People with type 2 diabetes whose diet followed a “Mediterranean” pattern – high in vegetables, legumes, fish, and unsaturated fats – saw global cognitive improvements over a 2-year period, compared with individuals with different eating patterns, even if the latter incorporated healthy dietary features. In addition, effective glycemic control seemed to have a role in sustaining the benefits associated with the Mediterranean-type diet.

Adults without type 2 diabetes, meanwhile, did not see the cognitive improvements associated with a Mediterranean diet, suggesting that the pathways linking diet to cognition may be different for individuals with and without diabetes, according to Josiemer Mattei, PhD, of the Harvard T.H. Chan School of Public Health in Boston and colleagues.

The investigators used data from the Boston Puerto Rican Health Study, a longitudinal cohort of about 1,499 adults aged 45-75 years who lived in Boston and identified as Puerto Rican, for their research, which was published in Diabetes Care.

At baseline, participants were administered a questionnaire to capture their eating patterns. Four diet-quality scores – Mediterranean Diet Score, Healthy Eating Index, Alternate Healthy Eating Index, and DASH (Dietary Approaches to Stop Hypertension) were analyzed. The participants were also screened for diabetes, and nearly 40% of them were found to have type 2 diabetes at baseline (74% uncontrolled). They underwent a battery of cognitive tests, including the Mini-Mental State Exam and tests for verbal fluency, executive function, word recognition, and figure copying. The study endpoints included 2-year change in global cognitive function as well as executive and memory function. At 2 years, data was available for 913 participants.

Among participants with type 2 diabetes, greater adherence to a Mediterranean-style diet was significantly associated with a higher positive change at the 2-year follow-up in global cognitive function score (0.027 [SD, 0.011]; P = .016), the Mini-Mental State Exam, and other individual tests. The association was significant for those who were under glycemic control at baseline and who remained stable or improved over 2 years, but not for those with poor or worsening glycemic control.

“The Mediterranean diet explained as much or more of the variability in predicting changes in cognitive function in our study as did age, especially for participants with type 2 diabetes under glycemic control. ... This dietary pattern may provide more cognitive benefits [in this patient group] than other modifiable and nonmodifiable factors,” the authors wrote in their analysis. They stressed that a Mediterranean dietary pattern can be realized through foods and dishes that are already standard in many Puerto Rican households.

In participants who did not have diabetes, improvement in memory function measures was seen in association with a Mediterranean diet, but also with adherence to other eating patterns that are deemed healthy. That suggests that for this subgroup, any evidence-based healthy diet – not just the Mediterranean diet – may have some benefits for memory function.

“Dietary recommendations for cognitive health may need to be tailored for individuals with versus without type 2 diabetes,” the authors concluded.

Dr. Mattei and colleagues acknowledged as a limitation of their study its observational design.

The study received funding from the National Heart, Lung, and Blood Institute; the National Institute on Aging; and Harvard University. The authors reported no financial conflicts of interest.

SOURCE: Mattei et al. Diabetes Care. 2019;42(8):1372-9.

People with type 2 diabetes whose diet followed a “Mediterranean” pattern – high in vegetables, legumes, fish, and unsaturated fats – saw global cognitive improvements over a 2-year period, compared with individuals with different eating patterns, even if the latter incorporated healthy dietary features. In addition, effective glycemic control seemed to have a role in sustaining the benefits associated with the Mediterranean-type diet.

Adults without type 2 diabetes, meanwhile, did not see the cognitive improvements associated with a Mediterranean diet, suggesting that the pathways linking diet to cognition may be different for individuals with and without diabetes, according to Josiemer Mattei, PhD, of the Harvard T.H. Chan School of Public Health in Boston and colleagues.

The investigators used data from the Boston Puerto Rican Health Study, a longitudinal cohort of about 1,499 adults aged 45-75 years who lived in Boston and identified as Puerto Rican, for their research, which was published in Diabetes Care.

At baseline, participants were administered a questionnaire to capture their eating patterns. Four diet-quality scores – Mediterranean Diet Score, Healthy Eating Index, Alternate Healthy Eating Index, and DASH (Dietary Approaches to Stop Hypertension) were analyzed. The participants were also screened for diabetes, and nearly 40% of them were found to have type 2 diabetes at baseline (74% uncontrolled). They underwent a battery of cognitive tests, including the Mini-Mental State Exam and tests for verbal fluency, executive function, word recognition, and figure copying. The study endpoints included 2-year change in global cognitive function as well as executive and memory function. At 2 years, data was available for 913 participants.

Among participants with type 2 diabetes, greater adherence to a Mediterranean-style diet was significantly associated with a higher positive change at the 2-year follow-up in global cognitive function score (0.027 [SD, 0.011]; P = .016), the Mini-Mental State Exam, and other individual tests. The association was significant for those who were under glycemic control at baseline and who remained stable or improved over 2 years, but not for those with poor or worsening glycemic control.

“The Mediterranean diet explained as much or more of the variability in predicting changes in cognitive function in our study as did age, especially for participants with type 2 diabetes under glycemic control. ... This dietary pattern may provide more cognitive benefits [in this patient group] than other modifiable and nonmodifiable factors,” the authors wrote in their analysis. They stressed that a Mediterranean dietary pattern can be realized through foods and dishes that are already standard in many Puerto Rican households.

In participants who did not have diabetes, improvement in memory function measures was seen in association with a Mediterranean diet, but also with adherence to other eating patterns that are deemed healthy. That suggests that for this subgroup, any evidence-based healthy diet – not just the Mediterranean diet – may have some benefits for memory function.

“Dietary recommendations for cognitive health may need to be tailored for individuals with versus without type 2 diabetes,” the authors concluded.

Dr. Mattei and colleagues acknowledged as a limitation of their study its observational design.

The study received funding from the National Heart, Lung, and Blood Institute; the National Institute on Aging; and Harvard University. The authors reported no financial conflicts of interest.

SOURCE: Mattei et al. Diabetes Care. 2019;42(8):1372-9.

People with type 2 diabetes whose diet followed a “Mediterranean” pattern – high in vegetables, legumes, fish, and unsaturated fats – saw global cognitive improvements over a 2-year period, compared with individuals with different eating patterns, even if the latter incorporated healthy dietary features. In addition, effective glycemic control seemed to have a role in sustaining the benefits associated with the Mediterranean-type diet.

Adults without type 2 diabetes, meanwhile, did not see the cognitive improvements associated with a Mediterranean diet, suggesting that the pathways linking diet to cognition may be different for individuals with and without diabetes, according to Josiemer Mattei, PhD, of the Harvard T.H. Chan School of Public Health in Boston and colleagues.

The investigators used data from the Boston Puerto Rican Health Study, a longitudinal cohort of about 1,499 adults aged 45-75 years who lived in Boston and identified as Puerto Rican, for their research, which was published in Diabetes Care.

At baseline, participants were administered a questionnaire to capture their eating patterns. Four diet-quality scores – Mediterranean Diet Score, Healthy Eating Index, Alternate Healthy Eating Index, and DASH (Dietary Approaches to Stop Hypertension) were analyzed. The participants were also screened for diabetes, and nearly 40% of them were found to have type 2 diabetes at baseline (74% uncontrolled). They underwent a battery of cognitive tests, including the Mini-Mental State Exam and tests for verbal fluency, executive function, word recognition, and figure copying. The study endpoints included 2-year change in global cognitive function as well as executive and memory function. At 2 years, data was available for 913 participants.

Among participants with type 2 diabetes, greater adherence to a Mediterranean-style diet was significantly associated with a higher positive change at the 2-year follow-up in global cognitive function score (0.027 [SD, 0.011]; P = .016), the Mini-Mental State Exam, and other individual tests. The association was significant for those who were under glycemic control at baseline and who remained stable or improved over 2 years, but not for those with poor or worsening glycemic control.

“The Mediterranean diet explained as much or more of the variability in predicting changes in cognitive function in our study as did age, especially for participants with type 2 diabetes under glycemic control. ... This dietary pattern may provide more cognitive benefits [in this patient group] than other modifiable and nonmodifiable factors,” the authors wrote in their analysis. They stressed that a Mediterranean dietary pattern can be realized through foods and dishes that are already standard in many Puerto Rican households.

In participants who did not have diabetes, improvement in memory function measures was seen in association with a Mediterranean diet, but also with adherence to other eating patterns that are deemed healthy. That suggests that for this subgroup, any evidence-based healthy diet – not just the Mediterranean diet – may have some benefits for memory function.

“Dietary recommendations for cognitive health may need to be tailored for individuals with versus without type 2 diabetes,” the authors concluded.

Dr. Mattei and colleagues acknowledged as a limitation of their study its observational design.

The study received funding from the National Heart, Lung, and Blood Institute; the National Institute on Aging; and Harvard University. The authors reported no financial conflicts of interest.

SOURCE: Mattei et al. Diabetes Care. 2019;42(8):1372-9.

Continuous blood pressure monitoring is significantly better than in-office measurements at predicting the risk of cardiovascular events and death, although the additional prognostic benefit is quite small, wrote Wen-Yi Yang, MD, and colleagues. Their report is in JAMA.

Ingram Publishing/ThinkStock

In light of this finding, 24-hour monitoring is probably best reserved for select patients – especially those with white coat hypertension, and those who self-report hypertension but test within normal parameters in the office, said Philip Greenland, MD, Harry W. Dingman Professor of Cardiology at Northwestern University, Chicago, who wrote a perspective piece published along with the study.

“The good news is that, for the average patient, the office measurement is highly predictive and performs extremely well,” Dr. Greenland said in an interview. “Ambulatory monitoring will get you very little additional information. But if you are getting a 24-hour reading, the measures you probably want to focus on are the nighttime pressures and the overall 24-hour average.”

Dr. Yang of the University of Leuven, Belgium, and his team were “trying to make sense of this huge amount of data that’s available now that ambulatory blood pressure monitoring systems are much more common,” Dr. Greenland said. “The real clinical question is, ‘If I’m getting all this information, how do I interpret it?’ ”

To investigate this, the authors evaluated blood pressure and cardiovascular outcomes among more than 11,000 subjects enrolled in the International Database on Ambulatory Blood Pressure in Relation to Cardiovascular Outcome (IDACO).

The median individual follow-up was about 14 years, although some patients were followed up to 22 years. All told, the study posted 153,140 person-years of follow-up. These patients were a mean of 55 years old at enrollment; almost 12% had a history of cardiovascular disease. Most (83%) had three automated in-office blood pressure measurements; 5% had two, and 2% had a single measurement. There were 55 24-hour ambulatory readings, 28 for daytime only, and 11 for nighttime.

The mean in-office automated BP was 135/82. The mean 24-hour BP was 123/74; the mean daytime pressure, 130/79; and the mean nighttime pressure, 113/65.

The authors recorded blood pressure–dipping status: 50% were normal, 18% had extreme dipping, 25% had no dipping, and 6% had reverse dipping. The mean dipping ratio was 0.87.

A regression analysis adjusted for sex, age, body mass index, smoking, and alcohol use, serum cholesterol, antihypertensive drugs, cardiovascular disease and diabetes.

Over the entire study period, there were 2,836 deaths and 2,049 cardiovascular events – a rate of 13.4 per 1,000 person-years. Both cardiovascular events and mortality were significantly associated with all ambulatory BP measurements, compared with in-office measurements. For nighttime systolic BP, the hazard ratio for mortality was 1.23 and 1.36 for cardiovascular events. For the 24-hour measure, the HR for mortality was 1.22, and for cardiovascular events, 1.45. Hazard ratios represented the risk associated with a 20–mm Hg higher systolic blood pressure or a 0.10 difference in dipping ratio.

However, the area under the curve for a single, in-office systolic BP was quite good, at 0.83 for mortality and 0.84 for cardiovascular events. Adding 24-hour measurements or nighttime systolic BP to the model resulted only in very, very small “incremental” improvements in AUC of 0.0013 and 0.0027, respectively

“The current population-based study confirmed previous research indicating that ambulatory BP monitoring over and beyond measures taken in clinicians’ offices improved risk stratification among patients with or suspected of having hypertension,” The authors wrote. “It strengthened the notion that nighttime BP measures carry valuable prognostic information.”

However, they admitted that the addition these measures offer to the AUC for BP measurements was “incremental.”

“This metric is not very sensitive in model comparisons if the basic model performs well, as was the case in the current study. … The prevailing perception among experts is that BP is the strongest modifiable risk factor. The small increments in change in the AUC challenge this concept. Thus an important issue in the evaluation of an additional risk prediction marker is how to interpret a small AUC increase, which many researchers believe is an imprecise metric because it increases only slightly with the introduction of an additional marker in multivariable-adjusted models, even if the marker under study carries great risk, as reflected by the odds ratio (or HR).”

One investigator, Krzysztof Narkiewicz, MD, reported receiving lecture fees from numerous pharmaceutical and device companies. No other disclosures were reported.

[email protected]

SOURCE: Yang W et al. JAMA. 2019;322(5):409-20.

Continuous blood pressure monitoring is significantly better than in-office measurements at predicting the risk of cardiovascular events and death, although the additional prognostic benefit is quite small, wrote Wen-Yi Yang, MD, and colleagues. Their report is in JAMA.

Ingram Publishing/ThinkStock

In light of this finding, 24-hour monitoring is probably best reserved for select patients – especially those with white coat hypertension, and those who self-report hypertension but test within normal parameters in the office, said Philip Greenland, MD, Harry W. Dingman Professor of Cardiology at Northwestern University, Chicago, who wrote a perspective piece published along with the study.

“The good news is that, for the average patient, the office measurement is highly predictive and performs extremely well,” Dr. Greenland said in an interview. “Ambulatory monitoring will get you very little additional information. But if you are getting a 24-hour reading, the measures you probably want to focus on are the nighttime pressures and the overall 24-hour average.”

Dr. Yang of the University of Leuven, Belgium, and his team were “trying to make sense of this huge amount of data that’s available now that ambulatory blood pressure monitoring systems are much more common,” Dr. Greenland said. “The real clinical question is, ‘If I’m getting all this information, how do I interpret it?’ ”

To investigate this, the authors evaluated blood pressure and cardiovascular outcomes among more than 11,000 subjects enrolled in the International Database on Ambulatory Blood Pressure in Relation to Cardiovascular Outcome (IDACO).

The median individual follow-up was about 14 years, although some patients were followed up to 22 years. All told, the study posted 153,140 person-years of follow-up. These patients were a mean of 55 years old at enrollment; almost 12% had a history of cardiovascular disease. Most (83%) had three automated in-office blood pressure measurements; 5% had two, and 2% had a single measurement. There were 55 24-hour ambulatory readings, 28 for daytime only, and 11 for nighttime.

The mean in-office automated BP was 135/82. The mean 24-hour BP was 123/74; the mean daytime pressure, 130/79; and the mean nighttime pressure, 113/65.

The authors recorded blood pressure–dipping status: 50% were normal, 18% had extreme dipping, 25% had no dipping, and 6% had reverse dipping. The mean dipping ratio was 0.87.

A regression analysis adjusted for sex, age, body mass index, smoking, and alcohol use, serum cholesterol, antihypertensive drugs, cardiovascular disease and diabetes.

Over the entire study period, there were 2,836 deaths and 2,049 cardiovascular events – a rate of 13.4 per 1,000 person-years. Both cardiovascular events and mortality were significantly associated with all ambulatory BP measurements, compared with in-office measurements. For nighttime systolic BP, the hazard ratio for mortality was 1.23 and 1.36 for cardiovascular events. For the 24-hour measure, the HR for mortality was 1.22, and for cardiovascular events, 1.45. Hazard ratios represented the risk associated with a 20–mm Hg higher systolic blood pressure or a 0.10 difference in dipping ratio.

However, the area under the curve for a single, in-office systolic BP was quite good, at 0.83 for mortality and 0.84 for cardiovascular events. Adding 24-hour measurements or nighttime systolic BP to the model resulted only in very, very small “incremental” improvements in AUC of 0.0013 and 0.0027, respectively

“The current population-based study confirmed previous research indicating that ambulatory BP monitoring over and beyond measures taken in clinicians’ offices improved risk stratification among patients with or suspected of having hypertension,” The authors wrote. “It strengthened the notion that nighttime BP measures carry valuable prognostic information.”

However, they admitted that the addition these measures offer to the AUC for BP measurements was “incremental.”

“This metric is not very sensitive in model comparisons if the basic model performs well, as was the case in the current study. … The prevailing perception among experts is that BP is the strongest modifiable risk factor. The small increments in change in the AUC challenge this concept. Thus an important issue in the evaluation of an additional risk prediction marker is how to interpret a small AUC increase, which many researchers believe is an imprecise metric because it increases only slightly with the introduction of an additional marker in multivariable-adjusted models, even if the marker under study carries great risk, as reflected by the odds ratio (or HR).”

One investigator, Krzysztof Narkiewicz, MD, reported receiving lecture fees from numerous pharmaceutical and device companies. No other disclosures were reported.

[email protected]

SOURCE: Yang W et al. JAMA. 2019;322(5):409-20.

Continuous blood pressure monitoring is significantly better than in-office measurements at predicting the risk of cardiovascular events and death, although the additional prognostic benefit is quite small, wrote Wen-Yi Yang, MD, and colleagues. Their report is in JAMA.

Ingram Publishing/ThinkStock

In light of this finding, 24-hour monitoring is probably best reserved for select patients – especially those with white coat hypertension, and those who self-report hypertension but test within normal parameters in the office, said Philip Greenland, MD, Harry W. Dingman Professor of Cardiology at Northwestern University, Chicago, who wrote a perspective piece published along with the study.

“The good news is that, for the average patient, the office measurement is highly predictive and performs extremely well,” Dr. Greenland said in an interview. “Ambulatory monitoring will get you very little additional information. But if you are getting a 24-hour reading, the measures you probably want to focus on are the nighttime pressures and the overall 24-hour average.”

