Having oral sex with more than 10 previous partners was associated with a 4.3 times’ greater likelihood of developing human papillomavirus (HPV)–related oropharyngeal cancer, according to new findings.

The study also found that having more partners in a shorter period (i.e., greater oral sex intensity) and starting oral sex at a younger age were associated with higher odds of having HPV-related cancer of the mouth and throat.

The new study, published online on Jan. 11 in Cancer, confirms previous findings and adds more nuance, say the researchers.

Previous studies have demonstrated that oral sex is a strong risk factor for HPV-related oropharyngeal cancer, which has increased in incidence in recent decades, particularly cancer of the base of the tongue and palatine and lingual tonsils.

“Our research adds more nuance in our understanding of how people acquire oral HPV infection and HPV-related oropharyngeal cancer,” said study author Gypsyamber D’Souza, PhD, professor of epidemiology at the Johns Hopkins Bloomberg School of Public Health, Baltimore. “It suggests that risk of infection is not only from the number of oral sexual partners but that the timing and type of partner also influence risk.”

The results of the study do not change the clinical care or screening of patients, Dr. D’Souza noted, but the study does add context for patients and providers in understanding, “Why did I get HPV-oropharyngeal cancer?” she said.

“We know that people who develop HPV-oropharyngeal cancer have a wide range of sexual histories, but we do not suggest sexual history be used for screening, as many patients have low-risk sexual histories,” she said. “By chance, it only takes one partner who is infected to acquire the infection, while others who have had many partners by chance do not get exposed, or who are exposed but clear the infection.”
 

Reinforces the need for vaccination

Approached for comment, Joseph Califano, MD, physician-in-chief at the Moores Cancer Center and director of the Head and Neck Cancer Center at the University of California, San Diego, noted that similar data have been published before. The novelty here is in the timing and intensity of oral sex. “It’s not new data, but it certainly reinforces what we knew,” he said in an interview.

These new data are not going to change monitoring, he suggested. “It’s not going to change how we screen, because we don’t do population-based screening for oropharyngeal cancer,” Dr. Califano said.

“It does underline the fact that vaccination is really the key to preventing HPV-mediated cancers,” he said.

He pointed out that some data show lower rates of high-risk oral HPV shedding by children who have been appropriately vaccinated.

“This paper really highlights the fact we need to get people vaccinated early, before sexual debut,” he said. “In this case, sexual debut doesn’t necessarily mean intercourse but oral sex, and that’s a different concept of when sex starts.”

These new data “reinforce the fact that early exposure is what we need to focus on,” he said.
 

Details of the new findings

The current study by Dr. D’Souza and colleagues included 163 patients with HPV-related oropharyngeal cancer who were enrolled in the Papillomavirus Role in Oral Cancer Viral Etiology (PROVE) study. These patients were compared with 345 matched control persons.

All participants completed a behavioral survey and provided a blood sample. For the patients with cancer, a tumor sample was obtained.

The majority of participants were male (85% and 82%), were aged 50-69 years, were currently married or living with a partner, and identified as heterosexual. Case patients were more likely to report a history of sexually transmitted infection than were control participants (P = .003).

Case patients were more likely to have ever performed oral sex compared to control persons (98.8% vs 90.4%; P < .001) and to have performed oral sex at the time of their sexual debut (33.3% of case patients vs 21.4% of control persons; P = .004; odds ratio [OR], 1.8).

Significantly more case patients than control persons reported starting oral sex before they were 18 years old (37.4% of cases vs. 22.6% of controls; P < .001; OR, 3.1), and they had a greater number of lifetime oral sex partners (44.8% of cases and 19.1% of controls reported having more than 10 partners; P < .001; OR, 4.3).

Intensity of oral sexual exposure, which the authors measured by number of partners per 10 years, was also significantly higher among cases than controls (30.8% vs 11.1%; P < .001; OR, 5.6).

After adjustment for confounders (such as the lifetime number of oral sex partners and tobacco use), ever performing oral sex (adjusted odds ratio [aOR], 4.4), early age of first oral sex encounter (20 years: aOR, 1.8), and oral sex intensity (aOR, 2.8) all remained significantly associated with increased odds of HPV-oropharyngeal cancer.

The type of sexual partner, such as partners who were older (OR, 1.7) and having a partner who engaged in extramarital sex (OR, 1.6), were also associated with increased odds of developing HPV-oropharyngeal cancer. In addition, seropositivity for antibodies to HPV16 E6 (OR, 286) and any HPV16 E protein (E1, E2, E6, E7; OR, 163) were also associated with increased odds of developing the disease.

The study was supported by the National Institute of Dental and Craniofacial Research and the National Institute on Deafness and Other Communication Disorders. Dr. D’Souza and Dr. Califano have disclosed no relevant financial relationships.

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

Having oral sex with more than 10 previous partners was associated with a 4.3 times’ greater likelihood of developing human papillomavirus (HPV)–related oropharyngeal cancer, according to new findings.

The study also found that having more partners in a shorter period (i.e., greater oral sex intensity) and starting oral sex at a younger age were associated with higher odds of having HPV-related cancer of the mouth and throat.

The new study, published online on Jan. 11 in Cancer, confirms previous findings and adds more nuance, say the researchers.

Previous studies have demonstrated that oral sex is a strong risk factor for HPV-related oropharyngeal cancer, which has increased in incidence in recent decades, particularly cancer of the base of the tongue and palatine and lingual tonsils.

“Our research adds more nuance in our understanding of how people acquire oral HPV infection and HPV-related oropharyngeal cancer,” said study author Gypsyamber D’Souza, PhD, professor of epidemiology at the Johns Hopkins Bloomberg School of Public Health, Baltimore. “It suggests that risk of infection is not only from the number of oral sexual partners but that the timing and type of partner also influence risk.”

The results of the study do not change the clinical care or screening of patients, Dr. D’Souza noted, but the study does add context for patients and providers in understanding, “Why did I get HPV-oropharyngeal cancer?” she said.

“We know that people who develop HPV-oropharyngeal cancer have a wide range of sexual histories, but we do not suggest sexual history be used for screening, as many patients have low-risk sexual histories,” she said. “By chance, it only takes one partner who is infected to acquire the infection, while others who have had many partners by chance do not get exposed, or who are exposed but clear the infection.”
 

Reinforces the need for vaccination

Approached for comment, Joseph Califano, MD, physician-in-chief at the Moores Cancer Center and director of the Head and Neck Cancer Center at the University of California, San Diego, noted that similar data have been published before. The novelty here is in the timing and intensity of oral sex. “It’s not new data, but it certainly reinforces what we knew,” he said in an interview.

These new data are not going to change monitoring, he suggested. “It’s not going to change how we screen, because we don’t do population-based screening for oropharyngeal cancer,” Dr. Califano said.

“It does underline the fact that vaccination is really the key to preventing HPV-mediated cancers,” he said.

He pointed out that some data show lower rates of high-risk oral HPV shedding by children who have been appropriately vaccinated.

“This paper really highlights the fact we need to get people vaccinated early, before sexual debut,” he said. “In this case, sexual debut doesn’t necessarily mean intercourse but oral sex, and that’s a different concept of when sex starts.”

