multiple treatments, and other burdens. Compared with those who had better responses to treatment, they were more likely to have four or more migraine headache days per month (46% vs. 31%), rebound or medication-overuse headaches (16% vs. 7%) and chronic migraine (12% vs. 5%, all P < .05).

They were also more likely have comorbid depression (38% vs. 22%) and psychological conditions other than depression and anxiety (8% vs. 4%, all P < .05).

As for treatment, insufficient response was higher in patients who waited until the appearance of pain to take medication (odds ratio = 1.83, 95% confidence interval [CI] 1.15–2.92, P = .011, after adjustment for covariates). And insufficient responders were more likely to have been prescribed at least three unique preventive regimens (12% vs. 6%), to take over-the-counter medications (50% vs. 38%) and to take opioid painkillers (16% vs. 8%, all P < .05).

The authors, who caution that the study does not prove cause and effect, wrote that insufficient responders “may benefit from education on how and when to use current treatments.”
 

Managing insufficient responders

Neurology Reviews editor-in-chief Alan M. Rapoport, MD, said the study “confirms a lot of what we knew.” Dr, Rapoport, who was not involved in the study, is clinical professor of neurology at the University of California, Los Angeles.

“As expected, the insufficient responders used more opioids and over-the-counter medications, which is not the ideal way to treat migraine,” he said. “That probably caused them to have medication-overuse headache, which might have caused them to respond poorly to even the best treatment regimen. They also had more severe symptoms, more comorbidities, and a poorer quality of life. They also had more impairment and greater impact on work, with more of them unemployed.”

The insufficient responders also “took medication at the time or after the pain began, rather than before it when they thought the attack was beginning due to premonitory symptoms,” he said.

Dr. Rapoport also noted a surprising and unusual finding: Patients who did not report sensitivity to light as their most bothersome symptom were more likely to be insufficient responders (OR = 2.3, 95% CI [1.21–4.37], P = .011). “In all recent migraine studies,” he said, “the majority of patients selected photophobia as their most bothersome symptom.”

In the big picture, he said, the study suggests that “a third triptan does not seem to work better than the first two, patients with medication-overuse headache and chronic migraine and those not on preventive medication do not respond that well to acute care treatment, and the same is true when depression is present.”

No study funding was reported. Four study authors reported ties with Eli Lilly, and two reported employment by Adelphi Real World, which provided the survey results..

SOURCE: Lombard L et al. Headache. 2020;60(7):1325-39. doi: 10.1111/head.13835.

Compared with their counterparts who get more relief, patients with difficult-to-treat migraine are more likely to delay acute treatment and take over-the-counter and opioid painkillers. They are also more likely to have depression and impairment. Overall, insufficient responders—patients less likely to get relief shortly after acute treatment—are “more medically and psychosocially complex,” wrote the authors of the study, which appeared in the July/August issue of Headache.

Common characteristics of insufficient responders

The researchers, led by Louise Lombard, M Nutr, of Eli Lilly and Company, analyzed data from a 2014 cross-sectional survey. They tracked 583 patients with migraine, including 200 (34%) who were considered insufficient responders because they failed to achieve freedom from pain within 2 hours of acute treatment in at least four of five attacks.

The insufficient and sufficient responder groups were similar in age (mean = 40 for both) and gender (80% and 75% female, respectively, P = .170) and race (72% and 77% white, P = .279).

However, insufficient responders were clearly more affected by headaches, multiple treatments, and other burdens. Compared with those who had better responses to treatment, they were more likely to have four or more migraine headache days per month (46% vs. 31%), rebound or medication-overuse headaches (16% vs. 7%) and chronic migraine (12% vs. 5%, all P < .05).

They were also more likely have comorbid depression (38% vs. 22%) and psychological conditions other than depression and anxiety (8% vs. 4%, all P < .05).

As for treatment, insufficient response was higher in patients who waited until the appearance of pain to take medication (odds ratio = 1.83, 95% confidence interval [CI] 1.15–2.92, P = .011, after adjustment for covariates). And insufficient responders were more likely to have been prescribed at least three unique preventive regimens (12% vs. 6%), to take over-the-counter medications (50% vs. 38%) and to take opioid painkillers (16% vs. 8%, all P < .05).