Dr. Yang of the University of Leuven, Belgium, and his team were “trying to make sense of this huge amount of data that’s available now that ambulatory blood pressure monitoring systems are much more common,” Dr. Greenland said. “The real clinical question is, ‘If I’m getting all this information, how do I interpret it?’ ”

To investigate this, the authors evaluated blood pressure and cardiovascular outcomes among more than 11,000 subjects enrolled in the International Database on Ambulatory Blood Pressure in Relation to Cardiovascular Outcome (IDACO).

The median individual follow-up was about 14 years, although some patients were followed up to 22 years. All told, the study posted 153,140 person-years of follow-up. These patients were a mean of 55 years old at enrollment; almost 12% had a history of cardiovascular disease. Most (83%) had three automated in-office blood pressure measurements; 5% had two, and 2% had a single measurement. There were 55 24-hour ambulatory readings, 28 for daytime only, and 11 for nighttime.

The mean in-office automated BP was 135/82. The mean 24-hour BP was 123/74; the mean daytime pressure, 130/79; and the mean nighttime pressure, 113/65.

The authors recorded blood pressure–dipping status: 50% were normal, 18% had extreme dipping, 25% had no dipping, and 6% had reverse dipping. The mean dipping ratio was 0.87.

A regression analysis adjusted for sex, age, body mass index, smoking, and alcohol use, serum cholesterol, antihypertensive drugs, cardiovascular disease and diabetes.

Over the entire study period, there were 2,836 deaths and 2,049 cardiovascular events – a rate of 13.4 per 1,000 person-years. Both cardiovascular events and mortality were significantly associated with all ambulatory BP measurements, compared with in-office measurements. For nighttime systolic BP, the hazard ratio for mortality was 1.23 and 1.36 for cardiovascular events. For the 24-hour measure, the HR for mortality was 1.22, and for cardiovascular events, 1.45. Hazard ratios represented the risk associated with a 20–mm Hg higher systolic blood pressure or a 0.10 difference in dipping ratio.

However, the area under the curve for a single, in-office systolic BP was quite good, at 0.83 for mortality and 0.84 for cardiovascular events. Adding 24-hour measurements or nighttime systolic BP to the model resulted only in very, very small “incremental” improvements in AUC of 0.0013 and 0.0027, respectively

“The current population-based study confirmed previous research indicating that ambulatory BP monitoring over and beyond measures taken in clinicians’ offices improved risk stratification among patients with or suspected of having hypertension,” The authors wrote. “It strengthened the notion that nighttime BP measures carry valuable prognostic information.”

However, they admitted that the addition these measures offer to the AUC for BP measurements was “incremental.”

“This metric is not very sensitive in model comparisons if the basic model performs well, as was the case in the current study. … The prevailing perception among experts is that BP is the strongest modifiable risk factor. The small increments in change in the AUC challenge this concept. Thus an important issue in the evaluation of an additional risk prediction marker is how to interpret a small AUC increase, which many researchers believe is an imprecise metric because it increases only slightly with the introduction of an additional marker in multivariable-adjusted models, even if the marker under study carries great risk, as reflected by the odds ratio (or HR).”

One investigator, Krzysztof Narkiewicz, MD, reported receiving lecture fees from numerous pharmaceutical and device companies. No other disclosures were reported.

[email protected]

SOURCE: Yang W et al. JAMA. 2019;322(5):409-20.

As psychiatry mourns Carl Compton Bell, MD, a giant in our field, we pay homage to his legacy of leadership and productivity.

Dr. Bell wore many hats: community psychiatrist par excellence, award-winning researcher, clinician, public health advocate, mentor, and activist. Eschewing the mold of the stereotypical psychiatrist, he lectured in cowboy hats, baseball caps, message T-shirts, and shades – all conveying his youthful, down-to-earth, yet serious, psychiatrist-of-the-people style. He demonstrated that scholarship could combat racial inequities and made it clear that he had much to accomplish yet little to prove.

Dr. Bell implored physicians to not only treat health problems but also to rectify “upstream” issues. He encouraged their engagement in “bent-nail research,” empirical study directly in the communities where they work – even with limited resources. This approach, rooted in public health and prevention, undergirds his groundbreaking work in the treatment of fetal alcohol exposure with choline and folic acid. HIV prevention in South Africa was another area of study where he developed innovative strategies with successful outcomes. In his study of trauma in youth, he underscored that “risk factors are not predictive factors because of protective factors.”

He promoted social fabric, an adult protective shield, connectedness, self-esteem, self-efficacy, and social skills as protective. He understood that, with treatment and community supports, children exposed to violence were not doomed to a life of aberrant behavior.

A prolific author, Dr. Bell’s peer-reviewed articles are often cited and have become the gospel for community mental health. He bemoaned the insufficient translation of published research into reality in the community. His writings suggested that psychiatry should not assume that its standards of diagnosis and treatment apply entirely to nonwhite populations. This fact remains a call to action for those of us he leaves behind.

As a clinician, Dr. Bell listened intently to his patients to understand their current situations, histories, family histories, and contexts in which they lived. He was so dedicated to their care that, when a mental health center he led for years abruptly closed its doors, he set up a makeshift office on the front sidewalk to serve patients who might not have known about its closure.

Dr. Bell was active in organized psychiatry, serving as past chair of the American Psychiatric Association Council on Social Issues and Public Psychiatry. He inspired the creation of the APA’s Transformational Leadership in Public Psychiatry Fellowship for early- and mid-career psychiatrists. A loyal member of the Black Psychiatrists of America, he took pride in having saved all of BPA’s newsletters dating back to its founding in 1969.

His participation in those associations and in the National Medical Association was an avenue through which his robust scholarship encouraged the next generations of black psychiatrists. Those countless psychiatrists who trusted Dr. Bell’s wise counsel have gone on to become leaders. They are proof that his extraordinary accomplishments and spirit will live on through the multiplier effect of their contributions to the field and mentorship of future psychiatrists for years to come.
 

Dr. Gordon-Achebe is a child, adolescent, and adult psychiatrist practicing in the Baltimore metropolitan area. She is the immediate past president of the American Psychiatric Association’s Caucus of Black Psychiatrists and vice chair for the Council on Children, Adolescents and Their Families.

Dr. Hairston is the psychiatry residency training director at Howard University in Washington. She is the newly elected president of the American Psychiatric Association’s Caucus of Black Psychiatrists and the scientific program committee chair for the Black Psychiatrists of America.

Dr. Starks is a geriatric psychiatrist and Health and Aging Policy Fellow currently working on Capitol Hill in Washington. He is the representative to the assembly for the APA Caucus of Black Psychiatrists. He has nurtured a keen interest in understanding the cultural and social effects of geriatric mental health conditions on the lives of patients and families.

Dr. Primm, a community psychiatrist based in Baltimore, is senior medical director of the Steve Fund, which is focused on the mental health and emotional well-being of young people of color, including college students. She formerly served as deputy medical director of the APA and director of APA’s division of diversity and health equity, previously known as the Office of Minority and National Affairs.

As psychiatry mourns Carl Compton Bell, MD, a giant in our field, we pay homage to his legacy of leadership and productivity.

Dr. Bell wore many hats: community psychiatrist par excellence, award-winning researcher, clinician, public health advocate, mentor, and activist. Eschewing the mold of the stereotypical psychiatrist, he lectured in cowboy hats, baseball caps, message T-shirts, and shades – all conveying his youthful, down-to-earth, yet serious, psychiatrist-of-the-people style. He demonstrated that scholarship could combat racial inequities and made it clear that he had much to accomplish yet little to prove.

Dr. Bell implored physicians to not only treat health problems but also to rectify “upstream” issues. He encouraged their engagement in “bent-nail research,” empirical study directly in the communities where they work – even with limited resources. This approach, rooted in public health and prevention, undergirds his groundbreaking work in the treatment of fetal alcohol exposure with choline and folic acid. HIV prevention in South Africa was another area of study where he developed innovative strategies with successful outcomes. In his study of trauma in youth, he underscored that “risk factors are not predictive factors because of protective factors.”

He promoted social fabric, an adult protective shield, connectedness, self-esteem, self-efficacy, and social skills as protective. He understood that, with treatment and community supports, children exposed to violence were not doomed to a life of aberrant behavior.

A prolific author, Dr. Bell’s peer-reviewed articles are often cited and have become the gospel for community mental health. He bemoaned the insufficient translation of published research into reality in the community. His writings suggested that psychiatry should not assume that its standards of diagnosis and treatment apply entirely to nonwhite populations. This fact remains a call to action for those of us he leaves behind.

As a clinician, Dr. Bell listened intently to his patients to understand their current situations, histories, family histories, and contexts in which they lived. He was so dedicated to their care that, when a mental health center he led for years abruptly closed its doors, he set up a makeshift office on the front sidewalk to serve patients who might not have known about its closure.

Dr. Bell was active in organized psychiatry, serving as past chair of the American Psychiatric Association Council on Social Issues and Public Psychiatry. He inspired the creation of the APA’s Transformational Leadership in Public Psychiatry Fellowship for early- and mid-career psychiatrists. A loyal member of the Black Psychiatrists of America, he took pride in having saved all of BPA’s newsletters dating back to its founding in 1969.

His participation in those associations and in the National Medical Association was an avenue through which his robust scholarship encouraged the next generations of black psychiatrists. Those countless psychiatrists who trusted Dr. Bell’s wise counsel have gone on to become leaders. They are proof that his extraordinary accomplishments and spirit will live on through the multiplier effect of their contributions to the field and mentorship of future psychiatrists for years to come.
 

Dr. Gordon-Achebe is a child, adolescent, and adult psychiatrist practicing in the Baltimore metropolitan area. She is the immediate past president of the American Psychiatric Association’s Caucus of Black Psychiatrists and vice chair for the Council on Children, Adolescents and Their Families.

Dr. Hairston is the psychiatry residency training director at Howard University in Washington. She is the newly elected president of the American Psychiatric Association’s Caucus of Black Psychiatrists and the scientific program committee chair for the Black Psychiatrists of America.

Dr. Starks is a geriatric psychiatrist and Health and Aging Policy Fellow currently working on Capitol Hill in Washington. He is the representative to the assembly for the APA Caucus of Black Psychiatrists. He has nurtured a keen interest in understanding the cultural and social effects of geriatric mental health conditions on the lives of patients and families.

Dr. Primm, a community psychiatrist based in Baltimore, is senior medical director of the Steve Fund, which is focused on the mental health and emotional well-being of young people of color, including college students. She formerly served as deputy medical director of the APA and director of APA’s division of diversity and health equity, previously known as the Office of Minority and National Affairs.

As psychiatry mourns Carl Compton Bell, MD, a giant in our field, we pay homage to his legacy of leadership and productivity.

Dr. Bell wore many hats: community psychiatrist par excellence, award-winning researcher, clinician, public health advocate, mentor, and activist. Eschewing the mold of the stereotypical psychiatrist, he lectured in cowboy hats, baseball caps, message T-shirts, and shades – all conveying his youthful, down-to-earth, yet serious, psychiatrist-of-the-people style. He demonstrated that scholarship could combat racial inequities and made it clear that he had much to accomplish yet little to prove.

Dr. Bell implored physicians to not only treat health problems but also to rectify “upstream” issues. He encouraged their engagement in “bent-nail research,” empirical study directly in the communities where they work – even with limited resources. This approach, rooted in public health and prevention, undergirds his groundbreaking work in the treatment of fetal alcohol exposure with choline and folic acid. HIV prevention in South Africa was another area of study where he developed innovative strategies with successful outcomes. In his study of trauma in youth, he underscored that “risk factors are not predictive factors because of protective factors.”

He promoted social fabric, an adult protective shield, connectedness, self-esteem, self-efficacy, and social skills as protective. He understood that, with treatment and community supports, children exposed to violence were not doomed to a life of aberrant behavior.

A prolific author, Dr. Bell’s peer-reviewed articles are often cited and have become the gospel for community mental health. He bemoaned the insufficient translation of published research into reality in the community. His writings suggested that psychiatry should not assume that its standards of diagnosis and treatment apply entirely to nonwhite populations. This fact remains a call to action for those of us he leaves behind.

As a clinician, Dr. Bell listened intently to his patients to understand their current situations, histories, family histories, and contexts in which they lived. He was so dedicated to their care that, when a mental health center he led for years abruptly closed its doors, he set up a makeshift office on the front sidewalk to serve patients who might not have known about its closure.

Dr. Bell was active in organized psychiatry, serving as past chair of the American Psychiatric Association Council on Social Issues and Public Psychiatry. He inspired the creation of the APA’s Transformational Leadership in Public Psychiatry Fellowship for early- and mid-career psychiatrists. A loyal member of the Black Psychiatrists of America, he took pride in having saved all of BPA’s newsletters dating back to its founding in 1969.

His participation in those associations and in the National Medical Association was an avenue through which his robust scholarship encouraged the next generations of black psychiatrists. Those countless psychiatrists who trusted Dr. Bell’s wise counsel have gone on to become leaders. They are proof that his extraordinary accomplishments and spirit will live on through the multiplier effect of their contributions to the field and mentorship of future psychiatrists for years to come.
 

Dr. Gordon-Achebe is a child, adolescent, and adult psychiatrist practicing in the Baltimore metropolitan area. She is the immediate past president of the American Psychiatric Association’s Caucus of Black Psychiatrists and vice chair for the Council on Children, Adolescents and Their Families.

Dr. Hairston is the psychiatry residency training director at Howard University in Washington. She is the newly elected president of the American Psychiatric Association’s Caucus of Black Psychiatrists and the scientific program committee chair for the Black Psychiatrists of America.

Dr. Starks is a geriatric psychiatrist and Health and Aging Policy Fellow currently working on Capitol Hill in Washington. He is the representative to the assembly for the APA Caucus of Black Psychiatrists. He has nurtured a keen interest in understanding the cultural and social effects of geriatric mental health conditions on the lives of patients and families.

Dr. Primm, a community psychiatrist based in Baltimore, is senior medical director of the Steve Fund, which is focused on the mental health and emotional well-being of young people of color, including college students. She formerly served as deputy medical director of the APA and director of APA’s division of diversity and health equity, previously known as the Office of Minority and National Affairs.

BANGKOK – It’s high time for the prediction of seizure outcomes after epilepsy surgery to step into the 21st century, Lara Jehi, MD, asserted at the International Epilepsy Congress.

Bruce Jancin/MDedge News

She and her colleagues have created and validated an online risk prediction tool that clinicians can use to predict a patient’s individualized likelihood of complete freedom from seizures 2 and 5 years after undergoing resective brain surgery for drug-resistant epilepsy. The risk predictor, known as the Epilepsy Surgery Nomogram, uses a handful of simple clinical characteristics – patient gender, pathologic cause of the seizures, the proposed type of epilepsy surgery, the presence or absence of generalized tonic-clonic seizures, epilepsy duration, and preoperative seizure frequency – and spits out the patient’s predicted seizure outcome, she explained at the congress, sponsored by the International League Against Epilepsy.

“The point here is that every patient is an individual. And to give people predictions based on 500- or 600-patient Kaplan-Meier-derived curves that just provide the average outcome for the whole cohort isn’t really going to give them what they need as far as their individualized chance of becoming seizure free,” said Dr. Jehi, a neurologist at the Cleveland Clinic.

Similarly, reliance solely upon clinical judgment is a minefield. Multiple biases prevent physicians from making objective medical predictions, she continued.

“We think of the process of medical decision-making and outcome prediction as being a process that is logical and rational, where the accumulation of knowledge improves the decisions that we make, and where past experience improves judgment, and where collective decisions are more reliable. This is what intuitively we all think. That’s why we think we are invincible as physicians. And to that I say, really? There is a wealth of literature that actually disproves each one of these points,” Dr. Jehi declared.

Outcomes of brain surgery for drug-resistant epilepsy have remained static for more than half a century: Ten years after surgery, roughly half of treated patients remain completely seizure free. The inability of clinicians to use advanced statistics to inform potential surgical candidates about their individualized chance of becoming seizure free has probably contributed to underutilization of epilepsy surgery, she added.

The Epilepsy Surgery Nomogram was developed through detailed analysis of the records of 846 patients who underwent epilepsy surgery at the Cleveland Clinic. The resultant nomogram was then validated in a cohort of 604 patients who had resective surgery at the Mayo Clinic and epilepsy surgery centers in Brazil, Italy, and France. In the development cohort, the rate of complete freedom from seizures was 57% at 2 years and 40% at 5 years. In the validation study, the nomogram had a concordance statistic of 0.60 for complete freedom from seizures, which is considered better than chance, but well below the 0.80 threshold defined as strong concordance (Lancet Neurol. 2015 Mar;14[3]:283-90).

However, in an era when personalized medicine has become a catch phrase, the Epilepsy Surgery Nomogram has captured the attention of officials at the National Institutes of Health. Indeed, Dr. Jehi and her coworkers have received a $3.4 million, 5-year grant from the NIH to improve their risk prediction model by incorporating additional variables, including EEG data, MRI findings, family history, and genetic information. The enhanced risk calculator also will include a predictor of the likelihood that an individual will experience clinically meaningful improvement in quality of life in response to epilepsy surgery, since that’s an important outcome even in the absence of 100% freedom from seizures.

Recently, Dr. Jehi and coworkers have developed and then externally validated nomograms to predict the individualized risk of clinically relevant postoperative naming decline after temporal lobe epilepsy surgery in adults. A model based upon five variables – side of surgery, sex, education, age at epilepsy onset, and age at epilepsy surgery – performed very well, with a concordance statistic of 0.81. Moreover, a second nomogram predicting moderate to severe postoperative naming decline on the basis of just three variables – side of surgery, age at epilepsy onset, and preoperative score on the Boston Naming Test – had a concordance statistic of 0.84 (Neurology. 2018 Dec 4;91[23]:e2144-e2152. doi: 10.1212/WNL.0000000000006629).