These new data “reinforce the fact that early exposure is what we need to focus on,” he said.
 

Details of the new findings

The current study by Dr. D’Souza and colleagues included 163 patients with HPV-related oropharyngeal cancer who were enrolled in the Papillomavirus Role in Oral Cancer Viral Etiology (PROVE) study. These patients were compared with 345 matched control persons.

All participants completed a behavioral survey and provided a blood sample. For the patients with cancer, a tumor sample was obtained.

The majority of participants were male (85% and 82%), were aged 50-69 years, were currently married or living with a partner, and identified as heterosexual. Case patients were more likely to report a history of sexually transmitted infection than were control participants (P = .003).

Case patients were more likely to have ever performed oral sex compared to control persons (98.8% vs 90.4%; P < .001) and to have performed oral sex at the time of their sexual debut (33.3% of case patients vs 21.4% of control persons; P = .004; odds ratio [OR], 1.8).

Significantly more case patients than control persons reported starting oral sex before they were 18 years old (37.4% of cases vs. 22.6% of controls; P < .001; OR, 3.1), and they had a greater number of lifetime oral sex partners (44.8% of cases and 19.1% of controls reported having more than 10 partners; P < .001; OR, 4.3).

Intensity of oral sexual exposure, which the authors measured by number of partners per 10 years, was also significantly higher among cases than controls (30.8% vs 11.1%; P < .001; OR, 5.6).

After adjustment for confounders (such as the lifetime number of oral sex partners and tobacco use), ever performing oral sex (adjusted odds ratio [aOR], 4.4), early age of first oral sex encounter (20 years: aOR, 1.8), and oral sex intensity (aOR, 2.8) all remained significantly associated with increased odds of HPV-oropharyngeal cancer.

The type of sexual partner, such as partners who were older (OR, 1.7) and having a partner who engaged in extramarital sex (OR, 1.6), were also associated with increased odds of developing HPV-oropharyngeal cancer. In addition, seropositivity for antibodies to HPV16 E6 (OR, 286) and any HPV16 E protein (E1, E2, E6, E7; OR, 163) were also associated with increased odds of developing the disease.

The study was supported by the National Institute of Dental and Craniofacial Research and the National Institute on Deafness and Other Communication Disorders. Dr. D’Souza and Dr. Califano have disclosed no relevant financial relationships.

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

Having oral sex with more than 10 previous partners was associated with a 4.3 times’ greater likelihood of developing human papillomavirus (HPV)–related oropharyngeal cancer, according to new findings.

The study also found that having more partners in a shorter period (i.e., greater oral sex intensity) and starting oral sex at a younger age were associated with higher odds of having HPV-related cancer of the mouth and throat.

The new study, published online on Jan. 11 in Cancer, confirms previous findings and adds more nuance, say the researchers.

Previous studies have demonstrated that oral sex is a strong risk factor for HPV-related oropharyngeal cancer, which has increased in incidence in recent decades, particularly cancer of the base of the tongue and palatine and lingual tonsils.

“Our research adds more nuance in our understanding of how people acquire oral HPV infection and HPV-related oropharyngeal cancer,” said study author Gypsyamber D’Souza, PhD, professor of epidemiology at the Johns Hopkins Bloomberg School of Public Health, Baltimore. “It suggests that risk of infection is not only from the number of oral sexual partners but that the timing and type of partner also influence risk.”

The results of the study do not change the clinical care or screening of patients, Dr. D’Souza noted, but the study does add context for patients and providers in understanding, “Why did I get HPV-oropharyngeal cancer?” she said.

“We know that people who develop HPV-oropharyngeal cancer have a wide range of sexual histories, but we do not suggest sexual history be used for screening, as many patients have low-risk sexual histories,” she said. “By chance, it only takes one partner who is infected to acquire the infection, while others who have had many partners by chance do not get exposed, or who are exposed but clear the infection.”
 

Reinforces the need for vaccination

Approached for comment, Joseph Califano, MD, physician-in-chief at the Moores Cancer Center and director of the Head and Neck Cancer Center at the University of California, San Diego, noted that similar data have been published before. The novelty here is in the timing and intensity of oral sex. “It’s not new data, but it certainly reinforces what we knew,” he said in an interview.

These new data are not going to change monitoring, he suggested. “It’s not going to change how we screen, because we don’t do population-based screening for oropharyngeal cancer,” Dr. Califano said.

“It does underline the fact that vaccination is really the key to preventing HPV-mediated cancers,” he said.

He pointed out that some data show lower rates of high-risk oral HPV shedding by children who have been appropriately vaccinated.

“This paper really highlights the fact we need to get people vaccinated early, before sexual debut,” he said. “In this case, sexual debut doesn’t necessarily mean intercourse but oral sex, and that’s a different concept of when sex starts.”

These new data “reinforce the fact that early exposure is what we need to focus on,” he said.
 

Details of the new findings

The current study by Dr. D’Souza and colleagues included 163 patients with HPV-related oropharyngeal cancer who were enrolled in the Papillomavirus Role in Oral Cancer Viral Etiology (PROVE) study. These patients were compared with 345 matched control persons.

All participants completed a behavioral survey and provided a blood sample. For the patients with cancer, a tumor sample was obtained.

The majority of participants were male (85% and 82%), were aged 50-69 years, were currently married or living with a partner, and identified as heterosexual. Case patients were more likely to report a history of sexually transmitted infection than were control participants (P = .003).

Case patients were more likely to have ever performed oral sex compared to control persons (98.8% vs 90.4%; P < .001) and to have performed oral sex at the time of their sexual debut (33.3% of case patients vs 21.4% of control persons; P = .004; odds ratio [OR], 1.8).

Significantly more case patients than control persons reported starting oral sex before they were 18 years old (37.4% of cases vs. 22.6% of controls; P < .001; OR, 3.1), and they had a greater number of lifetime oral sex partners (44.8% of cases and 19.1% of controls reported having more than 10 partners; P < .001; OR, 4.3).

Intensity of oral sexual exposure, which the authors measured by number of partners per 10 years, was also significantly higher among cases than controls (30.8% vs 11.1%; P < .001; OR, 5.6).

After adjustment for confounders (such as the lifetime number of oral sex partners and tobacco use), ever performing oral sex (adjusted odds ratio [aOR], 4.4), early age of first oral sex encounter (20 years: aOR, 1.8), and oral sex intensity (aOR, 2.8) all remained significantly associated with increased odds of HPV-oropharyngeal cancer.

The type of sexual partner, such as partners who were older (OR, 1.7) and having a partner who engaged in extramarital sex (OR, 1.6), were also associated with increased odds of developing HPV-oropharyngeal cancer. In addition, seropositivity for antibodies to HPV16 E6 (OR, 286) and any HPV16 E protein (E1, E2, E6, E7; OR, 163) were also associated with increased odds of developing the disease.

The study was supported by the National Institute of Dental and Craniofacial Research and the National Institute on Deafness and Other Communication Disorders. Dr. D’Souza and Dr. Califano have disclosed no relevant financial relationships.