The authors, who caution that the study does not prove cause and effect, wrote that insufficient responders “may benefit from education on how and when to use current treatments.”
 

Managing insufficient responders

Neurology Reviews editor-in-chief Alan M. Rapoport, MD, said the study “confirms a lot of what we knew.” Dr, Rapoport, who was not involved in the study, is clinical professor of neurology at the University of California, Los Angeles.

“As expected, the insufficient responders used more opioids and over-the-counter medications, which is not the ideal way to treat migraine,” he said. “That probably caused them to have medication-overuse headache, which might have caused them to respond poorly to even the best treatment regimen. They also had more severe symptoms, more comorbidities, and a poorer quality of life. They also had more impairment and greater impact on work, with more of them unemployed.”

The insufficient responders also “took medication at the time or after the pain began, rather than before it when they thought the attack was beginning due to premonitory symptoms,” he said.

Dr. Rapoport also noted a surprising and unusual finding: Patients who did not report sensitivity to light as their most bothersome symptom were more likely to be insufficient responders (OR = 2.3, 95% CI [1.21–4.37], P = .011). “In all recent migraine studies,” he said, “the majority of patients selected photophobia as their most bothersome symptom.”

In the big picture, he said, the study suggests that “a third triptan does not seem to work better than the first two, patients with medication-overuse headache and chronic migraine and those not on preventive medication do not respond that well to acute care treatment, and the same is true when depression is present.”

No study funding was reported. Four study authors reported ties with Eli Lilly, and two reported employment by Adelphi Real World, which provided the survey results..

SOURCE: Lombard L et al. Headache. 2020;60(7):1325-39. doi: 10.1111/head.13835.

Compared with their counterparts who get more relief, patients with difficult-to-treat migraine are more likely to delay acute treatment and take over-the-counter and opioid painkillers. They are also more likely to have depression and impairment. Overall, insufficient responders—patients less likely to get relief shortly after acute treatment—are “more medically and psychosocially complex,” wrote the authors of the study, which appeared in the July/August issue of Headache.

Common characteristics of insufficient responders

The researchers, led by Louise Lombard, M Nutr, of Eli Lilly and Company, analyzed data from a 2014 cross-sectional survey. They tracked 583 patients with migraine, including 200 (34%) who were considered insufficient responders because they failed to achieve freedom from pain within 2 hours of acute treatment in at least four of five attacks.

The insufficient and sufficient responder groups were similar in age (mean = 40 for both) and gender (80% and 75% female, respectively, P = .170) and race (72% and 77% white, P = .279).

However, insufficient responders were clearly more affected by headaches, multiple treatments, and other burdens. Compared with those who had better responses to treatment, they were more likely to have four or more migraine headache days per month (46% vs. 31%), rebound or medication-overuse headaches (16% vs. 7%) and chronic migraine (12% vs. 5%, all P < .05).

They were also more likely have comorbid depression (38% vs. 22%) and psychological conditions other than depression and anxiety (8% vs. 4%, all P < .05).

As for treatment, insufficient response was higher in patients who waited until the appearance of pain to take medication (odds ratio = 1.83, 95% confidence interval [CI] 1.15–2.92, P = .011, after adjustment for covariates). And insufficient responders were more likely to have been prescribed at least three unique preventive regimens (12% vs. 6%), to take over-the-counter medications (50% vs. 38%) and to take opioid painkillers (16% vs. 8%, all P < .05).

The authors, who caution that the study does not prove cause and effect, wrote that insufficient responders “may benefit from education on how and when to use current treatments.”
 

Managing insufficient responders

Neurology Reviews editor-in-chief Alan M. Rapoport, MD, said the study “confirms a lot of what we knew.” Dr, Rapoport, who was not involved in the study, is clinical professor of neurology at the University of California, Los Angeles.

“As expected, the insufficient responders used more opioids and over-the-counter medications, which is not the ideal way to treat migraine,” he said. “That probably caused them to have medication-overuse headache, which might have caused them to respond poorly to even the best treatment regimen. They also had more severe symptoms, more comorbidities, and a poorer quality of life. They also had more impairment and greater impact on work, with more of them unemployed.”