“Our future hopefully is one where there will always be room for gut feelings and intuition because we definitely need them. We want to honor them. But hopefully it is one where algorithms can help our guesses be more educated and where the science of algorithms and predictive modeling can help inform our outcome predictions and decision-making process,” she said.

The original Epilepsy Surgery Nomogram project was funded by the Cleveland Clinic Epilepsy Center. The postoperative naming decline nomograms project was funded by the NIH.

[email protected]

BANGKOK – It’s high time for the prediction of seizure outcomes after epilepsy surgery to step into the 21st century, Lara Jehi, MD, asserted at the International Epilepsy Congress.

Bruce Jancin/MDedge News

She and her colleagues have created and validated an online risk prediction tool that clinicians can use to predict a patient’s individualized likelihood of complete freedom from seizures 2 and 5 years after undergoing resective brain surgery for drug-resistant epilepsy. The risk predictor, known as the Epilepsy Surgery Nomogram, uses a handful of simple clinical characteristics – patient gender, pathologic cause of the seizures, the proposed type of epilepsy surgery, the presence or absence of generalized tonic-clonic seizures, epilepsy duration, and preoperative seizure frequency – and spits out the patient’s predicted seizure outcome, she explained at the congress, sponsored by the International League Against Epilepsy.

“The point here is that every patient is an individual. And to give people predictions based on 500- or 600-patient Kaplan-Meier-derived curves that just provide the average outcome for the whole cohort isn’t really going to give them what they need as far as their individualized chance of becoming seizure free,” said Dr. Jehi, a neurologist at the Cleveland Clinic.

Similarly, reliance solely upon clinical judgment is a minefield. Multiple biases prevent physicians from making objective medical predictions, she continued.

“We think of the process of medical decision-making and outcome prediction as being a process that is logical and rational, where the accumulation of knowledge improves the decisions that we make, and where past experience improves judgment, and where collective decisions are more reliable. This is what intuitively we all think. That’s why we think we are invincible as physicians. And to that I say, really? There is a wealth of literature that actually disproves each one of these points,” Dr. Jehi declared.

Outcomes of brain surgery for drug-resistant epilepsy have remained static for more than half a century: Ten years after surgery, roughly half of treated patients remain completely seizure free. The inability of clinicians to use advanced statistics to inform potential surgical candidates about their individualized chance of becoming seizure free has probably contributed to underutilization of epilepsy surgery, she added.

The Epilepsy Surgery Nomogram was developed through detailed analysis of the records of 846 patients who underwent epilepsy surgery at the Cleveland Clinic. The resultant nomogram was then validated in a cohort of 604 patients who had resective surgery at the Mayo Clinic and epilepsy surgery centers in Brazil, Italy, and France. In the development cohort, the rate of complete freedom from seizures was 57% at 2 years and 40% at 5 years. In the validation study, the nomogram had a concordance statistic of 0.60 for complete freedom from seizures, which is considered better than chance, but well below the 0.80 threshold defined as strong concordance (Lancet Neurol. 2015 Mar;14[3]:283-90).

However, in an era when personalized medicine has become a catch phrase, the Epilepsy Surgery Nomogram has captured the attention of officials at the National Institutes of Health. Indeed, Dr. Jehi and her coworkers have received a $3.4 million, 5-year grant from the NIH to improve their risk prediction model by incorporating additional variables, including EEG data, MRI findings, family history, and genetic information. The enhanced risk calculator also will include a predictor of the likelihood that an individual will experience clinically meaningful improvement in quality of life in response to epilepsy surgery, since that’s an important outcome even in the absence of 100% freedom from seizures.

Recently, Dr. Jehi and coworkers have developed and then externally validated nomograms to predict the individualized risk of clinically relevant postoperative naming decline after temporal lobe epilepsy surgery in adults. A model based upon five variables – side of surgery, sex, education, age at epilepsy onset, and age at epilepsy surgery – performed very well, with a concordance statistic of 0.81. Moreover, a second nomogram predicting moderate to severe postoperative naming decline on the basis of just three variables – side of surgery, age at epilepsy onset, and preoperative score on the Boston Naming Test – had a concordance statistic of 0.84 (Neurology. 2018 Dec 4;91[23]:e2144-e2152. doi: 10.1212/WNL.0000000000006629).

“Our future hopefully is one where there will always be room for gut feelings and intuition because we definitely need them. We want to honor them. But hopefully it is one where algorithms can help our guesses be more educated and where the science of algorithms and predictive modeling can help inform our outcome predictions and decision-making process,” she said.

The original Epilepsy Surgery Nomogram project was funded by the Cleveland Clinic Epilepsy Center. The postoperative naming decline nomograms project was funded by the NIH.

[email protected]

BANGKOK – It’s high time for the prediction of seizure outcomes after epilepsy surgery to step into the 21st century, Lara Jehi, MD, asserted at the International Epilepsy Congress.

Bruce Jancin/MDedge News

She and her colleagues have created and validated an online risk prediction tool that clinicians can use to predict a patient’s individualized likelihood of complete freedom from seizures 2 and 5 years after undergoing resective brain surgery for drug-resistant epilepsy. The risk predictor, known as the Epilepsy Surgery Nomogram, uses a handful of simple clinical characteristics – patient gender, pathologic cause of the seizures, the proposed type of epilepsy surgery, the presence or absence of generalized tonic-clonic seizures, epilepsy duration, and preoperative seizure frequency – and spits out the patient’s predicted seizure outcome, she explained at the congress, sponsored by the International League Against Epilepsy.

“The point here is that every patient is an individual. And to give people predictions based on 500- or 600-patient Kaplan-Meier-derived curves that just provide the average outcome for the whole cohort isn’t really going to give them what they need as far as their individualized chance of becoming seizure free,” said Dr. Jehi, a neurologist at the Cleveland Clinic.

Similarly, reliance solely upon clinical judgment is a minefield. Multiple biases prevent physicians from making objective medical predictions, she continued.

“We think of the process of medical decision-making and outcome prediction as being a process that is logical and rational, where the accumulation of knowledge improves the decisions that we make, and where past experience improves judgment, and where collective decisions are more reliable. This is what intuitively we all think. That’s why we think we are invincible as physicians. And to that I say, really? There is a wealth of literature that actually disproves each one of these points,” Dr. Jehi declared.

Outcomes of brain surgery for drug-resistant epilepsy have remained static for more than half a century: Ten years after surgery, roughly half of treated patients remain completely seizure free. The inability of clinicians to use advanced statistics to inform potential surgical candidates about their individualized chance of becoming seizure free has probably contributed to underutilization of epilepsy surgery, she added.

The Epilepsy Surgery Nomogram was developed through detailed analysis of the records of 846 patients who underwent epilepsy surgery at the Cleveland Clinic. The resultant nomogram was then validated in a cohort of 604 patients who had resective surgery at the Mayo Clinic and epilepsy surgery centers in Brazil, Italy, and France. In the development cohort, the rate of complete freedom from seizures was 57% at 2 years and 40% at 5 years. In the validation study, the nomogram had a concordance statistic of 0.60 for complete freedom from seizures, which is considered better than chance, but well below the 0.80 threshold defined as strong concordance (Lancet Neurol. 2015 Mar;14[3]:283-90).

However, in an era when personalized medicine has become a catch phrase, the Epilepsy Surgery Nomogram has captured the attention of officials at the National Institutes of Health. Indeed, Dr. Jehi and her coworkers have received a $3.4 million, 5-year grant from the NIH to improve their risk prediction model by incorporating additional variables, including EEG data, MRI findings, family history, and genetic information. The enhanced risk calculator also will include a predictor of the likelihood that an individual will experience clinically meaningful improvement in quality of life in response to epilepsy surgery, since that’s an important outcome even in the absence of 100% freedom from seizures.

Recently, Dr. Jehi and coworkers have developed and then externally validated nomograms to predict the individualized risk of clinically relevant postoperative naming decline after temporal lobe epilepsy surgery in adults. A model based upon five variables – side of surgery, sex, education, age at epilepsy onset, and age at epilepsy surgery – performed very well, with a concordance statistic of 0.81. Moreover, a second nomogram predicting moderate to severe postoperative naming decline on the basis of just three variables – side of surgery, age at epilepsy onset, and preoperative score on the Boston Naming Test – had a concordance statistic of 0.84 (Neurology. 2018 Dec 4;91[23]:e2144-e2152. doi: 10.1212/WNL.0000000000006629).

“Our future hopefully is one where there will always be room for gut feelings and intuition because we definitely need them. We want to honor them. But hopefully it is one where algorithms can help our guesses be more educated and where the science of algorithms and predictive modeling can help inform our outcome predictions and decision-making process,” she said.

The original Epilepsy Surgery Nomogram project was funded by the Cleveland Clinic Epilepsy Center. The postoperative naming decline nomograms project was funded by the NIH.

[email protected]

LOS ANGELES – A single look at the gut microbiome of patients with Alzheimer’s disease (AD) suggests an interaction between anti-inflammatory gut bacteria and long-term exposure to an investigational sigma 1 receptor agonist.

After up to 148 weeks treatment with Anavex 2-73, patients with stable or improved functional scores showed significantly higher levels of both Ruminococcaceae and Porphyromonadaceae, compared with patients who had declining function. Both bacterial families produce butyrate, an anti-inflammatory short-chain fatty acid.

Conversely, poor response was associated with a low level of Verrucomicrobia, a mucin-degrading phylum thought to be important in gut homeostasis. These bacteria live mainly in the intestinal mucosa – the physical interface between the microbiome and the rest of the body.

The data, presented at the Alzheimer’s Association International Conference, represent the first microbiome measurements reported in a clinical trial of an investigational Alzheimer’s therapy. Because they come from a single sample taken from a small group in an extension study, without a baseline comparator, it’s impossible to know what these associations mean. But the findings are enough to nudge Anavex Life Sciences into adding microbiome changes to its new study of Anavex 2-73, according to Christopher Missling, PhD, president and chief executive officer of the company.

The study, ramping up now, aims to recruit 450 patients with mild AD. They will be randomized to high-dose or mid-dose Anavex 2-73 for 48 weeks. The primary outcomes are measures of cognition and function. Stool sampling at baseline and at the end of the study will be included as well, Dr. Missling said in an interview.

Anavex 2-73 is a sigma-1 receptor agonist. A chaperone protein, sigma-1 is activated in response to acute and chronic cellular stressors, several which are important in neurodegeneration. The sigma-1 receptor is found on neurons and glia in many areas of the central nervous system. It modulates several processes implicated in neurodegenerative diseases, including glutamate and calcium activity, reaction to oxidative stress, and mitochondrial function. There is some evidence that sigma-1 receptor activation can induce neuronal regrowth and functional recovery after stroke. It also appears to play a role in helping cells clear misfolded proteins – a pathway that makes it an attractive drug target in Alzheimer’s disease, as well as other neurodegenerative diseases with aberrant proteins, such as Parkinson’s and Huntington’s diseases.

Anavex 2-73’s phase 2 development started with a 5-week crossover trial of 32 patients. This was followed by a 52-week, open-label extension trial of 10, 20, 30, and 50 mg/day orally, in which each patient was titrated to the maximum tolerated dose. The main endpoints were change on the Mini Mental State Exam and change on the Alzheimer’s Disease Cooperative Study-activities of daily living (ADCS-ADL) scale.

At 57 weeks, six patients had improved on the Mini Mental State Exam score: four with high plasma levels and two with low plasma levels, correlating to the dosage obtained. On the functional measure of activities of daily living, nine patients had improved, including five with high plasma levels, three with moderate levels, and one with a low level. One patient, with a moderate level, remained stable. The remaining 14 patients declined.

The company then enrolled 21 of the cohort in a 208-week extension trial, primarily because of patient request, Dr. Missling said. “They know they are doing better. Their families know they’re doing better. They did not want to give this up.”

Last fall, the company released 148-week functional and cognitive data confirming the initial findings: Patients with higher plasma levels (correlating with higher doses) declined about 2 points on the ADCS-ADL scale, compared with a mean decline of about 25 points among those with lower blood levels – an 88% difference in favor of treatment. Cognition scores showed a similar pattern, with the high-concentration group declining 64% less than the low-concentration group.

Sixteen patients consented to stool sampling. A sophisticated computer algorithm characterized the microbiome of each, measuring the relative abundance of phyla. Microbiome analysis wasn’t included as an endpoint in the original study design because, at that time, the idea of a connection between AD and the gut microbiome was barely on the research radar.

Things shifted dramatically in 2017, with a seminal paper finding that germ-free mice inoculated with stool from Parkinson’s patients developed Parkinson’s symptoms. This study was widely heralded as a breakthrough in the field – the first time any neurodegenerative disease had been conclusively linked to dysregulations in the human microbiome.

Last year, Vo Van Giau, PhD, of Gachon University, South Korea, and his colleagues published an extensive review of the data suggesting a similar link with Alzheimer’s disease.

Dr. Giau and his coauthors laid out a potential pathogenic pathway for this interaction.

“The microbiota is closely related to neurological dysfunction and plays a significant role in neuroinflammation through the secretion of proinflammatory cytokines. Changes in the homeostatic state of the microbiota lead to increased intestinal permeability, which may promote the translocation of bacteria and endotoxins across the epithelial barrier, inducing an immunological response associated with the production of proinflammatory cytokines. The activation of both enteric neurons and glial cells may result in various neurological disorders,” including Alzheimer’s, he wrote.

Dr. Missling said this paper, and smaller studies appearing at Alzheimer’s meetings, prompted the company to add the stool sampling as a follow-up measure.

“It’s something of great interest, we think, and deserves to be investigated.”

[email protected]

SOURCE: Missling C et al. AAIC 2019, Abstract 32260.

LOS ANGELES – A single look at the gut microbiome of patients with Alzheimer’s disease (AD) suggests an interaction between anti-inflammatory gut bacteria and long-term exposure to an investigational sigma 1 receptor agonist.

After up to 148 weeks treatment with Anavex 2-73, patients with stable or improved functional scores showed significantly higher levels of both Ruminococcaceae and Porphyromonadaceae, compared with patients who had declining function. Both bacterial families produce butyrate, an anti-inflammatory short-chain fatty acid.

Conversely, poor response was associated with a low level of Verrucomicrobia, a mucin-degrading phylum thought to be important in gut homeostasis. These bacteria live mainly in the intestinal mucosa – the physical interface between the microbiome and the rest of the body.

The data, presented at the Alzheimer’s Association International Conference, represent the first microbiome measurements reported in a clinical trial of an investigational Alzheimer’s therapy. Because they come from a single sample taken from a small group in an extension study, without a baseline comparator, it’s impossible to know what these associations mean. But the findings are enough to nudge Anavex Life Sciences into adding microbiome changes to its new study of Anavex 2-73, according to Christopher Missling, PhD, president and chief executive officer of the company.

The study, ramping up now, aims to recruit 450 patients with mild AD. They will be randomized to high-dose or mid-dose Anavex 2-73 for 48 weeks. The primary outcomes are measures of cognition and function. Stool sampling at baseline and at the end of the study will be included as well, Dr. Missling said in an interview.

Anavex 2-73 is a sigma-1 receptor agonist. A chaperone protein, sigma-1 is activated in response to acute and chronic cellular stressors, several which are important in neurodegeneration. The sigma-1 receptor is found on neurons and glia in many areas of the central nervous system. It modulates several processes implicated in neurodegenerative diseases, including glutamate and calcium activity, reaction to oxidative stress, and mitochondrial function. There is some evidence that sigma-1 receptor activation can induce neuronal regrowth and functional recovery after stroke. It also appears to play a role in helping cells clear misfolded proteins – a pathway that makes it an attractive drug target in Alzheimer’s disease, as well as other neurodegenerative diseases with aberrant proteins, such as Parkinson’s and Huntington’s diseases.

Anavex 2-73’s phase 2 development started with a 5-week crossover trial of 32 patients. This was followed by a 52-week, open-label extension trial of 10, 20, 30, and 50 mg/day orally, in which each patient was titrated to the maximum tolerated dose. The main endpoints were change on the Mini Mental State Exam and change on the Alzheimer’s Disease Cooperative Study-activities of daily living (ADCS-ADL) scale.

At 57 weeks, six patients had improved on the Mini Mental State Exam score: four with high plasma levels and two with low plasma levels, correlating to the dosage obtained. On the functional measure of activities of daily living, nine patients had improved, including five with high plasma levels, three with moderate levels, and one with a low level. One patient, with a moderate level, remained stable. The remaining 14 patients declined.

The company then enrolled 21 of the cohort in a 208-week extension trial, primarily because of patient request, Dr. Missling said. “They know they are doing better. Their families know they’re doing better. They did not want to give this up.”

Last fall, the company released 148-week functional and cognitive data confirming the initial findings: Patients with higher plasma levels (correlating with higher doses) declined about 2 points on the ADCS-ADL scale, compared with a mean decline of about 25 points among those with lower blood levels – an 88% difference in favor of treatment. Cognition scores showed a similar pattern, with the high-concentration group declining 64% less than the low-concentration group.

Sixteen patients consented to stool sampling. A sophisticated computer algorithm characterized the microbiome of each, measuring the relative abundance of phyla. Microbiome analysis wasn’t included as an endpoint in the original study design because, at that time, the idea of a connection between AD and the gut microbiome was barely on the research radar.

Things shifted dramatically in 2017, with a seminal paper finding that germ-free mice inoculated with stool from Parkinson’s patients developed Parkinson’s symptoms. This study was widely heralded as a breakthrough in the field – the first time any neurodegenerative disease had been conclusively linked to dysregulations in the human microbiome.