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

Compared with the standard 3-week regimen, a 1-week hypofractionated regimen of adjuvant whole-breast radiotherapy had similar efficacy and safety at 5 years of follow-up, according to the U.K. FAST-Forward trial.

The trial was designed to compare the standard regimen (40 Gy in 15 fractions over 3 weeks) with a higher-dose hypofractionated regimen (27 Gy in 5 fractions over 5 days) and a lower-dose hypofractionated regimen (26 Gy in 5 fractions over 5 days) in women who had undergone surgery for early invasive breast cancer.

The 5-year rate of ipsilateral breast tumor relapse was similar with all regimens – 2.1% with the 40-Gy regimen, 1.7% with the 27-Gy regimen, and 1.4% with the 26-Gy regimen. The 26-Gy regimen also had similar safety as the 40-Gy regimen.

These results were presented at the European Society for Radiology and Oncology 2020 Online Congress by Joanne S. Haviland, MSc, of the Institute of Cancer Research in London. Results were also published in The Lancet.

Ms. Haviland said that hypofractionated regimens are attractive because of their shorter overall treatment times, which translate to greater convenience and lower treatment costs.

The historic 5-week regimen (50 Gy in 25 fractions) has been replaced by a 3-week regimen (40 Gy in 15 fractions) in the United Kingdom and elsewhere, and ongoing efforts are exploring whether further hypofractionation can be achieved without compromising efficacy and safety.

“The FAST-Forward trial was the next step on from testing hypofractionated schedules evaluated in earlier trials, including the START trials in the early 2000s and the FAST trial, which published its 10-year results earlier this year,” Ms. Haviland explained.

FAST-Forward enrolled 4,096 women who had undergone breast-conserving surgery or mastectomy for early invasive breast cancer. The patients were randomized into the aforementioned groups for adjuvant whole-breast or chest-wall radiotherapy: 40 Gy in 15 fractions over 3 weeks, 27 Gy in 5 fractions over 5 days, or 26 Gy in 5 fractions over 5 days. Boosts were permitted for all regimens.
 

Relapse, safety, and patient reports

The median follow-up was 6 years. The 5-year rate of ipsilateral breast tumor relapse was 2.1% with the 40-Gy standard regimen, 1.7% with the 27-Gy hypofractionated regimen, and 1.4% with the 26-Gy hypofractionated regimen.

The upper bound of the 95% confidence interval for the difference comparing the hypofractionated regimens against the standard fell well within the 1.6% excess predefined for noninferiority for both the 27-Gy regimen and the 26-Gy regimen (0.9% and 0.3%, respectively).

The hazard ratio for ipsilateral breast tumor relapse, compared with the standard regimen, was 0.86 for the 27-Gy hypofractionated regimen and 0.67 for the 26-Gy hypofractionated regimen.

In terms of safety, the 5-year rate of late adverse effects of the breast or chest wall – distortion, shrinkage, induration, telangiectasia, or edema – rated as “moderate” or “marked” by clinicians was 10% with the standard regimen, 15% with the 27-Gy regimen (relative risk, 1.55 ; P < .001), and 12% with the 26-Gy regimen (RR, 1.19; P = .17).

Over the entire follow-up, women had significantly higher odds of all moderate or marked individual late adverse effects (except discomfort) with the 27-Gy regimen versus the standard regimen, whereas their odds were significantly higher only for induration and edema with the 26-Gy regimen.

However, absolute rates and risk differences between groups were small, Ms. Haviland pointed out. For example, the most common moderate or marked late adverse effect with the standard regimen was breast shrinkage, seen in 5% of patients, followed by discomfort, seen in 4%.

Patient-assessed change in breast appearance and shrinkage did not differ significantly across groups. But women in the 27-Gy group were more likely than peers in the standard regimen group to report a moderate or marked increase in breast hardness/firmness (21% vs. 14%; P = .008), and women in both the 27-Gy and 26-Gy groups were more likely to report moderate or marked breast swelling (5%; P = .007 and 4%; P = .02, respectively, vs. 2%).
 

A new standard

“We have shown noninferiority in terms of local tumor control for both 5-fraction schedules, compared with the control group of 40 Gy in 15 fractions,” Ms. Haviland summarized. “Late adverse effects in normal tissues were similar after 26 Gy in 5 fractions to 40 Gy in 15 fractions, and although rates were higher for the 27-Gy schedule, we noted that these are consistent with the historic standard of 50 Gy in 25 fractions.”

“There are obvious benefits to patients and health care systems of shorter radiotherapy treatments, particularly at the current time, and in fact, the COVID pandemic has accelerated uptake of the 26-Gy schedule around the world,” she added. “At a recent consensus meeting organized by the Royal College of Radiologists, the U.K. adopted the 26-Gy schedule as a new standard, also integrating this with partial breast irradiation, in close collaboration with the U.K. IMPORT Low trial.”

“This is very important work. I think this is one of the most important trials in the past few years. It has really changed practice,” commented session co-chair Ben Slotman, MD, PhD, of Vrije Universiteit Medical Center, Amsterdam, and AMC Amsterdam, who was not involved the trial.

Dr. Slotman wondered how extensive uptake of the new hypofractionated regimen has been. “I know it’s being used in the U.K. and the Netherlands, but do you have any idea about the rest of Europe? What do we need to make it the new standard?”

“I think there has been uptake in other countries in Europe and elsewhere around the world as well,” Ms. Haviland replied. But feedback suggests adoption has been tempered because of reservations related to the regimen’s safety in certain patient subgroups.

“We haven’t found any cause for concern in the subgroups, and also backed up by meta-analysis in the many patients randomized in the START trials,” she noted. “So I think there is very convincing evidence that it is safe as a new standard.”

FAST-Forward was sponsored by the Institute of Cancer Research and funded by the National Institute for Health Research Health Technology Assessment Programme. Ms. Haviland disclosed no conflicts of interest. Dr. Slotman has relationships with ViewRay and Varian Medical Systems.

SOURCE: Haviland J et al. ESTRO 2020, Abstract OC-0610.

Compared with the standard 3-week regimen, a 1-week hypofractionated regimen of adjuvant whole-breast radiotherapy had similar efficacy and safety at 5 years of follow-up, according to the U.K. FAST-Forward trial.

The trial was designed to compare the standard regimen (40 Gy in 15 fractions over 3 weeks) with a higher-dose hypofractionated regimen (27 Gy in 5 fractions over 5 days) and a lower-dose hypofractionated regimen (26 Gy in 5 fractions over 5 days) in women who had undergone surgery for early invasive breast cancer.

The 5-year rate of ipsilateral breast tumor relapse was similar with all regimens – 2.1% with the 40-Gy regimen, 1.7% with the 27-Gy regimen, and 1.4% with the 26-Gy regimen. The 26-Gy regimen also had similar safety as the 40-Gy regimen.

These results were presented at the European Society for Radiology and Oncology 2020 Online Congress by Joanne S. Haviland, MSc, of the Institute of Cancer Research in London. Results were also published in The Lancet.

Ms. Haviland said that hypofractionated regimens are attractive because of their shorter overall treatment times, which translate to greater convenience and lower treatment costs.

