Among adults who drink alcohol at relatively high amounts, regular weekly physical activity may reduce the mortality risk posed by alcohol-related cancers, concludes a new observational study involving 50,000-plus British adults.

Being physically active – for example, by walking, house cleaning, or playing a sport – could be promoted as a risk-minimization measure for alcohol-related cancers, say the authors, led by Emmanuel Stamatakis, PhD, professor of Physical Activity, Lifestyle, and Population Health, University of Sydney, Australia.

The researchers found a “strong direct association between alcohol consumption and mortality risk of [10] alcohol-related cancers.”

Specifically, when compared with never drinkers, there was a significantly higher risk of dying from such cancers among drinkers who consumed “hazardous” and “harmful” amounts of alcohol, and also for ex-drinkers.

Notably, occasional drinkers and drinkers within guidelines did not have statistically significantly higher risks for alcohol-related cancer mortality.

But the analysis also found that among the bigger drinkers, the risks were “substantially attenuated” in physically active participants who met at least the lower recommended limit of activity (>7.5 metabolic equivalent task [MET]–hours/week).

That’s not a taxing amount of activity because, for example, general household cleaning results in 3 METs/hour and walking slowly translates into 2 METs/hour. However, nearly a quarter of survey participants reported no physical activity.

The study was published online May 14 in the International Journal of Cancer.

The new results require confirmation because the findings “are limited in their statistical power,” with small numbers of cases in several categories, said Alpa Patel, PhD, an epidemiologist at the American Cancer Society, who was not involved in the study. For example, there were only 55 alcohol-related cancer deaths among the 1540 harmful drinkers.

Patel stressed that, “based on the collective evidence to date, it is best to both avoid alcohol consumption and engage in sufficient amounts of physical activity.” That amount is 150-300 minutes of moderate or 75-150 minutes of vigorous activity per week for cancer prevention.

Her message about abstinence is in-line with new ACS guidelines issued last month, as reported by Medscape Medical News. The ACS’s guidance was criticized by many readers in the comments section, who repeatedly encouraged “moderation.”

However, the ACS also recommended moderation, saying, for those adults who do drink, intake should be no more than 1 drink/day for women or 2 drinks/day for men. 

Study author Dr. Stamatakis commented on the alcohol debate.

“Any advice for complete abstinence is bound to alienate many people,” he told Medscape Medical News in an email. “Alcohol drinking has been an integral part of many societies for thousands of years.”

Dr. Stamatakis, who is an occasional beer drinker, also said, “there is no healthy level of alcohol drinking.”

This was also the conclusion of a 2018 study published in the Lancet, which stated that there is “no safe limit,” as even one drink a day increases the risk of cancer. A few years earlier, the 2014 World Cancer Report found a dose-response relationship between alcohol consumption and certain cancers.

However, epidemiological findings are not necessarily “clinically relevant,” commented Jennifer Ligibel, MD, a medical oncologist at the Dana-Farber Cancer Institute, Boston, Massachusetts, in a 2018 interview with Medscape Medical News.

Dr. Ligibel explained that there are 50 years of studies linking alcohol and cancers. “With the huge amount of data we have, even small differences [in consumption] are statistically significant.”

Dr. Ligibel cited an often-repeated statistic: for the average woman, there is a 12% lifetime risk of breast cancer. “If a woman consumes a drink a day, which is considered a low-level intake, that risk may become about 13% – which is statistically significant,” Dr. Ligibel explained.

But that risk increase is not clinically relevant, she added.

Mean 10 years of follow-up

The new study is the first to examine physical activity, drinking, and the 10 cancers that have been linked to alcohol consumption (oral cavity, throat, larynx, esophagus, liver, colorectal, stomach, breast, pancreas, and lung).

The authors used data from 10 British population-based health surveys from 1994-2008 and looked at adults aged 30 years and older. The mean follow-up period was 9.9 years.

Among 54,686 participants, there were 2039 alcohol-related site-specific cancer deaths.

Alcohol consumption categories were based on U.K. guidelines, with 1 unit equal to 8 grams (about 2 ounces) of pure alcohol. The categories were as follows: drinking within guidelines (<14 units/week for women, <21 units/week for men), hazardous level (14-35 units/week for women, 21-49 units/week for men), and harmful level (> 35 units/week for women, >49 units/week for men). The survey also queried participants about being ex-drinkers, occasional drinkers, and never drinkers.

Physical activity was assessed using self-reported accounts of the 4 weeks preceding the health survey and intensity of activity (light, moderate, or vigorous) was queried. Physical activity was categorized using the upper (15 MET-hours/week) and lower (the aforementioned <7 MET-hours/week) recommended limits.

The median age of participants was 51 years; 7.9% were never drinkers and 14.7% exceeded guideline amounts. For physical activity, 23% reported none. The median level of activity was 9 MET-hours/week.

The authors say that the “increased risks [among the harmful, hazardous, and ex-drinker categories] were eliminated” among the individuals who reported physical activity >7.5 MET-hours/week. That meant the hazard ratios for cancer mortality for each category were reduced to the point that they were no longer statistically significant.

For example, for all drinkers in the “hazardous” category, the risk of cancer-related mortality was significantly higher than for nondrinkers (with a hazard ratio of 1.39), but in the subgroup of these participants who were physically active at the lower recommended limit, the hazard ratio dropped to 1.21.

These “broad patterns of effect modification by physical activity persisted when the upper physical activity limit [15 MET-hours/week] was used,” write the authors.

The new study adds to the literature on cancer mortality and alcohol consumption. In another recent study, researchers looked at eight British cohorts and reported overall cancer mortality associated with alcohol consumption was eliminated among those meeting physical activity recommendations (Br J Sports Med. 2017;51:651-7). The new study added two more cohorts to this base of eight and only focused on cancers that have been linked to alcohol consumption. The earlier study included deaths from all types of cancer.

The refinement of focus in the current study is important, say Dr. Stamatakis and colleagues.

“This specificity adds biological plausibility and permits a more immediate translation of our findings into policy and practice,” they write. 

Dr. Stamatakis practices what he advocates, but is not a teetotaler.

“I exercise (e.g., dynamic yoga, HIIT cardio workouts, run, cycle, lift weights) for 45-60 minutes a day and I walk 8,000-14,000 steps daily. That would categorize me perhaps in the top 3%-5% for my age/sex group. And I enjoy 1-2 cans of craft beer a couple of times a week,” he said in an email.

Dr. Stamatakis and Dr. Patel have reported no relevant financial relationships.

This article first appeared on Medscape.com.

Among adults who drink alcohol at relatively high amounts, regular weekly physical activity may reduce the mortality risk posed by alcohol-related cancers, concludes a new observational study involving 50,000-plus British adults.

Being physically active – for example, by walking, house cleaning, or playing a sport – could be promoted as a risk-minimization measure for alcohol-related cancers, say the authors, led by Emmanuel Stamatakis, PhD, professor of Physical Activity, Lifestyle, and Population Health, University of Sydney, Australia.

The researchers found a “strong direct association between alcohol consumption and mortality risk of [10] alcohol-related cancers.”

Specifically, when compared with never drinkers, there was a significantly higher risk of dying from such cancers among drinkers who consumed “hazardous” and “harmful” amounts of alcohol, and also for ex-drinkers.

Notably, occasional drinkers and drinkers within guidelines did not have statistically significantly higher risks for alcohol-related cancer mortality.

But the analysis also found that among the bigger drinkers, the risks were “substantially attenuated” in physically active participants who met at least the lower recommended limit of activity (>7.5 metabolic equivalent task [MET]–hours/week).

That’s not a taxing amount of activity because, for example, general household cleaning results in 3 METs/hour and walking slowly translates into 2 METs/hour. However, nearly a quarter of survey participants reported no physical activity.

The study was published online May 14 in the International Journal of Cancer.

The new results require confirmation because the findings “are limited in their statistical power,” with small numbers of cases in several categories, said Alpa Patel, PhD, an epidemiologist at the American Cancer Society, who was not involved in the study. For example, there were only 55 alcohol-related cancer deaths among the 1540 harmful drinkers.

Patel stressed that, “based on the collective evidence to date, it is best to both avoid alcohol consumption and engage in sufficient amounts of physical activity.” That amount is 150-300 minutes of moderate or 75-150 minutes of vigorous activity per week for cancer prevention.

Her message about abstinence is in-line with new ACS guidelines issued last month, as reported by Medscape Medical News. The ACS’s guidance was criticized by many readers in the comments section, who repeatedly encouraged “moderation.”

However, the ACS also recommended moderation, saying, for those adults who do drink, intake should be no more than 1 drink/day for women or 2 drinks/day for men. 

Study author Dr. Stamatakis commented on the alcohol debate.

“Any advice for complete abstinence is bound to alienate many people,” he told Medscape Medical News in an email. “Alcohol drinking has been an integral part of many societies for thousands of years.”

Dr. Stamatakis, who is an occasional beer drinker, also said, “there is no healthy level of alcohol drinking.”

This was also the conclusion of a 2018 study published in the Lancet, which stated that there is “no safe limit,” as even one drink a day increases the risk of cancer. A few years earlier, the 2014 World Cancer Report found a dose-response relationship between alcohol consumption and certain cancers.

However, epidemiological findings are not necessarily “clinically relevant,” commented Jennifer Ligibel, MD, a medical oncologist at the Dana-Farber Cancer Institute, Boston, Massachusetts, in a 2018 interview with Medscape Medical News.

Dr. Ligibel explained that there are 50 years of studies linking alcohol and cancers. “With the huge amount of data we have, even small differences [in consumption] are statistically significant.”

Dr. Ligibel cited an often-repeated statistic: for the average woman, there is a 12% lifetime risk of breast cancer. “If a woman consumes a drink a day, which is considered a low-level intake, that risk may become about 13% – which is statistically significant,” Dr. Ligibel explained.

But that risk increase is not clinically relevant, she added.

Mean 10 years of follow-up

The new study is the first to examine physical activity, drinking, and the 10 cancers that have been linked to alcohol consumption (oral cavity, throat, larynx, esophagus, liver, colorectal, stomach, breast, pancreas, and lung).

The authors used data from 10 British population-based health surveys from 1994-2008 and looked at adults aged 30 years and older. The mean follow-up period was 9.9 years.

Among 54,686 participants, there were 2039 alcohol-related site-specific cancer deaths.

Alcohol consumption categories were based on U.K. guidelines, with 1 unit equal to 8 grams (about 2 ounces) of pure alcohol. The categories were as follows: drinking within guidelines (<14 units/week for women, <21 units/week for men), hazardous level (14-35 units/week for women, 21-49 units/week for men), and harmful level (> 35 units/week for women, >49 units/week for men). The survey also queried participants about being ex-drinkers, occasional drinkers, and never drinkers.

Physical activity was assessed using self-reported accounts of the 4 weeks preceding the health survey and intensity of activity (light, moderate, or vigorous) was queried. Physical activity was categorized using the upper (15 MET-hours/week) and lower (the aforementioned <7 MET-hours/week) recommended limits.

The median age of participants was 51 years; 7.9% were never drinkers and 14.7% exceeded guideline amounts. For physical activity, 23% reported none. The median level of activity was 9 MET-hours/week.

The authors say that the “increased risks [among the harmful, hazardous, and ex-drinker categories] were eliminated” among the individuals who reported physical activity >7.5 MET-hours/week. That meant the hazard ratios for cancer mortality for each category were reduced to the point that they were no longer statistically significant.

For example, for all drinkers in the “hazardous” category, the risk of cancer-related mortality was significantly higher than for nondrinkers (with a hazard ratio of 1.39), but in the subgroup of these participants who were physically active at the lower recommended limit, the hazard ratio dropped to 1.21.

These “broad patterns of effect modification by physical activity persisted when the upper physical activity limit [15 MET-hours/week] was used,” write the authors.

The new study adds to the literature on cancer mortality and alcohol consumption. In another recent study, researchers looked at eight British cohorts and reported overall cancer mortality associated with alcohol consumption was eliminated among those meeting physical activity recommendations (Br J Sports Med. 2017;51:651-7). The new study added two more cohorts to this base of eight and only focused on cancers that have been linked to alcohol consumption. The earlier study included deaths from all types of cancer.

The refinement of focus in the current study is important, say Dr. Stamatakis and colleagues.

“This specificity adds biological plausibility and permits a more immediate translation of our findings into policy and practice,” they write. 

Dr. Stamatakis practices what he advocates, but is not a teetotaler.

“I exercise (e.g., dynamic yoga, HIIT cardio workouts, run, cycle, lift weights) for 45-60 minutes a day and I walk 8,000-14,000 steps daily. That would categorize me perhaps in the top 3%-5% for my age/sex group. And I enjoy 1-2 cans of craft beer a couple of times a week,” he said in an email.

Dr. Stamatakis and Dr. Patel have reported no relevant financial relationships.

This article first appeared on Medscape.com.

Among adults who drink alcohol at relatively high amounts, regular weekly physical activity may reduce the mortality risk posed by alcohol-related cancers, concludes a new observational study involving 50,000-plus British adults.

Being physically active – for example, by walking, house cleaning, or playing a sport – could be promoted as a risk-minimization measure for alcohol-related cancers, say the authors, led by Emmanuel Stamatakis, PhD, professor of Physical Activity, Lifestyle, and Population Health, University of Sydney, Australia.

The researchers found a “strong direct association between alcohol consumption and mortality risk of [10] alcohol-related cancers.”

Specifically, when compared with never drinkers, there was a significantly higher risk of dying from such cancers among drinkers who consumed “hazardous” and “harmful” amounts of alcohol, and also for ex-drinkers.

Notably, occasional drinkers and drinkers within guidelines did not have statistically significantly higher risks for alcohol-related cancer mortality.

But the analysis also found that among the bigger drinkers, the risks were “substantially attenuated” in physically active participants who met at least the lower recommended limit of activity (>7.5 metabolic equivalent task [MET]–hours/week).

That’s not a taxing amount of activity because, for example, general household cleaning results in 3 METs/hour and walking slowly translates into 2 METs/hour. However, nearly a quarter of survey participants reported no physical activity.

The study was published online May 14 in the International Journal of Cancer.

The new results require confirmation because the findings “are limited in their statistical power,” with small numbers of cases in several categories, said Alpa Patel, PhD, an epidemiologist at the American Cancer Society, who was not involved in the study. For example, there were only 55 alcohol-related cancer deaths among the 1540 harmful drinkers.

Patel stressed that, “based on the collective evidence to date, it is best to both avoid alcohol consumption and engage in sufficient amounts of physical activity.” That amount is 150-300 minutes of moderate or 75-150 minutes of vigorous activity per week for cancer prevention.

Her message about abstinence is in-line with new ACS guidelines issued last month, as reported by Medscape Medical News. The ACS’s guidance was criticized by many readers in the comments section, who repeatedly encouraged “moderation.”

However, the ACS also recommended moderation, saying, for those adults who do drink, intake should be no more than 1 drink/day for women or 2 drinks/day for men. 

Study author Dr. Stamatakis commented on the alcohol debate.

“Any advice for complete abstinence is bound to alienate many people,” he told Medscape Medical News in an email. “Alcohol drinking has been an integral part of many societies for thousands of years.”

Dr. Stamatakis, who is an occasional beer drinker, also said, “there is no healthy level of alcohol drinking.”

This was also the conclusion of a 2018 study published in the Lancet, which stated that there is “no safe limit,” as even one drink a day increases the risk of cancer. A few years earlier, the 2014 World Cancer Report found a dose-response relationship between alcohol consumption and certain cancers.

However, epidemiological findings are not necessarily “clinically relevant,” commented Jennifer Ligibel, MD, a medical oncologist at the Dana-Farber Cancer Institute, Boston, Massachusetts, in a 2018 interview with Medscape Medical News.

Dr. Ligibel explained that there are 50 years of studies linking alcohol and cancers. “With the huge amount of data we have, even small differences [in consumption] are statistically significant.”

Dr. Ligibel cited an often-repeated statistic: for the average woman, there is a 12% lifetime risk of breast cancer. “If a woman consumes a drink a day, which is considered a low-level intake, that risk may become about 13% – which is statistically significant,” Dr. Ligibel explained.

But that risk increase is not clinically relevant, she added.

Mean 10 years of follow-up

The new study is the first to examine physical activity, drinking, and the 10 cancers that have been linked to alcohol consumption (oral cavity, throat, larynx, esophagus, liver, colorectal, stomach, breast, pancreas, and lung).

The authors used data from 10 British population-based health surveys from 1994-2008 and looked at adults aged 30 years and older. The mean follow-up period was 9.9 years.

Among 54,686 participants, there were 2039 alcohol-related site-specific cancer deaths.

Alcohol consumption categories were based on U.K. guidelines, with 1 unit equal to 8 grams (about 2 ounces) of pure alcohol. The categories were as follows: drinking within guidelines (<14 units/week for women, <21 units/week for men), hazardous level (14-35 units/week for women, 21-49 units/week for men), and harmful level (> 35 units/week for women, >49 units/week for men). The survey also queried participants about being ex-drinkers, occasional drinkers, and never drinkers.

Physical activity was assessed using self-reported accounts of the 4 weeks preceding the health survey and intensity of activity (light, moderate, or vigorous) was queried. Physical activity was categorized using the upper (15 MET-hours/week) and lower (the aforementioned <7 MET-hours/week) recommended limits.

The median age of participants was 51 years; 7.9% were never drinkers and 14.7% exceeded guideline amounts. For physical activity, 23% reported none. The median level of activity was 9 MET-hours/week.

The authors say that the “increased risks [among the harmful, hazardous, and ex-drinker categories] were eliminated” among the individuals who reported physical activity >7.5 MET-hours/week. That meant the hazard ratios for cancer mortality for each category were reduced to the point that they were no longer statistically significant.

For example, for all drinkers in the “hazardous” category, the risk of cancer-related mortality was significantly higher than for nondrinkers (with a hazard ratio of 1.39), but in the subgroup of these participants who were physically active at the lower recommended limit, the hazard ratio dropped to 1.21.

These “broad patterns of effect modification by physical activity persisted when the upper physical activity limit [15 MET-hours/week] was used,” write the authors.

The new study adds to the literature on cancer mortality and alcohol consumption. In another recent study, researchers looked at eight British cohorts and reported overall cancer mortality associated with alcohol consumption was eliminated among those meeting physical activity recommendations (Br J Sports Med. 2017;51:651-7). The new study added two more cohorts to this base of eight and only focused on cancers that have been linked to alcohol consumption. The earlier study included deaths from all types of cancer.

The refinement of focus in the current study is important, say Dr. Stamatakis and colleagues.

“This specificity adds biological plausibility and permits a more immediate translation of our findings into policy and practice,” they write. 

Dr. Stamatakis practices what he advocates, but is not a teetotaler.

“I exercise (e.g., dynamic yoga, HIIT cardio workouts, run, cycle, lift weights) for 45-60 minutes a day and I walk 8,000-14,000 steps daily. That would categorize me perhaps in the top 3%-5% for my age/sex group. And I enjoy 1-2 cans of craft beer a couple of times a week,” he said in an email.

Dr. Stamatakis and Dr. Patel have reported no relevant financial relationships.

This article first appeared on Medscape.com.

To avoid potentially life-threatening drug-drug interactions in patients with gastrointestinal cancers, clinicians should avoid polypharmacy, but if that is not possible, they should be on the lookout for potentially dangerous combinations and should monitor for adverse events, warned a leading expert in the field.

Rachel P. Riechelmann, MD, AC Camargo Cancer Center, São Paulo, Brazil, was delivering a keynote speech during the ESMO 22nd World Congress on Gastrointestinal Cancer Virtual Experience on July 4.

One of the drug-drug interactions that can have a deleterious effect on patients with GI cancers is that occurring between proton pump inhibitors (PPIs), such as omeprazole, and chemotherapy regimens containing capecitabine, she said.

She cited clinical trial data showing that the use of PPIs can increase the risk for progression in colorectal cancer patients being treated with adjuvant CapeOx (capecitabine with oxaliplatin) or FOLFOX (leucovorin calcium [folinic acid], fluorouracil, and oxaliplatin). Further clinical trial data from the LOGIC trial show that PPIs have a significant effect on both progression-free and overall survival in HER2+ gastric cancer patients being treated with CapOx with or without lapatinib.