Last year, Vo Van Giau, PhD, of Gachon University, South Korea, and his colleagues published an extensive review of the data suggesting a similar link with Alzheimer’s disease.

Dr. Giau and his coauthors laid out a potential pathogenic pathway for this interaction.

“The microbiota is closely related to neurological dysfunction and plays a significant role in neuroinflammation through the secretion of proinflammatory cytokines. Changes in the homeostatic state of the microbiota lead to increased intestinal permeability, which may promote the translocation of bacteria and endotoxins across the epithelial barrier, inducing an immunological response associated with the production of proinflammatory cytokines. The activation of both enteric neurons and glial cells may result in various neurological disorders,” including Alzheimer’s, he wrote.

Dr. Missling said this paper, and smaller studies appearing at Alzheimer’s meetings, prompted the company to add the stool sampling as a follow-up measure.

“It’s something of great interest, we think, and deserves to be investigated.”

[email protected]

SOURCE: Missling C et al. AAIC 2019, Abstract 32260.

LOS ANGELES – A single look at the gut microbiome of patients with Alzheimer’s disease (AD) suggests an interaction between anti-inflammatory gut bacteria and long-term exposure to an investigational sigma 1 receptor agonist.

After up to 148 weeks treatment with Anavex 2-73, patients with stable or improved functional scores showed significantly higher levels of both Ruminococcaceae and Porphyromonadaceae, compared with patients who had declining function. Both bacterial families produce butyrate, an anti-inflammatory short-chain fatty acid.

Conversely, poor response was associated with a low level of Verrucomicrobia, a mucin-degrading phylum thought to be important in gut homeostasis. These bacteria live mainly in the intestinal mucosa – the physical interface between the microbiome and the rest of the body.

The data, presented at the Alzheimer’s Association International Conference, represent the first microbiome measurements reported in a clinical trial of an investigational Alzheimer’s therapy. Because they come from a single sample taken from a small group in an extension study, without a baseline comparator, it’s impossible to know what these associations mean. But the findings are enough to nudge Anavex Life Sciences into adding microbiome changes to its new study of Anavex 2-73, according to Christopher Missling, PhD, president and chief executive officer of the company.

The study, ramping up now, aims to recruit 450 patients with mild AD. They will be randomized to high-dose or mid-dose Anavex 2-73 for 48 weeks. The primary outcomes are measures of cognition and function. Stool sampling at baseline and at the end of the study will be included as well, Dr. Missling said in an interview.

Anavex 2-73 is a sigma-1 receptor agonist. A chaperone protein, sigma-1 is activated in response to acute and chronic cellular stressors, several which are important in neurodegeneration. The sigma-1 receptor is found on neurons and glia in many areas of the central nervous system. It modulates several processes implicated in neurodegenerative diseases, including glutamate and calcium activity, reaction to oxidative stress, and mitochondrial function. There is some evidence that sigma-1 receptor activation can induce neuronal regrowth and functional recovery after stroke. It also appears to play a role in helping cells clear misfolded proteins – a pathway that makes it an attractive drug target in Alzheimer’s disease, as well as other neurodegenerative diseases with aberrant proteins, such as Parkinson’s and Huntington’s diseases.

Anavex 2-73’s phase 2 development started with a 5-week crossover trial of 32 patients. This was followed by a 52-week, open-label extension trial of 10, 20, 30, and 50 mg/day orally, in which each patient was titrated to the maximum tolerated dose. The main endpoints were change on the Mini Mental State Exam and change on the Alzheimer’s Disease Cooperative Study-activities of daily living (ADCS-ADL) scale.

At 57 weeks, six patients had improved on the Mini Mental State Exam score: four with high plasma levels and two with low plasma levels, correlating to the dosage obtained. On the functional measure of activities of daily living, nine patients had improved, including five with high plasma levels, three with moderate levels, and one with a low level. One patient, with a moderate level, remained stable. The remaining 14 patients declined.

The company then enrolled 21 of the cohort in a 208-week extension trial, primarily because of patient request, Dr. Missling said. “They know they are doing better. Their families know they’re doing better. They did not want to give this up.”

Last fall, the company released 148-week functional and cognitive data confirming the initial findings: Patients with higher plasma levels (correlating with higher doses) declined about 2 points on the ADCS-ADL scale, compared with a mean decline of about 25 points among those with lower blood levels – an 88% difference in favor of treatment. Cognition scores showed a similar pattern, with the high-concentration group declining 64% less than the low-concentration group.

Sixteen patients consented to stool sampling. A sophisticated computer algorithm characterized the microbiome of each, measuring the relative abundance of phyla. Microbiome analysis wasn’t included as an endpoint in the original study design because, at that time, the idea of a connection between AD and the gut microbiome was barely on the research radar.

Things shifted dramatically in 2017, with a seminal paper finding that germ-free mice inoculated with stool from Parkinson’s patients developed Parkinson’s symptoms. This study was widely heralded as a breakthrough in the field – the first time any neurodegenerative disease had been conclusively linked to dysregulations in the human microbiome.

Last year, Vo Van Giau, PhD, of Gachon University, South Korea, and his colleagues published an extensive review of the data suggesting a similar link with Alzheimer’s disease.

Dr. Giau and his coauthors laid out a potential pathogenic pathway for this interaction.

“The microbiota is closely related to neurological dysfunction and plays a significant role in neuroinflammation through the secretion of proinflammatory cytokines. Changes in the homeostatic state of the microbiota lead to increased intestinal permeability, which may promote the translocation of bacteria and endotoxins across the epithelial barrier, inducing an immunological response associated with the production of proinflammatory cytokines. The activation of both enteric neurons and glial cells may result in various neurological disorders,” including Alzheimer’s, he wrote.

Dr. Missling said this paper, and smaller studies appearing at Alzheimer’s meetings, prompted the company to add the stool sampling as a follow-up measure.

“It’s something of great interest, we think, and deserves to be investigated.”

[email protected]

SOURCE: Missling C et al. AAIC 2019, Abstract 32260.

LUGANO, SWITZERLAND – A combination of 5-azacytidine and romidepsin showed promising activity in patients with peripheral T cell lymphomas, particularly angioimmunoblastic T-cell lymphoma (AITL) and primary cutaneous follicular helper T-cell lymphoma (PTCL-TFH), results of a phase 2 study showed.

Of 16 patients with AITL or PTCL-TFH, 11 (69%) had a clinical response to the 5-azacytidine (AZA)/romidepsin combination, including 8 (50%) with complete responses (CRs), and 3 with partial responses (PRs), reported Lorenzo Falchi, MD, of Columbia University Medical Center and New York Presbyterian Hospital, New York, and colleagues.

“We show that the combination of oral AZA/romidepsin is remarkably active in patients with T-cell lymphomas. Clearly more patients with other subtypes are needed to better evaluate this combination,” Dr. Falchi said at the International Conference on Malignant Lymphoma.

The combination is intended to target epigenetic changes in PTCLs, which often bear mutations in TET2, DNMT3A, and IDH2. These mutations create global hypermethylation and cause transcriptional silencing of tumor suppressor genes, Dr. Falchi said.

Both histone deacetylase inhibitors such as romidepsin, and hypomethylating agents such as AZA have been shown to have single-agent activity against PTCL, and as previously reported at the 2018 T-cell Lymphoma Forum, the combination produced a higher overall response rate (ORR) and prolonged progression-free survival (PFS) in patients with T-cell lymphomas.

Dr. Falchi presented the phase 2 results at 15-ICML. A total of 25 patients with newly diagnosed or relapsed/refractory PTCL were treated with AZA 300 mg daily on days 1-14 and romidepsin 14 mg/m² on days 8, 15, and 22, every 35 days.

A total of 24 patients were evaluable for response. The ORR – the primary endpoint – was achieved in 14 patients (58%), and included 10 CRs and 4 PRs. Three additional patients had stable disease, and six patients experienced disease progression (response data for one patient was not complete at the time of the presentation).

In total, 11 of 16 patients with AITL/PTCL-TFH had responses, compared with 3 of 8 patients with other histologies.

A secondary analysis of 16 patients with information on mutational status showed that 10 of 12 patients with TET2 mutations (83%) had responses, including 8 CRs and 2 PRs. Two additional patients with TET2 mutations had disease progression. In contrast, among four patients without TET2 mutations, one had a CR, one a PR, and two had disease progression.

Of the 10 patients overall with CRs, 5 patients were receiving the combination in the first line, and 5 patients were receiving it for relapsed/refractory disease.

Median PFS among all patients was 8.7 months. The median overall survival has not been reached. Among patients with the AITL or PTCL-TFH subtypes, median PFS was 8.7 months, compared with 2.3 months for patients with other histologies.

The most frequent hematologic grade 3 or 4 adverse events were thrombocytopenia and neutropenia. The most frequent nonhematologic grade 3 or 4 events included lung infection and febrile neutropenia. Common grade 1 or 2 toxicities included anemia, diarrhea, fatigue, nausea, and vomiting. No patients discontinued therapy because of adverse events.

Dr. Falchi noted that a phase 1 trial evaluating the immune checkpoint inhibitor durvalumab (Imfinzi) with AZA or romidepsin alone or in combination, or pralatrexate and romidepsin, is currently recruiting.

Dr. Falchi reported having no financial disclosures. Other investigators reported funding from Celgene, which supported the study.

SOURCE: Falchi L et al. 15-ICML, Abstract 129.

LUGANO, SWITZERLAND – A combination of 5-azacytidine and romidepsin showed promising activity in patients with peripheral T cell lymphomas, particularly angioimmunoblastic T-cell lymphoma (AITL) and primary cutaneous follicular helper T-cell lymphoma (PTCL-TFH), results of a phase 2 study showed.

Of 16 patients with AITL or PTCL-TFH, 11 (69%) had a clinical response to the 5-azacytidine (AZA)/romidepsin combination, including 8 (50%) with complete responses (CRs), and 3 with partial responses (PRs), reported Lorenzo Falchi, MD, of Columbia University Medical Center and New York Presbyterian Hospital, New York, and colleagues.

“We show that the combination of oral AZA/romidepsin is remarkably active in patients with T-cell lymphomas. Clearly more patients with other subtypes are needed to better evaluate this combination,” Dr. Falchi said at the International Conference on Malignant Lymphoma.

The combination is intended to target epigenetic changes in PTCLs, which often bear mutations in TET2, DNMT3A, and IDH2. These mutations create global hypermethylation and cause transcriptional silencing of tumor suppressor genes, Dr. Falchi said.

Both histone deacetylase inhibitors such as romidepsin, and hypomethylating agents such as AZA have been shown to have single-agent activity against PTCL, and as previously reported at the 2018 T-cell Lymphoma Forum, the combination produced a higher overall response rate (ORR) and prolonged progression-free survival (PFS) in patients with T-cell lymphomas.

Dr. Falchi presented the phase 2 results at 15-ICML. A total of 25 patients with newly diagnosed or relapsed/refractory PTCL were treated with AZA 300 mg daily on days 1-14 and romidepsin 14 mg/m² on days 8, 15, and 22, every 35 days.

A total of 24 patients were evaluable for response. The ORR – the primary endpoint – was achieved in 14 patients (58%), and included 10 CRs and 4 PRs. Three additional patients had stable disease, and six patients experienced disease progression (response data for one patient was not complete at the time of the presentation).

In total, 11 of 16 patients with AITL/PTCL-TFH had responses, compared with 3 of 8 patients with other histologies.

A secondary analysis of 16 patients with information on mutational status showed that 10 of 12 patients with TET2 mutations (83%) had responses, including 8 CRs and 2 PRs. Two additional patients with TET2 mutations had disease progression. In contrast, among four patients without TET2 mutations, one had a CR, one a PR, and two had disease progression.

Of the 10 patients overall with CRs, 5 patients were receiving the combination in the first line, and 5 patients were receiving it for relapsed/refractory disease.

Median PFS among all patients was 8.7 months. The median overall survival has not been reached. Among patients with the AITL or PTCL-TFH subtypes, median PFS was 8.7 months, compared with 2.3 months for patients with other histologies.

The most frequent hematologic grade 3 or 4 adverse events were thrombocytopenia and neutropenia. The most frequent nonhematologic grade 3 or 4 events included lung infection and febrile neutropenia. Common grade 1 or 2 toxicities included anemia, diarrhea, fatigue, nausea, and vomiting. No patients discontinued therapy because of adverse events.

Dr. Falchi noted that a phase 1 trial evaluating the immune checkpoint inhibitor durvalumab (Imfinzi) with AZA or romidepsin alone or in combination, or pralatrexate and romidepsin, is currently recruiting.

Dr. Falchi reported having no financial disclosures. Other investigators reported funding from Celgene, which supported the study.

SOURCE: Falchi L et al. 15-ICML, Abstract 129.

LUGANO, SWITZERLAND – A combination of 5-azacytidine and romidepsin showed promising activity in patients with peripheral T cell lymphomas, particularly angioimmunoblastic T-cell lymphoma (AITL) and primary cutaneous follicular helper T-cell lymphoma (PTCL-TFH), results of a phase 2 study showed.

Of 16 patients with AITL or PTCL-TFH, 11 (69%) had a clinical response to the 5-azacytidine (AZA)/romidepsin combination, including 8 (50%) with complete responses (CRs), and 3 with partial responses (PRs), reported Lorenzo Falchi, MD, of Columbia University Medical Center and New York Presbyterian Hospital, New York, and colleagues.

“We show that the combination of oral AZA/romidepsin is remarkably active in patients with T-cell lymphomas. Clearly more patients with other subtypes are needed to better evaluate this combination,” Dr. Falchi said at the International Conference on Malignant Lymphoma.

The combination is intended to target epigenetic changes in PTCLs, which often bear mutations in TET2, DNMT3A, and IDH2. These mutations create global hypermethylation and cause transcriptional silencing of tumor suppressor genes, Dr. Falchi said.

Both histone deacetylase inhibitors such as romidepsin, and hypomethylating agents such as AZA have been shown to have single-agent activity against PTCL, and as previously reported at the 2018 T-cell Lymphoma Forum, the combination produced a higher overall response rate (ORR) and prolonged progression-free survival (PFS) in patients with T-cell lymphomas.

Dr. Falchi presented the phase 2 results at 15-ICML. A total of 25 patients with newly diagnosed or relapsed/refractory PTCL were treated with AZA 300 mg daily on days 1-14 and romidepsin 14 mg/m² on days 8, 15, and 22, every 35 days.

A total of 24 patients were evaluable for response. The ORR – the primary endpoint – was achieved in 14 patients (58%), and included 10 CRs and 4 PRs. Three additional patients had stable disease, and six patients experienced disease progression (response data for one patient was not complete at the time of the presentation).

In total, 11 of 16 patients with AITL/PTCL-TFH had responses, compared with 3 of 8 patients with other histologies.

A secondary analysis of 16 patients with information on mutational status showed that 10 of 12 patients with TET2 mutations (83%) had responses, including 8 CRs and 2 PRs. Two additional patients with TET2 mutations had disease progression. In contrast, among four patients without TET2 mutations, one had a CR, one a PR, and two had disease progression.

Of the 10 patients overall with CRs, 5 patients were receiving the combination in the first line, and 5 patients were receiving it for relapsed/refractory disease.

Median PFS among all patients was 8.7 months. The median overall survival has not been reached. Among patients with the AITL or PTCL-TFH subtypes, median PFS was 8.7 months, compared with 2.3 months for patients with other histologies.

The most frequent hematologic grade 3 or 4 adverse events were thrombocytopenia and neutropenia. The most frequent nonhematologic grade 3 or 4 events included lung infection and febrile neutropenia. Common grade 1 or 2 toxicities included anemia, diarrhea, fatigue, nausea, and vomiting. No patients discontinued therapy because of adverse events.

Dr. Falchi noted that a phase 1 trial evaluating the immune checkpoint inhibitor durvalumab (Imfinzi) with AZA or romidepsin alone or in combination, or pralatrexate and romidepsin, is currently recruiting.

Dr. Falchi reported having no financial disclosures. Other investigators reported funding from Celgene, which supported the study.

SOURCE: Falchi L et al. 15-ICML, Abstract 129.

Paclitaxel-coated devices, which are used to treat peripheral artery disease (PAD), appear to have a nearly 60% higher mortality risk than uncoated devices, according to a letter to health care providers from the Food and Drug Administration.

This letter updates details about long-term follow-up data and panel conclusions reviewed by the Food and Drug Administration, as well as recommendations from the agency regarding these devices. On Jan. 17, 2019, the FDA notified providers regarding an apparent increased late mortality risk seen with paclitaxel-eluting stents and paclitaxel-coated balloons placed in the femoropopliteal artery in patients with PAD. The agency issued an update March 15.

In a public meeting June 19-20, the Circulatory System Devices Panel of the Medical Devices Advisory Committee discussed long-term follow-up data that demonstrated a 57% relative increase in mortality among PAD patients treated with paclitaxel-coated devices when compared with those receiving uncoated devices. The panel concluded that the late mortality signal was real and warranted further study and action, a conclusion with which the FDA has concurred.

Among other recommendations issued by the FDA, health care professionals should continue to closely monitor patients who’ve already received the devices and fully discuss the risks and benefits of these devices with patients. The FDA has decided that, given the demonstrated short-term benefits of these devices, clinical studies may continue and should collect long-term safety and effectiveness data.

The magnitude of this late mortality signal should be interpreted with caution, the FDA noted in the update, because of the wide confidence intervals (although the relative risk was 1.57, the 95% confidence interval was 1.16-2.13, which translates to 16%-113% higher relative risk), pooling studies of different devices that weren’t meant to be combined, missing data, and other reasons.

The full letter, including more detailed data and the full list of recommendations, is available on the FDA’s website.

[email protected]

Paclitaxel-coated devices, which are used to treat peripheral artery disease (PAD), appear to have a nearly 60% higher mortality risk than uncoated devices, according to a letter to health care providers from the Food and Drug Administration.