The insufficient responders also “took medication at the time or after the pain began, rather than before it when they thought the attack was beginning due to premonitory symptoms,” he said.

Dr. Rapoport also noted a surprising and unusual finding: Patients who did not report sensitivity to light as their most bothersome symptom were more likely to be insufficient responders (OR = 2.3, 95% CI [1.21–4.37], P = .011). “In all recent migraine studies,” he said, “the majority of patients selected photophobia as their most bothersome symptom.”

In the big picture, he said, the study suggests that “a third triptan does not seem to work better than the first two, patients with medication-overuse headache and chronic migraine and those not on preventive medication do not respond that well to acute care treatment, and the same is true when depression is present.”

No study funding was reported. Four study authors reported ties with Eli Lilly, and two reported employment by Adelphi Real World, which provided the survey results..

SOURCE: Lombard L et al. Headache. 2020;60(7):1325-39. doi: 10.1111/head.13835.

A substantial decrease in hospital admissions for acute MI was accompanied by a rise in mortality, particularly for ST-segment elevation MI (STEMI), following the onset of the COVID-19 pandemic, according to a cross-sectional retrospective study.

Although it can’t be confirmed from these results that the observed increase in in-hospital acute MI (AMI) mortality are related to delays in seeking treatment, this is a reasonable working hypothesis until more is known, commented Harlan Krumholz, MD, who was not involved in the study.

The analysis, derived from data collected at 49 centers in a hospital system spread across six states, supports previous reports that patients with AMI were avoiding hospitalization, according to the investigators, who were led by Tyler J. Gluckman, MD, medical director of the Center for Cardiovascular Analytics, Providence Heart Institute, Portland, Ore.

When compared with a nearly 14-month period that preceded the COVID-19 pandemic, the rate of AMI-associated hospitalization fell by 19 cases per week (95% confidence interval, –29.0 to –9.0 cases) in the early COVID-19 period, which was defined by the investigators as spanning from Feb. 23, 2020 to March 28, 2020.

The case rate per week then increased by 10.5 (95% CI, 4.6-16.5 cases) in a subsequent 8-week period spanning between March 29, 2020, and May 16, 2020. Although a substantial increase from the early COVID-19 period, the case rate remained below the baseline established before COVID-19.

The analysis looked at 15,244 AMI hospitalizations among 14,724 patients treated in the Providence St. Joseph Hospital System, which has facilities in Alaska, California, Montana, Oregon, Texas, and Washington. The 1,915 AMI cases captured from Feb. 23, 2020, represented 13% of the total.
 

Differences in mortality, patients, treatment

In the early period, the ratio of observed-to-expected (O/E) mortality relative to the pre–COVID-19 baseline increased by 27% (odds ratio, 1.27; 95% CI, 1.07-1.48). When STEMI was analyzed separately, the O/E mortality was nearly double that of the baseline period (OR, 1.96; 95% CI, 1.22-2.70). In the latter post–COVID-19 period of observation, the overall increase in AMI-associated mortality on the basis of an O/E ratio was no longer significant relative to the baseline period (OR, 1.23; 95% CI, 0.98-1.47). However, the relative increase in STEMI-associated mortality on an O/E basis was even greater (OR, 2.40; 95% CI, 1.65-3.16) in the second COVID-19 period analyzed. Even after risk adjustment, the OR for STEMI mortality remained significantly elevated relative to baseline (1.52; 95% CI, 1.02-2.26).

The differences in AMI patients treated before the onset of the COVID-19 pandemic and those treated afterwards might be relevant, according to the investigators. Specifically, patients hospitalized after Feb. 23, 2020 were 1-3 years younger (P < .001) depending on type of AMI, and more likely to be Asian (P = .01).

The length of stay was 6 hours shorter in the early COVID-19 period and 7 hours shorter in the latter period relative to baseline, but an analysis of treatment approaches to non-STEMI and STEMI during the COVID-19 pandemic were not found to be significantly different from baseline.

Prior to the COVID-19 pandemic, 79% of STEMI patients and 77% of non-STEMI patients were discharged home, which was significantly lower than in the early COVID-19 period, when 83% (P = .02) of STEMI and 81% (P = .006) of non-STEMI patients were discharged home. In the latter period, discharge to home care was also significantly higher than in the baseline period.
 