Commenting on the presentation on Twitter, Jose Fernando Moura, MD, PhD, Medical Oncology, Real Hospital Português, Recife, Brazil, agreed that it is better to avoid PPIs during chemotherapy for colorectal and gastrointestinal tumors.

Benedikt Westphalen, MD, PhD, coordinator, molecular oncology, University of Munich Comprehensive Cancer Center, Munich, Germany, replied that the data presented by Dr. Riechelmann are “clearly interesting.”

He added his own checklist of things to consider in regard to drug-drug interactions, including changes in drug levels, the effect on the microbiome, and gender differences.

Previous studies, including many from Dr. Riechelmann’s group, have indicated that potential drug-drug interactions occur in about two thirds of inpatients and in approximately one third of outpatients.

The frequency of clinically relevant drug interactions in oncology patients enrolled in clinical trials is “not that high,” however, at between 3% and 17%, depending on the mechanism of interaction, she commented.

“But it should be zero, because all clinical trials have a list of combinations that should not be prescribed and drugs that should be avoided,” she added.

There have been very few studies on the occurrence of drug-drug interactions in oncology patients in the real world, Dr. Riechelmann commented.

One study suggested that 4% of oncology deaths in hospitals were due to adverse drug reactions or interactions. Another study, conducted by Dr. Riechelmann’s team, suggested that 2% of nonelective hospitalizations among oncology patients were for drug-drug interactions.

She said that common potential drug interactions in oncology involve the use of aspirin, warfarin, beta blockers, and corticosteroids.

She also singled out olaparib (Lynparza, AstraZeneca) as an interesting case. Coadministration of drugs that act as CYP3A4 inhibitors or inducers can effect exposure to this drug; itraconazole significantly increases exposure, and rifampin significantly reduces exposure.
 

Avoiding interactions

In conclusion, Dr. Riechelmann made a series of recommendations for avoiding dangerous drug-drug interactions in cancer patients, the first of which is to avoid polypharmacy in the first place.

She also suggested that high-risk patients, such as those taking many drugs and who have comorbid illness, should be screened for potential drug interactions, and attention should be paid to “dangerous” combinations.

Combinations to avoid include those of two drugs that each prolong the QT interval. These include quinolones, azithromycin, and clarithromycin.

“I think every one of us has to develop our own list of dangerous combinations” that should be avoided if possible, she said. If their use is necessary, patients should be informed of the potential risk and should be monitored closely for adverse events.

No funding for the study has been reported. The investigators have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

To avoid potentially life-threatening drug-drug interactions in patients with gastrointestinal cancers, clinicians should avoid polypharmacy, but if that is not possible, they should be on the lookout for potentially dangerous combinations and should monitor for adverse events, warned a leading expert in the field.

Rachel P. Riechelmann, MD, AC Camargo Cancer Center, São Paulo, Brazil, was delivering a keynote speech during the ESMO 22nd World Congress on Gastrointestinal Cancer Virtual Experience on July 4.

One of the drug-drug interactions that can have a deleterious effect on patients with GI cancers is that occurring between proton pump inhibitors (PPIs), such as omeprazole, and chemotherapy regimens containing capecitabine, she said.

She cited clinical trial data showing that the use of PPIs can increase the risk for progression in colorectal cancer patients being treated with adjuvant CapeOx (capecitabine with oxaliplatin) or FOLFOX (leucovorin calcium [folinic acid], fluorouracil, and oxaliplatin). Further clinical trial data from the LOGIC trial show that PPIs have a significant effect on both progression-free and overall survival in HER2+ gastric cancer patients being treated with CapOx with or without lapatinib.

Commenting on the presentation on Twitter, Jose Fernando Moura, MD, PhD, Medical Oncology, Real Hospital Português, Recife, Brazil, agreed that it is better to avoid PPIs during chemotherapy for colorectal and gastrointestinal tumors.

Benedikt Westphalen, MD, PhD, coordinator, molecular oncology, University of Munich Comprehensive Cancer Center, Munich, Germany, replied that the data presented by Dr. Riechelmann are “clearly interesting.”

He added his own checklist of things to consider in regard to drug-drug interactions, including changes in drug levels, the effect on the microbiome, and gender differences.

Previous studies, including many from Dr. Riechelmann’s group, have indicated that potential drug-drug interactions occur in about two thirds of inpatients and in approximately one third of outpatients.

The frequency of clinically relevant drug interactions in oncology patients enrolled in clinical trials is “not that high,” however, at between 3% and 17%, depending on the mechanism of interaction, she commented.

“But it should be zero, because all clinical trials have a list of combinations that should not be prescribed and drugs that should be avoided,” she added.

There have been very few studies on the occurrence of drug-drug interactions in oncology patients in the real world, Dr. Riechelmann commented.

One study suggested that 4% of oncology deaths in hospitals were due to adverse drug reactions or interactions. Another study, conducted by Dr. Riechelmann’s team, suggested that 2% of nonelective hospitalizations among oncology patients were for drug-drug interactions.

She said that common potential drug interactions in oncology involve the use of aspirin, warfarin, beta blockers, and corticosteroids.

She also singled out olaparib (Lynparza, AstraZeneca) as an interesting case. Coadministration of drugs that act as CYP3A4 inhibitors or inducers can effect exposure to this drug; itraconazole significantly increases exposure, and rifampin significantly reduces exposure.
 

Avoiding interactions

In conclusion, Dr. Riechelmann made a series of recommendations for avoiding dangerous drug-drug interactions in cancer patients, the first of which is to avoid polypharmacy in the first place.

She also suggested that high-risk patients, such as those taking many drugs and who have comorbid illness, should be screened for potential drug interactions, and attention should be paid to “dangerous” combinations.

Combinations to avoid include those of two drugs that each prolong the QT interval. These include quinolones, azithromycin, and clarithromycin.

“I think every one of us has to develop our own list of dangerous combinations” that should be avoided if possible, she said. If their use is necessary, patients should be informed of the potential risk and should be monitored closely for adverse events.

No funding for the study has been reported. The investigators have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

To avoid potentially life-threatening drug-drug interactions in patients with gastrointestinal cancers, clinicians should avoid polypharmacy, but if that is not possible, they should be on the lookout for potentially dangerous combinations and should monitor for adverse events, warned a leading expert in the field.

Rachel P. Riechelmann, MD, AC Camargo Cancer Center, São Paulo, Brazil, was delivering a keynote speech during the ESMO 22nd World Congress on Gastrointestinal Cancer Virtual Experience on July 4.

One of the drug-drug interactions that can have a deleterious effect on patients with GI cancers is that occurring between proton pump inhibitors (PPIs), such as omeprazole, and chemotherapy regimens containing capecitabine, she said.

She cited clinical trial data showing that the use of PPIs can increase the risk for progression in colorectal cancer patients being treated with adjuvant CapeOx (capecitabine with oxaliplatin) or FOLFOX (leucovorin calcium [folinic acid], fluorouracil, and oxaliplatin). Further clinical trial data from the LOGIC trial show that PPIs have a significant effect on both progression-free and overall survival in HER2+ gastric cancer patients being treated with CapOx with or without lapatinib.

Commenting on the presentation on Twitter, Jose Fernando Moura, MD, PhD, Medical Oncology, Real Hospital Português, Recife, Brazil, agreed that it is better to avoid PPIs during chemotherapy for colorectal and gastrointestinal tumors.

Benedikt Westphalen, MD, PhD, coordinator, molecular oncology, University of Munich Comprehensive Cancer Center, Munich, Germany, replied that the data presented by Dr. Riechelmann are “clearly interesting.”

He added his own checklist of things to consider in regard to drug-drug interactions, including changes in drug levels, the effect on the microbiome, and gender differences.

Previous studies, including many from Dr. Riechelmann’s group, have indicated that potential drug-drug interactions occur in about two thirds of inpatients and in approximately one third of outpatients.

The frequency of clinically relevant drug interactions in oncology patients enrolled in clinical trials is “not that high,” however, at between 3% and 17%, depending on the mechanism of interaction, she commented.

“But it should be zero, because all clinical trials have a list of combinations that should not be prescribed and drugs that should be avoided,” she added.

There have been very few studies on the occurrence of drug-drug interactions in oncology patients in the real world, Dr. Riechelmann commented.

One study suggested that 4% of oncology deaths in hospitals were due to adverse drug reactions or interactions. Another study, conducted by Dr. Riechelmann’s team, suggested that 2% of nonelective hospitalizations among oncology patients were for drug-drug interactions.

She said that common potential drug interactions in oncology involve the use of aspirin, warfarin, beta blockers, and corticosteroids.

She also singled out olaparib (Lynparza, AstraZeneca) as an interesting case. Coadministration of drugs that act as CYP3A4 inhibitors or inducers can effect exposure to this drug; itraconazole significantly increases exposure, and rifampin significantly reduces exposure.
 

Avoiding interactions

In conclusion, Dr. Riechelmann made a series of recommendations for avoiding dangerous drug-drug interactions in cancer patients, the first of which is to avoid polypharmacy in the first place.

She also suggested that high-risk patients, such as those taking many drugs and who have comorbid illness, should be screened for potential drug interactions, and attention should be paid to “dangerous” combinations.

Combinations to avoid include those of two drugs that each prolong the QT interval. These include quinolones, azithromycin, and clarithromycin.

“I think every one of us has to develop our own list of dangerous combinations” that should be avoided if possible, she said. If their use is necessary, patients should be informed of the potential risk and should be monitored closely for adverse events.

No funding for the study has been reported. The investigators have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

The clinical findings and medical history were consistent with drug-induced hyperpigmentation and minocycline was the likely culprit. Other medications commonly implicated in drug-induced hyperpigmentation include heavy metals (eg, gold, iron, silver), anticonvulsants, hydroxychloroquine, and amiodarone.

Common sites for minocycline pigment deposition—besides the fingernails—include the gingiva, dorsal hands, shins, and old scars. The diagnosis of drug-induced hyperpigmentation is clinical and does not require a biopsy.

While the use of antibiotics for chronic disease can lead to antimicrobial resistance (and should be avoided when possible), certain cases of rosacea may require chronic therapy, and tetracyclines most commonly are used. When minocycline is chosen as a chronic therapy, part of the treatment surveillance should include monitoring for drug-induced hyperpigmentation.

When drug-induced hyperpigmentation does occur, treatment involves discontinuing the offending agent. It can take years for pigment to develop and years for it to resolve—if it completely resolves at all.

In this case, the physician was concerned about the pigmentation worsening or spreading to other sites, so he discontinued the minocycline and prescribed a topical agent for the patient’s rosacea. Ultimately, the patient required occasional use of doxycycline for flares.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.

The clinical findings and medical history were consistent with drug-induced hyperpigmentation and minocycline was the likely culprit. Other medications commonly implicated in drug-induced hyperpigmentation include heavy metals (eg, gold, iron, silver), anticonvulsants, hydroxychloroquine, and amiodarone.

Common sites for minocycline pigment deposition—besides the fingernails—include the gingiva, dorsal hands, shins, and old scars. The diagnosis of drug-induced hyperpigmentation is clinical and does not require a biopsy.

While the use of antibiotics for chronic disease can lead to antimicrobial resistance (and should be avoided when possible), certain cases of rosacea may require chronic therapy, and tetracyclines most commonly are used. When minocycline is chosen as a chronic therapy, part of the treatment surveillance should include monitoring for drug-induced hyperpigmentation.

When drug-induced hyperpigmentation does occur, treatment involves discontinuing the offending agent. It can take years for pigment to develop and years for it to resolve—if it completely resolves at all.

In this case, the physician was concerned about the pigmentation worsening or spreading to other sites, so he discontinued the minocycline and prescribed a topical agent for the patient’s rosacea. Ultimately, the patient required occasional use of doxycycline for flares.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.

The clinical findings and medical history were consistent with drug-induced hyperpigmentation and minocycline was the likely culprit. Other medications commonly implicated in drug-induced hyperpigmentation include heavy metals (eg, gold, iron, silver), anticonvulsants, hydroxychloroquine, and amiodarone.

Common sites for minocycline pigment deposition—besides the fingernails—include the gingiva, dorsal hands, shins, and old scars. The diagnosis of drug-induced hyperpigmentation is clinical and does not require a biopsy.

While the use of antibiotics for chronic disease can lead to antimicrobial resistance (and should be avoided when possible), certain cases of rosacea may require chronic therapy, and tetracyclines most commonly are used. When minocycline is chosen as a chronic therapy, part of the treatment surveillance should include monitoring for drug-induced hyperpigmentation.

When drug-induced hyperpigmentation does occur, treatment involves discontinuing the offending agent. It can take years for pigment to develop and years for it to resolve—if it completely resolves at all.

In this case, the physician was concerned about the pigmentation worsening or spreading to other sites, so he discontinued the minocycline and prescribed a topical agent for the patient’s rosacea. Ultimately, the patient required occasional use of doxycycline for flares.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.

A recent teleconference brought together an ad hoc panel of pediatric hospitalists, with more than 100 diverse voices discussing whether there ought to be an additional professional recognition or designation for the subspecialty, apart from the new pediatric hospital medicine (PHM) board certification that was launched in 2019.

The heterogeneity of PHM was on display during the discussion, as participants included university-based pediatric hospitalists and those from community hospitals, physicians trained in combined medicine and pediatrics or in family medicine, doctors who completed a general pediatric residency before going straight into PHM, niche practitioners such as newborn hospitalists, trainees, and a small but growing number of graduates of PHM fellowship programs. There are 61 PHM fellowships, and these programs graduate approximately 70 new fellows per year.

Although a route to some kind of professional designation for PHM – separate from board certification – was the centerpiece of the conference call, there is no proposal actively under consideration for developing such a designation, said Weijen W. Chang, MD, FAAP, SFHM, chief of pediatric hospital medicine at Baystate Medical Center in Springfield, Mass., and associate professor of pediatrics at the University of Massachusetts–Baystate Campus.

Who might develop such a proposal? “The hope is that the three major professional societies involved in pediatric hospital medicine – the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association – would jointly develop such a designation,” Dr. Chang said. However, it is not clear whether the three societies could agree on this. An online survey of 551 pediatric hospitalists, shared during the conference call, found that the majority would like to see some kind of alternate designation.

The reality of the boards

The pediatric subspecialty of PHM was recognized by the American Board of Medical Specialties in 2015 following a petition by a group of PHM leaders seeking a way to credential their unique skill set. The first PHM board certification exam was offered by the American Board of Pediatrics on Nov. 12, 2019, with 1,491 hospitalists sitting for the exam and 84% passing. An estimated 4,000 pediatric hospitalists currently work in the field.

Certification as a subspecialty typically requires completing a fellowship, but new subspecialties often offer a “practice pathway” allowing those who already have experience working in the field to sit for the exam. A PHM practice pathway, and a combined fellowship and experience option for those whose fellowship training was less than 2 years, was offered for last year’s exam and will be offered again in 2021 and 2023. After that, board certification will only be available to graduates of recognized fellowships.

But concerns began to emerge last summer in advance of ABM’s initial PHM board exam, when some applicants were told that they weren’t eligible to sit for it, said H. Barrett Fromme, MD, associate dean for faculty development in medical education and section chief for pediatric hospital medicine at the University of Chicago. She also chairs the section of hospital medicine for the AAP.

Concerns including unintended gender bias against women, such as those hospitalists whose training is interrupted for maternity leave, were raised in a petition to ABP. The board promptly responded that gender bias was not supported by the facts, although its response did not account for selection bias in the data. But the ABP removed its practice interruption criteria.^1,2

There are various reasons why a pediatric hospitalist might not be able or willing to pursue a 2-year fellowship or otherwise qualify for certification, Dr. Fromme said, including time and cost. For some, the practice pathway’s requirements, including a minimum number of hours worked in pediatrics in the previous 4 years, may be impossible to meet. Pediatric hospitalists boarded in family medicine are not eligible.

For hospitalists who can’t achieve board certification, what might that mean in terms of their future salary, employment opportunities, reimbursement, other career goals? Might they find themselves unable to qualify for PHM jobs at some university-based medical centers? The answers are not yet known.

What might self-designation look like?

PHM is distinct from adult hospital medicine by virtue of its designation as a board-certified subspecialty. But it can look to the broader HM field for examples of designations that bestow a kind of professional recognition, Dr. Chang said. These include SHM’s merit-based Fellow in Hospital Medicine program and the American Board of Medical Specialties’ Focused Practice in Hospital Medicine, a pathway for board recertification in internal medicine and family medicine, he said.

But PHM self-designation is not necessarily a pathway to hospital privileges. “If we build it, will they come? If they come, will it mean anything to them? That’s the million-dollar question?” Dr. Chang said.

Hospitalists need to appreciate that this issue is important to all three PHM professional societies, SHM, AAP, and APA, Dr. Fromme said. “We are concerned about how to support all of our members – certified, noncertified, nonphysician. Alternate designation is one idea, but we need time to understand it. We need a lot more conversations and a lot of people thinking about it.”

Dr. Fromme is part of the Council on Pediatric Hospital Medicine, a small circle of leaders of PHM interest groups within the three professional associations. It meets quarterly and will be reviewing the results of the conference call.

“I personally think we don’t understand the scope of the problem or the needs of pediatric hospitalists who are not able to sit for boards or pursue a fellowship,” she said. “We have empathy and concern for our colleagues who can’t take the boards. We don’t want them to feel excluded, and that includes advanced practice nurses and residents. But does an alternative designation actually provide what people think it provides?”

There are other ways to demonstrate that professionals are engaged with and serious about developing their practice. If they are looking to better themselves at quality improvement, leadership, education, and other elements of PHM practice, the associations can endeavor to provide more educational opportunities, Dr. Fromme said. “But if it’s about how they look as a candidate for hire, relative to board-certified candidates, that’s a different beast, and we need to think about what can help them the most.”
 

References

1. American Board of Pediatrics, Response to the Pediatric Hospital Medicine Petition. 2019 Aug 20. https://www.abp.org/sites/abp/files/phm-petition-response.pdf.

2. Chang WW et al. J Hosp Med. 2019 Oct;14(10):589-90.

A recent teleconference brought together an ad hoc panel of pediatric hospitalists, with more than 100 diverse voices discussing whether there ought to be an additional professional recognition or designation for the subspecialty, apart from the new pediatric hospital medicine (PHM) board certification that was launched in 2019.

The heterogeneity of PHM was on display during the discussion, as participants included university-based pediatric hospitalists and those from community hospitals, physicians trained in combined medicine and pediatrics or in family medicine, doctors who completed a general pediatric residency before going straight into PHM, niche practitioners such as newborn hospitalists, trainees, and a small but growing number of graduates of PHM fellowship programs. There are 61 PHM fellowships, and these programs graduate approximately 70 new fellows per year.

Although a route to some kind of professional designation for PHM – separate from board certification – was the centerpiece of the conference call, there is no proposal actively under consideration for developing such a designation, said Weijen W. Chang, MD, FAAP, SFHM, chief of pediatric hospital medicine at Baystate Medical Center in Springfield, Mass., and associate professor of pediatrics at the University of Massachusetts–Baystate Campus.

Who might develop such a proposal? “The hope is that the three major professional societies involved in pediatric hospital medicine – the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association – would jointly develop such a designation,” Dr. Chang said. However, it is not clear whether the three societies could agree on this. An online survey of 551 pediatric hospitalists, shared during the conference call, found that the majority would like to see some kind of alternate designation.

The reality of the boards

The pediatric subspecialty of PHM was recognized by the American Board of Medical Specialties in 2015 following a petition by a group of PHM leaders seeking a way to credential their unique skill set. The first PHM board certification exam was offered by the American Board of Pediatrics on Nov. 12, 2019, with 1,491 hospitalists sitting for the exam and 84% passing. An estimated 4,000 pediatric hospitalists currently work in the field.

Certification as a subspecialty typically requires completing a fellowship, but new subspecialties often offer a “practice pathway” allowing those who already have experience working in the field to sit for the exam. A PHM practice pathway, and a combined fellowship and experience option for those whose fellowship training was less than 2 years, was offered for last year’s exam and will be offered again in 2021 and 2023. After that, board certification will only be available to graduates of recognized fellowships.