This letter updates details about long-term follow-up data and panel conclusions reviewed by the Food and Drug Administration, as well as recommendations from the agency regarding these devices. On Jan. 17, 2019, the FDA notified providers regarding an apparent increased late mortality risk seen with paclitaxel-eluting stents and paclitaxel-coated balloons placed in the femoropopliteal artery in patients with PAD. The agency issued an update March 15.

In a public meeting June 19-20, the Circulatory System Devices Panel of the Medical Devices Advisory Committee discussed long-term follow-up data that demonstrated a 57% relative increase in mortality among PAD patients treated with paclitaxel-coated devices when compared with those receiving uncoated devices. The panel concluded that the late mortality signal was real and warranted further study and action, a conclusion with which the FDA has concurred.

Among other recommendations issued by the FDA, health care professionals should continue to closely monitor patients who’ve already received the devices and fully discuss the risks and benefits of these devices with patients. The FDA has decided that, given the demonstrated short-term benefits of these devices, clinical studies may continue and should collect long-term safety and effectiveness data.

The magnitude of this late mortality signal should be interpreted with caution, the FDA noted in the update, because of the wide confidence intervals (although the relative risk was 1.57, the 95% confidence interval was 1.16-2.13, which translates to 16%-113% higher relative risk), pooling studies of different devices that weren’t meant to be combined, missing data, and other reasons.

The full letter, including more detailed data and the full list of recommendations, is available on the FDA’s website.

[email protected]

Paclitaxel-coated devices, which are used to treat peripheral artery disease (PAD), appear to have a nearly 60% higher mortality risk than uncoated devices, according to a letter to health care providers from the Food and Drug Administration.

This letter updates details about long-term follow-up data and panel conclusions reviewed by the Food and Drug Administration, as well as recommendations from the agency regarding these devices. On Jan. 17, 2019, the FDA notified providers regarding an apparent increased late mortality risk seen with paclitaxel-eluting stents and paclitaxel-coated balloons placed in the femoropopliteal artery in patients with PAD. The agency issued an update March 15.

In a public meeting June 19-20, the Circulatory System Devices Panel of the Medical Devices Advisory Committee discussed long-term follow-up data that demonstrated a 57% relative increase in mortality among PAD patients treated with paclitaxel-coated devices when compared with those receiving uncoated devices. The panel concluded that the late mortality signal was real and warranted further study and action, a conclusion with which the FDA has concurred.

Among other recommendations issued by the FDA, health care professionals should continue to closely monitor patients who’ve already received the devices and fully discuss the risks and benefits of these devices with patients. The FDA has decided that, given the demonstrated short-term benefits of these devices, clinical studies may continue and should collect long-term safety and effectiveness data.

The magnitude of this late mortality signal should be interpreted with caution, the FDA noted in the update, because of the wide confidence intervals (although the relative risk was 1.57, the 95% confidence interval was 1.16-2.13, which translates to 16%-113% higher relative risk), pooling studies of different devices that weren’t meant to be combined, missing data, and other reasons.

The full letter, including more detailed data and the full list of recommendations, is available on the FDA’s website.

[email protected]

To the Editor:

In the April 2019 Cutis article by John and Lipner,¹ the authors critiqued the American Academy of Dermatology Basic Dermatology Curriculum (BDC) for not providing an adequate scaffolding of nail findings on which dermatology residents can build their knowledge base; however, that criticism belies a misunderstanding of the BDC’s purpose. It was carefully designed to address the needs of undifferentiated medical students and primary care learners based on needs assessments from practicing primary care physicians and experienced dermatology educators.^2,3 Given the limited amount of time to teach, a basic curriculum must focus on the most high-yield items. The BDC work group developed goals and objectives based on needs assessments for primary care practice with 38 core dermatology diagnoses, including 3 diagnoses with important nail findings: onychomycosis, melanoma, and psoriasis. Much repetition is built into the BDC, and the same diagnosis is used in multiple cases in different modules to encourage retention of information. Therefore, “analysis of nail-related content” should focus on diagnoses rather than cases, and for each diagnosis, note whether the nail findings are a pertinent negative or pertinent positive. In cases of the other 35 diagnoses covered in the BDC, nail findings are omitted for space because they are not relevant (eg, in cases of seborrheic dermatitis or rosacea). Normal nail findings are not pertinent negatives for most diagnoses in the BDC, except in cases with diagnoses for which psoriasis is in the differential, such as nummular dermatitis or pityriasis rosea.

Furthermore, a true analysis of the needs of medical students and primary care learners with regard to nail findings would begin with a needs assessment of the most common nail conditions evaluated in the primary care and urgent care settings. Ingrown nails, paronychia, onychomycosis, and subungual hematomas and other nail traumas are the most common nail conditions encountered in primary care and urgent care,^4-10 but John and Lipner¹ failed to perform analysis or needs assessment based on the incidence of nail diagnoses in these settings.

Other sources for medical students and primary care residents include excellent introductions to nail findings. The newly revised skin chapter of Bates’ Guide to Physical Examination and History Taking¹¹ includes updated photographs of common nail findings and discusses the importance of examining nails in the full-body skin examination. Additionally, Clinical Dermatology: A Color Guide to Diagnosis and Therapy,¹²Lookingbill and Marks’ Principles of Dermatology,¹³ and The Color Atlas and Synopsis of Family Medicine¹⁴ cover nail disease beautifully for medical students and primary care learners. The BDC was never meant to supplant these bountiful resources.

The authors referred to lack of confidence in nail diagnoses among dermatology residents,¹ which is a very real problem that must be addressed by dermatology residency programs. The BDC is not the proper vehicle for training dermatology residents about these conditions; that is the responsibility and challenge of our dermatology residency programs. The authors also suggested teaching how to perform nail biopsies in the BDC.¹ It not reasonable to expect that our primary care colleagues will be performing nail biopsies. A more appropriate level of expectation is that they would know when to refer patients to dermatology; for example, they should know that a pigmented streak on a single nail that is expanding is an indication for referral to a dermatologist.

If the authors or others were to propose an additional nail module to the BDC work group, they would need to include an analysis of the literature regarding the incidence of nail disease seen in primary care and urgent care settings rather than the nail conditions seen by referral bias experienced by consulting dermatologists. The analysis would be worth considering and worthy of the goodwill engendered by the creation of the BDC in the first place.

Sincerely,

Patrick E. McCleskey, MD

From the Department of Dermatology, Kaiser Permanente Oakland Medical Center, California.

Dr. McCleskey previously served as Chair of the American Academy of Dermatology Basic Dermatology Curriculum Work Group (2013-2017) .

Correspondence: Patrick E. McCleskey, MD, 3701 Broadway, 4th Floor, Oakland, CA 94611 ([email protected]).
 

References

1. John JJ, Lipner SR. Analysis of nail-related content in the basic dermatology curriculum. Cutis. 2019;103:214-216.

2. Hansra NK, O’Sullivan P, Chen CL, et al. Medical school dermatology curriculum: are we adequately preparing primary care physicians? J Am Acad Dermatol. 2009;61:23-29.

3. McCleskey PE, Gilson RT, Devillez R. Medical student core curriculum in dermatology survey. J Am Acad Dermatol. 2009;61:30-35.

4. Vierhoeven EWM, Kraaimaat FW, van Wheel C, et al. Skin diseases in family medicine: prevalence and health care use. Ann Fam Med. 2008;6:349-354.

5. Fleisher AB, Herbert CR, Feldman SR, et al. Diagnosis of skin disease by non-dermatologists. Am J Manag Care. 2000;6;1149-1156.

6. Akbas A, Kilinc F, Yakut HI, et al. Nail disorders in children, a clinical study. Our Dermatol Online. 2016;7:149-154.

7. Nadkarni A, Domeisen N, Hill D, et al. The most common dermatology diagnoses in the emergency department. J Am Acad Dermatol. 2016;75:1261-1262.

8. Baibergenova A, Shear NH. Skin conditions that bring patients to emergency departments. Arch Dermatol. 2011;147:118-120.

9. Wang E, Lim BL, Than KY. Dermatological conditions presenting at an emergency department in Singapore. Singapore Med J. 2009;50:881-884.

10. Lai-Kwon J, Weiland TJ, Chong AH, et al. Which dermatological conditions present to an emergency department in Australia? Emerg Med Int. 2014;2014:463026.

11. McCleskey PE. The skin, hair, and nails. In: Bickley L, ed. Bates’ Guide to Physical Examination and History Taking. 12th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2017:173-214.

12. Habif TP. Nail diseases. In: Habif TP, ed. Clinical Dermatology: A Color Guide to Diagnosis and Therapy. 6th ed. China: Elsevier; 2016:960-985.

13. Marks JG, Miller JJ. Nail disorders. In: Marks JG, Miller JJ, eds. Lookingbill and Marks’ Principles of Dermatology. 6th ed. China: Elsevier; 2019:277-282.

14. Mayeaux EJ Jr, Williams J. Hair and nail conditions. In: Usatine RP, Smith MA, Mayeaux EJ Jr, et al. The Color Atlas and Synopsis of Family Medicine. 3rd ed. New York, NY: McGraw-Hill Education; 2019.

Author Response

I thank Dr. McCleskey for his interest in our article. Although I acknowledge that the Basic Dermatology Curriculum (BDC) serves as an introduction to dermatology for medical students and primary care physicians, I disagree that the current curriculum should be limited to only 3 diagnoses with important nail findings—onychomycosis, melanoma, and psoriasis—and exclude other common and potentially fatal nail diseases.

To characterize the overall nail burden of ambulatory care visits in the United States, data from the National Ambulatory Medical Care Survey from 2007 to 2016 were analyzed and there were more than 20 million outpatient visits for nail concerns during this period; furthermore, although many patients were seen by dermatologists, a considerable number were seen by pediatricians and general practitioners (Lipner SR, Hancock J, Fleischer AB Jr; unpublished data; July 2019). These findings underscore the importance of educating medical students and primary care physicians on the diagnosis and appropriate referral of patients with nail diseases.

Some limited information on nail unit melanomas is included in the BDC, but it is essential that medical students and general practitioners be educated about early diagnosis of squamous cell carcinomas and melanomas of the nail unit, which may help avoid unnecessary amputations and decrease mortality.¹ Unfortunately, the vast majority of nail unit melanomas are diagnosed at stage II or later, which has been partially attributed to clinical knowledge gaps in the understanding of nail disease.²

Several studies have shown that many physicians fail to examine their patients’ nails during physical examinations, either due to concealment with nail polish or lack of clinical awareness. In a survey-based study analyzing patients’ awareness of longitudinal melanonychia and worrisome signs of nail unit melanoma, only 12% of patients (43/363) stated that their dermatologist or internist specifically asked them about nail changes.³ Furthermore, in another survey-based study of nail examinations at a free cancer screening by the American Academy of Dermatology, more than half of female participants (47/87 [54%]) stated that they were wearing nail polish at the time of screening.^4,5 Therefore, examinations of the nails were not performed as part of the total-body skin examination.

In summary, nail diseases are an important concern in clinical practice with aesthetic and functional consequences. There is a strong need to emphasize the importance of nail examinations for diagnostic purposes and to incorporate more expansive nail-related content into the BDC, which can result in longer and more functional lives for our patients.

Sincerely,

Shari R. Lipner, MD, PhD
 

From the Department of Dermatology, Weill Cornell Medicine, New York, New York.

The author reports no conflict of interest.

References

1. Lipner SR. Ulcerated nodule of the fingernail. JAMA. 2018;319:713.

2. Tan KB, Moncrieff M, Thompson JF, et al. Subungual melanoma: a study of 124 cases highlighting features of early lesions, potential pitfalls in diagnosis, and guidelines for histologic reporting. Am J Surg Pathol. 2007;31:1902-1912.

3. Halteh P, Scher R, Artis A, et al. Assessment of patient knowledge of longitudinal melanonychia: a survey study of patients in outpatient clinics. Skin Appendage Disord. 2017;2:156-161.

4. Ko D, Lipner SR. A survey-based study on nail examinations at an American Academy of Dermatology free skin cancer screening. J Am Acad Dermatol. 2018;79:975-978.

5. Ko D, Lipner SR. Comment on: “The first 30 years of the American Academy of Dermatology skin cancer screening program: 1985-2014.” J Am Acad Dermatol. 2019;80:e23.

To the Editor:

In the April 2019 Cutis article by John and Lipner,¹ the authors critiqued the American Academy of Dermatology Basic Dermatology Curriculum (BDC) for not providing an adequate scaffolding of nail findings on which dermatology residents can build their knowledge base; however, that criticism belies a misunderstanding of the BDC’s purpose. It was carefully designed to address the needs of undifferentiated medical students and primary care learners based on needs assessments from practicing primary care physicians and experienced dermatology educators.^2,3 Given the limited amount of time to teach, a basic curriculum must focus on the most high-yield items. The BDC work group developed goals and objectives based on needs assessments for primary care practice with 38 core dermatology diagnoses, including 3 diagnoses with important nail findings: onychomycosis, melanoma, and psoriasis. Much repetition is built into the BDC, and the same diagnosis is used in multiple cases in different modules to encourage retention of information. Therefore, “analysis of nail-related content” should focus on diagnoses rather than cases, and for each diagnosis, note whether the nail findings are a pertinent negative or pertinent positive. In cases of the other 35 diagnoses covered in the BDC, nail findings are omitted for space because they are not relevant (eg, in cases of seborrheic dermatitis or rosacea). Normal nail findings are not pertinent negatives for most diagnoses in the BDC, except in cases with diagnoses for which psoriasis is in the differential, such as nummular dermatitis or pityriasis rosea.

Furthermore, a true analysis of the needs of medical students and primary care learners with regard to nail findings would begin with a needs assessment of the most common nail conditions evaluated in the primary care and urgent care settings. Ingrown nails, paronychia, onychomycosis, and subungual hematomas and other nail traumas are the most common nail conditions encountered in primary care and urgent care,^4-10 but John and Lipner¹ failed to perform analysis or needs assessment based on the incidence of nail diagnoses in these settings.

Other sources for medical students and primary care residents include excellent introductions to nail findings. The newly revised skin chapter of Bates’ Guide to Physical Examination and History Taking¹¹ includes updated photographs of common nail findings and discusses the importance of examining nails in the full-body skin examination. Additionally, Clinical Dermatology: A Color Guide to Diagnosis and Therapy,¹²Lookingbill and Marks’ Principles of Dermatology,¹³ and The Color Atlas and Synopsis of Family Medicine¹⁴ cover nail disease beautifully for medical students and primary care learners. The BDC was never meant to supplant these bountiful resources.

The authors referred to lack of confidence in nail diagnoses among dermatology residents,¹ which is a very real problem that must be addressed by dermatology residency programs. The BDC is not the proper vehicle for training dermatology residents about these conditions; that is the responsibility and challenge of our dermatology residency programs. The authors also suggested teaching how to perform nail biopsies in the BDC.¹ It not reasonable to expect that our primary care colleagues will be performing nail biopsies. A more appropriate level of expectation is that they would know when to refer patients to dermatology; for example, they should know that a pigmented streak on a single nail that is expanding is an indication for referral to a dermatologist.

If the authors or others were to propose an additional nail module to the BDC work group, they would need to include an analysis of the literature regarding the incidence of nail disease seen in primary care and urgent care settings rather than the nail conditions seen by referral bias experienced by consulting dermatologists. The analysis would be worth considering and worthy of the goodwill engendered by the creation of the BDC in the first place.

Sincerely,

Patrick E. McCleskey, MD

From the Department of Dermatology, Kaiser Permanente Oakland Medical Center, California.

Dr. McCleskey previously served as Chair of the American Academy of Dermatology Basic Dermatology Curriculum Work Group (2013-2017) .

Correspondence: Patrick E. McCleskey, MD, 3701 Broadway, 4th Floor, Oakland, CA 94611 ([email protected]).
 

References

1. John JJ, Lipner SR. Analysis of nail-related content in the basic dermatology curriculum. Cutis. 2019;103:214-216.

2. Hansra NK, O’Sullivan P, Chen CL, et al. Medical school dermatology curriculum: are we adequately preparing primary care physicians? J Am Acad Dermatol. 2009;61:23-29.

3. McCleskey PE, Gilson RT, Devillez R. Medical student core curriculum in dermatology survey. J Am Acad Dermatol. 2009;61:30-35.

4. Vierhoeven EWM, Kraaimaat FW, van Wheel C, et al. Skin diseases in family medicine: prevalence and health care use. Ann Fam Med. 2008;6:349-354.

5. Fleisher AB, Herbert CR, Feldman SR, et al. Diagnosis of skin disease by non-dermatologists. Am J Manag Care. 2000;6;1149-1156.

6. Akbas A, Kilinc F, Yakut HI, et al. Nail disorders in children, a clinical study. Our Dermatol Online. 2016;7:149-154.

7. Nadkarni A, Domeisen N, Hill D, et al. The most common dermatology diagnoses in the emergency department. J Am Acad Dermatol. 2016;75:1261-1262.

8. Baibergenova A, Shear NH. Skin conditions that bring patients to emergency departments. Arch Dermatol. 2011;147:118-120.

9. Wang E, Lim BL, Than KY. Dermatological conditions presenting at an emergency department in Singapore. Singapore Med J. 2009;50:881-884.

10. Lai-Kwon J, Weiland TJ, Chong AH, et al. Which dermatological conditions present to an emergency department in Australia? Emerg Med Int. 2014;2014:463026.

11. McCleskey PE. The skin, hair, and nails. In: Bickley L, ed. Bates’ Guide to Physical Examination and History Taking. 12th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2017:173-214.

12. Habif TP. Nail diseases. In: Habif TP, ed. Clinical Dermatology: A Color Guide to Diagnosis and Therapy. 6th ed. China: Elsevier; 2016:960-985.