The historic 5-week regimen (50 Gy in 25 fractions) has been replaced by a 3-week regimen (40 Gy in 15 fractions) in the United Kingdom and elsewhere, and ongoing efforts are exploring whether further hypofractionation can be achieved without compromising efficacy and safety.

“The FAST-Forward trial was the next step on from testing hypofractionated schedules evaluated in earlier trials, including the START trials in the early 2000s and the FAST trial, which published its 10-year results earlier this year,” Ms. Haviland explained.

FAST-Forward enrolled 4,096 women who had undergone breast-conserving surgery or mastectomy for early invasive breast cancer. The patients were randomized into the aforementioned groups for adjuvant whole-breast or chest-wall radiotherapy: 40 Gy in 15 fractions over 3 weeks, 27 Gy in 5 fractions over 5 days, or 26 Gy in 5 fractions over 5 days. Boosts were permitted for all regimens.
 

Relapse, safety, and patient reports

The median follow-up was 6 years. The 5-year rate of ipsilateral breast tumor relapse was 2.1% with the 40-Gy standard regimen, 1.7% with the 27-Gy hypofractionated regimen, and 1.4% with the 26-Gy hypofractionated regimen.

The upper bound of the 95% confidence interval for the difference comparing the hypofractionated regimens against the standard fell well within the 1.6% excess predefined for noninferiority for both the 27-Gy regimen and the 26-Gy regimen (0.9% and 0.3%, respectively).

The hazard ratio for ipsilateral breast tumor relapse, compared with the standard regimen, was 0.86 for the 27-Gy hypofractionated regimen and 0.67 for the 26-Gy hypofractionated regimen.

In terms of safety, the 5-year rate of late adverse effects of the breast or chest wall – distortion, shrinkage, induration, telangiectasia, or edema – rated as “moderate” or “marked” by clinicians was 10% with the standard regimen, 15% with the 27-Gy regimen (relative risk, 1.55 ; P < .001), and 12% with the 26-Gy regimen (RR, 1.19; P = .17).

Over the entire follow-up, women had significantly higher odds of all moderate or marked individual late adverse effects (except discomfort) with the 27-Gy regimen versus the standard regimen, whereas their odds were significantly higher only for induration and edema with the 26-Gy regimen.

However, absolute rates and risk differences between groups were small, Ms. Haviland pointed out. For example, the most common moderate or marked late adverse effect with the standard regimen was breast shrinkage, seen in 5% of patients, followed by discomfort, seen in 4%.

Patient-assessed change in breast appearance and shrinkage did not differ significantly across groups. But women in the 27-Gy group were more likely than peers in the standard regimen group to report a moderate or marked increase in breast hardness/firmness (21% vs. 14%; P = .008), and women in both the 27-Gy and 26-Gy groups were more likely to report moderate or marked breast swelling (5%; P = .007 and 4%; P = .02, respectively, vs. 2%).
 

A new standard

“We have shown noninferiority in terms of local tumor control for both 5-fraction schedules, compared with the control group of 40 Gy in 15 fractions,” Ms. Haviland summarized. “Late adverse effects in normal tissues were similar after 26 Gy in 5 fractions to 40 Gy in 15 fractions, and although rates were higher for the 27-Gy schedule, we noted that these are consistent with the historic standard of 50 Gy in 25 fractions.”

“There are obvious benefits to patients and health care systems of shorter radiotherapy treatments, particularly at the current time, and in fact, the COVID pandemic has accelerated uptake of the 26-Gy schedule around the world,” she added. “At a recent consensus meeting organized by the Royal College of Radiologists, the U.K. adopted the 26-Gy schedule as a new standard, also integrating this with partial breast irradiation, in close collaboration with the U.K. IMPORT Low trial.”

“This is very important work. I think this is one of the most important trials in the past few years. It has really changed practice,” commented session co-chair Ben Slotman, MD, PhD, of Vrije Universiteit Medical Center, Amsterdam, and AMC Amsterdam, who was not involved the trial.

Dr. Slotman wondered how extensive uptake of the new hypofractionated regimen has been. “I know it’s being used in the U.K. and the Netherlands, but do you have any idea about the rest of Europe? What do we need to make it the new standard?”

“I think there has been uptake in other countries in Europe and elsewhere around the world as well,” Ms. Haviland replied. But feedback suggests adoption has been tempered because of reservations related to the regimen’s safety in certain patient subgroups.

“We haven’t found any cause for concern in the subgroups, and also backed up by meta-analysis in the many patients randomized in the START trials,” she noted. “So I think there is very convincing evidence that it is safe as a new standard.”

FAST-Forward was sponsored by the Institute of Cancer Research and funded by the National Institute for Health Research Health Technology Assessment Programme. Ms. Haviland disclosed no conflicts of interest. Dr. Slotman has relationships with ViewRay and Varian Medical Systems.

SOURCE: Haviland J et al. ESTRO 2020, Abstract OC-0610.

Compared with the standard 3-week regimen, a 1-week hypofractionated regimen of adjuvant whole-breast radiotherapy had similar efficacy and safety at 5 years of follow-up, according to the U.K. FAST-Forward trial.

The trial was designed to compare the standard regimen (40 Gy in 15 fractions over 3 weeks) with a higher-dose hypofractionated regimen (27 Gy in 5 fractions over 5 days) and a lower-dose hypofractionated regimen (26 Gy in 5 fractions over 5 days) in women who had undergone surgery for early invasive breast cancer.

The 5-year rate of ipsilateral breast tumor relapse was similar with all regimens – 2.1% with the 40-Gy regimen, 1.7% with the 27-Gy regimen, and 1.4% with the 26-Gy regimen. The 26-Gy regimen also had similar safety as the 40-Gy regimen.

These results were presented at the European Society for Radiology and Oncology 2020 Online Congress by Joanne S. Haviland, MSc, of the Institute of Cancer Research in London. Results were also published in The Lancet.

Ms. Haviland said that hypofractionated regimens are attractive because of their shorter overall treatment times, which translate to greater convenience and lower treatment costs.

The historic 5-week regimen (50 Gy in 25 fractions) has been replaced by a 3-week regimen (40 Gy in 15 fractions) in the United Kingdom and elsewhere, and ongoing efforts are exploring whether further hypofractionation can be achieved without compromising efficacy and safety.

“The FAST-Forward trial was the next step on from testing hypofractionated schedules evaluated in earlier trials, including the START trials in the early 2000s and the FAST trial, which published its 10-year results earlier this year,” Ms. Haviland explained.

FAST-Forward enrolled 4,096 women who had undergone breast-conserving surgery or mastectomy for early invasive breast cancer. The patients were randomized into the aforementioned groups for adjuvant whole-breast or chest-wall radiotherapy: 40 Gy in 15 fractions over 3 weeks, 27 Gy in 5 fractions over 5 days, or 26 Gy in 5 fractions over 5 days. Boosts were permitted for all regimens.
 

Relapse, safety, and patient reports

The median follow-up was 6 years. The 5-year rate of ipsilateral breast tumor relapse was 2.1% with the 40-Gy standard regimen, 1.7% with the 27-Gy hypofractionated regimen, and 1.4% with the 26-Gy hypofractionated regimen.