More than fear of COVID-19?

One theory to account for the reduction in AMI hospitalizations and the increase in AMI-related mortality is the possibility that patients were slow to seek care at acute care hospitals because of concern about COVID-19 infection, according to Dr. Gluckman and coinvestigators.

“Given the time-sensitive nature of STEMI, any delay by patients, emergency medical services, the emergency department, or cardiac catheterization laboratory may have played a role,” they suggested.

In an interview, Dr. Gluckman said that further effort to identify the reasons for the increased AMI-related mortality is planned. Pulling data from the electronic medical records of the patients included in this retrospective analysis might be a “challenge,” but Dr. Gluckman reported that he and his coinvestigators plan to look at a different set of registry data that might provide information on sources of delay, particularly in the STEMI population.

“This includes looking at a number of time factors, such as symptom onset to first medical contact, first medical contact to device, and door-in-door-out times,” Dr. Gluckman said. The goal is to “better understand if delays [in treatment] occurred during the pandemic and, if so, how they may have contributed to increases in risk adjusted mortality.”

Dr. Krumholz, director of the Yale Center for Outcomes Research and Evaluation, New Haven, Conn., called this study a “useful” confirmation of changes in AMI-related care with the onset of the COVID-19 pandemic. As reported anecdotally, the study “indicates marked decreases in hospitalizations of patients with AMI even in areas that were not experiencing big outbreaks but did have some restrictions to limit spread,” he noted.

More data gathered by other centers might provide information about what it all means.

“There remain so many questions about what happened and what consequences accrued,” Dr. Krumholz observed. “In the meantime, we need to continue to send the message that people with symptoms that suggest a heart attack need to rapidly seek care.”

The investigators reported having no financial conflicts of interest.

SOURCE: Gluckman TJ et al. JAMA Cardiol. 2020 Aug 7. doi: 10.1001/jamacardio.2020.3629.

A substantial decrease in hospital admissions for acute MI was accompanied by a rise in mortality, particularly for ST-segment elevation MI (STEMI), following the onset of the COVID-19 pandemic, according to a cross-sectional retrospective study.

Although it can’t be confirmed from these results that the observed increase in in-hospital acute MI (AMI) mortality are related to delays in seeking treatment, this is a reasonable working hypothesis until more is known, commented Harlan Krumholz, MD, who was not involved in the study.

The analysis, derived from data collected at 49 centers in a hospital system spread across six states, supports previous reports that patients with AMI were avoiding hospitalization, according to the investigators, who were led by Tyler J. Gluckman, MD, medical director of the Center for Cardiovascular Analytics, Providence Heart Institute, Portland, Ore.

When compared with a nearly 14-month period that preceded the COVID-19 pandemic, the rate of AMI-associated hospitalization fell by 19 cases per week (95% confidence interval, –29.0 to –9.0 cases) in the early COVID-19 period, which was defined by the investigators as spanning from Feb. 23, 2020 to March 28, 2020.

The case rate per week then increased by 10.5 (95% CI, 4.6-16.5 cases) in a subsequent 8-week period spanning between March 29, 2020, and May 16, 2020. Although a substantial increase from the early COVID-19 period, the case rate remained below the baseline established before COVID-19.

The analysis looked at 15,244 AMI hospitalizations among 14,724 patients treated in the Providence St. Joseph Hospital System, which has facilities in Alaska, California, Montana, Oregon, Texas, and Washington. The 1,915 AMI cases captured from Feb. 23, 2020, represented 13% of the total.
 

Differences in mortality, patients, treatment

In the early period, the ratio of observed-to-expected (O/E) mortality relative to the pre–COVID-19 baseline increased by 27% (odds ratio, 1.27; 95% CI, 1.07-1.48). When STEMI was analyzed separately, the O/E mortality was nearly double that of the baseline period (OR, 1.96; 95% CI, 1.22-2.70). In the latter post–COVID-19 period of observation, the overall increase in AMI-associated mortality on the basis of an O/E ratio was no longer significant relative to the baseline period (OR, 1.23; 95% CI, 0.98-1.47). However, the relative increase in STEMI-associated mortality on an O/E basis was even greater (OR, 2.40; 95% CI, 1.65-3.16) in the second COVID-19 period analyzed. Even after risk adjustment, the OR for STEMI mortality remained significantly elevated relative to baseline (1.52; 95% CI, 1.02-2.26).