13. Marks JG, Miller JJ. Nail disorders. In: Marks JG, Miller JJ, eds. Lookingbill and Marks’ Principles of Dermatology. 6th ed. China: Elsevier; 2019:277-282.

14. Mayeaux EJ Jr, Williams J. Hair and nail conditions. In: Usatine RP, Smith MA, Mayeaux EJ Jr, et al. The Color Atlas and Synopsis of Family Medicine. 3rd ed. New York, NY: McGraw-Hill Education; 2019.

Author Response

I thank Dr. McCleskey for his interest in our article. Although I acknowledge that the Basic Dermatology Curriculum (BDC) serves as an introduction to dermatology for medical students and primary care physicians, I disagree that the current curriculum should be limited to only 3 diagnoses with important nail findings—onychomycosis, melanoma, and psoriasis—and exclude other common and potentially fatal nail diseases.

To characterize the overall nail burden of ambulatory care visits in the United States, data from the National Ambulatory Medical Care Survey from 2007 to 2016 were analyzed and there were more than 20 million outpatient visits for nail concerns during this period; furthermore, although many patients were seen by dermatologists, a considerable number were seen by pediatricians and general practitioners (Lipner SR, Hancock J, Fleischer AB Jr; unpublished data; July 2019). These findings underscore the importance of educating medical students and primary care physicians on the diagnosis and appropriate referral of patients with nail diseases.

Some limited information on nail unit melanomas is included in the BDC, but it is essential that medical students and general practitioners be educated about early diagnosis of squamous cell carcinomas and melanomas of the nail unit, which may help avoid unnecessary amputations and decrease mortality.¹ Unfortunately, the vast majority of nail unit melanomas are diagnosed at stage II or later, which has been partially attributed to clinical knowledge gaps in the understanding of nail disease.²

Several studies have shown that many physicians fail to examine their patients’ nails during physical examinations, either due to concealment with nail polish or lack of clinical awareness. In a survey-based study analyzing patients’ awareness of longitudinal melanonychia and worrisome signs of nail unit melanoma, only 12% of patients (43/363) stated that their dermatologist or internist specifically asked them about nail changes.³ Furthermore, in another survey-based study of nail examinations at a free cancer screening by the American Academy of Dermatology, more than half of female participants (47/87 [54%]) stated that they were wearing nail polish at the time of screening.^4,5 Therefore, examinations of the nails were not performed as part of the total-body skin examination.

In summary, nail diseases are an important concern in clinical practice with aesthetic and functional consequences. There is a strong need to emphasize the importance of nail examinations for diagnostic purposes and to incorporate more expansive nail-related content into the BDC, which can result in longer and more functional lives for our patients.

Sincerely,

Shari R. Lipner, MD, PhD
 

From the Department of Dermatology, Weill Cornell Medicine, New York, New York.

The author reports no conflict of interest.

References

1. Lipner SR. Ulcerated nodule of the fingernail. JAMA. 2018;319:713.

2. Tan KB, Moncrieff M, Thompson JF, et al. Subungual melanoma: a study of 124 cases highlighting features of early lesions, potential pitfalls in diagnosis, and guidelines for histologic reporting. Am J Surg Pathol. 2007;31:1902-1912.

3. Halteh P, Scher R, Artis A, et al. Assessment of patient knowledge of longitudinal melanonychia: a survey study of patients in outpatient clinics. Skin Appendage Disord. 2017;2:156-161.

4. Ko D, Lipner SR. A survey-based study on nail examinations at an American Academy of Dermatology free skin cancer screening. J Am Acad Dermatol. 2018;79:975-978.

5. Ko D, Lipner SR. Comment on: “The first 30 years of the American Academy of Dermatology skin cancer screening program: 1985-2014.” J Am Acad Dermatol. 2019;80:e23.

To the Editor:

In the April 2019 Cutis article by John and Lipner,¹ the authors critiqued the American Academy of Dermatology Basic Dermatology Curriculum (BDC) for not providing an adequate scaffolding of nail findings on which dermatology residents can build their knowledge base; however, that criticism belies a misunderstanding of the BDC’s purpose. It was carefully designed to address the needs of undifferentiated medical students and primary care learners based on needs assessments from practicing primary care physicians and experienced dermatology educators.^2,3 Given the limited amount of time to teach, a basic curriculum must focus on the most high-yield items. The BDC work group developed goals and objectives based on needs assessments for primary care practice with 38 core dermatology diagnoses, including 3 diagnoses with important nail findings: onychomycosis, melanoma, and psoriasis. Much repetition is built into the BDC, and the same diagnosis is used in multiple cases in different modules to encourage retention of information. Therefore, “analysis of nail-related content” should focus on diagnoses rather than cases, and for each diagnosis, note whether the nail findings are a pertinent negative or pertinent positive. In cases of the other 35 diagnoses covered in the BDC, nail findings are omitted for space because they are not relevant (eg, in cases of seborrheic dermatitis or rosacea). Normal nail findings are not pertinent negatives for most diagnoses in the BDC, except in cases with diagnoses for which psoriasis is in the differential, such as nummular dermatitis or pityriasis rosea.

Furthermore, a true analysis of the needs of medical students and primary care learners with regard to nail findings would begin with a needs assessment of the most common nail conditions evaluated in the primary care and urgent care settings. Ingrown nails, paronychia, onychomycosis, and subungual hematomas and other nail traumas are the most common nail conditions encountered in primary care and urgent care,^4-10 but John and Lipner¹ failed to perform analysis or needs assessment based on the incidence of nail diagnoses in these settings.

Other sources for medical students and primary care residents include excellent introductions to nail findings. The newly revised skin chapter of Bates’ Guide to Physical Examination and History Taking¹¹ includes updated photographs of common nail findings and discusses the importance of examining nails in the full-body skin examination. Additionally, Clinical Dermatology: A Color Guide to Diagnosis and Therapy,¹²Lookingbill and Marks’ Principles of Dermatology,¹³ and The Color Atlas and Synopsis of Family Medicine¹⁴ cover nail disease beautifully for medical students and primary care learners. The BDC was never meant to supplant these bountiful resources.

The authors referred to lack of confidence in nail diagnoses among dermatology residents,¹ which is a very real problem that must be addressed by dermatology residency programs. The BDC is not the proper vehicle for training dermatology residents about these conditions; that is the responsibility and challenge of our dermatology residency programs. The authors also suggested teaching how to perform nail biopsies in the BDC.¹ It not reasonable to expect that our primary care colleagues will be performing nail biopsies. A more appropriate level of expectation is that they would know when to refer patients to dermatology; for example, they should know that a pigmented streak on a single nail that is expanding is an indication for referral to a dermatologist.

If the authors or others were to propose an additional nail module to the BDC work group, they would need to include an analysis of the literature regarding the incidence of nail disease seen in primary care and urgent care settings rather than the nail conditions seen by referral bias experienced by consulting dermatologists. The analysis would be worth considering and worthy of the goodwill engendered by the creation of the BDC in the first place.

Sincerely,

Patrick E. McCleskey, MD

From the Department of Dermatology, Kaiser Permanente Oakland Medical Center, California.

Dr. McCleskey previously served as Chair of the American Academy of Dermatology Basic Dermatology Curriculum Work Group (2013-2017) .

Correspondence: Patrick E. McCleskey, MD, 3701 Broadway, 4th Floor, Oakland, CA 94611 ([email protected]).
 

References

1. John JJ, Lipner SR. Analysis of nail-related content in the basic dermatology curriculum. Cutis. 2019;103:214-216.

2. Hansra NK, O’Sullivan P, Chen CL, et al. Medical school dermatology curriculum: are we adequately preparing primary care physicians? J Am Acad Dermatol. 2009;61:23-29.

3. McCleskey PE, Gilson RT, Devillez R. Medical student core curriculum in dermatology survey. J Am Acad Dermatol. 2009;61:30-35.

4. Vierhoeven EWM, Kraaimaat FW, van Wheel C, et al. Skin diseases in family medicine: prevalence and health care use. Ann Fam Med. 2008;6:349-354.

5. Fleisher AB, Herbert CR, Feldman SR, et al. Diagnosis of skin disease by non-dermatologists. Am J Manag Care. 2000;6;1149-1156.

6. Akbas A, Kilinc F, Yakut HI, et al. Nail disorders in children, a clinical study. Our Dermatol Online. 2016;7:149-154.

7. Nadkarni A, Domeisen N, Hill D, et al. The most common dermatology diagnoses in the emergency department. J Am Acad Dermatol. 2016;75:1261-1262.

8. Baibergenova A, Shear NH. Skin conditions that bring patients to emergency departments. Arch Dermatol. 2011;147:118-120.

9. Wang E, Lim BL, Than KY. Dermatological conditions presenting at an emergency department in Singapore. Singapore Med J. 2009;50:881-884.

10. Lai-Kwon J, Weiland TJ, Chong AH, et al. Which dermatological conditions present to an emergency department in Australia? Emerg Med Int. 2014;2014:463026.

11. McCleskey PE. The skin, hair, and nails. In: Bickley L, ed. Bates’ Guide to Physical Examination and History Taking. 12th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2017:173-214.

12. Habif TP. Nail diseases. In: Habif TP, ed. Clinical Dermatology: A Color Guide to Diagnosis and Therapy. 6th ed. China: Elsevier; 2016:960-985.

13. Marks JG, Miller JJ. Nail disorders. In: Marks JG, Miller JJ, eds. Lookingbill and Marks’ Principles of Dermatology. 6th ed. China: Elsevier; 2019:277-282.

14. Mayeaux EJ Jr, Williams J. Hair and nail conditions. In: Usatine RP, Smith MA, Mayeaux EJ Jr, et al. The Color Atlas and Synopsis of Family Medicine. 3rd ed. New York, NY: McGraw-Hill Education; 2019.

Author Response

I thank Dr. McCleskey for his interest in our article. Although I acknowledge that the Basic Dermatology Curriculum (BDC) serves as an introduction to dermatology for medical students and primary care physicians, I disagree that the current curriculum should be limited to only 3 diagnoses with important nail findings—onychomycosis, melanoma, and psoriasis—and exclude other common and potentially fatal nail diseases.

To characterize the overall nail burden of ambulatory care visits in the United States, data from the National Ambulatory Medical Care Survey from 2007 to 2016 were analyzed and there were more than 20 million outpatient visits for nail concerns during this period; furthermore, although many patients were seen by dermatologists, a considerable number were seen by pediatricians and general practitioners (Lipner SR, Hancock J, Fleischer AB Jr; unpublished data; July 2019). These findings underscore the importance of educating medical students and primary care physicians on the diagnosis and appropriate referral of patients with nail diseases.

Some limited information on nail unit melanomas is included in the BDC, but it is essential that medical students and general practitioners be educated about early diagnosis of squamous cell carcinomas and melanomas of the nail unit, which may help avoid unnecessary amputations and decrease mortality.¹ Unfortunately, the vast majority of nail unit melanomas are diagnosed at stage II or later, which has been partially attributed to clinical knowledge gaps in the understanding of nail disease.²

Several studies have shown that many physicians fail to examine their patients’ nails during physical examinations, either due to concealment with nail polish or lack of clinical awareness. In a survey-based study analyzing patients’ awareness of longitudinal melanonychia and worrisome signs of nail unit melanoma, only 12% of patients (43/363) stated that their dermatologist or internist specifically asked them about nail changes.³ Furthermore, in another survey-based study of nail examinations at a free cancer screening by the American Academy of Dermatology, more than half of female participants (47/87 [54%]) stated that they were wearing nail polish at the time of screening.^4,5 Therefore, examinations of the nails were not performed as part of the total-body skin examination.

In summary, nail diseases are an important concern in clinical practice with aesthetic and functional consequences. There is a strong need to emphasize the importance of nail examinations for diagnostic purposes and to incorporate more expansive nail-related content into the BDC, which can result in longer and more functional lives for our patients.

Sincerely,

Shari R. Lipner, MD, PhD
 

From the Department of Dermatology, Weill Cornell Medicine, New York, New York.

The author reports no conflict of interest.

References

1. Lipner SR. Ulcerated nodule of the fingernail. JAMA. 2018;319:713.

2. Tan KB, Moncrieff M, Thompson JF, et al. Subungual melanoma: a study of 124 cases highlighting features of early lesions, potential pitfalls in diagnosis, and guidelines for histologic reporting. Am J Surg Pathol. 2007;31:1902-1912.

3. Halteh P, Scher R, Artis A, et al. Assessment of patient knowledge of longitudinal melanonychia: a survey study of patients in outpatient clinics. Skin Appendage Disord. 2017;2:156-161.

4. Ko D, Lipner SR. A survey-based study on nail examinations at an American Academy of Dermatology free skin cancer screening. J Am Acad Dermatol. 2018;79:975-978.

5. Ko D, Lipner SR. Comment on: “The first 30 years of the American Academy of Dermatology skin cancer screening program: 1985-2014.” J Am Acad Dermatol. 2019;80:e23.

The frequency of drug shortages in the United States has considerably increased over the last decade, affecting different areas of health care practice.^1,2 Basic products needed to care for patients in hospitals and clinics are many of the same drugs that are in short supply.³ This issue has become an ongoing public health concern that directly affects health care providers and their patients.⁴ In dermatology, similar to other specialties, success often is influenced by the efficacy of medications used to treat patients, and lack of appropriate medications has the potential to diminish health outcomes. Therefore, it is imperative for dermatology providers to recognize the factors that contribute to this issue, understand the effects of drug shortages on patients, and learn how they can improve stewardship of scarce resources and contribute to the solution.

Causes of Drug Shortages

Drug shortages can occur due to discontinuations, delays, or manufacturing and quality problems.⁵ Shortages of the most basic hospital products represent market failure.¹ In such cases, a small number of manufacturers supply these products, and if a manufacturer discontinues a particular product—as in the case of lidocaine with epinephrine—a shortage results, as the current system does not have the capacity to deal with such as issue.^1,6

An important playmaker affecting the market for medical supplies and drugs are group purchasing organizations (GPOs). The 4 largest GPOs in the United States account for 90% of the medical supply market.⁷ Although they have simplified the process for hospitals to purchase supplies by taking on the work and expense of dealing with hundreds of manufacturers, GPOs have considerable power to affect the supply chain. By allowing certain manufacturers to become the sole suppliers of products in return for premium fees, GPOs have narrowed the supply chain of key products to sometimes only 1 or 2 manufacturers.⁷ This practice may lead to decreased capacity of regional and national supply chains, setting up the system to eventual product shortage in scenarios of production problems or a decrease in the already limited number of manufacturers.

The US Food and Drug Administration (FDA) works closely with manufacturers to prevent or reduce the impact of drug shortages. Although the FDA recently has taken more action to address the issue, solutions such as allowing imported products and underlying or approving new suppliers are only temporary fixes.¹ The root of the problem needs to be dealt with by ensuring there is a broad competitive supply chain.

Impact on Dermatologists

The nationwide shortage of lidocaine with epinephrine that occurred in 2017 is a specific example of how drug shortages affect dermatologists.⁶ This product is used in the typical dermatology clinic on a daily basis for biopsies. Possible solutions to decrease usage include drawing up 1.5 mL lidocaine with epinephrine instead of 3 mL and mixing readily available normal saline with lidocaine to produce a 1:200,000 mixture to yield a 0.5% concentration that still maintains good vasoconstrictor effects. Options for dermatologists who run out of lidocaine with epinephrine are to either use lidocaine without epinephrine, which disrupts optimal patient care, or to purchase 1% lidocaine with epinephrine at a much higher cost.⁶ A study that analyzed changes in drug pricing following shortages in the United States indicated that prices of drugs facing a shortage increased more than twice as quickly as expected between 2015 and 2016 vs those that were not in shortage, which may reflect opportunistic behaviors of drug manufacturers during shortages.⁸

The American Academy of Dermatology Association has created a letter and encouraged patients to notify their lawmakers about the severity of the drug shortage issue. Given the shortage of local anesthetics and their importance to the practice of dermatology, the American Academy of Dermatology Association also has created guidelines discussing local anesthetics that could be an alternative to lidocaine for office-based dermatologic surgery.⁹

Final Thoughts

Dermatology practitioners should be aware of current shortages impacting their practice and address the potential shortage proactively. We propose that dermatology clinics should keep an emergency reservoir of products routinely used in practice that currently are on the FDA drug shortage list, particularly lidocaine hydrochloride (with and without epinephrine) and sodium bicarbonate,¹⁰ which may diminish the negative impact a shortage may have on the high quality of health care we strive to provide. On a bigger scale, providers should be more proactive to have their voices heard and get involved with policymaking given the potential for patient harm and suboptimal care associated with drug shortages.

The frequency of drug shortages in the United States has considerably increased over the last decade, affecting different areas of health care practice.^1,2 Basic products needed to care for patients in hospitals and clinics are many of the same drugs that are in short supply.³ This issue has become an ongoing public health concern that directly affects health care providers and their patients.⁴ In dermatology, similar to other specialties, success often is influenced by the efficacy of medications used to treat patients, and lack of appropriate medications has the potential to diminish health outcomes. Therefore, it is imperative for dermatology providers to recognize the factors that contribute to this issue, understand the effects of drug shortages on patients, and learn how they can improve stewardship of scarce resources and contribute to the solution.