The upper bound of the 95% confidence interval for the difference comparing the hypofractionated regimens against the standard fell well within the 1.6% excess predefined for noninferiority for both the 27-Gy regimen and the 26-Gy regimen (0.9% and 0.3%, respectively).

The hazard ratio for ipsilateral breast tumor relapse, compared with the standard regimen, was 0.86 for the 27-Gy hypofractionated regimen and 0.67 for the 26-Gy hypofractionated regimen.

In terms of safety, the 5-year rate of late adverse effects of the breast or chest wall – distortion, shrinkage, induration, telangiectasia, or edema – rated as “moderate” or “marked” by clinicians was 10% with the standard regimen, 15% with the 27-Gy regimen (relative risk, 1.55 ; P < .001), and 12% with the 26-Gy regimen (RR, 1.19; P = .17).

Over the entire follow-up, women had significantly higher odds of all moderate or marked individual late adverse effects (except discomfort) with the 27-Gy regimen versus the standard regimen, whereas their odds were significantly higher only for induration and edema with the 26-Gy regimen.

However, absolute rates and risk differences between groups were small, Ms. Haviland pointed out. For example, the most common moderate or marked late adverse effect with the standard regimen was breast shrinkage, seen in 5% of patients, followed by discomfort, seen in 4%.

Patient-assessed change in breast appearance and shrinkage did not differ significantly across groups. But women in the 27-Gy group were more likely than peers in the standard regimen group to report a moderate or marked increase in breast hardness/firmness (21% vs. 14%; P = .008), and women in both the 27-Gy and 26-Gy groups were more likely to report moderate or marked breast swelling (5%; P = .007 and 4%; P = .02, respectively, vs. 2%).
 

A new standard

“We have shown noninferiority in terms of local tumor control for both 5-fraction schedules, compared with the control group of 40 Gy in 15 fractions,” Ms. Haviland summarized. “Late adverse effects in normal tissues were similar after 26 Gy in 5 fractions to 40 Gy in 15 fractions, and although rates were higher for the 27-Gy schedule, we noted that these are consistent with the historic standard of 50 Gy in 25 fractions.”

“There are obvious benefits to patients and health care systems of shorter radiotherapy treatments, particularly at the current time, and in fact, the COVID pandemic has accelerated uptake of the 26-Gy schedule around the world,” she added. “At a recent consensus meeting organized by the Royal College of Radiologists, the U.K. adopted the 26-Gy schedule as a new standard, also integrating this with partial breast irradiation, in close collaboration with the U.K. IMPORT Low trial.”

“This is very important work. I think this is one of the most important trials in the past few years. It has really changed practice,” commented session co-chair Ben Slotman, MD, PhD, of Vrije Universiteit Medical Center, Amsterdam, and AMC Amsterdam, who was not involved the trial.

Dr. Slotman wondered how extensive uptake of the new hypofractionated regimen has been. “I know it’s being used in the U.K. and the Netherlands, but do you have any idea about the rest of Europe? What do we need to make it the new standard?”

“I think there has been uptake in other countries in Europe and elsewhere around the world as well,” Ms. Haviland replied. But feedback suggests adoption has been tempered because of reservations related to the regimen’s safety in certain patient subgroups.

“We haven’t found any cause for concern in the subgroups, and also backed up by meta-analysis in the many patients randomized in the START trials,” she noted. “So I think there is very convincing evidence that it is safe as a new standard.”

FAST-Forward was sponsored by the Institute of Cancer Research and funded by the National Institute for Health Research Health Technology Assessment Programme. Ms. Haviland disclosed no conflicts of interest. Dr. Slotman has relationships with ViewRay and Varian Medical Systems.

SOURCE: Haviland J et al. ESTRO 2020, Abstract OC-0610.

Aspirin “rescued” a cystic intestinal phenotype driven by the Wnt pathway, reduced stem cell expression and function, and increased the expression of Dickkopf (DKK)–1, a Wnt antagonist that is frequently lost as colorectal cancer (CRC) progresses, according to recent study findings.

“Dysregulated Wnt signaling, [which is] primarily driven by adenomatous polyposis coli (APC) gene mutations, is fundamental to cancer initiation in both sporadic CRC and familial adenomatous polyposis (FAP). ... Our observations reveal a novel mechanism of aspirin-mediated Wnt inhibition through DKK-1 increase and potential ‘pheno-markers’ for chemoprevention and adjuvant aspirin human trials,” wrote Karen Dunbar, PhD, and her associates in Cellular and Molecular Gastroenterology and Hepatology.

Aspirin shows benefits in sporadic and familial adenoma, significantly reduces CRC incidence, and may delay disease progression while improving survival. “Understanding the biology responsible for this protective effect is key to developing biomarker-led approaches for rational clinical use,” wrote Dr. Dunbar, now with the University of Dundee (Scotland) and colleagues.

She and her coinvestigators found that aspirin promoted the wild-type (budding, noncystic) phenotype in intestinal organoids derived from APC-deficient mice and humans with FAP. They saw the same effect in live APC-deficient mice. With the help of an RNAscope, they confirmed that aspirin significantly reduced RNA transcripts for Lgr5 and TROY, which are stem cell markers in CRC. Aspirin also reduced Lgr5 expression in APC-deficient mice and in human organoids derived from normal colonic mucosa, sporadic colorectal tumors, and colorectal tumors from patients with FAP.

In wound-closure models, aspirin inhibited Wnt and epithelial-mesenchymal transition (EMT) while decreasing migration and invasion by colorectal cancer cells. Aspirin accomplished this by increasing the phosphorylation of GSK-3beta and beta-catenin. Notably, aspirin increased the production of E-cadherin, which buffers excess beta-catenin and thereby limits overactivated Wnt to promote an epithelial, rather than mesenchymal, phenotype. “The novel observation that the aspirin-mediated E-cadherin increase is paralleled by greater E-cadherin–beta-catenin binding further supports the hypothesis that aspirin promotes an epithelial phenotype through Wnt inhibition,” the researchers wrote.

In colorectal cells and FAP organoids, aspirin also increased the expression of the Wnt antagonist DKK-1, which in turn correlated with lower stem cell function. “In humans, high serum DKK-1 correlates with increasing colorectal cancer stage, whereas tissue DKK-1 expression is lost with cancer progression,” the researchers explained. “Here, we demonstrate that aspirin robustly increases DKK-1 expression in CRC models, which contributes to EMT and [cancer stem cell] inhibition observed with aspirin.”

Taken together, the findings “highlight two novel phenotypic indicators of aspirin response, the cystic-phenotype rescue and reduced stem cell marker expression, which may serve as enhanced biomarkers, compared with individual Wnt components,” they concluded. “Through targeting Wnt signaling at multiple levels, aspirin enhances commitment to differentiation, and hence, phenotypic markers of Wnt inhibition represent better targets [for] therapeutic exploitation.”

Dr. Dunbar and her associates reported having no relevant conflicts of interest. The work was supported by Cancer Research UK and the Chief Scientist Office of Scotland, the MRC Centre, and the CRUK.

SOURCE: Dunbar K et al. Cell Mol Gastroenterol Hepatol. 2020 Sep 21. doi: 10.1016/j.jcmgh.2020.09.010.