But concerns began to emerge last summer in advance of ABM’s initial PHM board exam, when some applicants were told that they weren’t eligible to sit for it, said H. Barrett Fromme, MD, associate dean for faculty development in medical education and section chief for pediatric hospital medicine at the University of Chicago. She also chairs the section of hospital medicine for the AAP.

Concerns including unintended gender bias against women, such as those hospitalists whose training is interrupted for maternity leave, were raised in a petition to ABP. The board promptly responded that gender bias was not supported by the facts, although its response did not account for selection bias in the data. But the ABP removed its practice interruption criteria.^1,2

There are various reasons why a pediatric hospitalist might not be able or willing to pursue a 2-year fellowship or otherwise qualify for certification, Dr. Fromme said, including time and cost. For some, the practice pathway’s requirements, including a minimum number of hours worked in pediatrics in the previous 4 years, may be impossible to meet. Pediatric hospitalists boarded in family medicine are not eligible.

For hospitalists who can’t achieve board certification, what might that mean in terms of their future salary, employment opportunities, reimbursement, other career goals? Might they find themselves unable to qualify for PHM jobs at some university-based medical centers? The answers are not yet known.

What might self-designation look like?

PHM is distinct from adult hospital medicine by virtue of its designation as a board-certified subspecialty. But it can look to the broader HM field for examples of designations that bestow a kind of professional recognition, Dr. Chang said. These include SHM’s merit-based Fellow in Hospital Medicine program and the American Board of Medical Specialties’ Focused Practice in Hospital Medicine, a pathway for board recertification in internal medicine and family medicine, he said.

But PHM self-designation is not necessarily a pathway to hospital privileges. “If we build it, will they come? If they come, will it mean anything to them? That’s the million-dollar question?” Dr. Chang said.

Hospitalists need to appreciate that this issue is important to all three PHM professional societies, SHM, AAP, and APA, Dr. Fromme said. “We are concerned about how to support all of our members – certified, noncertified, nonphysician. Alternate designation is one idea, but we need time to understand it. We need a lot more conversations and a lot of people thinking about it.”

Dr. Fromme is part of the Council on Pediatric Hospital Medicine, a small circle of leaders of PHM interest groups within the three professional associations. It meets quarterly and will be reviewing the results of the conference call.

“I personally think we don’t understand the scope of the problem or the needs of pediatric hospitalists who are not able to sit for boards or pursue a fellowship,” she said. “We have empathy and concern for our colleagues who can’t take the boards. We don’t want them to feel excluded, and that includes advanced practice nurses and residents. But does an alternative designation actually provide what people think it provides?”

There are other ways to demonstrate that professionals are engaged with and serious about developing their practice. If they are looking to better themselves at quality improvement, leadership, education, and other elements of PHM practice, the associations can endeavor to provide more educational opportunities, Dr. Fromme said. “But if it’s about how they look as a candidate for hire, relative to board-certified candidates, that’s a different beast, and we need to think about what can help them the most.”
 

References

1. American Board of Pediatrics, Response to the Pediatric Hospital Medicine Petition. 2019 Aug 20. https://www.abp.org/sites/abp/files/phm-petition-response.pdf.

2. Chang WW et al. J Hosp Med. 2019 Oct;14(10):589-90.

A recent teleconference brought together an ad hoc panel of pediatric hospitalists, with more than 100 diverse voices discussing whether there ought to be an additional professional recognition or designation for the subspecialty, apart from the new pediatric hospital medicine (PHM) board certification that was launched in 2019.

The heterogeneity of PHM was on display during the discussion, as participants included university-based pediatric hospitalists and those from community hospitals, physicians trained in combined medicine and pediatrics or in family medicine, doctors who completed a general pediatric residency before going straight into PHM, niche practitioners such as newborn hospitalists, trainees, and a small but growing number of graduates of PHM fellowship programs. There are 61 PHM fellowships, and these programs graduate approximately 70 new fellows per year.

Although a route to some kind of professional designation for PHM – separate from board certification – was the centerpiece of the conference call, there is no proposal actively under consideration for developing such a designation, said Weijen W. Chang, MD, FAAP, SFHM, chief of pediatric hospital medicine at Baystate Medical Center in Springfield, Mass., and associate professor of pediatrics at the University of Massachusetts–Baystate Campus.

Who might develop such a proposal? “The hope is that the three major professional societies involved in pediatric hospital medicine – the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association – would jointly develop such a designation,” Dr. Chang said. However, it is not clear whether the three societies could agree on this. An online survey of 551 pediatric hospitalists, shared during the conference call, found that the majority would like to see some kind of alternate designation.

The reality of the boards

The pediatric subspecialty of PHM was recognized by the American Board of Medical Specialties in 2015 following a petition by a group of PHM leaders seeking a way to credential their unique skill set. The first PHM board certification exam was offered by the American Board of Pediatrics on Nov. 12, 2019, with 1,491 hospitalists sitting for the exam and 84% passing. An estimated 4,000 pediatric hospitalists currently work in the field.

Certification as a subspecialty typically requires completing a fellowship, but new subspecialties often offer a “practice pathway” allowing those who already have experience working in the field to sit for the exam. A PHM practice pathway, and a combined fellowship and experience option for those whose fellowship training was less than 2 years, was offered for last year’s exam and will be offered again in 2021 and 2023. After that, board certification will only be available to graduates of recognized fellowships.

But concerns began to emerge last summer in advance of ABM’s initial PHM board exam, when some applicants were told that they weren’t eligible to sit for it, said H. Barrett Fromme, MD, associate dean for faculty development in medical education and section chief for pediatric hospital medicine at the University of Chicago. She also chairs the section of hospital medicine for the AAP.

Concerns including unintended gender bias against women, such as those hospitalists whose training is interrupted for maternity leave, were raised in a petition to ABP. The board promptly responded that gender bias was not supported by the facts, although its response did not account for selection bias in the data. But the ABP removed its practice interruption criteria.^1,2

There are various reasons why a pediatric hospitalist might not be able or willing to pursue a 2-year fellowship or otherwise qualify for certification, Dr. Fromme said, including time and cost. For some, the practice pathway’s requirements, including a minimum number of hours worked in pediatrics in the previous 4 years, may be impossible to meet. Pediatric hospitalists boarded in family medicine are not eligible.

For hospitalists who can’t achieve board certification, what might that mean in terms of their future salary, employment opportunities, reimbursement, other career goals? Might they find themselves unable to qualify for PHM jobs at some university-based medical centers? The answers are not yet known.

What might self-designation look like?

PHM is distinct from adult hospital medicine by virtue of its designation as a board-certified subspecialty. But it can look to the broader HM field for examples of designations that bestow a kind of professional recognition, Dr. Chang said. These include SHM’s merit-based Fellow in Hospital Medicine program and the American Board of Medical Specialties’ Focused Practice in Hospital Medicine, a pathway for board recertification in internal medicine and family medicine, he said.

But PHM self-designation is not necessarily a pathway to hospital privileges. “If we build it, will they come? If they come, will it mean anything to them? That’s the million-dollar question?” Dr. Chang said.

Hospitalists need to appreciate that this issue is important to all three PHM professional societies, SHM, AAP, and APA, Dr. Fromme said. “We are concerned about how to support all of our members – certified, noncertified, nonphysician. Alternate designation is one idea, but we need time to understand it. We need a lot more conversations and a lot of people thinking about it.”

Dr. Fromme is part of the Council on Pediatric Hospital Medicine, a small circle of leaders of PHM interest groups within the three professional associations. It meets quarterly and will be reviewing the results of the conference call.

“I personally think we don’t understand the scope of the problem or the needs of pediatric hospitalists who are not able to sit for boards or pursue a fellowship,” she said. “We have empathy and concern for our colleagues who can’t take the boards. We don’t want them to feel excluded, and that includes advanced practice nurses and residents. But does an alternative designation actually provide what people think it provides?”

There are other ways to demonstrate that professionals are engaged with and serious about developing their practice. If they are looking to better themselves at quality improvement, leadership, education, and other elements of PHM practice, the associations can endeavor to provide more educational opportunities, Dr. Fromme said. “But if it’s about how they look as a candidate for hire, relative to board-certified candidates, that’s a different beast, and we need to think about what can help them the most.”
 

References

1. American Board of Pediatrics, Response to the Pediatric Hospital Medicine Petition. 2019 Aug 20. https://www.abp.org/sites/abp/files/phm-petition-response.pdf.

2. Chang WW et al. J Hosp Med. 2019 Oct;14(10):589-90.

The COVID-19 literature has been peppered with reports about myocarditis accompanying the disease. If true, this could, in part, explain some of the observed cardiac injury and arrhythmias in seriously ill patients, but also have implications for prognosis.

But endomyocardial biopsies and autopsies, the gold-standard confirmation tests, have been few and far between. That has led some cardiologists to question the true rate of myocarditis with SARS-CoV-2, or even if there is definitive proof the virus causes myocarditis.

Predictors of death in COVID-19 are older age, cardiovascular comorbidities, and elevated troponin or NT-proBNP – none of which actually fit well with the epidemiology of myocarditis due to other causes, Alida L.P. Caforio, MD, of Padua (Italy) University said in an interview. Myocarditis is traditionally a disease of the young, and most cases are immune-mediated and do not release troponin.

Moreover, myocarditis is a diagnosis of exclusion. For it to be made with any certainty requires proof, by biopsy or autopsy, of inflammatory infiltrates within the myocardium with myocyte necrosis not typical of myocardial infarction, said Dr. Caforio, who chaired the European Society of Cardiology’s writing committee for its 2013 position statement on myocardial and pericardial diseases.

“We have one biopsy-proven case, and in this case there were no viruses in the myocardium, including COVID-19,” she said. “There’s no proof that we have COVID-19 causing myocarditis because it has not been found in the cardiomyocytes.”
 

Emerging evidence

The virus-negative case from Lombardy, Italy, followed an early case series suggesting fulminant myocarditis was involved in 7% of COVID-related deaths in Wuhan, China.

Other case reports include cardiac magnetic resonance (CMR) findings typical of acute myocarditis in a man with no lung involvement or fever but a massive troponin spike, and myocarditis presenting as reverse takotsubo syndrome in a woman undergoing CMR and endomyocardial biopsy.

A CMR analysis in May said acute myocarditis, by 2018 Lake Louise Criteria, was present in eight of 10 patients with “myocarditis-like syndrome,” and a study just out June 30 said the coronavirus can infect heart cells in a lab dish.

Among the few autopsy series, a preprint on 12 patients with COVID-19 in the Seattle area showed coronavirus in the heart tissue of 1 patient.

“It was a low level, so there’s the possibility that it could be viremia, but the fact we do see actual cardiomyocyte injury associated with inflammation, that’s a myocarditis pattern. So it could be related to the SARS-CoV-2 virus,” said Desiree Marshall, MD, director of autopsy and after-death services, University of Washington Medical Center, Seattle.

The “waters are a little bit muddy,” however, because the patient had a coinfection clinically with influenza and methicillin-susceptible Staphylococcus aureus, which raises the specter that influenza could also have contributed, she said.

Data pending publication from two additional patients show no coronavirus in the heart. Acute respiratory distress syndrome pathology was common in all patients, but there was no evidence of vascular inflammation, such as endotheliitis, Dr. Marshall said.

SARS-CoV-2 cell entry depends on the angiotensin-converting enzyme 2 (ACE2) receptor, which is widely expressed in the heart and on endothelial cells and is linked to inflammatory activation. Autopsy data from three COVID-19 patients showed endothelial cell infection in the heart and diffuse endothelial inflammation, but no sign of lymphocytic myocarditis.
 

Defining myocarditis

“There are some experts who believe we’re likely still dealing with myocarditis but with atypical features, while others suggest there is no myocarditis by strict classic criteria,” said Peter Liu, MD, chief scientific officer/vice president of research, University of Ottawa Heart Institute.

“I don’t think either extreme is accurate,” he said. “The truth is likely somewhere in between, with evidence of both cardiac injury and inflammation. But nothing in COVID-19, as we know today, is classic; it’s a new disease, so we need to be more open minded as new data emerge.”

Part of the divide may indeed stem from the way myocarditis is defined. “Based on traditional Dallas criteria, classic myocarditis requires evidence of myocyte necrosis, which we have, but also inflammatory cell infiltrate, which we don’t consistently have,” he said. “But on the other hand, there is evidence of inflammation-induced cardiac damage, often aggregated around blood vessels.”

The situation is evolving in recent days, and new data under review demonstrated inflammatory infiltrates, which fits the traditional myocarditis criteria, Dr. Liu noted. Yet the viral etiology for the inflammation is still elusive in definitive proof.

In traditional myocarditis, there is an abundance of lymphocytes and foci of inflammation in the myocardium, but COVID-19 is very unusual, in that these lymphocytes are not as exuberant, he said. Lymphopenia or low lymphocyte counts occur in up to 80% of patients. Also, older patients, who initially made up the bulk of the severe COVID-19 cases, are less T-lymphocyte responsive.

“So the lower your lymphocyte count, the worse your outcome is going to be and the more likely you’re going to get cytokine storm,” Dr. Liu said. “And that may be the reason the suspected myocarditis in COVID-19 is atypical because the lymphocytes, in fact, are being suppressed and there is instead more vasculitis.”

Recent data from myocardial gene expression analysis showed that the viral receptor ACE2 is present in the myocardium, and can be upregulated in conditions such as heart failure, he said. However, the highest ACE2 expression is found in pericytes around blood vessels, not myocytes. “This may explain the preferential vascular involvement often observed.”
 

Cardiac damage in the young

Evidence started evolving in early April that young COVID-19 patients without lung disease, generally in their 20s and 30s, can have very high troponin peaks and a form of cardiac damage that does not appear to be related to sepsis, systemic shock, or cytokine storm.

“That’s the group that I do think has some myocarditis, but it’s different. It’s not lymphocytic myocarditis, like enteroviral myocarditis,” Leslie T. Cooper Jr., MD, a myocarditis expert at Mayo Clinic, Jacksonville, Florida, said in an interview.

“The data to date suggest that most SARS cardiac injury is related to stress or high circulating cytokine levels. However, myocarditis probably does affect some patients, he added. “The few published cases suggest a role for macrophages or endothelial cells, which could affect cardiac myocyte function. This type of injury could cause the ST-segment elevation MI-like patterns we have seen in young people with normal epicardial coronary arteries.”

Dr. Cooper, who coauthored a report on the management of COVID-19 cardiovascular syndrome, pointed out that it’s been hard for researchers to isolate genome from autopsy samples because of RNA degradation prior to autopsy and the use of formalin fixation for tissues prior to RNA extraction.

“Most labs are not doing next-generation sequencing, and even with that, RNA protection and fresh tissue may be required to detect viral genome,” he said.
 

No proven therapy

Although up to 50% of acute myocarditis cases undergo spontaneous healing, recognition and multidisciplinary management of clinically suspected myocarditis is important. The optimal treatment remains unclear.

An early case report suggested use of methylprednisolone and intravenous immunoglobulin helped spare the life of a 37-year-old with clinically suspected fulminant myocarditis with cardiogenic shock.

In a related commentary, Dr. Caforio and colleagues pointed out that the World Health Organization considers the use of IV corticosteroids controversial, even in pneumonia due to COVID-19, because it may reduce viral clearance and increase sepsis risk. Intravenous immunoglobulin is also questionable because there is no IgG response to COVID-19 in the plasma donors’ pool.

“Immunosuppression should be reserved for only virus-negative non-COVID myocarditis,” Dr. Caforio said in an interview. “There is no appropriate treatment nowadays for clinically suspected COVID-19 myocarditis. There is no proven therapy for COVID-19, even less for COVID-19 myocarditis.”

Although definitive publication of the RECOVERY trial is still pending, the benefits of dexamethasone – a steroid that works predominantly through its anti-inflammatory effects – appear to be in the sickest patients, such as those requiring ICU admission or respiratory support.

“Many of the same patients would have systemic inflammation and would have also shown elevated cardiac biomarkers,” Dr. Liu observed. “Therefore, it is conceivable that a subset who had cardiac inflammation also benefited from the treatment. Further data, possibly through subgroup analysis and eventually meta-analysis, may help us to understand if dexamethasone also benefited patients with dominant cardiac injury.”

Dr. Caforio, Dr. Marshall, Dr. Liu, and Dr. Cooper reported having no relevant conflicts of interest.

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

The COVID-19 literature has been peppered with reports about myocarditis accompanying the disease. If true, this could, in part, explain some of the observed cardiac injury and arrhythmias in seriously ill patients, but also have implications for prognosis.

But endomyocardial biopsies and autopsies, the gold-standard confirmation tests, have been few and far between. That has led some cardiologists to question the true rate of myocarditis with SARS-CoV-2, or even if there is definitive proof the virus causes myocarditis.

Predictors of death in COVID-19 are older age, cardiovascular comorbidities, and elevated troponin or NT-proBNP – none of which actually fit well with the epidemiology of myocarditis due to other causes, Alida L.P. Caforio, MD, of Padua (Italy) University said in an interview. Myocarditis is traditionally a disease of the young, and most cases are immune-mediated and do not release troponin.

Moreover, myocarditis is a diagnosis of exclusion. For it to be made with any certainty requires proof, by biopsy or autopsy, of inflammatory infiltrates within the myocardium with myocyte necrosis not typical of myocardial infarction, said Dr. Caforio, who chaired the European Society of Cardiology’s writing committee for its 2013 position statement on myocardial and pericardial diseases.

“We have one biopsy-proven case, and in this case there were no viruses in the myocardium, including COVID-19,” she said. “There’s no proof that we have COVID-19 causing myocarditis because it has not been found in the cardiomyocytes.”
 

Emerging evidence

The virus-negative case from Lombardy, Italy, followed an early case series suggesting fulminant myocarditis was involved in 7% of COVID-related deaths in Wuhan, China.

Other case reports include cardiac magnetic resonance (CMR) findings typical of acute myocarditis in a man with no lung involvement or fever but a massive troponin spike, and myocarditis presenting as reverse takotsubo syndrome in a woman undergoing CMR and endomyocardial biopsy.

A CMR analysis in May said acute myocarditis, by 2018 Lake Louise Criteria, was present in eight of 10 patients with “myocarditis-like syndrome,” and a study just out June 30 said the coronavirus can infect heart cells in a lab dish.

Among the few autopsy series, a preprint on 12 patients with COVID-19 in the Seattle area showed coronavirus in the heart tissue of 1 patient.

“It was a low level, so there’s the possibility that it could be viremia, but the fact we do see actual cardiomyocyte injury associated with inflammation, that’s a myocarditis pattern. So it could be related to the SARS-CoV-2 virus,” said Desiree Marshall, MD, director of autopsy and after-death services, University of Washington Medical Center, Seattle.

The “waters are a little bit muddy,” however, because the patient had a coinfection clinically with influenza and methicillin-susceptible Staphylococcus aureus, which raises the specter that influenza could also have contributed, she said.

Data pending publication from two additional patients show no coronavirus in the heart. Acute respiratory distress syndrome pathology was common in all patients, but there was no evidence of vascular inflammation, such as endotheliitis, Dr. Marshall said.

SARS-CoV-2 cell entry depends on the angiotensin-converting enzyme 2 (ACE2) receptor, which is widely expressed in the heart and on endothelial cells and is linked to inflammatory activation. Autopsy data from three COVID-19 patients showed endothelial cell infection in the heart and diffuse endothelial inflammation, but no sign of lymphocytic myocarditis.
 

Defining myocarditis

“There are some experts who believe we’re likely still dealing with myocarditis but with atypical features, while others suggest there is no myocarditis by strict classic criteria,” said Peter Liu, MD, chief scientific officer/vice president of research, University of Ottawa Heart Institute.

“I don’t think either extreme is accurate,” he said. “The truth is likely somewhere in between, with evidence of both cardiac injury and inflammation. But nothing in COVID-19, as we know today, is classic; it’s a new disease, so we need to be more open minded as new data emerge.”