The differences in AMI patients treated before the onset of the COVID-19 pandemic and those treated afterwards might be relevant, according to the investigators. Specifically, patients hospitalized after Feb. 23, 2020 were 1-3 years younger (P < .001) depending on type of AMI, and more likely to be Asian (P = .01).

The length of stay was 6 hours shorter in the early COVID-19 period and 7 hours shorter in the latter period relative to baseline, but an analysis of treatment approaches to non-STEMI and STEMI during the COVID-19 pandemic were not found to be significantly different from baseline.

Prior to the COVID-19 pandemic, 79% of STEMI patients and 77% of non-STEMI patients were discharged home, which was significantly lower than in the early COVID-19 period, when 83% (P = .02) of STEMI and 81% (P = .006) of non-STEMI patients were discharged home. In the latter period, discharge to home care was also significantly higher than in the baseline period.
 

More than fear of COVID-19?

One theory to account for the reduction in AMI hospitalizations and the increase in AMI-related mortality is the possibility that patients were slow to seek care at acute care hospitals because of concern about COVID-19 infection, according to Dr. Gluckman and coinvestigators.

“Given the time-sensitive nature of STEMI, any delay by patients, emergency medical services, the emergency department, or cardiac catheterization laboratory may have played a role,” they suggested.

In an interview, Dr. Gluckman said that further effort to identify the reasons for the increased AMI-related mortality is planned. Pulling data from the electronic medical records of the patients included in this retrospective analysis might be a “challenge,” but Dr. Gluckman reported that he and his coinvestigators plan to look at a different set of registry data that might provide information on sources of delay, particularly in the STEMI population.

“This includes looking at a number of time factors, such as symptom onset to first medical contact, first medical contact to device, and door-in-door-out times,” Dr. Gluckman said. The goal is to “better understand if delays [in treatment] occurred during the pandemic and, if so, how they may have contributed to increases in risk adjusted mortality.”

Dr. Krumholz, director of the Yale Center for Outcomes Research and Evaluation, New Haven, Conn., called this study a “useful” confirmation of changes in AMI-related care with the onset of the COVID-19 pandemic. As reported anecdotally, the study “indicates marked decreases in hospitalizations of patients with AMI even in areas that were not experiencing big outbreaks but did have some restrictions to limit spread,” he noted.

More data gathered by other centers might provide information about what it all means.

“There remain so many questions about what happened and what consequences accrued,” Dr. Krumholz observed. “In the meantime, we need to continue to send the message that people with symptoms that suggest a heart attack need to rapidly seek care.”

The investigators reported having no financial conflicts of interest.

SOURCE: Gluckman TJ et al. JAMA Cardiol. 2020 Aug 7. doi: 10.1001/jamacardio.2020.3629.

A substantial decrease in hospital admissions for acute MI was accompanied by a rise in mortality, particularly for ST-segment elevation MI (STEMI), following the onset of the COVID-19 pandemic, according to a cross-sectional retrospective study.

Although it can’t be confirmed from these results that the observed increase in in-hospital acute MI (AMI) mortality are related to delays in seeking treatment, this is a reasonable working hypothesis until more is known, commented Harlan Krumholz, MD, who was not involved in the study.

The analysis, derived from data collected at 49 centers in a hospital system spread across six states, supports previous reports that patients with AMI were avoiding hospitalization, according to the investigators, who were led by Tyler J. Gluckman, MD, medical director of the Center for Cardiovascular Analytics, Providence Heart Institute, Portland, Ore.

When compared with a nearly 14-month period that preceded the COVID-19 pandemic, the rate of AMI-associated hospitalization fell by 19 cases per week (95% confidence interval, –29.0 to –9.0 cases) in the early COVID-19 period, which was defined by the investigators as spanning from Feb. 23, 2020 to March 28, 2020.