Aspirin “rescued” a cystic intestinal phenotype driven by the Wnt pathway, reduced stem cell expression and function, and increased the expression of Dickkopf (DKK)–1, a Wnt antagonist that is frequently lost as colorectal cancer (CRC) progresses, according to recent study findings.

“Dysregulated Wnt signaling, [which is] primarily driven by adenomatous polyposis coli (APC) gene mutations, is fundamental to cancer initiation in both sporadic CRC and familial adenomatous polyposis (FAP). ... Our observations reveal a novel mechanism of aspirin-mediated Wnt inhibition through DKK-1 increase and potential ‘pheno-markers’ for chemoprevention and adjuvant aspirin human trials,” wrote Karen Dunbar, PhD, and her associates in Cellular and Molecular Gastroenterology and Hepatology.

Aspirin shows benefits in sporadic and familial adenoma, significantly reduces CRC incidence, and may delay disease progression while improving survival. “Understanding the biology responsible for this protective effect is key to developing biomarker-led approaches for rational clinical use,” wrote Dr. Dunbar, now with the University of Dundee (Scotland) and colleagues.

She and her coinvestigators found that aspirin promoted the wild-type (budding, noncystic) phenotype in intestinal organoids derived from APC-deficient mice and humans with FAP. They saw the same effect in live APC-deficient mice. With the help of an RNAscope, they confirmed that aspirin significantly reduced RNA transcripts for Lgr5 and TROY, which are stem cell markers in CRC. Aspirin also reduced Lgr5 expression in APC-deficient mice and in human organoids derived from normal colonic mucosa, sporadic colorectal tumors, and colorectal tumors from patients with FAP.

In wound-closure models, aspirin inhibited Wnt and epithelial-mesenchymal transition (EMT) while decreasing migration and invasion by colorectal cancer cells. Aspirin accomplished this by increasing the phosphorylation of GSK-3beta and beta-catenin. Notably, aspirin increased the production of E-cadherin, which buffers excess beta-catenin and thereby limits overactivated Wnt to promote an epithelial, rather than mesenchymal, phenotype. “The novel observation that the aspirin-mediated E-cadherin increase is paralleled by greater E-cadherin–beta-catenin binding further supports the hypothesis that aspirin promotes an epithelial phenotype through Wnt inhibition,” the researchers wrote.

In colorectal cells and FAP organoids, aspirin also increased the expression of the Wnt antagonist DKK-1, which in turn correlated with lower stem cell function. “In humans, high serum DKK-1 correlates with increasing colorectal cancer stage, whereas tissue DKK-1 expression is lost with cancer progression,” the researchers explained. “Here, we demonstrate that aspirin robustly increases DKK-1 expression in CRC models, which contributes to EMT and [cancer stem cell] inhibition observed with aspirin.”

Taken together, the findings “highlight two novel phenotypic indicators of aspirin response, the cystic-phenotype rescue and reduced stem cell marker expression, which may serve as enhanced biomarkers, compared with individual Wnt components,” they concluded. “Through targeting Wnt signaling at multiple levels, aspirin enhances commitment to differentiation, and hence, phenotypic markers of Wnt inhibition represent better targets [for] therapeutic exploitation.”

Dr. Dunbar and her associates reported having no relevant conflicts of interest. The work was supported by Cancer Research UK and the Chief Scientist Office of Scotland, the MRC Centre, and the CRUK.

SOURCE: Dunbar K et al. Cell Mol Gastroenterol Hepatol. 2020 Sep 21. doi: 10.1016/j.jcmgh.2020.09.010.

Aspirin “rescued” a cystic intestinal phenotype driven by the Wnt pathway, reduced stem cell expression and function, and increased the expression of Dickkopf (DKK)–1, a Wnt antagonist that is frequently lost as colorectal cancer (CRC) progresses, according to recent study findings.

“Dysregulated Wnt signaling, [which is] primarily driven by adenomatous polyposis coli (APC) gene mutations, is fundamental to cancer initiation in both sporadic CRC and familial adenomatous polyposis (FAP). ... Our observations reveal a novel mechanism of aspirin-mediated Wnt inhibition through DKK-1 increase and potential ‘pheno-markers’ for chemoprevention and adjuvant aspirin human trials,” wrote Karen Dunbar, PhD, and her associates in Cellular and Molecular Gastroenterology and Hepatology.

Aspirin shows benefits in sporadic and familial adenoma, significantly reduces CRC incidence, and may delay disease progression while improving survival. “Understanding the biology responsible for this protective effect is key to developing biomarker-led approaches for rational clinical use,” wrote Dr. Dunbar, now with the University of Dundee (Scotland) and colleagues.

She and her coinvestigators found that aspirin promoted the wild-type (budding, noncystic) phenotype in intestinal organoids derived from APC-deficient mice and humans with FAP. They saw the same effect in live APC-deficient mice. With the help of an RNAscope, they confirmed that aspirin significantly reduced RNA transcripts for Lgr5 and TROY, which are stem cell markers in CRC. Aspirin also reduced Lgr5 expression in APC-deficient mice and in human organoids derived from normal colonic mucosa, sporadic colorectal tumors, and colorectal tumors from patients with FAP.

In wound-closure models, aspirin inhibited Wnt and epithelial-mesenchymal transition (EMT) while decreasing migration and invasion by colorectal cancer cells. Aspirin accomplished this by increasing the phosphorylation of GSK-3beta and beta-catenin. Notably, aspirin increased the production of E-cadherin, which buffers excess beta-catenin and thereby limits overactivated Wnt to promote an epithelial, rather than mesenchymal, phenotype. “The novel observation that the aspirin-mediated E-cadherin increase is paralleled by greater E-cadherin–beta-catenin binding further supports the hypothesis that aspirin promotes an epithelial phenotype through Wnt inhibition,” the researchers wrote.

In colorectal cells and FAP organoids, aspirin also increased the expression of the Wnt antagonist DKK-1, which in turn correlated with lower stem cell function. “In humans, high serum DKK-1 correlates with increasing colorectal cancer stage, whereas tissue DKK-1 expression is lost with cancer progression,” the researchers explained. “Here, we demonstrate that aspirin robustly increases DKK-1 expression in CRC models, which contributes to EMT and [cancer stem cell] inhibition observed with aspirin.”

Taken together, the findings “highlight two novel phenotypic indicators of aspirin response, the cystic-phenotype rescue and reduced stem cell marker expression, which may serve as enhanced biomarkers, compared with individual Wnt components,” they concluded. “Through targeting Wnt signaling at multiple levels, aspirin enhances commitment to differentiation, and hence, phenotypic markers of Wnt inhibition represent better targets [for] therapeutic exploitation.”

Dr. Dunbar and her associates reported having no relevant conflicts of interest. The work was supported by Cancer Research UK and the Chief Scientist Office of Scotland, the MRC Centre, and the CRUK.

SOURCE: Dunbar K et al. Cell Mol Gastroenterol Hepatol. 2020 Sep 21. doi: 10.1016/j.jcmgh.2020.09.010.

Patients will soon be able to read the notes that physicians make during an episode of care, as well as information about diagnostic testing and imaging results, tests for STDs, fetal ultrasounds, and cancer biopsies. This open access is raising concerns among physicians.