Part of the divide may indeed stem from the way myocarditis is defined. “Based on traditional Dallas criteria, classic myocarditis requires evidence of myocyte necrosis, which we have, but also inflammatory cell infiltrate, which we don’t consistently have,” he said. “But on the other hand, there is evidence of inflammation-induced cardiac damage, often aggregated around blood vessels.”

The situation is evolving in recent days, and new data under review demonstrated inflammatory infiltrates, which fits the traditional myocarditis criteria, Dr. Liu noted. Yet the viral etiology for the inflammation is still elusive in definitive proof.

In traditional myocarditis, there is an abundance of lymphocytes and foci of inflammation in the myocardium, but COVID-19 is very unusual, in that these lymphocytes are not as exuberant, he said. Lymphopenia or low lymphocyte counts occur in up to 80% of patients. Also, older patients, who initially made up the bulk of the severe COVID-19 cases, are less T-lymphocyte responsive.

“So the lower your lymphocyte count, the worse your outcome is going to be and the more likely you’re going to get cytokine storm,” Dr. Liu said. “And that may be the reason the suspected myocarditis in COVID-19 is atypical because the lymphocytes, in fact, are being suppressed and there is instead more vasculitis.”

Recent data from myocardial gene expression analysis showed that the viral receptor ACE2 is present in the myocardium, and can be upregulated in conditions such as heart failure, he said. However, the highest ACE2 expression is found in pericytes around blood vessels, not myocytes. “This may explain the preferential vascular involvement often observed.”
 

Cardiac damage in the young

Evidence started evolving in early April that young COVID-19 patients without lung disease, generally in their 20s and 30s, can have very high troponin peaks and a form of cardiac damage that does not appear to be related to sepsis, systemic shock, or cytokine storm.

“That’s the group that I do think has some myocarditis, but it’s different. It’s not lymphocytic myocarditis, like enteroviral myocarditis,” Leslie T. Cooper Jr., MD, a myocarditis expert at Mayo Clinic, Jacksonville, Florida, said in an interview.

“The data to date suggest that most SARS cardiac injury is related to stress or high circulating cytokine levels. However, myocarditis probably does affect some patients, he added. “The few published cases suggest a role for macrophages or endothelial cells, which could affect cardiac myocyte function. This type of injury could cause the ST-segment elevation MI-like patterns we have seen in young people with normal epicardial coronary arteries.”

Dr. Cooper, who coauthored a report on the management of COVID-19 cardiovascular syndrome, pointed out that it’s been hard for researchers to isolate genome from autopsy samples because of RNA degradation prior to autopsy and the use of formalin fixation for tissues prior to RNA extraction.

“Most labs are not doing next-generation sequencing, and even with that, RNA protection and fresh tissue may be required to detect viral genome,” he said.
 

No proven therapy

Although up to 50% of acute myocarditis cases undergo spontaneous healing, recognition and multidisciplinary management of clinically suspected myocarditis is important. The optimal treatment remains unclear.

An early case report suggested use of methylprednisolone and intravenous immunoglobulin helped spare the life of a 37-year-old with clinically suspected fulminant myocarditis with cardiogenic shock.

In a related commentary, Dr. Caforio and colleagues pointed out that the World Health Organization considers the use of IV corticosteroids controversial, even in pneumonia due to COVID-19, because it may reduce viral clearance and increase sepsis risk. Intravenous immunoglobulin is also questionable because there is no IgG response to COVID-19 in the plasma donors’ pool.

“Immunosuppression should be reserved for only virus-negative non-COVID myocarditis,” Dr. Caforio said in an interview. “There is no appropriate treatment nowadays for clinically suspected COVID-19 myocarditis. There is no proven therapy for COVID-19, even less for COVID-19 myocarditis.”

Although definitive publication of the RECOVERY trial is still pending, the benefits of dexamethasone – a steroid that works predominantly through its anti-inflammatory effects – appear to be in the sickest patients, such as those requiring ICU admission or respiratory support.

“Many of the same patients would have systemic inflammation and would have also shown elevated cardiac biomarkers,” Dr. Liu observed. “Therefore, it is conceivable that a subset who had cardiac inflammation also benefited from the treatment. Further data, possibly through subgroup analysis and eventually meta-analysis, may help us to understand if dexamethasone also benefited patients with dominant cardiac injury.”

Dr. Caforio, Dr. Marshall, Dr. Liu, and Dr. Cooper reported having no relevant conflicts of interest.

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

The COVID-19 literature has been peppered with reports about myocarditis accompanying the disease. If true, this could, in part, explain some of the observed cardiac injury and arrhythmias in seriously ill patients, but also have implications for prognosis.

But endomyocardial biopsies and autopsies, the gold-standard confirmation tests, have been few and far between. That has led some cardiologists to question the true rate of myocarditis with SARS-CoV-2, or even if there is definitive proof the virus causes myocarditis.

Predictors of death in COVID-19 are older age, cardiovascular comorbidities, and elevated troponin or NT-proBNP – none of which actually fit well with the epidemiology of myocarditis due to other causes, Alida L.P. Caforio, MD, of Padua (Italy) University said in an interview. Myocarditis is traditionally a disease of the young, and most cases are immune-mediated and do not release troponin.

Moreover, myocarditis is a diagnosis of exclusion. For it to be made with any certainty requires proof, by biopsy or autopsy, of inflammatory infiltrates within the myocardium with myocyte necrosis not typical of myocardial infarction, said Dr. Caforio, who chaired the European Society of Cardiology’s writing committee for its 2013 position statement on myocardial and pericardial diseases.

“We have one biopsy-proven case, and in this case there were no viruses in the myocardium, including COVID-19,” she said. “There’s no proof that we have COVID-19 causing myocarditis because it has not been found in the cardiomyocytes.”
 

Emerging evidence

The virus-negative case from Lombardy, Italy, followed an early case series suggesting fulminant myocarditis was involved in 7% of COVID-related deaths in Wuhan, China.

Other case reports include cardiac magnetic resonance (CMR) findings typical of acute myocarditis in a man with no lung involvement or fever but a massive troponin spike, and myocarditis presenting as reverse takotsubo syndrome in a woman undergoing CMR and endomyocardial biopsy.

A CMR analysis in May said acute myocarditis, by 2018 Lake Louise Criteria, was present in eight of 10 patients with “myocarditis-like syndrome,” and a study just out June 30 said the coronavirus can infect heart cells in a lab dish.

Among the few autopsy series, a preprint on 12 patients with COVID-19 in the Seattle area showed coronavirus in the heart tissue of 1 patient.

“It was a low level, so there’s the possibility that it could be viremia, but the fact we do see actual cardiomyocyte injury associated with inflammation, that’s a myocarditis pattern. So it could be related to the SARS-CoV-2 virus,” said Desiree Marshall, MD, director of autopsy and after-death services, University of Washington Medical Center, Seattle.

The “waters are a little bit muddy,” however, because the patient had a coinfection clinically with influenza and methicillin-susceptible Staphylococcus aureus, which raises the specter that influenza could also have contributed, she said.

Data pending publication from two additional patients show no coronavirus in the heart. Acute respiratory distress syndrome pathology was common in all patients, but there was no evidence of vascular inflammation, such as endotheliitis, Dr. Marshall said.

SARS-CoV-2 cell entry depends on the angiotensin-converting enzyme 2 (ACE2) receptor, which is widely expressed in the heart and on endothelial cells and is linked to inflammatory activation. Autopsy data from three COVID-19 patients showed endothelial cell infection in the heart and diffuse endothelial inflammation, but no sign of lymphocytic myocarditis.
 

Defining myocarditis

“There are some experts who believe we’re likely still dealing with myocarditis but with atypical features, while others suggest there is no myocarditis by strict classic criteria,” said Peter Liu, MD, chief scientific officer/vice president of research, University of Ottawa Heart Institute.

“I don’t think either extreme is accurate,” he said. “The truth is likely somewhere in between, with evidence of both cardiac injury and inflammation. But nothing in COVID-19, as we know today, is classic; it’s a new disease, so we need to be more open minded as new data emerge.”

Part of the divide may indeed stem from the way myocarditis is defined. “Based on traditional Dallas criteria, classic myocarditis requires evidence of myocyte necrosis, which we have, but also inflammatory cell infiltrate, which we don’t consistently have,” he said. “But on the other hand, there is evidence of inflammation-induced cardiac damage, often aggregated around blood vessels.”

The situation is evolving in recent days, and new data under review demonstrated inflammatory infiltrates, which fits the traditional myocarditis criteria, Dr. Liu noted. Yet the viral etiology for the inflammation is still elusive in definitive proof.

In traditional myocarditis, there is an abundance of lymphocytes and foci of inflammation in the myocardium, but COVID-19 is very unusual, in that these lymphocytes are not as exuberant, he said. Lymphopenia or low lymphocyte counts occur in up to 80% of patients. Also, older patients, who initially made up the bulk of the severe COVID-19 cases, are less T-lymphocyte responsive.

“So the lower your lymphocyte count, the worse your outcome is going to be and the more likely you’re going to get cytokine storm,” Dr. Liu said. “And that may be the reason the suspected myocarditis in COVID-19 is atypical because the lymphocytes, in fact, are being suppressed and there is instead more vasculitis.”

Recent data from myocardial gene expression analysis showed that the viral receptor ACE2 is present in the myocardium, and can be upregulated in conditions such as heart failure, he said. However, the highest ACE2 expression is found in pericytes around blood vessels, not myocytes. “This may explain the preferential vascular involvement often observed.”
 

Cardiac damage in the young

Evidence started evolving in early April that young COVID-19 patients without lung disease, generally in their 20s and 30s, can have very high troponin peaks and a form of cardiac damage that does not appear to be related to sepsis, systemic shock, or cytokine storm.

“That’s the group that I do think has some myocarditis, but it’s different. It’s not lymphocytic myocarditis, like enteroviral myocarditis,” Leslie T. Cooper Jr., MD, a myocarditis expert at Mayo Clinic, Jacksonville, Florida, said in an interview.

“The data to date suggest that most SARS cardiac injury is related to stress or high circulating cytokine levels. However, myocarditis probably does affect some patients, he added. “The few published cases suggest a role for macrophages or endothelial cells, which could affect cardiac myocyte function. This type of injury could cause the ST-segment elevation MI-like patterns we have seen in young people with normal epicardial coronary arteries.”

Dr. Cooper, who coauthored a report on the management of COVID-19 cardiovascular syndrome, pointed out that it’s been hard for researchers to isolate genome from autopsy samples because of RNA degradation prior to autopsy and the use of formalin fixation for tissues prior to RNA extraction.

“Most labs are not doing next-generation sequencing, and even with that, RNA protection and fresh tissue may be required to detect viral genome,” he said.
 

No proven therapy

Although up to 50% of acute myocarditis cases undergo spontaneous healing, recognition and multidisciplinary management of clinically suspected myocarditis is important. The optimal treatment remains unclear.

An early case report suggested use of methylprednisolone and intravenous immunoglobulin helped spare the life of a 37-year-old with clinically suspected fulminant myocarditis with cardiogenic shock.

In a related commentary, Dr. Caforio and colleagues pointed out that the World Health Organization considers the use of IV corticosteroids controversial, even in pneumonia due to COVID-19, because it may reduce viral clearance and increase sepsis risk. Intravenous immunoglobulin is also questionable because there is no IgG response to COVID-19 in the plasma donors’ pool.

“Immunosuppression should be reserved for only virus-negative non-COVID myocarditis,” Dr. Caforio said in an interview. “There is no appropriate treatment nowadays for clinically suspected COVID-19 myocarditis. There is no proven therapy for COVID-19, even less for COVID-19 myocarditis.”

Although definitive publication of the RECOVERY trial is still pending, the benefits of dexamethasone – a steroid that works predominantly through its anti-inflammatory effects – appear to be in the sickest patients, such as those requiring ICU admission or respiratory support.

“Many of the same patients would have systemic inflammation and would have also shown elevated cardiac biomarkers,” Dr. Liu observed. “Therefore, it is conceivable that a subset who had cardiac inflammation also benefited from the treatment. Further data, possibly through subgroup analysis and eventually meta-analysis, may help us to understand if dexamethasone also benefited patients with dominant cardiac injury.”

Dr. Caforio, Dr. Marshall, Dr. Liu, and Dr. Cooper reported having no relevant conflicts of interest.

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

Background: NRT use after smoking cessation helps smokers transition to abstinence by reducing the intensity of craving and withdrawal symptoms. It is uncertain which forms of NRTs are more likely to result in long-term smoking cessation.

Combination NRT (for example, the patch & a fast-acting form such as gum or lozenge) increases long-term quit rates versus single-form NRT (risk ratio, 1.25; 95% confidence interval, 1.15-1.36). Researchers compared 4 mg to 2 mg nicotine gum and found a benefit of the higher dose (RR, 1.43; 95% CI, 1.12-1.83), although possibly only among heavy users.

Bottom line: Prescribe combination patch and short-acting NRTs to smokers motivated to quit.

Citation: Lindson N et al. Different doses, durations, and modes of delivery of nicotine replacement therapy for smoking cessation. Cochrane Database Syst Rev. 2019 Apr 18;4:CD013308. doi: 10.1002/14651858.CD013308.

Dr. Miller is a hospitalist at the University of Colorado at Denver, Aurora.

Background: NRT use after smoking cessation helps smokers transition to abstinence by reducing the intensity of craving and withdrawal symptoms. It is uncertain which forms of NRTs are more likely to result in long-term smoking cessation.

Combination NRT (for example, the patch & a fast-acting form such as gum or lozenge) increases long-term quit rates versus single-form NRT (risk ratio, 1.25; 95% confidence interval, 1.15-1.36). Researchers compared 4 mg to 2 mg nicotine gum and found a benefit of the higher dose (RR, 1.43; 95% CI, 1.12-1.83), although possibly only among heavy users.

Bottom line: Prescribe combination patch and short-acting NRTs to smokers motivated to quit.

Citation: Lindson N et al. Different doses, durations, and modes of delivery of nicotine replacement therapy for smoking cessation. Cochrane Database Syst Rev. 2019 Apr 18;4:CD013308. doi: 10.1002/14651858.CD013308.

Dr. Miller is a hospitalist at the University of Colorado at Denver, Aurora.

Background: NRT use after smoking cessation helps smokers transition to abstinence by reducing the intensity of craving and withdrawal symptoms. It is uncertain which forms of NRTs are more likely to result in long-term smoking cessation.

Combination NRT (for example, the patch & a fast-acting form such as gum or lozenge) increases long-term quit rates versus single-form NRT (risk ratio, 1.25; 95% confidence interval, 1.15-1.36). Researchers compared 4 mg to 2 mg nicotine gum and found a benefit of the higher dose (RR, 1.43; 95% CI, 1.12-1.83), although possibly only among heavy users.

Bottom line: Prescribe combination patch and short-acting NRTs to smokers motivated to quit.

Citation: Lindson N et al. Different doses, durations, and modes of delivery of nicotine replacement therapy for smoking cessation. Cochrane Database Syst Rev. 2019 Apr 18;4:CD013308. doi: 10.1002/14651858.CD013308.

Dr. Miller is a hospitalist at the University of Colorado at Denver, Aurora.

As more jurisdictions mandate facial coverings in public, questions have arisen about whether it’s safe for everyone – including those with lung disease – to wear masks. Stories about people who claim to be unable to wear masks because of breathing problems are appearing in the news with increasing frequency, and patients are starting to call their doctors to request medical exemptions to public mask requirements.

David Fuentes Prieto/Shutterstock

To address these issues, Medscape spoke with the chief medical officer of the American Lung Association, Dr. Albert Rizzo.
 

The CDC recommendations on mask wearing say, “Cloth face coverings should not be placed on young children under age 2, anyone who has trouble breathing, or is unconscious, incapacitated, or otherwise unable to remove the mask without assistance.” Does this language suggest that there indeed is a subset of the adult population with lung disease who shouldn’t wear masks?

It makes sense to say that if it makes you uncomfortable to wear a mask because it affects your breathing, you should think twice about getting in a situation where you would have to wear a mask.

I’ve told many of my high-risk patients, “The best way to avoid getting COVID-19 is to stay home and stay away from sick people, especially if you feel that you are not going to be able to wear a mask or facial covering of some sort.”

The reason that some people have trouble with a mask is that they haven’t tried the right style of mask – by that I mean how tightly it fits and the material it’s made out of. Sometimes it really is just that people with lung disease don’t like to have anything covering their faces. Many of these patients feel better where there is air blowing across their faces – they will have a fan blowing even in the middle of winter because they feel more comfortable.

I won’t say it’s all in their heads, but sometimes it’s a matter of desensitizing themselves to wearing a mask. I liken it to people who have sleep apnea. We often have to desensitize them to wearing a mask for sleeping. We tell them to put it on while they are watching TV — don’t hook it up to anything yet, just get used to having something on your face.

I’ve told my patients the same thing about masks for COVID-19. Put on the mask, see how it feels. If you become uncomfortable breathing with it on, take it off, but maybe you can handle it for a half hour or 45 minutes. Find out how much time you have for a trip to the grocery store based on how comfortable you are wearing it at home.

It’s a matter of training the patient, giving them options of how to get comfortable with it, and then making them realize that they have to weigh the benefits and risks of wearing the mask and feeling out of breath versus going out in public and being potentially exposed to coronavirus. And the bottom line is, anybody who is wearing a mask and starts to feel uncomfortable, they can take the mask off.
 

You mentioned different types of masks. Is there a type of mask that is typically more breathable that clinicians can recommend to patients with lung disease?

First, I remind patients who think they will have trouble breathing with a mask on that they are choosing a mask not so much to protect themselves – that would take an N95 mask to filter out the virus. The mask is worn so that when they cough or drink or speak, they aren’t sending respiratory droplets out into the environment. Even when we speak, respiratory droplets can easily go out as far as 6 feet, or further with coughing or sneezing. With facial coverings, we try to keep those respiratory droplets from getting out and infecting others.

So when choosing a mask, you don’t have to worry as much about a tight-fitting mask. I recommend a loose-fitting mask that covers the nose and mouth and isn’t going to fall off but isn’t so tight around the ears and neck to make them feel uncomfortable. Even though it doesn’t really protect the wearer, it is cutting down on the ability to breathe in droplets – maybe not microscopic particles, but it’s better than nothing.
 

Is a face shield a reasonable alternative for someone who feels they can’t breathe with a mask on?

Yes. I’m surprised that face shields don’t get more attention. I’ve tried them out, and they are actually more comfortable than masks. They do impede the spilling out of droplets into the public, but they are not as close fitting to the face as a mask. If you want to protect others, the face shield should be adequate. It is not as good at preventing you from breathing in viral particles.

Some people have claimed that wearing a mask makes them hyperventilate and feel like they are going to pass out, or the mask causes them to become hypoxic. Are these valid concerns?

We get two questions about masks from patients who feel that they are short of breath or are worried about wearing a mask. One is whether their oxygen level is dropping. It’s usually not that. It’s usually because they feel that the mask is an impediment to getting air in. Their oxygen levels are stable.

The other question is whether the mask causes CO₂ retention. For the mask to trap enough exhaled CO₂ and for us to breathe enough of that CO₂ back in to raise our CO₂ level, it has to be a pretty tight-fitting mask. With the type of masks we are suggesting that people wear, that’s very unlikely to occur.
 

What can clinicians do to reassure patients with some type of lung disease that they can safely wear masks?

There are a few things they can do right in the office. Have them put the mask on for a few minutes and make sure they feel comfortable with it. With an oximeter, patients can see that their oxygen levels don’t change when they are breathing through the mask for a period of time.

You can’t really measure CO₂ retention that easily, but most patients with chronic obstructive pulmonary disease or pulmonary fibrosis don’t have an elevated CO₂ at baseline. A little more education is helpful in those situations. In most cases, they aren’t going to retain enough CO₂ to have problems wearing a mask.

Only a small percentage of patients with lung disease are CO₂ retainers, and many of those patients are being seen by pulmonary specialists. Those are the patients you might want to be more cautious with, to make sure they aren’t wearing anything that is tight fitting or that makes them work harder to breathe. It’s not that the mask is causing CO₂ retention, but the increased work of breathing may make it harder to exhale the CO₂.
 

Does a mask interfere with supplemental oxygen in any way?