Causes of Drug Shortages

Drug shortages can occur due to discontinuations, delays, or manufacturing and quality problems.⁵ Shortages of the most basic hospital products represent market failure.¹ In such cases, a small number of manufacturers supply these products, and if a manufacturer discontinues a particular product—as in the case of lidocaine with epinephrine—a shortage results, as the current system does not have the capacity to deal with such as issue.^1,6

An important playmaker affecting the market for medical supplies and drugs are group purchasing organizations (GPOs). The 4 largest GPOs in the United States account for 90% of the medical supply market.⁷ Although they have simplified the process for hospitals to purchase supplies by taking on the work and expense of dealing with hundreds of manufacturers, GPOs have considerable power to affect the supply chain. By allowing certain manufacturers to become the sole suppliers of products in return for premium fees, GPOs have narrowed the supply chain of key products to sometimes only 1 or 2 manufacturers.⁷ This practice may lead to decreased capacity of regional and national supply chains, setting up the system to eventual product shortage in scenarios of production problems or a decrease in the already limited number of manufacturers.

The US Food and Drug Administration (FDA) works closely with manufacturers to prevent or reduce the impact of drug shortages. Although the FDA recently has taken more action to address the issue, solutions such as allowing imported products and underlying or approving new suppliers are only temporary fixes.¹ The root of the problem needs to be dealt with by ensuring there is a broad competitive supply chain.

Impact on Dermatologists

The nationwide shortage of lidocaine with epinephrine that occurred in 2017 is a specific example of how drug shortages affect dermatologists.⁶ This product is used in the typical dermatology clinic on a daily basis for biopsies. Possible solutions to decrease usage include drawing up 1.5 mL lidocaine with epinephrine instead of 3 mL and mixing readily available normal saline with lidocaine to produce a 1:200,000 mixture to yield a 0.5% concentration that still maintains good vasoconstrictor effects. Options for dermatologists who run out of lidocaine with epinephrine are to either use lidocaine without epinephrine, which disrupts optimal patient care, or to purchase 1% lidocaine with epinephrine at a much higher cost.⁶ A study that analyzed changes in drug pricing following shortages in the United States indicated that prices of drugs facing a shortage increased more than twice as quickly as expected between 2015 and 2016 vs those that were not in shortage, which may reflect opportunistic behaviors of drug manufacturers during shortages.⁸

The American Academy of Dermatology Association has created a letter and encouraged patients to notify their lawmakers about the severity of the drug shortage issue. Given the shortage of local anesthetics and their importance to the practice of dermatology, the American Academy of Dermatology Association also has created guidelines discussing local anesthetics that could be an alternative to lidocaine for office-based dermatologic surgery.⁹

Final Thoughts

Dermatology practitioners should be aware of current shortages impacting their practice and address the potential shortage proactively. We propose that dermatology clinics should keep an emergency reservoir of products routinely used in practice that currently are on the FDA drug shortage list, particularly lidocaine hydrochloride (with and without epinephrine) and sodium bicarbonate,¹⁰ which may diminish the negative impact a shortage may have on the high quality of health care we strive to provide. On a bigger scale, providers should be more proactive to have their voices heard and get involved with policymaking given the potential for patient harm and suboptimal care associated with drug shortages.

The frequency of drug shortages in the United States has considerably increased over the last decade, affecting different areas of health care practice.^1,2 Basic products needed to care for patients in hospitals and clinics are many of the same drugs that are in short supply.³ This issue has become an ongoing public health concern that directly affects health care providers and their patients.⁴ In dermatology, similar to other specialties, success often is influenced by the efficacy of medications used to treat patients, and lack of appropriate medications has the potential to diminish health outcomes. Therefore, it is imperative for dermatology providers to recognize the factors that contribute to this issue, understand the effects of drug shortages on patients, and learn how they can improve stewardship of scarce resources and contribute to the solution.

Causes of Drug Shortages

Drug shortages can occur due to discontinuations, delays, or manufacturing and quality problems.⁵ Shortages of the most basic hospital products represent market failure.¹ In such cases, a small number of manufacturers supply these products, and if a manufacturer discontinues a particular product—as in the case of lidocaine with epinephrine—a shortage results, as the current system does not have the capacity to deal with such as issue.^1,6

An important playmaker affecting the market for medical supplies and drugs are group purchasing organizations (GPOs). The 4 largest GPOs in the United States account for 90% of the medical supply market.⁷ Although they have simplified the process for hospitals to purchase supplies by taking on the work and expense of dealing with hundreds of manufacturers, GPOs have considerable power to affect the supply chain. By allowing certain manufacturers to become the sole suppliers of products in return for premium fees, GPOs have narrowed the supply chain of key products to sometimes only 1 or 2 manufacturers.⁷ This practice may lead to decreased capacity of regional and national supply chains, setting up the system to eventual product shortage in scenarios of production problems or a decrease in the already limited number of manufacturers.

The US Food and Drug Administration (FDA) works closely with manufacturers to prevent or reduce the impact of drug shortages. Although the FDA recently has taken more action to address the issue, solutions such as allowing imported products and underlying or approving new suppliers are only temporary fixes.¹ The root of the problem needs to be dealt with by ensuring there is a broad competitive supply chain.

Impact on Dermatologists

The nationwide shortage of lidocaine with epinephrine that occurred in 2017 is a specific example of how drug shortages affect dermatologists.⁶ This product is used in the typical dermatology clinic on a daily basis for biopsies. Possible solutions to decrease usage include drawing up 1.5 mL lidocaine with epinephrine instead of 3 mL and mixing readily available normal saline with lidocaine to produce a 1:200,000 mixture to yield a 0.5% concentration that still maintains good vasoconstrictor effects. Options for dermatologists who run out of lidocaine with epinephrine are to either use lidocaine without epinephrine, which disrupts optimal patient care, or to purchase 1% lidocaine with epinephrine at a much higher cost.⁶ A study that analyzed changes in drug pricing following shortages in the United States indicated that prices of drugs facing a shortage increased more than twice as quickly as expected between 2015 and 2016 vs those that were not in shortage, which may reflect opportunistic behaviors of drug manufacturers during shortages.⁸

The American Academy of Dermatology Association has created a letter and encouraged patients to notify their lawmakers about the severity of the drug shortage issue. Given the shortage of local anesthetics and their importance to the practice of dermatology, the American Academy of Dermatology Association also has created guidelines discussing local anesthetics that could be an alternative to lidocaine for office-based dermatologic surgery.⁹

Final Thoughts

Dermatology practitioners should be aware of current shortages impacting their practice and address the potential shortage proactively. We propose that dermatology clinics should keep an emergency reservoir of products routinely used in practice that currently are on the FDA drug shortage list, particularly lidocaine hydrochloride (with and without epinephrine) and sodium bicarbonate,¹⁰ which may diminish the negative impact a shortage may have on the high quality of health care we strive to provide. On a bigger scale, providers should be more proactive to have their voices heard and get involved with policymaking given the potential for patient harm and suboptimal care associated with drug shortages.

A growing body of evidence shows that electrosurgical smoke contains both harmful chemicals as well as live material, including blood particles, bacteria, and viruses.¹ Both human immunodeficiency virus and human papillomavirus have been identified in surgical smoke plumes, and bacterial colony growth has been demonstrated from electrosurgical smoke specimens, specifically Staphylococcus, Corynebacterium, and Neisseria species.^2-8 Treating 1 g of tissue with electrocoagulation produces chemical by-products equivalent to burning 6 unfiltered cigarettes,⁹ which is twice the amount of chemical by-products produced by CO₂ laser vaporization of the same quantity of tissue. It is a common misconception that electrosurgical smoke is less hazardous than smoke produced by ablative CO₂ procedures.⁹ Many chemicals are present in electrosurgical smoke plumes, including nitriles, benzenes, carbon monoxide, hydrogen cyanide, indoles, phenols, pyridine, pyrrole, styrene, toluene, and xylene.^10-12 In animal model studies of rat lungs exposed to surgical smoke, pathologic changes, including interstitial pneumonia, bronchiolitis, and emphysema, have been shown in a dose-dependent manner.^1,13-16 Diseases and symptoms linked to inhalation of electrosurgical smoke in humans include anemia, eye irritation, hypoxia, dizziness, nasopharyngeal lesions, vomiting, sneezing, throat irritation, and weakness.^1,8,17-19 A study of 153 dermatology residents found that more than 70% reported receiving no formal education on the hazards of electrosurgical smoke.²⁰ Approximately 45% were unaware if they had access to smoke evacuation in rooms where electrosurgery was performed. More than 76% were concerned with the infectious risk of electrosurgical smoke, and more than 71% were concerned with its potential carcinogenic risk.²⁰

We surveyed dermatologists who perform skin surgery as well as staff members with respect to their experiences with electrosurgical smoke and to observe any difference that information on the potential hazards of electrosurgical smoke may have on their attitudes and preferences.

Materials and Methods

Survey Instrument
We developed a REDCap survey consisting of 17 questions that was approved by the executive committees of the American College of Mohs Surgery and the American Society for Dermatologic Surgery for distribution to their dermatologist memberships. It was emailed to eligible participants using their mailing lists. Although the survey was sent directly to member physicians, it was recommended that they forward the survey to their clinical staff to complete.

After responding to an initial set of survey questions, respondents were informed that there is growing evidence of potential harms of inhalation of surgical smoke. They then were asked the same series of survey questions in light of this information.

Statistical Analysis
Statistical analysis of the survey responses was then completed, and free-text responses as a final question of the survey were assessed for themes. Preintervention responses of staff and clinicians noticing smoke and being bothered by smoke were assessed using proportions and 95% confidence interval (CI) estimates of the proportions. On most questions, respondents could answer on a scale of 1 to 10. Responses of 5 to 10 on noticing smoke and 5 to 10 on being bothered or troubled by the smoke smell were grouped for analyses. A cross-tabulation using the Bhapkar test for marginal homogeneity was used to assess if information presented on potential smoke hazards changed responses. A Cochran-Mantel-Haenszel test for ordinal responses was used to determine differences between surgeons and staff. A McNemar test was used to determine statistical significance of change in responses to cost. Statistical analysis was performed using SAS version 9.

Results

There was a total of 443 responses to our questionnaire. Two respondents answered that they did not work in an office where skin surgery was performed, and 4 respondents did not answer any questions and were therefore excluded, leaving a total of 437 responses (402 physicians and 35 staff members). A summary of the characteristics of the respondents is shown in the Table. Some respondents did not answer each question, leading to fewer than 437 answers for some questions.

Two hundred eighty-two respondents (64.5%) never or very rarely used smoke evacuation during skin surgical procedures, and only 85 (19.5%) used smoke evacuation with nearly every case. The remaining respondents sometimes used smoke evacuation (Figure 1).

Prior to being presented with the potential dangers of electrosurgical smoke and using a value of 5 to 10 to determine if respondents noticed smoke, 54.4% (95% CI, 49.5%-59.1%) did notice intraoperative smoke during procedures. Using a value of 5 to 10 to indicate if respondents were bothered or troubled by the smoke smell, 35.5% (95% CI, 31.0%-40.2%) were bothered or troubled by intraoperative smoke prior to potential hazards being presented.

Regarding acceptable increase in cost per procedure for smoke evacuation at baseline, 68.9% of respondents favored additional cost; 57.8% of respondents chose the lowest cost grouping of $1 to $30. After being presented with information about the potential harm of intraoperative smoke, the respondents in favor of additional cost increased to 71.5%, which was a small but statistically significant change (P=.0075)(Figure 2).

After being presented with the potential risks of electrosurgical smoke, 29 more respondents answered that they were severely bothered by electrosurgical smoke, whereas 45 fewer respondents selected that they were not bothered or troubled at all by electrosurgical smoke (Figure 3). This difference was statistically significant (P<.0001). Fifteen more respondents answered that they would be much more likely to choose to work at a practice with smoke evacuation once the potential harm of electrosurgical smoke was introduced, and 11 were somewhat more likely to choose a practice with smoke evacuation (P<.0001).

Comment

Developing evidence of health risks associated with electrosurgical smoke plumes has led to an increasing interest in the use of smoke protection or remediation tools during surgical procedures. High-filtration face masks and smoke-evacuation devices protect physicians, staff members, and patients, as well as improve the patient’s clinical experience.

Our study was designed to query dermatologists who perform skin surgery as well as staff members with respect to their experiences with electrosurgical smoke and to observe any difference that information on the potential hazards of electrosurgical smoke may have on their attitudes and preferences. We received 437 responses to our survey (Table). At baseline, 54.4% of respondents noticed and 35.5% were bothered or troubled by the smoke smell produced during skin electrosurgery. These data were intuitively associated in a statistically significant manner with the use of smoke evacuation for respondents; those respondents who more commonly used smoke evacuation were bothered less by electrosurgical smoke, and those respondents who used smoke evacuation less often were more likely to notice and be bothered by surgical smoke.

Once our respondents were presented with the potentially harmful effects of electrosurgical smoke, they became significantly more likely to be bothered by electrosurgical smoke and to want to work in a practice where smoke evacuation was available. This information, however, did not change respondents’ satisfaction with their work environment, and no statistically significant differences were noted between physicians and staff.

At baseline, 68.9% of respondents favored additional cost for smoke evacuation, with approximately 58% favoring the lowest cost category we presented ($1–$30). After being presented with information about the potential dangers of electrosurgical smoke, 71.5% were in favor of increased cost for smoke evacuation, which was a small but statistically significant increase.

The open-comment section of the survey provided interesting insight into the opinions of our respondents on smoke remediation. It is important to note that statistical analysis cannot be performed with these data, and firm generalizable conclusions cannot be drawn from them; however, they reveal topics that may guide further research and policy and certainly merit mention. Of 437 respondents, 108 left free-text comments. Twenty-six percent were categorized as unqualified proponents (in favor of smoke remediation) and 45% as qualified proponents (defined as an individual who verbalized a desire for smoke remediation but also cited a factor limiting their ability to use it, such as cost or staff availability). Only 12% were firmly against smoke remediation, while the remaining 17% did not comment discernibly for or against smoke remediation, indicating that a majority (71% of our comment section respondents) were in favor of some type of smoke remediation, especially if obstacles such as cost could be addressed. Only a small minority was firmly against smoke remediation.

The comments section of our survey highlighted some of the concerns that dermatologic surgeons and their staff have with electrosurgical smoke evacuation. Thirty percent cited cost as an obstacle to use of these devices, and several comments raised concern about increasing overhead and regulatory demands placed on practices. Many indicated that, without sufficient evidence of the harm caused by electrosurgical smoke, regulation that forces use of smoke remediation devices would represent a costly unfunded mandate. Others referenced the logistical challenges of smoke evacuation and the need for staff assistance. Newer smoke-evacuation wands built into cautery pens address much of this concern regarding logistical and staff challenges and further allow the evacuator tip to be located where it is most effective: 1 cm to 2 in from the point of cautery.^21,22

Additionally, 12% of commenters noted that their patients were bothered by the smell of electrosurgical smoke, which is a point that requires further research and is the focus of a current randomized trial at our institution (ClinicalTrials.gov Identifier NCT02958826).

Our current study is limited in that it is a survey and therefore is subject to response bias. Further, some may assert that the hazards of electrosurgical smoke are not settled science, and although we agree with this point on some level, the study aim was not to prove risk but rather to assess current attitudes and see if awareness of a potential risk influenced those attitudes. Additionally, most responses were from physicians—only 35 responses were from nonphysician staff—so it may be difficult to generalize the findings of this study to staff. The large number of physician respondents, however, can be seen as a strength, and the findings are likely much more generalizable to providers who routinely perform clinic-based surgical procedures involving electrosurgery.

Conclusion

Our study shows that most dermatologists who perform skin surgery notice and are bothered by the smoke produced by electrosurgery to at least some extent. When presented with the possibility that inhaling electrosurgical smoke may be harmful, dermatologists were more likely to be bothered by electrosurgical smoke, more likely to prefer a practice environment where smoke evacuation was available, and more likely to be willing to bear additional cost for smoke evacuation. The free-text comments on our survey highlighted that many dermatologic surgeons are proponents of smoke evacuation but have concerns about cost and potential regulatory challenges associated with smoke evacuation, especially if the potential risks are not settled science. Many logistical concerns for smoke evacuation are addressed with the use of integrated devices. More research is needed to determine the health effects of the surgical smoke we are exposed to daily and the optimal way to limit any risk.

Acknowledgment
The authors would like to thank Richard W. Madsen, PhD (Columbia, Missouri), biostatistician, for his valuable guidance in the statistical analysis of data, interpretation of results, and editorial support in finalizing the manuscript.

A growing body of evidence shows that electrosurgical smoke contains both harmful chemicals as well as live material, including blood particles, bacteria, and viruses.¹ Both human immunodeficiency virus and human papillomavirus have been identified in surgical smoke plumes, and bacterial colony growth has been demonstrated from electrosurgical smoke specimens, specifically Staphylococcus, Corynebacterium, and Neisseria species.^2-8 Treating 1 g of tissue with electrocoagulation produces chemical by-products equivalent to burning 6 unfiltered cigarettes,⁹ which is twice the amount of chemical by-products produced by CO₂ laser vaporization of the same quantity of tissue. It is a common misconception that electrosurgical smoke is less hazardous than smoke produced by ablative CO₂ procedures.⁹ Many chemicals are present in electrosurgical smoke plumes, including nitriles, benzenes, carbon monoxide, hydrogen cyanide, indoles, phenols, pyridine, pyrrole, styrene, toluene, and xylene.^10-12 In animal model studies of rat lungs exposed to surgical smoke, pathologic changes, including interstitial pneumonia, bronchiolitis, and emphysema, have been shown in a dose-dependent manner.^1,13-16 Diseases and symptoms linked to inhalation of electrosurgical smoke in humans include anemia, eye irritation, hypoxia, dizziness, nasopharyngeal lesions, vomiting, sneezing, throat irritation, and weakness.^1,8,17-19 A study of 153 dermatology residents found that more than 70% reported receiving no formal education on the hazards of electrosurgical smoke.²⁰ Approximately 45% were unaware if they had access to smoke evacuation in rooms where electrosurgery was performed. More than 76% were concerned with the infectious risk of electrosurgical smoke, and more than 71% were concerned with its potential carcinogenic risk.²⁰

We surveyed dermatologists who perform skin surgery as well as staff members with respect to their experiences with electrosurgical smoke and to observe any difference that information on the potential hazards of electrosurgical smoke may have on their attitudes and preferences.