As part of the 21st Century Cures Act, patients have the right to see their medical notes. Known as Open Notes, the policy will go into effect on April 5, 2021. The Department of Health & Human Services recently changed the original start date, which was to be Nov. 2, 2020.

The mandate has some physicians worrying about potential legal risks and possible violation of doctor-patient confidentiality. When asked to share their views on the new Open Notes mandate, many physicians expressed their concerns but also cited some of the positive effects that could come from this.
 

Potentially more legal woes for physicians?

A key concern raised by one physician commenter is that patients could misunderstand legitimate medical terminology or even put a physician in legal crosshairs. For example, a medical term such as “spontaneous abortion” could be misconstrued by patients. A physician might write notes with the idea that a patient is reading them and thus might alter those notes in a way that creates legal trouble.

“This layers another level of censorship and legal liability onto physicians, who in attempting to be [politically correct], may omit critical information or have to use euphemisms in order to avoid conflict,” one physician said.

She also questioned whether notes might now have to be run through legal counsel before being posted to avoid potential liability.

Another doctor questioned how physicians would be able to document patients suspected of faking injuries for pain medication, for example. Could such documentation lead to lawsuits for the doctor?

As one physician noted, some patients “are drug seekers. Some refuse to aid in their own care. Some are malingerers. Not documenting that is bad medicine.”

The possibility of violating doctor-patient confidentiality laws, particularly for teenagers, could be another negative effect of Open Notes, said one physician.

“Won’t this violate the statutes that teenagers have the right to confidential evaluations?” the commenter mused. “If charts are to be immediately available, then STDs and pregnancies they weren’t ready to talk about will now be suddenly known by their parents.”

One doctor has already faced this issue. “I already ran into this problem once,” he noted. “Now I warn those on their parents’ insurance before I start the visit. I have literally had a patient state, ‘well then we are done,’ and leave without being seen due to it.”

Another physician questioned the possibility of having to write notes differently than they do now, especially if the patients have lower reading comprehension abilities.

One physician who uses Open Notes said he receives patient requests for changes that have little to do with the actual diagnosis and relate to ancillary issues. He highlighted patients who “don’t want psych diagnosis in their chart or are concerned a diagnosis will raise their insurance premium, so they ask me to delete it.”
 

Will Open Notes erode patient communication?

One physician questioned whether it would lead to patients being less open and forthcoming about their medical concerns with doctors.

“The main problem I see is the patient not telling me the whole story, or worse, telling me the story, and then asking me not to document it (as many have done in the past) because they don’t want their spouse, family, etc. to read the notes and they have already given their permission for them to do so, for a variety of reasons,” he commented. “This includes topics of STDs, infidelity, depression, suicidal thoughts, and other symptoms the patient doesn’t want their family to read about.”
 

Some physicians envision positive developments

Many physicians are unconcerned by the new mandate. “I see some potential good in this, such as improving doctor-patient communication and more scrupulous charting,” one physician said.

A doctor working in the U.S. federal health care system noted that open access has been a part of that system for decades.

“Since health care providers work in this unveiled setting for their entire career, they usually know how to write appropriate clinical notes and what information needs to be included in them,” he wrote. “Now it’s time for the rest of the medical community to catch up to a reality that we have worked within for decades now.

“The world did not end, malpractice complaints did not increase, and physician/patient relationships were not damaged. Living in the information age, archaic practices like private notes were surely going to end at some point.”

One doctor who has been using Open Notes has had experiences in which the patient noted an error in the medical chart that needed correcting. “I have had one patient correct me on a timeline in the HPI which was helpful and I made the requested correction in that instance,” he said.

Another physician agreed. “I’ve had patients add or correct valuable information I’ve missed. Good probably outweighs the bad if we set limits on behaviors expressed by the personality disordered group. The majority of people don’t seem to care and still ask me ‘what would you do’ or ‘tell me what to do.’ It’s all about patient/physician trust.”

Another talked about how Open Notes should have little or no impact. “Here’s a novel concept – talking to our patients,” he commented. “There is nothing in every one of my chart notes that has not already been discussed with my patients and I dictate (speech to text) my findings and plan in front of them. So, if they are reviewing my office notes, it will only serve to reinforce what we have already discussed.”

“I don’t intend to change anything,” he added. “Chances are if they were to see a test result before I have a chance to discuss it with them, they will have already ‘Googled’ its meaning and we can have more meaningful interaction if they have a basic understanding of the test.”

“I understand that this is anxiety provoking, but in general I think it is appropriate for patients to have access to their notes,” said another physician. “If physicians write lousy notes that say they did things they didn’t do, that fail to actually state a diagnosis and a plan (and they often do), that is the doc’s problem, not the patient’s.”

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

Patients will soon be able to read the notes that physicians make during an episode of care, as well as information about diagnostic testing and imaging results, tests for STDs, fetal ultrasounds, and cancer biopsies. This open access is raising concerns among physicians.

As part of the 21st Century Cures Act, patients have the right to see their medical notes. Known as Open Notes, the policy will go into effect on April 5, 2021. The Department of Health & Human Services recently changed the original start date, which was to be Nov. 2, 2020.

The mandate has some physicians worrying about potential legal risks and possible violation of doctor-patient confidentiality. When asked to share their views on the new Open Notes mandate, many physicians expressed their concerns but also cited some of the positive effects that could come from this.
 

Potentially more legal woes for physicians?

A key concern raised by one physician commenter is that patients could misunderstand legitimate medical terminology or even put a physician in legal crosshairs. For example, a medical term such as “spontaneous abortion” could be misconstrued by patients. A physician might write notes with the idea that a patient is reading them and thus might alter those notes in a way that creates legal trouble.

“This layers another level of censorship and legal liability onto physicians, who in attempting to be [politically correct], may omit critical information or have to use euphemisms in order to avoid conflict,” one physician said.

She also questioned whether notes might now have to be run through legal counsel before being posted to avoid potential liability.

Another doctor questioned how physicians would be able to document patients suspected of faking injuries for pain medication, for example. Could such documentation lead to lawsuits for the doctor?

As one physician noted, some patients “are drug seekers. Some refuse to aid in their own care. Some are malingerers. Not documenting that is bad medicine.”

The possibility of violating doctor-patient confidentiality laws, particularly for teenagers, could be another negative effect of Open Notes, said one physician.

“Won’t this violate the statutes that teenagers have the right to confidential evaluations?” the commenter mused. “If charts are to be immediately available, then STDs and pregnancies they weren’t ready to talk about will now be suddenly known by their parents.”

One doctor has already faced this issue. “I already ran into this problem once,” he noted. “Now I warn those on their parents’ insurance before I start the visit. I have literally had a patient state, ‘well then we are done,’ and leave without being seen due to it.”

Another physician questioned the possibility of having to write notes differently than they do now, especially if the patients have lower reading comprehension abilities.

One physician who uses Open Notes said he receives patient requests for changes that have little to do with the actual diagnosis and relate to ancillary issues. He highlighted patients who “don’t want psych diagnosis in their chart or are concerned a diagnosis will raise their insurance premium, so they ask me to delete it.”
 