Supplemental oxygen is typically supplied through a nasal cannula, so 100% oxygen is still getting to the nasal passages and entrained down into the airway, so it shouldn’t be a problem.

Some of the resistance to wearing masks has come from people with asthma. Is it safe for patients with asthma to wear masks, or should these patients be exempt from wearing masks?

In general, the breathing of people with mild asthma, both young and old, should not be impeded by the wearing of facial coverings. The concerns about oxygen and carbon dioxide among patients with more severe lung disease should not play a role in asthma.

Since younger adults with COVID-19 seem to have fewer or no symptoms and may actually be carrying the virus unknowingly, this should be the main population who should wear masks to prevent transmission to others.

Exemptions for mask wearing for mild asthma should be discouraged and dealt with on a case-by-case basis if there is a particular concern for that individual.
 

How do you respond if a patient asks you for a formal medical exemption to wearing a mask?

We’ve been asked to do a lot of letter writing for patients around going back to work, as well as the issue of wearing masks. The discussion usually revolves around trying to avoid going somewhere where you would have to wear a mask if it makes you feel uncomfortable.

I do not recommend automatically exempting individuals from wearing masks, even many of my pulmonary patients. There needs to be an understanding by the patient regarding the purpose of the mask and the overall advice to stay out of situations where social distancing is not being practiced. If you can take the time to discuss options as mentioned above – mask styles, desensitization, etc – the patient usually understands and will try wearing a mask.

On a case-by-case basis, some individuals may need to be exempted, but I feel this is a small number. I prefer my high-risk (older, chronic disease, etc) patients do everything they can to avoid infection – handwashing, mask wearing, and socially distancing.

They should also realize that even with a note, it is not going to help if they are in the middle of the grocery store and someone confronts them about not wearing a mask. It may help as they enter a store that says “masks required” and they can show it to someone monitoring the door. But I’m not really sure in what situations having that note is going to be helpful if confrontations occur.

Patients are also asking how safe is it for them to go back to work and be out in public. I tell them, nothing is going to be 100% safe. Until we have an effective vaccine, we are all going to have to weigh the potential risks of going to an area where social distancing isn’t maintained, people aren’t wearing face masks, and you can’t wash your hands as much as you’d like to. That’s going to be a struggle for all of us to get back out into situations where people interact socially.

Albert A. Rizzo, MD, is chief medical officer for the American Lung Association, chief of the Section of Pulmonary and Critical Care Medicine at the Christiana Care Health System in Newark, Delaware, and a member of Christiana Care Pulmonary Associates. He is board certified in internal medicine, pulmonary medicine, critical care medicine, and sleep medicine and is a clinical assistant professor of medicine at Thomas Jefferson University Medical School, Philadelphia.

This article first appeared on Medscape.com.

As more jurisdictions mandate facial coverings in public, questions have arisen about whether it’s safe for everyone – including those with lung disease – to wear masks. Stories about people who claim to be unable to wear masks because of breathing problems are appearing in the news with increasing frequency, and patients are starting to call their doctors to request medical exemptions to public mask requirements.

David Fuentes Prieto/Shutterstock

To address these issues, Medscape spoke with the chief medical officer of the American Lung Association, Dr. Albert Rizzo.
 

The CDC recommendations on mask wearing say, “Cloth face coverings should not be placed on young children under age 2, anyone who has trouble breathing, or is unconscious, incapacitated, or otherwise unable to remove the mask without assistance.” Does this language suggest that there indeed is a subset of the adult population with lung disease who shouldn’t wear masks?

It makes sense to say that if it makes you uncomfortable to wear a mask because it affects your breathing, you should think twice about getting in a situation where you would have to wear a mask.

I’ve told many of my high-risk patients, “The best way to avoid getting COVID-19 is to stay home and stay away from sick people, especially if you feel that you are not going to be able to wear a mask or facial covering of some sort.”

The reason that some people have trouble with a mask is that they haven’t tried the right style of mask – by that I mean how tightly it fits and the material it’s made out of. Sometimes it really is just that people with lung disease don’t like to have anything covering their faces. Many of these patients feel better where there is air blowing across their faces – they will have a fan blowing even in the middle of winter because they feel more comfortable.

I won’t say it’s all in their heads, but sometimes it’s a matter of desensitizing themselves to wearing a mask. I liken it to people who have sleep apnea. We often have to desensitize them to wearing a mask for sleeping. We tell them to put it on while they are watching TV — don’t hook it up to anything yet, just get used to having something on your face.

I’ve told my patients the same thing about masks for COVID-19. Put on the mask, see how it feels. If you become uncomfortable breathing with it on, take it off, but maybe you can handle it for a half hour or 45 minutes. Find out how much time you have for a trip to the grocery store based on how comfortable you are wearing it at home.

It’s a matter of training the patient, giving them options of how to get comfortable with it, and then making them realize that they have to weigh the benefits and risks of wearing the mask and feeling out of breath versus going out in public and being potentially exposed to coronavirus. And the bottom line is, anybody who is wearing a mask and starts to feel uncomfortable, they can take the mask off.
 

You mentioned different types of masks. Is there a type of mask that is typically more breathable that clinicians can recommend to patients with lung disease?

First, I remind patients who think they will have trouble breathing with a mask on that they are choosing a mask not so much to protect themselves – that would take an N95 mask to filter out the virus. The mask is worn so that when they cough or drink or speak, they aren’t sending respiratory droplets out into the environment. Even when we speak, respiratory droplets can easily go out as far as 6 feet, or further with coughing or sneezing. With facial coverings, we try to keep those respiratory droplets from getting out and infecting others.

So when choosing a mask, you don’t have to worry as much about a tight-fitting mask. I recommend a loose-fitting mask that covers the nose and mouth and isn’t going to fall off but isn’t so tight around the ears and neck to make them feel uncomfortable. Even though it doesn’t really protect the wearer, it is cutting down on the ability to breathe in droplets – maybe not microscopic particles, but it’s better than nothing.
 

Is a face shield a reasonable alternative for someone who feels they can’t breathe with a mask on?

Yes. I’m surprised that face shields don’t get more attention. I’ve tried them out, and they are actually more comfortable than masks. They do impede the spilling out of droplets into the public, but they are not as close fitting to the face as a mask. If you want to protect others, the face shield should be adequate. It is not as good at preventing you from breathing in viral particles.

Some people have claimed that wearing a mask makes them hyperventilate and feel like they are going to pass out, or the mask causes them to become hypoxic. Are these valid concerns?

We get two questions about masks from patients who feel that they are short of breath or are worried about wearing a mask. One is whether their oxygen level is dropping. It’s usually not that. It’s usually because they feel that the mask is an impediment to getting air in. Their oxygen levels are stable.

The other question is whether the mask causes CO₂ retention. For the mask to trap enough exhaled CO₂ and for us to breathe enough of that CO₂ back in to raise our CO₂ level, it has to be a pretty tight-fitting mask. With the type of masks we are suggesting that people wear, that’s very unlikely to occur.
 

What can clinicians do to reassure patients with some type of lung disease that they can safely wear masks?

There are a few things they can do right in the office. Have them put the mask on for a few minutes and make sure they feel comfortable with it. With an oximeter, patients can see that their oxygen levels don’t change when they are breathing through the mask for a period of time.

You can’t really measure CO₂ retention that easily, but most patients with chronic obstructive pulmonary disease or pulmonary fibrosis don’t have an elevated CO₂ at baseline. A little more education is helpful in those situations. In most cases, they aren’t going to retain enough CO₂ to have problems wearing a mask.

Only a small percentage of patients with lung disease are CO₂ retainers, and many of those patients are being seen by pulmonary specialists. Those are the patients you might want to be more cautious with, to make sure they aren’t wearing anything that is tight fitting or that makes them work harder to breathe. It’s not that the mask is causing CO₂ retention, but the increased work of breathing may make it harder to exhale the CO₂.
 

Does a mask interfere with supplemental oxygen in any way?

Supplemental oxygen is typically supplied through a nasal cannula, so 100% oxygen is still getting to the nasal passages and entrained down into the airway, so it shouldn’t be a problem.

Some of the resistance to wearing masks has come from people with asthma. Is it safe for patients with asthma to wear masks, or should these patients be exempt from wearing masks?

In general, the breathing of people with mild asthma, both young and old, should not be impeded by the wearing of facial coverings. The concerns about oxygen and carbon dioxide among patients with more severe lung disease should not play a role in asthma.

Since younger adults with COVID-19 seem to have fewer or no symptoms and may actually be carrying the virus unknowingly, this should be the main population who should wear masks to prevent transmission to others.

Exemptions for mask wearing for mild asthma should be discouraged and dealt with on a case-by-case basis if there is a particular concern for that individual.
 

How do you respond if a patient asks you for a formal medical exemption to wearing a mask?

We’ve been asked to do a lot of letter writing for patients around going back to work, as well as the issue of wearing masks. The discussion usually revolves around trying to avoid going somewhere where you would have to wear a mask if it makes you feel uncomfortable.

I do not recommend automatically exempting individuals from wearing masks, even many of my pulmonary patients. There needs to be an understanding by the patient regarding the purpose of the mask and the overall advice to stay out of situations where social distancing is not being practiced. If you can take the time to discuss options as mentioned above – mask styles, desensitization, etc – the patient usually understands and will try wearing a mask.

On a case-by-case basis, some individuals may need to be exempted, but I feel this is a small number. I prefer my high-risk (older, chronic disease, etc) patients do everything they can to avoid infection – handwashing, mask wearing, and socially distancing.

They should also realize that even with a note, it is not going to help if they are in the middle of the grocery store and someone confronts them about not wearing a mask. It may help as they enter a store that says “masks required” and they can show it to someone monitoring the door. But I’m not really sure in what situations having that note is going to be helpful if confrontations occur.

Patients are also asking how safe is it for them to go back to work and be out in public. I tell them, nothing is going to be 100% safe. Until we have an effective vaccine, we are all going to have to weigh the potential risks of going to an area where social distancing isn’t maintained, people aren’t wearing face masks, and you can’t wash your hands as much as you’d like to. That’s going to be a struggle for all of us to get back out into situations where people interact socially.

Albert A. Rizzo, MD, is chief medical officer for the American Lung Association, chief of the Section of Pulmonary and Critical Care Medicine at the Christiana Care Health System in Newark, Delaware, and a member of Christiana Care Pulmonary Associates. He is board certified in internal medicine, pulmonary medicine, critical care medicine, and sleep medicine and is a clinical assistant professor of medicine at Thomas Jefferson University Medical School, Philadelphia.

This article first appeared on Medscape.com.

As more jurisdictions mandate facial coverings in public, questions have arisen about whether it’s safe for everyone – including those with lung disease – to wear masks. Stories about people who claim to be unable to wear masks because of breathing problems are appearing in the news with increasing frequency, and patients are starting to call their doctors to request medical exemptions to public mask requirements.

David Fuentes Prieto/Shutterstock

To address these issues, Medscape spoke with the chief medical officer of the American Lung Association, Dr. Albert Rizzo.
 

The CDC recommendations on mask wearing say, “Cloth face coverings should not be placed on young children under age 2, anyone who has trouble breathing, or is unconscious, incapacitated, or otherwise unable to remove the mask without assistance.” Does this language suggest that there indeed is a subset of the adult population with lung disease who shouldn’t wear masks?

It makes sense to say that if it makes you uncomfortable to wear a mask because it affects your breathing, you should think twice about getting in a situation where you would have to wear a mask.

I’ve told many of my high-risk patients, “The best way to avoid getting COVID-19 is to stay home and stay away from sick people, especially if you feel that you are not going to be able to wear a mask or facial covering of some sort.”

The reason that some people have trouble with a mask is that they haven’t tried the right style of mask – by that I mean how tightly it fits and the material it’s made out of. Sometimes it really is just that people with lung disease don’t like to have anything covering their faces. Many of these patients feel better where there is air blowing across their faces – they will have a fan blowing even in the middle of winter because they feel more comfortable.

I won’t say it’s all in their heads, but sometimes it’s a matter of desensitizing themselves to wearing a mask. I liken it to people who have sleep apnea. We often have to desensitize them to wearing a mask for sleeping. We tell them to put it on while they are watching TV — don’t hook it up to anything yet, just get used to having something on your face.

I’ve told my patients the same thing about masks for COVID-19. Put on the mask, see how it feels. If you become uncomfortable breathing with it on, take it off, but maybe you can handle it for a half hour or 45 minutes. Find out how much time you have for a trip to the grocery store based on how comfortable you are wearing it at home.

It’s a matter of training the patient, giving them options of how to get comfortable with it, and then making them realize that they have to weigh the benefits and risks of wearing the mask and feeling out of breath versus going out in public and being potentially exposed to coronavirus. And the bottom line is, anybody who is wearing a mask and starts to feel uncomfortable, they can take the mask off.
 

You mentioned different types of masks. Is there a type of mask that is typically more breathable that clinicians can recommend to patients with lung disease?

First, I remind patients who think they will have trouble breathing with a mask on that they are choosing a mask not so much to protect themselves – that would take an N95 mask to filter out the virus. The mask is worn so that when they cough or drink or speak, they aren’t sending respiratory droplets out into the environment. Even when we speak, respiratory droplets can easily go out as far as 6 feet, or further with coughing or sneezing. With facial coverings, we try to keep those respiratory droplets from getting out and infecting others.

So when choosing a mask, you don’t have to worry as much about a tight-fitting mask. I recommend a loose-fitting mask that covers the nose and mouth and isn’t going to fall off but isn’t so tight around the ears and neck to make them feel uncomfortable. Even though it doesn’t really protect the wearer, it is cutting down on the ability to breathe in droplets – maybe not microscopic particles, but it’s better than nothing.
 

Is a face shield a reasonable alternative for someone who feels they can’t breathe with a mask on?

Yes. I’m surprised that face shields don’t get more attention. I’ve tried them out, and they are actually more comfortable than masks. They do impede the spilling out of droplets into the public, but they are not as close fitting to the face as a mask. If you want to protect others, the face shield should be adequate. It is not as good at preventing you from breathing in viral particles.

Some people have claimed that wearing a mask makes them hyperventilate and feel like they are going to pass out, or the mask causes them to become hypoxic. Are these valid concerns?

We get two questions about masks from patients who feel that they are short of breath or are worried about wearing a mask. One is whether their oxygen level is dropping. It’s usually not that. It’s usually because they feel that the mask is an impediment to getting air in. Their oxygen levels are stable.

The other question is whether the mask causes CO₂ retention. For the mask to trap enough exhaled CO₂ and for us to breathe enough of that CO₂ back in to raise our CO₂ level, it has to be a pretty tight-fitting mask. With the type of masks we are suggesting that people wear, that’s very unlikely to occur.
 

What can clinicians do to reassure patients with some type of lung disease that they can safely wear masks?

There are a few things they can do right in the office. Have them put the mask on for a few minutes and make sure they feel comfortable with it. With an oximeter, patients can see that their oxygen levels don’t change when they are breathing through the mask for a period of time.

You can’t really measure CO₂ retention that easily, but most patients with chronic obstructive pulmonary disease or pulmonary fibrosis don’t have an elevated CO₂ at baseline. A little more education is helpful in those situations. In most cases, they aren’t going to retain enough CO₂ to have problems wearing a mask.

Only a small percentage of patients with lung disease are CO₂ retainers, and many of those patients are being seen by pulmonary specialists. Those are the patients you might want to be more cautious with, to make sure they aren’t wearing anything that is tight fitting or that makes them work harder to breathe. It’s not that the mask is causing CO₂ retention, but the increased work of breathing may make it harder to exhale the CO₂.
 

Does a mask interfere with supplemental oxygen in any way?

Supplemental oxygen is typically supplied through a nasal cannula, so 100% oxygen is still getting to the nasal passages and entrained down into the airway, so it shouldn’t be a problem.

Some of the resistance to wearing masks has come from people with asthma. Is it safe for patients with asthma to wear masks, or should these patients be exempt from wearing masks?

In general, the breathing of people with mild asthma, both young and old, should not be impeded by the wearing of facial coverings. The concerns about oxygen and carbon dioxide among patients with more severe lung disease should not play a role in asthma.

Since younger adults with COVID-19 seem to have fewer or no symptoms and may actually be carrying the virus unknowingly, this should be the main population who should wear masks to prevent transmission to others.

Exemptions for mask wearing for mild asthma should be discouraged and dealt with on a case-by-case basis if there is a particular concern for that individual.
 

How do you respond if a patient asks you for a formal medical exemption to wearing a mask?

We’ve been asked to do a lot of letter writing for patients around going back to work, as well as the issue of wearing masks. The discussion usually revolves around trying to avoid going somewhere where you would have to wear a mask if it makes you feel uncomfortable.

I do not recommend automatically exempting individuals from wearing masks, even many of my pulmonary patients. There needs to be an understanding by the patient regarding the purpose of the mask and the overall advice to stay out of situations where social distancing is not being practiced. If you can take the time to discuss options as mentioned above – mask styles, desensitization, etc – the patient usually understands and will try wearing a mask.

On a case-by-case basis, some individuals may need to be exempted, but I feel this is a small number. I prefer my high-risk (older, chronic disease, etc) patients do everything they can to avoid infection – handwashing, mask wearing, and socially distancing.

They should also realize that even with a note, it is not going to help if they are in the middle of the grocery store and someone confronts them about not wearing a mask. It may help as they enter a store that says “masks required” and they can show it to someone monitoring the door. But I’m not really sure in what situations having that note is going to be helpful if confrontations occur.

Patients are also asking how safe is it for them to go back to work and be out in public. I tell them, nothing is going to be 100% safe. Until we have an effective vaccine, we are all going to have to weigh the potential risks of going to an area where social distancing isn’t maintained, people aren’t wearing face masks, and you can’t wash your hands as much as you’d like to. That’s going to be a struggle for all of us to get back out into situations where people interact socially.

Albert A. Rizzo, MD, is chief medical officer for the American Lung Association, chief of the Section of Pulmonary and Critical Care Medicine at the Christiana Care Health System in Newark, Delaware, and a member of Christiana Care Pulmonary Associates. He is board certified in internal medicine, pulmonary medicine, critical care medicine, and sleep medicine and is a clinical assistant professor of medicine at Thomas Jefferson University Medical School, Philadelphia.

This article first appeared on Medscape.com.

Hypnosis during catheter ablation for atrial flutter (AFlut) seemed to significantly improve perceived levels of pain and curb reliance on morphine, compared with standard relaxation techniques used as a control, in a small randomized trial.

Ablation is typically performed using conscious sedation and “requires sometimes very high dosages of morphine, and there are sometimes some complications, blood pressure drop, or oxygen desaturation,” Rodrigue Garcia, MD, Poitiers (France) University Hospital, said in an interview.

But patients in the study assigned to undergo hypnosis during the AFlut ablation, performed by practitioners hailing from the French Hypnosis Association, consistently perceived significantly less pain throughout the procedure than those in the active-control group.

They also used almost two-thirds less morphine, which was available to both groups on demand, reported Dr. Garcia, who presented the results of the PAINLESS study at the European Heart Rhythm Association 2020 Virtual Congress. The annual meeting was conducted online this year because of the COVID-19 pandemic.

Hypnotism for pain control may not be widely available in hospitals, “but it’s becoming more and more frequent in the different centers, especially in France,” he said.

The technique is probably also suitable for catheter ablation of ventricular tachycardia, Dr. Garcia said, and “we already use it for atrial fibrillation ablation, because it’s a very common procedure and because, in France, for example, there is a lack of anesthesiologists.” One limitation of hypnosis for such procedures, he said, is that it requires a practitioner with a lot of training and experience.

The current study, “I think, is one of the few, if not the first, randomized trial on this topic, at least for flutter,” Elena Arbelo, MD, PhD, MSc, Hospital Clinic of Barcelona and the University of Barcelona, said in an interview.

“I thought it was very interesting. Many centers have the issue of not having anesthesiology support for their procedures. We have the option of having anesthesiology with us only a few days a week,” said Dr. Arbelo, who was not an investigator with the study.

“If it’s validated in larger cohorts and in different cultures, it may be an interesting way of reducing the need for anesthesiology support, which is a main issue. I know for sure in Europe,” she said, that “some centers do struggle to have anesthesiology support for their EP procedures.”