Materials and Methods

Survey Instrument
We developed a REDCap survey consisting of 17 questions that was approved by the executive committees of the American College of Mohs Surgery and the American Society for Dermatologic Surgery for distribution to their dermatologist memberships. It was emailed to eligible participants using their mailing lists. Although the survey was sent directly to member physicians, it was recommended that they forward the survey to their clinical staff to complete.

After responding to an initial set of survey questions, respondents were informed that there is growing evidence of potential harms of inhalation of surgical smoke. They then were asked the same series of survey questions in light of this information.

Statistical Analysis
Statistical analysis of the survey responses was then completed, and free-text responses as a final question of the survey were assessed for themes. Preintervention responses of staff and clinicians noticing smoke and being bothered by smoke were assessed using proportions and 95% confidence interval (CI) estimates of the proportions. On most questions, respondents could answer on a scale of 1 to 10. Responses of 5 to 10 on noticing smoke and 5 to 10 on being bothered or troubled by the smoke smell were grouped for analyses. A cross-tabulation using the Bhapkar test for marginal homogeneity was used to assess if information presented on potential smoke hazards changed responses. A Cochran-Mantel-Haenszel test for ordinal responses was used to determine differences between surgeons and staff. A McNemar test was used to determine statistical significance of change in responses to cost. Statistical analysis was performed using SAS version 9.

Results

There was a total of 443 responses to our questionnaire. Two respondents answered that they did not work in an office where skin surgery was performed, and 4 respondents did not answer any questions and were therefore excluded, leaving a total of 437 responses (402 physicians and 35 staff members). A summary of the characteristics of the respondents is shown in the Table. Some respondents did not answer each question, leading to fewer than 437 answers for some questions.

Two hundred eighty-two respondents (64.5%) never or very rarely used smoke evacuation during skin surgical procedures, and only 85 (19.5%) used smoke evacuation with nearly every case. The remaining respondents sometimes used smoke evacuation (Figure 1).

Prior to being presented with the potential dangers of electrosurgical smoke and using a value of 5 to 10 to determine if respondents noticed smoke, 54.4% (95% CI, 49.5%-59.1%) did notice intraoperative smoke during procedures. Using a value of 5 to 10 to indicate if respondents were bothered or troubled by the smoke smell, 35.5% (95% CI, 31.0%-40.2%) were bothered or troubled by intraoperative smoke prior to potential hazards being presented.

Regarding acceptable increase in cost per procedure for smoke evacuation at baseline, 68.9% of respondents favored additional cost; 57.8% of respondents chose the lowest cost grouping of $1 to $30. After being presented with information about the potential harm of intraoperative smoke, the respondents in favor of additional cost increased to 71.5%, which was a small but statistically significant change (P=.0075)(Figure 2).

After being presented with the potential risks of electrosurgical smoke, 29 more respondents answered that they were severely bothered by electrosurgical smoke, whereas 45 fewer respondents selected that they were not bothered or troubled at all by electrosurgical smoke (Figure 3). This difference was statistically significant (P<.0001). Fifteen more respondents answered that they would be much more likely to choose to work at a practice with smoke evacuation once the potential harm of electrosurgical smoke was introduced, and 11 were somewhat more likely to choose a practice with smoke evacuation (P<.0001).

Comment

Developing evidence of health risks associated with electrosurgical smoke plumes has led to an increasing interest in the use of smoke protection or remediation tools during surgical procedures. High-filtration face masks and smoke-evacuation devices protect physicians, staff members, and patients, as well as improve the patient’s clinical experience.

Our study was designed to query dermatologists who perform skin surgery as well as staff members with respect to their experiences with electrosurgical smoke and to observe any difference that information on the potential hazards of electrosurgical smoke may have on their attitudes and preferences. We received 437 responses to our survey (Table). At baseline, 54.4% of respondents noticed and 35.5% were bothered or troubled by the smoke smell produced during skin electrosurgery. These data were intuitively associated in a statistically significant manner with the use of smoke evacuation for respondents; those respondents who more commonly used smoke evacuation were bothered less by electrosurgical smoke, and those respondents who used smoke evacuation less often were more likely to notice and be bothered by surgical smoke.

Once our respondents were presented with the potentially harmful effects of electrosurgical smoke, they became significantly more likely to be bothered by electrosurgical smoke and to want to work in a practice where smoke evacuation was available. This information, however, did not change respondents’ satisfaction with their work environment, and no statistically significant differences were noted between physicians and staff.

At baseline, 68.9% of respondents favored additional cost for smoke evacuation, with approximately 58% favoring the lowest cost category we presented ($1–$30). After being presented with information about the potential dangers of electrosurgical smoke, 71.5% were in favor of increased cost for smoke evacuation, which was a small but statistically significant increase.

The open-comment section of the survey provided interesting insight into the opinions of our respondents on smoke remediation. It is important to note that statistical analysis cannot be performed with these data, and firm generalizable conclusions cannot be drawn from them; however, they reveal topics that may guide further research and policy and certainly merit mention. Of 437 respondents, 108 left free-text comments. Twenty-six percent were categorized as unqualified proponents (in favor of smoke remediation) and 45% as qualified proponents (defined as an individual who verbalized a desire for smoke remediation but also cited a factor limiting their ability to use it, such as cost or staff availability). Only 12% were firmly against smoke remediation, while the remaining 17% did not comment discernibly for or against smoke remediation, indicating that a majority (71% of our comment section respondents) were in favor of some type of smoke remediation, especially if obstacles such as cost could be addressed. Only a small minority was firmly against smoke remediation.

The comments section of our survey highlighted some of the concerns that dermatologic surgeons and their staff have with electrosurgical smoke evacuation. Thirty percent cited cost as an obstacle to use of these devices, and several comments raised concern about increasing overhead and regulatory demands placed on practices. Many indicated that, without sufficient evidence of the harm caused by electrosurgical smoke, regulation that forces use of smoke remediation devices would represent a costly unfunded mandate. Others referenced the logistical challenges of smoke evacuation and the need for staff assistance. Newer smoke-evacuation wands built into cautery pens address much of this concern regarding logistical and staff challenges and further allow the evacuator tip to be located where it is most effective: 1 cm to 2 in from the point of cautery.^21,22

Additionally, 12% of commenters noted that their patients were bothered by the smell of electrosurgical smoke, which is a point that requires further research and is the focus of a current randomized trial at our institution (ClinicalTrials.gov Identifier NCT02958826).

Our current study is limited in that it is a survey and therefore is subject to response bias. Further, some may assert that the hazards of electrosurgical smoke are not settled science, and although we agree with this point on some level, the study aim was not to prove risk but rather to assess current attitudes and see if awareness of a potential risk influenced those attitudes. Additionally, most responses were from physicians—only 35 responses were from nonphysician staff—so it may be difficult to generalize the findings of this study to staff. The large number of physician respondents, however, can be seen as a strength, and the findings are likely much more generalizable to providers who routinely perform clinic-based surgical procedures involving electrosurgery.

Conclusion

Our study shows that most dermatologists who perform skin surgery notice and are bothered by the smoke produced by electrosurgery to at least some extent. When presented with the possibility that inhaling electrosurgical smoke may be harmful, dermatologists were more likely to be bothered by electrosurgical smoke, more likely to prefer a practice environment where smoke evacuation was available, and more likely to be willing to bear additional cost for smoke evacuation. The free-text comments on our survey highlighted that many dermatologic surgeons are proponents of smoke evacuation but have concerns about cost and potential regulatory challenges associated with smoke evacuation, especially if the potential risks are not settled science. Many logistical concerns for smoke evacuation are addressed with the use of integrated devices. More research is needed to determine the health effects of the surgical smoke we are exposed to daily and the optimal way to limit any risk.

Acknowledgment
The authors would like to thank Richard W. Madsen, PhD (Columbia, Missouri), biostatistician, for his valuable guidance in the statistical analysis of data, interpretation of results, and editorial support in finalizing the manuscript.

A growing body of evidence shows that electrosurgical smoke contains both harmful chemicals as well as live material, including blood particles, bacteria, and viruses.¹ Both human immunodeficiency virus and human papillomavirus have been identified in surgical smoke plumes, and bacterial colony growth has been demonstrated from electrosurgical smoke specimens, specifically Staphylococcus, Corynebacterium, and Neisseria species.^2-8 Treating 1 g of tissue with electrocoagulation produces chemical by-products equivalent to burning 6 unfiltered cigarettes,⁹ which is twice the amount of chemical by-products produced by CO₂ laser vaporization of the same quantity of tissue. It is a common misconception that electrosurgical smoke is less hazardous than smoke produced by ablative CO₂ procedures.⁹ Many chemicals are present in electrosurgical smoke plumes, including nitriles, benzenes, carbon monoxide, hydrogen cyanide, indoles, phenols, pyridine, pyrrole, styrene, toluene, and xylene.^10-12 In animal model studies of rat lungs exposed to surgical smoke, pathologic changes, including interstitial pneumonia, bronchiolitis, and emphysema, have been shown in a dose-dependent manner.^1,13-16 Diseases and symptoms linked to inhalation of electrosurgical smoke in humans include anemia, eye irritation, hypoxia, dizziness, nasopharyngeal lesions, vomiting, sneezing, throat irritation, and weakness.^1,8,17-19 A study of 153 dermatology residents found that more than 70% reported receiving no formal education on the hazards of electrosurgical smoke.²⁰ Approximately 45% were unaware if they had access to smoke evacuation in rooms where electrosurgery was performed. More than 76% were concerned with the infectious risk of electrosurgical smoke, and more than 71% were concerned with its potential carcinogenic risk.²⁰

We surveyed dermatologists who perform skin surgery as well as staff members with respect to their experiences with electrosurgical smoke and to observe any difference that information on the potential hazards of electrosurgical smoke may have on their attitudes and preferences.

Materials and Methods

Survey Instrument
We developed a REDCap survey consisting of 17 questions that was approved by the executive committees of the American College of Mohs Surgery and the American Society for Dermatologic Surgery for distribution to their dermatologist memberships. It was emailed to eligible participants using their mailing lists. Although the survey was sent directly to member physicians, it was recommended that they forward the survey to their clinical staff to complete.

After responding to an initial set of survey questions, respondents were informed that there is growing evidence of potential harms of inhalation of surgical smoke. They then were asked the same series of survey questions in light of this information.

Statistical Analysis
Statistical analysis of the survey responses was then completed, and free-text responses as a final question of the survey were assessed for themes. Preintervention responses of staff and clinicians noticing smoke and being bothered by smoke were assessed using proportions and 95% confidence interval (CI) estimates of the proportions. On most questions, respondents could answer on a scale of 1 to 10. Responses of 5 to 10 on noticing smoke and 5 to 10 on being bothered or troubled by the smoke smell were grouped for analyses. A cross-tabulation using the Bhapkar test for marginal homogeneity was used to assess if information presented on potential smoke hazards changed responses. A Cochran-Mantel-Haenszel test for ordinal responses was used to determine differences between surgeons and staff. A McNemar test was used to determine statistical significance of change in responses to cost. Statistical analysis was performed using SAS version 9.

Results

There was a total of 443 responses to our questionnaire. Two respondents answered that they did not work in an office where skin surgery was performed, and 4 respondents did not answer any questions and were therefore excluded, leaving a total of 437 responses (402 physicians and 35 staff members). A summary of the characteristics of the respondents is shown in the Table. Some respondents did not answer each question, leading to fewer than 437 answers for some questions.

Two hundred eighty-two respondents (64.5%) never or very rarely used smoke evacuation during skin surgical procedures, and only 85 (19.5%) used smoke evacuation with nearly every case. The remaining respondents sometimes used smoke evacuation (Figure 1).

Prior to being presented with the potential dangers of electrosurgical smoke and using a value of 5 to 10 to determine if respondents noticed smoke, 54.4% (95% CI, 49.5%-59.1%) did notice intraoperative smoke during procedures. Using a value of 5 to 10 to indicate if respondents were bothered or troubled by the smoke smell, 35.5% (95% CI, 31.0%-40.2%) were bothered or troubled by intraoperative smoke prior to potential hazards being presented.

Regarding acceptable increase in cost per procedure for smoke evacuation at baseline, 68.9% of respondents favored additional cost; 57.8% of respondents chose the lowest cost grouping of $1 to $30. After being presented with information about the potential harm of intraoperative smoke, the respondents in favor of additional cost increased to 71.5%, which was a small but statistically significant change (P=.0075)(Figure 2).

After being presented with the potential risks of electrosurgical smoke, 29 more respondents answered that they were severely bothered by electrosurgical smoke, whereas 45 fewer respondents selected that they were not bothered or troubled at all by electrosurgical smoke (Figure 3). This difference was statistically significant (P<.0001). Fifteen more respondents answered that they would be much more likely to choose to work at a practice with smoke evacuation once the potential harm of electrosurgical smoke was introduced, and 11 were somewhat more likely to choose a practice with smoke evacuation (P<.0001).

Comment

Developing evidence of health risks associated with electrosurgical smoke plumes has led to an increasing interest in the use of smoke protection or remediation tools during surgical procedures. High-filtration face masks and smoke-evacuation devices protect physicians, staff members, and patients, as well as improve the patient’s clinical experience.

Our study was designed to query dermatologists who perform skin surgery as well as staff members with respect to their experiences with electrosurgical smoke and to observe any difference that information on the potential hazards of electrosurgical smoke may have on their attitudes and preferences. We received 437 responses to our survey (Table). At baseline, 54.4% of respondents noticed and 35.5% were bothered or troubled by the smoke smell produced during skin electrosurgery. These data were intuitively associated in a statistically significant manner with the use of smoke evacuation for respondents; those respondents who more commonly used smoke evacuation were bothered less by electrosurgical smoke, and those respondents who used smoke evacuation less often were more likely to notice and be bothered by surgical smoke.

Once our respondents were presented with the potentially harmful effects of electrosurgical smoke, they became significantly more likely to be bothered by electrosurgical smoke and to want to work in a practice where smoke evacuation was available. This information, however, did not change respondents’ satisfaction with their work environment, and no statistically significant differences were noted between physicians and staff.

At baseline, 68.9% of respondents favored additional cost for smoke evacuation, with approximately 58% favoring the lowest cost category we presented ($1–$30). After being presented with information about the potential dangers of electrosurgical smoke, 71.5% were in favor of increased cost for smoke evacuation, which was a small but statistically significant increase.

The open-comment section of the survey provided interesting insight into the opinions of our respondents on smoke remediation. It is important to note that statistical analysis cannot be performed with these data, and firm generalizable conclusions cannot be drawn from them; however, they reveal topics that may guide further research and policy and certainly merit mention. Of 437 respondents, 108 left free-text comments. Twenty-six percent were categorized as unqualified proponents (in favor of smoke remediation) and 45% as qualified proponents (defined as an individual who verbalized a desire for smoke remediation but also cited a factor limiting their ability to use it, such as cost or staff availability). Only 12% were firmly against smoke remediation, while the remaining 17% did not comment discernibly for or against smoke remediation, indicating that a majority (71% of our comment section respondents) were in favor of some type of smoke remediation, especially if obstacles such as cost could be addressed. Only a small minority was firmly against smoke remediation.

The comments section of our survey highlighted some of the concerns that dermatologic surgeons and their staff have with electrosurgical smoke evacuation. Thirty percent cited cost as an obstacle to use of these devices, and several comments raised concern about increasing overhead and regulatory demands placed on practices. Many indicated that, without sufficient evidence of the harm caused by electrosurgical smoke, regulation that forces use of smoke remediation devices would represent a costly unfunded mandate. Others referenced the logistical challenges of smoke evacuation and the need for staff assistance. Newer smoke-evacuation wands built into cautery pens address much of this concern regarding logistical and staff challenges and further allow the evacuator tip to be located where it is most effective: 1 cm to 2 in from the point of cautery.^21,22

Additionally, 12% of commenters noted that their patients were bothered by the smell of electrosurgical smoke, which is a point that requires further research and is the focus of a current randomized trial at our institution (ClinicalTrials.gov Identifier NCT02958826).

Our current study is limited in that it is a survey and therefore is subject to response bias. Further, some may assert that the hazards of electrosurgical smoke are not settled science, and although we agree with this point on some level, the study aim was not to prove risk but rather to assess current attitudes and see if awareness of a potential risk influenced those attitudes. Additionally, most responses were from physicians—only 35 responses were from nonphysician staff—so it may be difficult to generalize the findings of this study to staff. The large number of physician respondents, however, can be seen as a strength, and the findings are likely much more generalizable to providers who routinely perform clinic-based surgical procedures involving electrosurgery.

Conclusion

Our study shows that most dermatologists who perform skin surgery notice and are bothered by the smoke produced by electrosurgery to at least some extent. When presented with the possibility that inhaling electrosurgical smoke may be harmful, dermatologists were more likely to be bothered by electrosurgical smoke, more likely to prefer a practice environment where smoke evacuation was available, and more likely to be willing to bear additional cost for smoke evacuation. The free-text comments on our survey highlighted that many dermatologic surgeons are proponents of smoke evacuation but have concerns about cost and potential regulatory challenges associated with smoke evacuation, especially if the potential risks are not settled science. Many logistical concerns for smoke evacuation are addressed with the use of integrated devices. More research is needed to determine the health effects of the surgical smoke we are exposed to daily and the optimal way to limit any risk.

Acknowledgment
The authors would like to thank Richard W. Madsen, PhD (Columbia, Missouri), biostatistician, for his valuable guidance in the statistical analysis of data, interpretation of results, and editorial support in finalizing the manuscript.