The case rate per week then increased by 10.5 (95% CI, 4.6-16.5 cases) in a subsequent 8-week period spanning between March 29, 2020, and May 16, 2020. Although a substantial increase from the early COVID-19 period, the case rate remained below the baseline established before COVID-19.

The analysis looked at 15,244 AMI hospitalizations among 14,724 patients treated in the Providence St. Joseph Hospital System, which has facilities in Alaska, California, Montana, Oregon, Texas, and Washington. The 1,915 AMI cases captured from Feb. 23, 2020, represented 13% of the total.
 

Differences in mortality, patients, treatment

In the early period, the ratio of observed-to-expected (O/E) mortality relative to the pre–COVID-19 baseline increased by 27% (odds ratio, 1.27; 95% CI, 1.07-1.48). When STEMI was analyzed separately, the O/E mortality was nearly double that of the baseline period (OR, 1.96; 95% CI, 1.22-2.70). In the latter post–COVID-19 period of observation, the overall increase in AMI-associated mortality on the basis of an O/E ratio was no longer significant relative to the baseline period (OR, 1.23; 95% CI, 0.98-1.47). However, the relative increase in STEMI-associated mortality on an O/E basis was even greater (OR, 2.40; 95% CI, 1.65-3.16) in the second COVID-19 period analyzed. Even after risk adjustment, the OR for STEMI mortality remained significantly elevated relative to baseline (1.52; 95% CI, 1.02-2.26).

The differences in AMI patients treated before the onset of the COVID-19 pandemic and those treated afterwards might be relevant, according to the investigators. Specifically, patients hospitalized after Feb. 23, 2020 were 1-3 years younger (P < .001) depending on type of AMI, and more likely to be Asian (P = .01).

The length of stay was 6 hours shorter in the early COVID-19 period and 7 hours shorter in the latter period relative to baseline, but an analysis of treatment approaches to non-STEMI and STEMI during the COVID-19 pandemic were not found to be significantly different from baseline.

Prior to the COVID-19 pandemic, 79% of STEMI patients and 77% of non-STEMI patients were discharged home, which was significantly lower than in the early COVID-19 period, when 83% (P = .02) of STEMI and 81% (P = .006) of non-STEMI patients were discharged home. In the latter period, discharge to home care was also significantly higher than in the baseline period.
 

More than fear of COVID-19?

One theory to account for the reduction in AMI hospitalizations and the increase in AMI-related mortality is the possibility that patients were slow to seek care at acute care hospitals because of concern about COVID-19 infection, according to Dr. Gluckman and coinvestigators.

“Given the time-sensitive nature of STEMI, any delay by patients, emergency medical services, the emergency department, or cardiac catheterization laboratory may have played a role,” they suggested.

In an interview, Dr. Gluckman said that further effort to identify the reasons for the increased AMI-related mortality is planned. Pulling data from the electronic medical records of the patients included in this retrospective analysis might be a “challenge,” but Dr. Gluckman reported that he and his coinvestigators plan to look at a different set of registry data that might provide information on sources of delay, particularly in the STEMI population.

“This includes looking at a number of time factors, such as symptom onset to first medical contact, first medical contact to device, and door-in-door-out times,” Dr. Gluckman said. The goal is to “better understand if delays [in treatment] occurred during the pandemic and, if so, how they may have contributed to increases in risk adjusted mortality.”

Dr. Krumholz, director of the Yale Center for Outcomes Research and Evaluation, New Haven, Conn., called this study a “useful” confirmation of changes in AMI-related care with the onset of the COVID-19 pandemic. As reported anecdotally, the study “indicates marked decreases in hospitalizations of patients with AMI even in areas that were not experiencing big outbreaks but did have some restrictions to limit spread,” he noted.

More data gathered by other centers might provide information about what it all means.

“There remain so many questions about what happened and what consequences accrued,” Dr. Krumholz observed. “In the meantime, we need to continue to send the message that people with symptoms that suggest a heart attack need to rapidly seek care.”

The investigators reported having no financial conflicts of interest.

SOURCE: Gluckman TJ et al. JAMA Cardiol. 2020 Aug 7. doi: 10.1001/jamacardio.2020.3629.