The single-center trial randomized adults slated to undergo cavotricuspid isthmus ablation (n = 116) for AFlut to receive hypnosis or a control procedure, consisting of nonhypnotic relaxation suggestions and white noise delivered through earphones – 56 and 57 patients, respectively, after exclusion of several who ultimately did not undergo ablation. Any patient could receive 1 mg of morphine if self-reported pain was 5 or greater on a 10-point visual analog scale, or simply on demand.

The hypnosis and control groups were predominantly male and well matched for age (mean, about 69 years in both groups), prevalence of atrial fibrillation, and left ventricular ejection fraction (about 55% for both). Also, in both groups, the procedure duration was approximately 36 minutes.

Asked if all patients in the hypnosis group were actually hypnotized, Dr. Garcia said: “That’s a tricky question” because there was no prespecified definition for successful hypnosis. Between 70% and 80% achieved a hypnotized state, he estimated.

Hypnosis was superior to the control intervention for the primary outcome of pain self-assessment during the ablation procedure, as recorded 45 minutes after ablation. Also, using a 10-point visual analog scale, the hypnosis group rated the average pain intensity as 4.0, whereas the control group rated it as 5.5 (P < .001).

Similarly, instantaneous pain intensity, rated on a 10-point scale every 5 minutes, was lower throughout the procedure for the hypnosis patients than for the control patients (P < .05 at all assessments). Maximum pain intensities, which occurred at the 15- to 25-minute points, were no greater than 3 for hypnosis patients and peaked at approximately 5 for the control patients.

Two of three secondary end points favored the hypnosis group. Morphine consumption averaged 1.3 mg, compared with 3.6 mg for the control group (P < .001). Observer-assessed degrees of sedation were 8.3 and 5.4, respectively, on a 10-point scale (P < .001). And patient self-assessment of anxiety during the procedure was 1.5 in the hypnosis group and 2.5 in the control group on a similar scale.

Regarding morphine use in the two groups, Dr. Garcia said, “It was more than 2 mg of difference, and this can be very important, especially in certain types of patients,” such as those with compromised lung function.

All six complications (11%) observed during the study occurred in the control group. There were four severe hypotensive episodes, one case of oxygen desaturation, and one case of pericardial effusion (P = .03 vs the hypnosis group).

After pointing out the substantial risk for adverse events associated with deep analgesia, particularly from the use of opiates, Paulus Kirchhof, MD, PhD, said, “I think it’s a clinically relevant topic, in the context of reducing the risk of ablation procedures, to try to minimize the use of opiates or other strong anesthetics.”

A multicenter trial could be the next step, said Dr. Kirchhof, from the University Heart and Vascular Center UKE Hamburg (Germany). That would potentially provide “the first evidence for me that this is not sort of something that works in one specific setting, but that it is transferable to other centers, other countries, where practices and complication rates of analgosedation may be different.”

Dr. Kirchhof praised the study design for comparing hypnosis with an active standard-of-care control group. “That is one of the strengths of the study; they tried to design it in a way that didn’t disadvantage the control group.”

The study was funded by the University Hospital of Poitiers. Dr. Garcia and Dr. Arbelo reported no conflicts of interest. Dr. Kirchhof reported support for basic, translational, and clinical research projects from the European Union, the British Heart Foundation, the Leducq Foundation, the Medical Research Council, and the German Centre for Cardiovascular Research, and from several drug and device companies active in atrial fibrillation, from which he received honoraria more than 3 years ago; he is listed as inventor on two patents held by the University of Birmingham (England).

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

Hypnosis during catheter ablation for atrial flutter (AFlut) seemed to significantly improve perceived levels of pain and curb reliance on morphine, compared with standard relaxation techniques used as a control, in a small randomized trial.

Ablation is typically performed using conscious sedation and “requires sometimes very high dosages of morphine, and there are sometimes some complications, blood pressure drop, or oxygen desaturation,” Rodrigue Garcia, MD, Poitiers (France) University Hospital, said in an interview.

But patients in the study assigned to undergo hypnosis during the AFlut ablation, performed by practitioners hailing from the French Hypnosis Association, consistently perceived significantly less pain throughout the procedure than those in the active-control group.

They also used almost two-thirds less morphine, which was available to both groups on demand, reported Dr. Garcia, who presented the results of the PAINLESS study at the European Heart Rhythm Association 2020 Virtual Congress. The annual meeting was conducted online this year because of the COVID-19 pandemic.

Hypnotism for pain control may not be widely available in hospitals, “but it’s becoming more and more frequent in the different centers, especially in France,” he said.

The technique is probably also suitable for catheter ablation of ventricular tachycardia, Dr. Garcia said, and “we already use it for atrial fibrillation ablation, because it’s a very common procedure and because, in France, for example, there is a lack of anesthesiologists.” One limitation of hypnosis for such procedures, he said, is that it requires a practitioner with a lot of training and experience.

The current study, “I think, is one of the few, if not the first, randomized trial on this topic, at least for flutter,” Elena Arbelo, MD, PhD, MSc, Hospital Clinic of Barcelona and the University of Barcelona, said in an interview.

“I thought it was very interesting. Many centers have the issue of not having anesthesiology support for their procedures. We have the option of having anesthesiology with us only a few days a week,” said Dr. Arbelo, who was not an investigator with the study.

“If it’s validated in larger cohorts and in different cultures, it may be an interesting way of reducing the need for anesthesiology support, which is a main issue. I know for sure in Europe,” she said, that “some centers do struggle to have anesthesiology support for their EP procedures.”

The single-center trial randomized adults slated to undergo cavotricuspid isthmus ablation (n = 116) for AFlut to receive hypnosis or a control procedure, consisting of nonhypnotic relaxation suggestions and white noise delivered through earphones – 56 and 57 patients, respectively, after exclusion of several who ultimately did not undergo ablation. Any patient could receive 1 mg of morphine if self-reported pain was 5 or greater on a 10-point visual analog scale, or simply on demand.

The hypnosis and control groups were predominantly male and well matched for age (mean, about 69 years in both groups), prevalence of atrial fibrillation, and left ventricular ejection fraction (about 55% for both). Also, in both groups, the procedure duration was approximately 36 minutes.

Asked if all patients in the hypnosis group were actually hypnotized, Dr. Garcia said: “That’s a tricky question” because there was no prespecified definition for successful hypnosis. Between 70% and 80% achieved a hypnotized state, he estimated.

Hypnosis was superior to the control intervention for the primary outcome of pain self-assessment during the ablation procedure, as recorded 45 minutes after ablation. Also, using a 10-point visual analog scale, the hypnosis group rated the average pain intensity as 4.0, whereas the control group rated it as 5.5 (P < .001).

Similarly, instantaneous pain intensity, rated on a 10-point scale every 5 minutes, was lower throughout the procedure for the hypnosis patients than for the control patients (P < .05 at all assessments). Maximum pain intensities, which occurred at the 15- to 25-minute points, were no greater than 3 for hypnosis patients and peaked at approximately 5 for the control patients.

Two of three secondary end points favored the hypnosis group. Morphine consumption averaged 1.3 mg, compared with 3.6 mg for the control group (P < .001). Observer-assessed degrees of sedation were 8.3 and 5.4, respectively, on a 10-point scale (P < .001). And patient self-assessment of anxiety during the procedure was 1.5 in the hypnosis group and 2.5 in the control group on a similar scale.

Regarding morphine use in the two groups, Dr. Garcia said, “It was more than 2 mg of difference, and this can be very important, especially in certain types of patients,” such as those with compromised lung function.

All six complications (11%) observed during the study occurred in the control group. There were four severe hypotensive episodes, one case of oxygen desaturation, and one case of pericardial effusion (P = .03 vs the hypnosis group).

After pointing out the substantial risk for adverse events associated with deep analgesia, particularly from the use of opiates, Paulus Kirchhof, MD, PhD, said, “I think it’s a clinically relevant topic, in the context of reducing the risk of ablation procedures, to try to minimize the use of opiates or other strong anesthetics.”

A multicenter trial could be the next step, said Dr. Kirchhof, from the University Heart and Vascular Center UKE Hamburg (Germany). That would potentially provide “the first evidence for me that this is not sort of something that works in one specific setting, but that it is transferable to other centers, other countries, where practices and complication rates of analgosedation may be different.”

Dr. Kirchhof praised the study design for comparing hypnosis with an active standard-of-care control group. “That is one of the strengths of the study; they tried to design it in a way that didn’t disadvantage the control group.”

The study was funded by the University Hospital of Poitiers. Dr. Garcia and Dr. Arbelo reported no conflicts of interest. Dr. Kirchhof reported support for basic, translational, and clinical research projects from the European Union, the British Heart Foundation, the Leducq Foundation, the Medical Research Council, and the German Centre for Cardiovascular Research, and from several drug and device companies active in atrial fibrillation, from which he received honoraria more than 3 years ago; he is listed as inventor on two patents held by the University of Birmingham (England).

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

Hypnosis during catheter ablation for atrial flutter (AFlut) seemed to significantly improve perceived levels of pain and curb reliance on morphine, compared with standard relaxation techniques used as a control, in a small randomized trial.

Ablation is typically performed using conscious sedation and “requires sometimes very high dosages of morphine, and there are sometimes some complications, blood pressure drop, or oxygen desaturation,” Rodrigue Garcia, MD, Poitiers (France) University Hospital, said in an interview.

But patients in the study assigned to undergo hypnosis during the AFlut ablation, performed by practitioners hailing from the French Hypnosis Association, consistently perceived significantly less pain throughout the procedure than those in the active-control group.

They also used almost two-thirds less morphine, which was available to both groups on demand, reported Dr. Garcia, who presented the results of the PAINLESS study at the European Heart Rhythm Association 2020 Virtual Congress. The annual meeting was conducted online this year because of the COVID-19 pandemic.

Hypnotism for pain control may not be widely available in hospitals, “but it’s becoming more and more frequent in the different centers, especially in France,” he said.

The technique is probably also suitable for catheter ablation of ventricular tachycardia, Dr. Garcia said, and “we already use it for atrial fibrillation ablation, because it’s a very common procedure and because, in France, for example, there is a lack of anesthesiologists.” One limitation of hypnosis for such procedures, he said, is that it requires a practitioner with a lot of training and experience.

The current study, “I think, is one of the few, if not the first, randomized trial on this topic, at least for flutter,” Elena Arbelo, MD, PhD, MSc, Hospital Clinic of Barcelona and the University of Barcelona, said in an interview.

“I thought it was very interesting. Many centers have the issue of not having anesthesiology support for their procedures. We have the option of having anesthesiology with us only a few days a week,” said Dr. Arbelo, who was not an investigator with the study.

“If it’s validated in larger cohorts and in different cultures, it may be an interesting way of reducing the need for anesthesiology support, which is a main issue. I know for sure in Europe,” she said, that “some centers do struggle to have anesthesiology support for their EP procedures.”

The single-center trial randomized adults slated to undergo cavotricuspid isthmus ablation (n = 116) for AFlut to receive hypnosis or a control procedure, consisting of nonhypnotic relaxation suggestions and white noise delivered through earphones – 56 and 57 patients, respectively, after exclusion of several who ultimately did not undergo ablation. Any patient could receive 1 mg of morphine if self-reported pain was 5 or greater on a 10-point visual analog scale, or simply on demand.

The hypnosis and control groups were predominantly male and well matched for age (mean, about 69 years in both groups), prevalence of atrial fibrillation, and left ventricular ejection fraction (about 55% for both). Also, in both groups, the procedure duration was approximately 36 minutes.

Asked if all patients in the hypnosis group were actually hypnotized, Dr. Garcia said: “That’s a tricky question” because there was no prespecified definition for successful hypnosis. Between 70% and 80% achieved a hypnotized state, he estimated.

Hypnosis was superior to the control intervention for the primary outcome of pain self-assessment during the ablation procedure, as recorded 45 minutes after ablation. Also, using a 10-point visual analog scale, the hypnosis group rated the average pain intensity as 4.0, whereas the control group rated it as 5.5 (P < .001).

Similarly, instantaneous pain intensity, rated on a 10-point scale every 5 minutes, was lower throughout the procedure for the hypnosis patients than for the control patients (P < .05 at all assessments). Maximum pain intensities, which occurred at the 15- to 25-minute points, were no greater than 3 for hypnosis patients and peaked at approximately 5 for the control patients.

Two of three secondary end points favored the hypnosis group. Morphine consumption averaged 1.3 mg, compared with 3.6 mg for the control group (P < .001). Observer-assessed degrees of sedation were 8.3 and 5.4, respectively, on a 10-point scale (P < .001). And patient self-assessment of anxiety during the procedure was 1.5 in the hypnosis group and 2.5 in the control group on a similar scale.

Regarding morphine use in the two groups, Dr. Garcia said, “It was more than 2 mg of difference, and this can be very important, especially in certain types of patients,” such as those with compromised lung function.

All six complications (11%) observed during the study occurred in the control group. There were four severe hypotensive episodes, one case of oxygen desaturation, and one case of pericardial effusion (P = .03 vs the hypnosis group).

After pointing out the substantial risk for adverse events associated with deep analgesia, particularly from the use of opiates, Paulus Kirchhof, MD, PhD, said, “I think it’s a clinically relevant topic, in the context of reducing the risk of ablation procedures, to try to minimize the use of opiates or other strong anesthetics.”

A multicenter trial could be the next step, said Dr. Kirchhof, from the University Heart and Vascular Center UKE Hamburg (Germany). That would potentially provide “the first evidence for me that this is not sort of something that works in one specific setting, but that it is transferable to other centers, other countries, where practices and complication rates of analgosedation may be different.”

Dr. Kirchhof praised the study design for comparing hypnosis with an active standard-of-care control group. “That is one of the strengths of the study; they tried to design it in a way that didn’t disadvantage the control group.”

The study was funded by the University Hospital of Poitiers. Dr. Garcia and Dr. Arbelo reported no conflicts of interest. Dr. Kirchhof reported support for basic, translational, and clinical research projects from the European Union, the British Heart Foundation, the Leducq Foundation, the Medical Research Council, and the German Centre for Cardiovascular Research, and from several drug and device companies active in atrial fibrillation, from which he received honoraria more than 3 years ago; he is listed as inventor on two patents held by the University of Birmingham (England).

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

Low to moderate alcohol consumption is associated with better cognitive function and slower cognitive decline in middle-aged and older adults, new research suggests. However, at least one expert urges caution in interpreting the findings.

Investigators found that consuming 10-14 alcoholic drinks per week had the strongest cognitive benefit. The findings “add more weight” to the growing body of research identifying beneficial cognitive effects of moderate alcohol consumption, said lead author, Ruiyuan Zhang, MD, of the department of epidemiology and biostatistics at the University of Georgia, Athens. However, Dr. Zhang emphasized that nondrinkers should not take up drinking to protect brain function, as alcohol can have negative effects.

The study was published online in JAMA Network Open.
 

Slower cognitive decline

The observational study was a secondary analysis of data from the Health and Retirement Study, a nationally representative U.S. survey of middle-aged and older adults. The survey, which began in 1992, is conducted every 2 years and collects health and economic data.

The current analysis used data from 1996 to 2008 and included information from individuals who participated in at least three surveys. The study included 19,887 participants, with a mean age 61.8 years. Most (60.1%) were women and white (85.2%). Mean follow-up was 9.1 years.

Researchers measured cognitive domains of mental status, word recall, and vocabulary. They also calculated a total cognition score, with higher scores indicating better cognitive abilities.

For each cognitive function measure, researchers categorized participants into a consistently low–trajectory group in which cognitive test scores from baseline through follow-up were consistently low or a consistently high–trajectory group, where cognitive test scores from baseline through follow-up were consistently high.

Based on self-reports, the investigators categorized participants as never drinkers (41.8%), former drinkers (39.5%), or current drinkers (18.7%). For current drinkers, researchers determined the number of drinking days per week and number of drinks per day. They further categorized these participants as low to moderate drinkers or heavy drinkers.

One drink was defined as a 12-ounce bottle of beer, a 5-ounce glass of wine, or a 1.5-ounce shot of spirits, said Dr. Zhang.

Women who consumed 8 or more drinks per week and men who drank 15 or more drinks per week were considered heavy drinkers. Other current drinkers were deemed low to moderate drinkers. Most current drinkers (85.2%) were low to moderate drinkers.

Other covariates included age, sex, race/ethnicity, years of education, marital status, tobacco smoking status, and body mass index.

Results showed moderate drinking was associated with relatively high cognitive test scores. After controlling for all covariates, compared with never drinkers, current low to moderate drinkers were significantly less likely to have consistently low trajectories for total cognitive score (odds ratio, 0.66; 95% confidence interval, 0.59-0.74), mental status (OR, 0.71; 95% CI, 0.63-0.81), word recall (OR, 0.74; 95% CI, 0.69-0.80), and vocabulary (OR, 0.64; 95% CI, 0.56-0.74) (all P < .001).

Former drinkers also had better cognitive outcomes for all cognitive domains. Heavy drinkers had lower odds of being in the consistently low trajectory group only for the vocabulary test.
 

Heavy drinking ‘risky’

Because few participants were deemed to be heavy drinkers, the power to identify an association between heavy drinking and cognitive function was limited. Dr. Zhang acknowledged, though he noted that heavy drinking is “risky.”

“We found that, after the drinking dosage passes the moderate level, the risk of low cognitive function increases very fast, which indicates that heavy drinking may harm cognitive function.” Limiting alcohol consumption “is still very important,” he said.

The associations of alcohol and cognitive functions differed by race/ethnicity. Low to moderate drinking was significantly associated with a lower odds of having a consistently low trajectory for all four cognitive function measures only among white participants.

A possible reason for this is that the study had so few African Americans (who made up only 14.8% of the sample), which limited the ability to identify relationships between alcohol intake and cognitive function, said Dr. Zhang. “Another reason is that the sensitivity to alcohol may be different between white and African American subjects.”

There was a significant U-shaped association between weekly amounts of alcohol and the odds of being in the consistently low–trajectory group for all cognitive functions. Depending on the function tested, the optimal number of weekly drinks ranged from 10-14.

Dr. Zhang noted that, when women were examined separately, alcohol consumption had a significant U-shaped relationship only with word recall, with the optimal dosage being around eight drinks.
 

U-shaped relationship an ‘important finding’

The U-shaped relationship is “an important finding,” said Dr. Zhang. “It shows that the human body may act differently to low and high doses of alcohol. Knowing why and how this happens is very important as it would help us understand how alcohol affects the function of the human body.”

Sensitivity analyses among participants with no chronic diseases showed the U-shaped association was still significant for scores of total word recall and vocabulary, but not for mental status or total cognition score.

The authors noted that 77.2% of participants had at least one chronic disease. They maintained that the association between alcohol consumption and cognitive function may be applicable both to healthy people and to those with a chronic disease.

The study also found that low to moderate drinkers had slower rates of cognitive decline over time for all cognition domains.

Although the mechanisms underlying the cognitive benefits of alcohol consumption are unclear, the authors believe it may be via cerebrovascular and cardiovascular pathways.

Alcohol may increase levels of brain-derived neurotrophic factor, a key regulator of neuronal plasticity and development in the dorsal striatum, they noted.
 

Balancing act

However, there’s also evidence that drinking, especially heavy drinking, increases the risk of hypertension, stroke, liver damage, and some cancers. “We think the role of alcohol drinking in cognitive function may be a balance of its beneficial and harmful effects on the cardiovascular system,” said Dr. Zhang.

“For the low to moderate drinker, the beneficial effects may outweigh the harmful effects on the small blood vessels in the brain. In this way, it could preserve cognition,” he added.

Dr. Zhang also noted that the study focused on middle-aged and older adults. “We can’t say whether or not moderate alcohol could benefit younger people” because they may have different characteristics, he said.

The findings of other studies examining the effects of alcohol on cognitive function are mixed. While studies have identified a beneficial effect, others have uncovered no, minimal, or adverse effects. This could be due to the use of different tests of cognitive function or different study populations, said Dr. Zhang.

A limitation of the current study was that assessment of alcohol consumption was based on self-report, which might have introduced recall bias. In addition, because individuals tend to underestimate their alcohol consumption, heavy drinkers could be misclassified as low to moderate drinkers, and low to moderate drinkers as former drinkers.

“This may make our study underestimate the association between low to moderate drinking and cognitive function,” said Dr. Zhang. In addition, alcohol consumption tended to change with time, and this change may be associated with other factors that led to changes in cognitive function, the authors noted.
 

Interpret with caution

Commenting on the study, Brent P. Forester, MD, chief of the Center of Excellence in Geriatric Psychiatry at McLean Hospital in Belmont, Mass., associate professor of psychiatry at Harvard Medical School, Boston, and a member of the American Psychiatric Association Council on Geriatric Psychiatry, said he views the study with some trepidation.

“As a clinician taking care of older adults, I would be very cautious about overinterpreting the beneficial effects of alcohol before we understand the mechanism better,” he said.

He noted that all of the risk factors associated with heart attack and stroke are also risk factors for Alzheimer’s disease and cognitive decline more broadly. “One of the issues here is how in the world does alcohol reduce cardiovascular and cerebrovascular risks, if you know it increases the risk of hypertension and stroke, regardless of dose.”

With regard to the possible impact of alcohol on brain-derived neurotrophic factor, Dr. Forester said, “it’s an interesting idea” but the actual mechanism is still unclear.

Even with dietary studies, such as those on the Mediterranean diet that include red wine, showing cognitive benefit, Dr. Forester said he’s still concerned about the adverse effects of alcohol on older people. These can include falls and sleep disturbances in addition to cognitive issues, and these effects can increase with age.

He was somewhat surprised at the level of alcohol that the study determined was beneficial. “Essentially, what they’re saying here is that, for men, it’s two drinks a day.” This could be “problematic” as two drinks per day can quickly escalate as individuals build tolerance.

He also pointed out that the study does not determine cause and effect, noting that it’s only an association.

Dr. Forester said the study raises a number of questions, including the type of alcohol study participants consumed and whether this has any impact on cognitive benefit. He also questioned whether the mediating effects of alcohol were associated with something that wasn’t measured, such as socioeconomic status.

Another question, he said, is what factors in individuals’ medical or psychiatric history determine whether they are more or less likely to benefit from low to moderate alcohol intake.

Perhaps alcohol should be recommended only for “select subpopulations” – for example, those who are healthy and have a family history of cognitive decline –but not for those with a history of substance abuse, including alcohol abuse, said Dr. Forester.

“For this population, the last thing you want to do is recommend alcohol to reduce risk of cognitive decline,” he cautioned.

The study was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health. The investigators and Dr. Forester have reported no relevant financial disclosures.

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

Low to moderate alcohol consumption is associated with better cognitive function and slower cognitive decline in middle-aged and older adults, new research suggests. However, at least one expert urges caution in interpreting the findings.

Investigators found that consuming 10-14 alcoholic drinks per week had the strongest cognitive benefit. The findings “add more weight” to the growing body of research identifying beneficial cognitive effects of moderate alcohol consumption, said lead author, Ruiyuan Zhang, MD, of the department of epidemiology and biostatistics at the University of Georgia, Athens. However, Dr. Zhang emphasized that nondrinkers should not take up drinking to protect brain function, as alcohol can have negative effects.

The study was published online in JAMA Network Open.
 

Slower cognitive decline

The observational study was a secondary analysis of data from the Health and Retirement Study, a nationally representative U.S. survey of middle-aged and older adults. The survey, which began in 1992, is conducted every 2 years and collects health and economic data.

The current analysis used data from 1996 to 2008 and included information from individuals who participated in at least three surveys. The study included 19,887 participants, with a mean age 61.8 years. Most (60.1%) were women and white (85.2%). Mean follow-up was 9.1 years.

Researchers measured cognitive domains of mental status, word recall, and vocabulary. They also calculated a total cognition score, with higher scores indicating better cognitive abilities.

For each cognitive function measure, researchers categorized participants into a consistently low–trajectory group in which cognitive test scores from baseline through follow-up were consistently low or a consistently high–trajectory group, where cognitive test scores from baseline through follow-up were consistently high.

Based on self-reports, the investigators categorized participants as never drinkers (41.8%), former drinkers (39.5%), or current drinkers (18.7%). For current drinkers, researchers determined the number of drinking days per week and number of drinks per day. They further categorized these participants as low to moderate drinkers or heavy drinkers.

One drink was defined as a 12-ounce bottle of beer, a 5-ounce glass of wine, or a 1.5-ounce shot of spirits, said Dr. Zhang.

Women who consumed 8 or more drinks per week and men who drank 15 or more drinks per week were considered heavy drinkers. Other current drinkers were deemed low to moderate drinkers. Most current drinkers (85.2%) were low to moderate drinkers.

Other covariates included age, sex, race/ethnicity, years of education, marital status, tobacco smoking status, and body mass index.

Results showed moderate drinking was associated with relatively high cognitive test scores. After controlling for all covariates, compared with never drinkers, current low to moderate drinkers were significantly less likely to have consistently low trajectories for total cognitive score (odds ratio, 0.66; 95% confidence interval, 0.59-0.74), mental status (OR, 0.71; 95% CI, 0.63-0.81), word recall (OR, 0.74; 95% CI, 0.69-0.80), and vocabulary (OR, 0.64; 95% CI, 0.56-0.74) (all P < .001).

Former drinkers also had better cognitive outcomes for all cognitive domains. Heavy drinkers had lower odds of being in the consistently low trajectory group only for the vocabulary test.
 

Heavy drinking ‘risky’

Because few participants were deemed to be heavy drinkers, the power to identify an association between heavy drinking and cognitive function was limited. Dr. Zhang acknowledged, though he noted that heavy drinking is “risky.”

“We found that, after the drinking dosage passes the moderate level, the risk of low cognitive function increases very fast, which indicates that heavy drinking may harm cognitive function.” Limiting alcohol consumption “is still very important,” he said.

The associations of alcohol and cognitive functions differed by race/ethnicity. Low to moderate drinking was significantly associated with a lower odds of having a consistently low trajectory for all four cognitive function measures only among white participants.

A possible reason for this is that the study had so few African Americans (who made up only 14.8% of the sample), which limited the ability to identify relationships between alcohol intake and cognitive function, said Dr. Zhang. “Another reason is that the sensitivity to alcohol may be different between white and African American subjects.”

There was a significant U-shaped association between weekly amounts of alcohol and the odds of being in the consistently low–trajectory group for all cognitive functions. Depending on the function tested, the optimal number of weekly drinks ranged from 10-14.

Dr. Zhang noted that, when women were examined separately, alcohol consumption had a significant U-shaped relationship only with word recall, with the optimal dosage being around eight drinks.
 

U-shaped relationship an ‘important finding’

The U-shaped relationship is “an important finding,” said Dr. Zhang. “It shows that the human body may act differently to low and high doses of alcohol. Knowing why and how this happens is very important as it would help us understand how alcohol affects the function of the human body.”

Sensitivity analyses among participants with no chronic diseases showed the U-shaped association was still significant for scores of total word recall and vocabulary, but not for mental status or total cognition score.

The authors noted that 77.2% of participants had at least one chronic disease. They maintained that the association between alcohol consumption and cognitive function may be applicable both to healthy people and to those with a chronic disease.

The study also found that low to moderate drinkers had slower rates of cognitive decline over time for all cognition domains.

Although the mechanisms underlying the cognitive benefits of alcohol consumption are unclear, the authors believe it may be via cerebrovascular and cardiovascular pathways.

Alcohol may increase levels of brain-derived neurotrophic factor, a key regulator of neuronal plasticity and development in the dorsal striatum, they noted.
 

Balancing act

However, there’s also evidence that drinking, especially heavy drinking, increases the risk of hypertension, stroke, liver damage, and some cancers. “We think the role of alcohol drinking in cognitive function may be a balance of its beneficial and harmful effects on the cardiovascular system,” said Dr. Zhang.

“For the low to moderate drinker, the beneficial effects may outweigh the harmful effects on the small blood vessels in the brain. In this way, it could preserve cognition,” he added.

Dr. Zhang also noted that the study focused on middle-aged and older adults. “We can’t say whether or not moderate alcohol could benefit younger people” because they may have different characteristics, he said.

The findings of other studies examining the effects of alcohol on cognitive function are mixed. While studies have identified a beneficial effect, others have uncovered no, minimal, or adverse effects. This could be due to the use of different tests of cognitive function or different study populations, said Dr. Zhang.

A limitation of the current study was that assessment of alcohol consumption was based on self-report, which might have introduced recall bias. In addition, because individuals tend to underestimate their alcohol consumption, heavy drinkers could be misclassified as low to moderate drinkers, and low to moderate drinkers as former drinkers.

“This may make our study underestimate the association between low to moderate drinking and cognitive function,” said Dr. Zhang. In addition, alcohol consumption tended to change with time, and this change may be associated with other factors that led to changes in cognitive function, the authors noted.
 

Interpret with caution

Commenting on the study, Brent P. Forester, MD, chief of the Center of Excellence in Geriatric Psychiatry at McLean Hospital in Belmont, Mass., associate professor of psychiatry at Harvard Medical School, Boston, and a member of the American Psychiatric Association Council on Geriatric Psychiatry, said he views the study with some trepidation.

“As a clinician taking care of older adults, I would be very cautious about overinterpreting the beneficial effects of alcohol before we understand the mechanism better,” he said.

He noted that all of the risk factors associated with heart attack and stroke are also risk factors for Alzheimer’s disease and cognitive decline more broadly. “One of the issues here is how in the world does alcohol reduce cardiovascular and cerebrovascular risks, if you know it increases the risk of hypertension and stroke, regardless of dose.”

With regard to the possible impact of alcohol on brain-derived neurotrophic factor, Dr. Forester said, “it’s an interesting idea” but the actual mechanism is still unclear.

Even with dietary studies, such as those on the Mediterranean diet that include red wine, showing cognitive benefit, Dr. Forester said he’s still concerned about the adverse effects of alcohol on older people. These can include falls and sleep disturbances in addition to cognitive issues, and these effects can increase with age.

He was somewhat surprised at the level of alcohol that the study determined was beneficial. “Essentially, what they’re saying here is that, for men, it’s two drinks a day.” This could be “problematic” as two drinks per day can quickly escalate as individuals build tolerance.

He also pointed out that the study does not determine cause and effect, noting that it’s only an association.

Dr. Forester said the study raises a number of questions, including the type of alcohol study participants consumed and whether this has any impact on cognitive benefit. He also questioned whether the mediating effects of alcohol were associated with something that wasn’t measured, such as socioeconomic status.

Another question, he said, is what factors in individuals’ medical or psychiatric history determine whether they are more or less likely to benefit from low to moderate alcohol intake.

Perhaps alcohol should be recommended only for “select subpopulations” – for example, those who are healthy and have a family history of cognitive decline –but not for those with a history of substance abuse, including alcohol abuse, said Dr. Forester.

“For this population, the last thing you want to do is recommend alcohol to reduce risk of cognitive decline,” he cautioned.

The study was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health. The investigators and Dr. Forester have reported no relevant financial disclosures.

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

Low to moderate alcohol consumption is associated with better cognitive function and slower cognitive decline in middle-aged and older adults, new research suggests. However, at least one expert urges caution in interpreting the findings.

Investigators found that consuming 10-14 alcoholic drinks per week had the strongest cognitive benefit. The findings “add more weight” to the growing body of research identifying beneficial cognitive effects of moderate alcohol consumption, said lead author, Ruiyuan Zhang, MD, of the department of epidemiology and biostatistics at the University of Georgia, Athens. However, Dr. Zhang emphasized that nondrinkers should not take up drinking to protect brain function, as alcohol can have negative effects.

The study was published online in JAMA Network Open.
 

Slower cognitive decline

The observational study was a secondary analysis of data from the Health and Retirement Study, a nationally representative U.S. survey of middle-aged and older adults. The survey, which began in 1992, is conducted every 2 years and collects health and economic data.

The current analysis used data from 1996 to 2008 and included information from individuals who participated in at least three surveys. The study included 19,887 participants, with a mean age 61.8 years. Most (60.1%) were women and white (85.2%). Mean follow-up was 9.1 years.

Researchers measured cognitive domains of mental status, word recall, and vocabulary. They also calculated a total cognition score, with higher scores indicating better cognitive abilities.

For each cognitive function measure, researchers categorized participants into a consistently low–trajectory group in which cognitive test scores from baseline through follow-up were consistently low or a consistently high–trajectory group, where cognitive test scores from baseline through follow-up were consistently high.

Based on self-reports, the investigators categorized participants as never drinkers (41.8%), former drinkers (39.5%), or current drinkers (18.7%). For current drinkers, researchers determined the number of drinking days per week and number of drinks per day. They further categorized these participants as low to moderate drinkers or heavy drinkers.

One drink was defined as a 12-ounce bottle of beer, a 5-ounce glass of wine, or a 1.5-ounce shot of spirits, said Dr. Zhang.

Women who consumed 8 or more drinks per week and men who drank 15 or more drinks per week were considered heavy drinkers. Other current drinkers were deemed low to moderate drinkers. Most current drinkers (85.2%) were low to moderate drinkers.

Other covariates included age, sex, race/ethnicity, years of education, marital status, tobacco smoking status, and body mass index.

Results showed moderate drinking was associated with relatively high cognitive test scores. After controlling for all covariates, compared with never drinkers, current low to moderate drinkers were significantly less likely to have consistently low trajectories for total cognitive score (odds ratio, 0.66; 95% confidence interval, 0.59-0.74), mental status (OR, 0.71; 95% CI, 0.63-0.81), word recall (OR, 0.74; 95% CI, 0.69-0.80), and vocabulary (OR, 0.64; 95% CI, 0.56-0.74) (all P < .001).

Former drinkers also had better cognitive outcomes for all cognitive domains. Heavy drinkers had lower odds of being in the consistently low trajectory group only for the vocabulary test.
 

Heavy drinking ‘risky’

Because few participants were deemed to be heavy drinkers, the power to identify an association between heavy drinking and cognitive function was limited. Dr. Zhang acknowledged, though he noted that heavy drinking is “risky.”

“We found that, after the drinking dosage passes the moderate level, the risk of low cognitive function increases very fast, which indicates that heavy drinking may harm cognitive function.” Limiting alcohol consumption “is still very important,” he said.

The associations of alcohol and cognitive functions differed by race/ethnicity. Low to moderate drinking was significantly associated with a lower odds of having a consistently low trajectory for all four cognitive function measures only among white participants.

A possible reason for this is that the study had so few African Americans (who made up only 14.8% of the sample), which limited the ability to identify relationships between alcohol intake and cognitive function, said Dr. Zhang. “Another reason is that the sensitivity to alcohol may be different between white and African American subjects.”

There was a significant U-shaped association between weekly amounts of alcohol and the odds of being in the consistently low–trajectory group for all cognitive functions. Depending on the function tested, the optimal number of weekly drinks ranged from 10-14.

Dr. Zhang noted that, when women were examined separately, alcohol consumption had a significant U-shaped relationship only with word recall, with the optimal dosage being around eight drinks.
 

U-shaped relationship an ‘important finding’

The U-shaped relationship is “an important finding,” said Dr. Zhang. “It shows that the human body may act differently to low and high doses of alcohol. Knowing why and how this happens is very important as it would help us understand how alcohol affects the function of the human body.”

Sensitivity analyses among participants with no chronic diseases showed the U-shaped association was still significant for scores of total word recall and vocabulary, but not for mental status or total cognition score.

The authors noted that 77.2% of participants had at least one chronic disease. They maintained that the association between alcohol consumption and cognitive function may be applicable both to healthy people and to those with a chronic disease.

The study also found that low to moderate drinkers had slower rates of cognitive decline over time for all cognition domains.

Although the mechanisms underlying the cognitive benefits of alcohol consumption are unclear, the authors believe it may be via cerebrovascular and cardiovascular pathways.

Alcohol may increase levels of brain-derived neurotrophic factor, a key regulator of neuronal plasticity and development in the dorsal striatum, they noted.
 

Balancing act

However, there’s also evidence that drinking, especially heavy drinking, increases the risk of hypertension, stroke, liver damage, and some cancers. “We think the role of alcohol drinking in cognitive function may be a balance of its beneficial and harmful effects on the cardiovascular system,” said Dr. Zhang.

“For the low to moderate drinker, the beneficial effects may outweigh the harmful effects on the small blood vessels in the brain. In this way, it could preserve cognition,” he added.

Dr. Zhang also noted that the study focused on middle-aged and older adults. “We can’t say whether or not moderate alcohol could benefit younger people” because they may have different characteristics, he said.

The findings of other studies examining the effects of alcohol on cognitive function are mixed. While studies have identified a beneficial effect, others have uncovered no, minimal, or adverse effects. This could be due to the use of different tests of cognitive function or different study populations, said Dr. Zhang.

A limitation of the current study was that assessment of alcohol consumption was based on self-report, which might have introduced recall bias. In addition, because individuals tend to underestimate their alcohol consumption, heavy drinkers could be misclassified as low to moderate drinkers, and low to moderate drinkers as former drinkers.

“This may make our study underestimate the association between low to moderate drinking and cognitive function,” said Dr. Zhang. In addition, alcohol consumption tended to change with time, and this change may be associated with other factors that led to changes in cognitive function, the authors noted.
 

Interpret with caution

Commenting on the study, Brent P. Forester, MD, chief of the Center of Excellence in Geriatric Psychiatry at McLean Hospital in Belmont, Mass., associate professor of psychiatry at Harvard Medical School, Boston, and a member of the American Psychiatric Association Council on Geriatric Psychiatry, said he views the study with some trepidation.

“As a clinician taking care of older adults, I would be very cautious about overinterpreting the beneficial effects of alcohol before we understand the mechanism better,” he said.

He noted that all of the risk factors associated with heart attack and stroke are also risk factors for Alzheimer’s disease and cognitive decline more broadly. “One of the issues here is how in the world does alcohol reduce cardiovascular and cerebrovascular risks, if you know it increases the risk of hypertension and stroke, regardless of dose.”

With regard to the possible impact of alcohol on brain-derived neurotrophic factor, Dr. Forester said, “it’s an interesting idea” but the actual mechanism is still unclear.

Even with dietary studies, such as those on the Mediterranean diet that include red wine, showing cognitive benefit, Dr. Forester said he’s still concerned about the adverse effects of alcohol on older people. These can include falls and sleep disturbances in addition to cognitive issues, and these effects can increase with age.

He was somewhat surprised at the level of alcohol that the study determined was beneficial. “Essentially, what they’re saying here is that, for men, it’s two drinks a day.” This could be “problematic” as two drinks per day can quickly escalate as individuals build tolerance.

He also pointed out that the study does not determine cause and effect, noting that it’s only an association.

Dr. Forester said the study raises a number of questions, including the type of alcohol study participants consumed and whether this has any impact on cognitive benefit. He also questioned whether the mediating effects of alcohol were associated with something that wasn’t measured, such as socioeconomic status.

Another question, he said, is what factors in individuals’ medical or psychiatric history determine whether they are more or less likely to benefit from low to moderate alcohol intake.

Perhaps alcohol should be recommended only for “select subpopulations” – for example, those who are healthy and have a family history of cognitive decline –but not for those with a history of substance abuse, including alcohol abuse, said Dr. Forester.

“For this population, the last thing you want to do is recommend alcohol to reduce risk of cognitive decline,” he cautioned.

The study was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health. The investigators and Dr. Forester have reported no relevant financial disclosures.

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

A small number of U.S. health systems, as well as some individual physicians, have begun dropping the African American–specific modifier when recording estimated glomerular filtration rate (eGFR), a measure of renal function.

The move aims to correct a race-based health access inequity that’s been in place for more than 2 decades, say advocates, while others voice concern that the change threatens over-diagnosis of both chronic and end-stage kidney disease in some patients.

In late June, the Boston-based Massachusetts General Brigham health system stopped noting the race-based modifier when its laboratories reported eGFR, and the leadership sent its staff a message discouraging them from applying the modifier. A similar change in eGFR reporting started on June 1 at the University of Washington health system, UW Medicine, Seattle.

These steps followed what is widely regarded as the first institutional change away from race-based adjustment of eGFR, which began in March 2017 at Beth Israel Deaconess Medical Center in Boston, and they have come amid a growing movement by some individual U.S. physicians to drop the modifier from their practice.

“Momentum is clearly building,” said Nwamaka D. Eneanya, MD, a nephrologist at the University of Pennsylvania in Philadelphia and lead author of a commentary published a little more than a year ago that laid out the case for reconsidering how to calculate eGFR in African Americans.

“Many discussions are happening at other [US] academic medical centers,” Dr. Eneanya added, including the system where she works.
 

Why was the decision taken to modify eGFR in African Americans?

The concept is that the formula used to calculate eGFR systematically underestimates the value in African Americans. Hence, it requires a small but meaningful up-adjustment, which can be traced back to the introduction of the Modification of Diet in Renal Disease (MDRD) study equation in 1999.

The idea was perpetuated in an improved calculation formula, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), that came out a decade later.

These are the most widely used U.S. approaches to eGFR calculation, with the newer CKD-EPI formula predominating.

The rationale for including a modifier for Blacks in the 2009 formula was for improved accuracy relative to the standard reference measure based on iothalamate clearance.

The data used to develop the CKD-EPI formula showed that Black individuals in the dataset had, on average, GFR levels that were 16% higher than people of other races with the same age, sex, and serum creatinine level, according to a recent commentary. The first author, Andrew S. Levey, MD, was also lead author of the reports that introduced both the MDRD and CKD-EPI equations.

But the argument withers in the light of both its flimsy underpinning – race assessment – and the medical and social consequences of its application, say those who have sought change.
 

Reporting eGFR by race might do more harm than good

“Race is a social, not a biological, construct and the kidney-function race multiplier ignores the substantial genetic diversity within self-identified Black patients,” said Thomas D. Sequist, MD, professor of medicine at Harvard Medical School in Boston and chief patient experience and equity officer for Mass General Brigham, who spearheaded the policy change for that system.

“Do we really believe that the population breaks down into just ‘Black’ and ‘not Black,’ as the CKD-EPI equation asks us to believe?” he said in an interview. “The equation was developed from a few thousand patients, and we now apply it to millions of people using a very imprecise measure – race.”

“Reporting eGFR by race perpetuates a notion that race is a biologic construct when it’s not,” agreed Rajnish Mehrotra, MD, a professor and chief of nephrology at the University of Washington in Seattle and leader of the eGFR change within his medical system.

Equally compelling, said Dr. Mehrotra, Dr. Sequist, and others, are the health inequities that have resulted from routinely raising the eGFR in African Americans.

This has led to “withholding treatment from people longer than needed. We arrived at the conclusion that reporting eGFR by race does more harm than good,” Dr. Mehrotra said in an interview.

Dr. Sequist added: “Researchers across Mass General Brigham have demonstrated that use of these race multipliers can lead to important delays in care for Black patients, such as timely evaluation for kidney transplantation.”

“Our main concern is that race correction is creating harm.”

Dr. Eneanya concurs: “It was never designed to oppress patients, but that’s where we are. No one ever thought about the repercussions of using race.”

And while the movement to eliminate the race modifier is clearly gaining steam, it’s also receiving pushback from those who see benefit from the modification and have concern that its abolition could lead to overestimates of kidney disease severity.

Some clinicians “have a hard time letting the race modifier go,” Dr. Eneanya noted.
 

“In the nephrology community, it’s pretty controversial”

In their 2020 commentary, Levey and coauthors wrote: “We propose a more cautious approach that maintains and improves accuracy of GFR estimates and avoids disadvantaging any racial group.”

Their suggested remedies included full disclosure of use of race, accommodation of people who decline to self-identify themselves that way, shared decision-making, and “mindful” use of cystatin C, an alternative to serum creatinine for calculating eGFR.

The latter is regarded as more precise and accurate than serum creatinine across populations but is often not as readily available to many clinicians. Their article also supported looking for even better and more accessible ways to calculate eGFR.

“In the nephrology community, it’s pretty controversial,” said Mallika L. Mendu, MD, a nephrologist at Brigham and Women’s Hospital in Boston, Massachusetts, who has studied the effects of using the modifier on patient assessment.

Her recent review of Mass General Brigham patients found that close to a third of African Americans would have been reclassified with a more severe form of kidney disease if their eGFR had remained unmodified.

“That raised concerns that, by using race adjustment we’re potentially leading to less equitable outcomes for African American patients,” she said. “I’d rather over diagnose than not diagnose in a timely way.”

The research that led to development of the MDRD and CKD-EPI equations “are gold-standard studies” that “saw a real difference,” Dr. Mendu acknowledged in an interview. “But the way those studies were run and the way they defined the patients was problematic.” Despite that, “many nephrologists” agree with the position taken by Dr. Levey and coauthors in their recent commentary, she said.

She added that she stopped using the modifier about a year ago in her own practice, well before the system where she works adopted the same approach.
 

Consensus takes time

In one sign of the controversy, a quartet of clinicians affiliated with San Francisco General Hospital (SFGH) recently posted an online petition in which they noted that the race modifier had been eliminated in eGFR reports from the hospital’s laboratory in October 2019, but more recently had been slated for reinstitution. “We were deeply distressed to recently discover the intended plan to revert back to race-based eGFR reporting at SFGH,” they noted.

The same four clinicians also wrote an opinion piece calling for elimination of the modifier in November 2019 in the San Francisco Examiner.

Controversy will likely linger as the movement to withdraw the race modifier spreads without clear agreement on what to do instead.

Dr. Mehrotra said he’s received inquiries about his system’s experience from clinicians at several U.S. medical centers and systems, and he remains comfortable applying the unadjusted CKD-EPI formula to all adults, an approach he called “sufficient.”

Other physicians, like nephrologist Vanessa Grubbs, MD, call for a rapid shift to a cystatin C–based, fully race-neutral method for calculating eGFR, a position she detailed in a recent editorial.

And at the University of Pennsylvania, where the health system continues to issue eGFR reports with the race modifier, Dr. Eneanya says that she stopped using the modifier “some time” ago.

“People have a hard time letting it go because it is so important in clinical care. Getting everyone to come to a consensus takes time,” she said.

Dr. Eneanya, Dr. Sequist, and Dr. Mendu have reported no relevant financial relationships. Dr. Mehrotra has been a consultant for Baxter Healthcare.

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

A small number of U.S. health systems, as well as some individual physicians, have begun dropping the African American–specific modifier when recording estimated glomerular filtration rate (eGFR), a measure of renal function.

The move aims to correct a race-based health access inequity that’s been in place for more than 2 decades, say advocates, while others voice concern that the change threatens over-diagnosis of both chronic and end-stage kidney disease in some patients.

In late June, the Boston-based Massachusetts General Brigham health system stopped noting the race-based modifier when its laboratories reported eGFR, and the leadership sent its staff a message discouraging them from applying the modifier. A similar change in eGFR reporting started on June 1 at the University of Washington health system, UW Medicine, Seattle.

These steps followed what is widely regarded as the first institutional change away from race-based adjustment of eGFR, which began in March 2017 at Beth Israel Deaconess Medical Center in Boston, and they have come amid a growing movement by some individual U.S. physicians to drop the modifier from their practice.

“Momentum is clearly building,” said Nwamaka D. Eneanya, MD, a nephrologist at the University of Pennsylvania in Philadelphia and lead author of a commentary published a little more than a year ago that laid out the case for reconsidering how to calculate eGFR in African Americans.

“Many discussions are happening at other [US] academic medical centers,” Dr. Eneanya added, including the system where she works.
 

Why was the decision taken to modify eGFR in African Americans?

The concept is that the formula used to calculate eGFR systematically underestimates the value in African Americans. Hence, it requires a small but meaningful up-adjustment, which can be traced back to the introduction of the Modification of Diet in Renal Disease (MDRD) study equation in 1999.

The idea was perpetuated in an improved calculation formula, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), that came out a decade later.

These are the most widely used U.S. approaches to eGFR calculation, with the newer CKD-EPI formula predominating.

The rationale for including a modifier for Blacks in the 2009 formula was for improved accuracy relative to the standard reference measure based on iothalamate clearance.

The data used to develop the CKD-EPI formula showed that Black individuals in the dataset had, on average, GFR levels that were 16% higher than people of other races with the same age, sex, and serum creatinine level, according to a recent commentary. The first author, Andrew S. Levey, MD, was also lead author of the reports that introduced both the MDRD and CKD-EPI equations.

But the argument withers in the light of both its flimsy underpinning – race assessment – and the medical and social consequences of its application, say those who have sought change.
 

Reporting eGFR by race might do more harm than good

“Race is a social, not a biological, construct and the kidney-function race multiplier ignores the substantial genetic diversity within self-identified Black patients,” said Thomas D. Sequist, MD, professor of medicine at Harvard Medical School in Boston and chief patient experience and equity officer for Mass General Brigham, who spearheaded the policy change for that system.

“Do we really believe that the population breaks down into just ‘Black’ and ‘not Black,’ as the CKD-EPI equation asks us to believe?” he said in an interview. “The equation was developed from a few thousand patients, and we now apply it to millions of people using a very imprecise measure – race.”

“Reporting eGFR by race perpetuates a notion that race is a biologic construct when it’s not,” agreed Rajnish Mehrotra, MD, a professor and chief of nephrology at the University of Washington in Seattle and leader of the eGFR change within his medical system.

Equally compelling, said Dr. Mehrotra, Dr. Sequist, and others, are the health inequities that have resulted from routinely raising the eGFR in African Americans.

This has led to “withholding treatment from people longer than needed. We arrived at the conclusion that reporting eGFR by race does more harm than good,” Dr. Mehrotra said in an interview.

Dr. Sequist added: “Researchers across Mass General Brigham have demonstrated that use of these race multipliers can lead to important delays in care for Black patients, such as timely evaluation for kidney transplantation.”

“Our main concern is that race correction is creating harm.”

Dr. Eneanya concurs: “It was never designed to oppress patients, but that’s where we are. No one ever thought about the repercussions of using race.”

And while the movement to eliminate the race modifier is clearly gaining steam, it’s also receiving pushback from those who see benefit from the modification and have concern that its abolition could lead to overestimates of kidney disease severity.

Some clinicians “have a hard time letting the race modifier go,” Dr. Eneanya noted.
 

“In the nephrology community, it’s pretty controversial”

In their 2020 commentary, Levey and coauthors wrote: “We propose a more cautious approach that maintains and improves accuracy of GFR estimates and avoids disadvantaging any racial group.”

Their suggested remedies included full disclosure of use of race, accommodation of people who decline to self-identify themselves that way, shared decision-making, and “mindful” use of cystatin C, an alternative to serum creatinine for calculating eGFR.

The latter is regarded as more precise and accurate than serum creatinine across populations but is often not as readily available to many clinicians. Their article also supported looking for even better and more accessible ways to calculate eGFR.

“In the nephrology community, it’s pretty controversial,” said Mallika L. Mendu, MD, a nephrologist at Brigham and Women’s Hospital in Boston, Massachusetts, who has studied the effects of using the modifier on patient assessment.

Her recent review of Mass General Brigham patients found that close to a third of African Americans would have been reclassified with a more severe form of kidney disease if their eGFR had remained unmodified.

“That raised concerns that, by using race adjustment we’re potentially leading to less equitable outcomes for African American patients,” she said. “I’d rather over diagnose than not diagnose in a timely way.”

The research that led to development of the MDRD and CKD-EPI equations “are gold-standard studies” that “saw a real difference,” Dr. Mendu acknowledged in an interview. “But the way those studies were run and the way they defined the patients was problematic.” Despite that, “many nephrologists” agree with the position taken by Dr. Levey and coauthors in their recent commentary, she said.

She added that she stopped using the modifier about a year ago in her own practice, well before the system where she works adopted the same approach.
 

Consensus takes time

In one sign of the controversy, a quartet of clinicians affiliated with San Francisco General Hospital (SFGH) recently posted an online petition in which they noted that the race modifier had been eliminated in eGFR reports from the hospital’s laboratory in October 2019, but more recently had been slated for reinstitution. “We were deeply distressed to recently discover the intended plan to revert back to race-based eGFR reporting at SFGH,” they noted.

The same four clinicians also wrote an opinion piece calling for elimination of the modifier in November 2019 in the San Francisco Examiner.

Controversy will likely linger as the movement to withdraw the race modifier spreads without clear agreement on what to do instead.

Dr. Mehrotra said he’s received inquiries about his system’s experience from clinicians at several U.S. medical centers and systems, and he remains comfortable applying the unadjusted CKD-EPI formula to all adults, an approach he called “sufficient.”

Other physicians, like nephrologist Vanessa Grubbs, MD, call for a rapid shift to a cystatin C–based, fully race-neutral method for calculating eGFR, a position she detailed in a recent editorial.

And at the University of Pennsylvania, where the health system continues to issue eGFR reports with the race modifier, Dr. Eneanya says that she stopped using the modifier “some time” ago.

“People have a hard time letting it go because it is so important in clinical care. Getting everyone to come to a consensus takes time,” she said.

Dr. Eneanya, Dr. Sequist, and Dr. Mendu have reported no relevant financial relationships. Dr. Mehrotra has been a consultant for Baxter Healthcare.

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

A small number of U.S. health systems, as well as some individual physicians, have begun dropping the African American–specific modifier when recording estimated glomerular filtration rate (eGFR), a measure of renal function.

The move aims to correct a race-based health access inequity that’s been in place for more than 2 decades, say advocates, while others voice concern that the change threatens over-diagnosis of both chronic and end-stage kidney disease in some patients.

In late June, the Boston-based Massachusetts General Brigham health system stopped noting the race-based modifier when its laboratories reported eGFR, and the leadership sent its staff a message discouraging them from applying the modifier. A similar change in eGFR reporting started on June 1 at the University of Washington health system, UW Medicine, Seattle.

These steps followed what is widely regarded as the first institutional change away from race-based adjustment of eGFR, which began in March 2017 at Beth Israel Deaconess Medical Center in Boston, and they have come amid a growing movement by some individual U.S. physicians to drop the modifier from their practice.

“Momentum is clearly building,” said Nwamaka D. Eneanya, MD, a nephrologist at the University of Pennsylvania in Philadelphia and lead author of a commentary published a little more than a year ago that laid out the case for reconsidering how to calculate eGFR in African Americans.

“Many discussions are happening at other [US] academic medical centers,” Dr. Eneanya added, including the system where she works.
 

Why was the decision taken to modify eGFR in African Americans?

The concept is that the formula used to calculate eGFR systematically underestimates the value in African Americans. Hence, it requires a small but meaningful up-adjustment, which can be traced back to the introduction of the Modification of Diet in Renal Disease (MDRD) study equation in 1999.

The idea was perpetuated in an improved calculation formula, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), that came out a decade later.

These are the most widely used U.S. approaches to eGFR calculation, with the newer CKD-EPI formula predominating.

The rationale for including a modifier for Blacks in the 2009 formula was for improved accuracy relative to the standard reference measure based on iothalamate clearance.

The data used to develop the CKD-EPI formula showed that Black individuals in the dataset had, on average, GFR levels that were 16% higher than people of other races with the same age, sex, and serum creatinine level, according to a recent commentary. The first author, Andrew S. Levey, MD, was also lead author of the reports that introduced both the MDRD and CKD-EPI equations.

But the argument withers in the light of both its flimsy underpinning – race assessment – and the medical and social consequences of its application, say those who have sought change.
 

Reporting eGFR by race might do more harm than good

“Race is a social, not a biological, construct and the kidney-function race multiplier ignores the substantial genetic diversity within self-identified Black patients,” said Thomas D. Sequist, MD, professor of medicine at Harvard Medical School in Boston and chief patient experience and equity officer for Mass General Brigham, who spearheaded the policy change for that system.

“Do we really believe that the population breaks down into just ‘Black’ and ‘not Black,’ as the CKD-EPI equation asks us to believe?” he said in an interview. “The equation was developed from a few thousand patients, and we now apply it to millions of people using a very imprecise measure – race.”

“Reporting eGFR by race perpetuates a notion that race is a biologic construct when it’s not,” agreed Rajnish Mehrotra, MD, a professor and chief of nephrology at the University of Washington in Seattle and leader of the eGFR change within his medical system.

Equally compelling, said Dr. Mehrotra, Dr. Sequist, and others, are the health inequities that have resulted from routinely raising the eGFR in African Americans.

This has led to “withholding treatment from people longer than needed. We arrived at the conclusion that reporting eGFR by race does more harm than good,” Dr. Mehrotra said in an interview.

Dr. Sequist added: “Researchers across Mass General Brigham have demonstrated that use of these race multipliers can lead to important delays in care for Black patients, such as timely evaluation for kidney transplantation.”

“Our main concern is that race correction is creating harm.”

Dr. Eneanya concurs: “It was never designed to oppress patients, but that’s where we are. No one ever thought about the repercussions of using race.”

And while the movement to eliminate the race modifier is clearly gaining steam, it’s also receiving pushback from those who see benefit from the modification and have concern that its abolition could lead to overestimates of kidney disease severity.

Some clinicians “have a hard time letting the race modifier go,” Dr. Eneanya noted.
 

“In the nephrology community, it’s pretty controversial”

In their 2020 commentary, Levey and coauthors wrote: “We propose a more cautious approach that maintains and improves accuracy of GFR estimates and avoids disadvantaging any racial group.”

Their suggested remedies included full disclosure of use of race, accommodation of people who decline to self-identify themselves that way, shared decision-making, and “mindful” use of cystatin C, an alternative to serum creatinine for calculating eGFR.

The latter is regarded as more precise and accurate than serum creatinine across populations but is often not as readily available to many clinicians. Their article also supported looking for even better and more accessible ways to calculate eGFR.

“In the nephrology community, it’s pretty controversial,” said Mallika L. Mendu, MD, a nephrologist at Brigham and Women’s Hospital in Boston, Massachusetts, who has studied the effects of using the modifier on patient assessment.

Her recent review of Mass General Brigham patients found that close to a third of African Americans would have been reclassified with a more severe form of kidney disease if their eGFR had remained unmodified.

“That raised concerns that, by using race adjustment we’re potentially leading to less equitable outcomes for African American patients,” she said. “I’d rather over diagnose than not diagnose in a timely way.”

The research that led to development of the MDRD and CKD-EPI equations “are gold-standard studies” that “saw a real difference,” Dr. Mendu acknowledged in an interview. “But the way those studies were run and the way they defined the patients was problematic.” Despite that, “many nephrologists” agree with the position taken by Dr. Levey and coauthors in their recent commentary, she said.

She added that she stopped using the modifier about a year ago in her own practice, well before the system where she works adopted the same approach.
 

Consensus takes time

In one sign of the controversy, a quartet of clinicians affiliated with San Francisco General Hospital (SFGH) recently posted an online petition in which they noted that the race modifier had been eliminated in eGFR reports from the hospital’s laboratory in October 2019, but more recently had been slated for reinstitution. “We were deeply distressed to recently discover the intended plan to revert back to race-based eGFR reporting at SFGH,” they noted.

The same four clinicians also wrote an opinion piece calling for elimination of the modifier in November 2019 in the San Francisco Examiner.

Controversy will likely linger as the movement to withdraw the race modifier spreads without clear agreement on what to do instead.

Dr. Mehrotra said he’s received inquiries about his system’s experience from clinicians at several U.S. medical centers and systems, and he remains comfortable applying the unadjusted CKD-EPI formula to all adults, an approach he called “sufficient.”

Other physicians, like nephrologist Vanessa Grubbs, MD, call for a rapid shift to a cystatin C–based, fully race-neutral method for calculating eGFR, a position she detailed in a recent editorial.

And at the University of Pennsylvania, where the health system continues to issue eGFR reports with the race modifier, Dr. Eneanya says that she stopped using the modifier “some time” ago.

“People have a hard time letting it go because it is so important in clinical care. Getting everyone to come to a consensus takes time,” she said.

Dr. Eneanya, Dr. Sequist, and Dr. Mendu have reported no relevant financial relationships. Dr. Mehrotra has been a consultant for Baxter Healthcare.

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