Will Open Notes erode patient communication?

One physician questioned whether it would lead to patients being less open and forthcoming about their medical concerns with doctors.

“The main problem I see is the patient not telling me the whole story, or worse, telling me the story, and then asking me not to document it (as many have done in the past) because they don’t want their spouse, family, etc. to read the notes and they have already given their permission for them to do so, for a variety of reasons,” he commented. “This includes topics of STDs, infidelity, depression, suicidal thoughts, and other symptoms the patient doesn’t want their family to read about.”
 

Some physicians envision positive developments

Many physicians are unconcerned by the new mandate. “I see some potential good in this, such as improving doctor-patient communication and more scrupulous charting,” one physician said.

A doctor working in the U.S. federal health care system noted that open access has been a part of that system for decades.

“Since health care providers work in this unveiled setting for their entire career, they usually know how to write appropriate clinical notes and what information needs to be included in them,” he wrote. “Now it’s time for the rest of the medical community to catch up to a reality that we have worked within for decades now.

“The world did not end, malpractice complaints did not increase, and physician/patient relationships were not damaged. Living in the information age, archaic practices like private notes were surely going to end at some point.”

One doctor who has been using Open Notes has had experiences in which the patient noted an error in the medical chart that needed correcting. “I have had one patient correct me on a timeline in the HPI which was helpful and I made the requested correction in that instance,” he said.

Another physician agreed. “I’ve had patients add or correct valuable information I’ve missed. Good probably outweighs the bad if we set limits on behaviors expressed by the personality disordered group. The majority of people don’t seem to care and still ask me ‘what would you do’ or ‘tell me what to do.’ It’s all about patient/physician trust.”

Another talked about how Open Notes should have little or no impact. “Here’s a novel concept – talking to our patients,” he commented. “There is nothing in every one of my chart notes that has not already been discussed with my patients and I dictate (speech to text) my findings and plan in front of them. So, if they are reviewing my office notes, it will only serve to reinforce what we have already discussed.”

“I don’t intend to change anything,” he added. “Chances are if they were to see a test result before I have a chance to discuss it with them, they will have already ‘Googled’ its meaning and we can have more meaningful interaction if they have a basic understanding of the test.”

“I understand that this is anxiety provoking, but in general I think it is appropriate for patients to have access to their notes,” said another physician. “If physicians write lousy notes that say they did things they didn’t do, that fail to actually state a diagnosis and a plan (and they often do), that is the doc’s problem, not the patient’s.”

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

Patients will soon be able to read the notes that physicians make during an episode of care, as well as information about diagnostic testing and imaging results, tests for STDs, fetal ultrasounds, and cancer biopsies. This open access is raising concerns among physicians.

As part of the 21st Century Cures Act, patients have the right to see their medical notes. Known as Open Notes, the policy will go into effect on April 5, 2021. The Department of Health & Human Services recently changed the original start date, which was to be Nov. 2, 2020.

The mandate has some physicians worrying about potential legal risks and possible violation of doctor-patient confidentiality. When asked to share their views on the new Open Notes mandate, many physicians expressed their concerns but also cited some of the positive effects that could come from this.
 

Potentially more legal woes for physicians?

A key concern raised by one physician commenter is that patients could misunderstand legitimate medical terminology or even put a physician in legal crosshairs. For example, a medical term such as “spontaneous abortion” could be misconstrued by patients. A physician might write notes with the idea that a patient is reading them and thus might alter those notes in a way that creates legal trouble.

“This layers another level of censorship and legal liability onto physicians, who in attempting to be [politically correct], may omit critical information or have to use euphemisms in order to avoid conflict,” one physician said.

She also questioned whether notes might now have to be run through legal counsel before being posted to avoid potential liability.

Another doctor questioned how physicians would be able to document patients suspected of faking injuries for pain medication, for example. Could such documentation lead to lawsuits for the doctor?

As one physician noted, some patients “are drug seekers. Some refuse to aid in their own care. Some are malingerers. Not documenting that is bad medicine.”

The possibility of violating doctor-patient confidentiality laws, particularly for teenagers, could be another negative effect of Open Notes, said one physician.

“Won’t this violate the statutes that teenagers have the right to confidential evaluations?” the commenter mused. “If charts are to be immediately available, then STDs and pregnancies they weren’t ready to talk about will now be suddenly known by their parents.”

One doctor has already faced this issue. “I already ran into this problem once,” he noted. “Now I warn those on their parents’ insurance before I start the visit. I have literally had a patient state, ‘well then we are done,’ and leave without being seen due to it.”

Another physician questioned the possibility of having to write notes differently than they do now, especially if the patients have lower reading comprehension abilities.

One physician who uses Open Notes said he receives patient requests for changes that have little to do with the actual diagnosis and relate to ancillary issues. He highlighted patients who “don’t want psych diagnosis in their chart or are concerned a diagnosis will raise their insurance premium, so they ask me to delete it.”
 

Will Open Notes erode patient communication?

One physician questioned whether it would lead to patients being less open and forthcoming about their medical concerns with doctors.

“The main problem I see is the patient not telling me the whole story, or worse, telling me the story, and then asking me not to document it (as many have done in the past) because they don’t want their spouse, family, etc. to read the notes and they have already given their permission for them to do so, for a variety of reasons,” he commented. “This includes topics of STDs, infidelity, depression, suicidal thoughts, and other symptoms the patient doesn’t want their family to read about.”
 

Some physicians envision positive developments

Many physicians are unconcerned by the new mandate. “I see some potential good in this, such as improving doctor-patient communication and more scrupulous charting,” one physician said.

A doctor working in the U.S. federal health care system noted that open access has been a part of that system for decades.

“Since health care providers work in this unveiled setting for their entire career, they usually know how to write appropriate clinical notes and what information needs to be included in them,” he wrote. “Now it’s time for the rest of the medical community to catch up to a reality that we have worked within for decades now.

“The world did not end, malpractice complaints did not increase, and physician/patient relationships were not damaged. Living in the information age, archaic practices like private notes were surely going to end at some point.”

One doctor who has been using Open Notes has had experiences in which the patient noted an error in the medical chart that needed correcting. “I have had one patient correct me on a timeline in the HPI which was helpful and I made the requested correction in that instance,” he said.

Another physician agreed. “I’ve had patients add or correct valuable information I’ve missed. Good probably outweighs the bad if we set limits on behaviors expressed by the personality disordered group. The majority of people don’t seem to care and still ask me ‘what would you do’ or ‘tell me what to do.’ It’s all about patient/physician trust.”

Another talked about how Open Notes should have little or no impact. “Here’s a novel concept – talking to our patients,” he commented. “There is nothing in every one of my chart notes that has not already been discussed with my patients and I dictate (speech to text) my findings and plan in front of them. So, if they are reviewing my office notes, it will only serve to reinforce what we have already discussed.”

“I don’t intend to change anything,” he added. “Chances are if they were to see a test result before I have a chance to discuss it with them, they will have already ‘Googled’ its meaning and we can have more meaningful interaction if they have a basic understanding of the test.”

“I understand that this is anxiety provoking, but in general I think it is appropriate for patients to have access to their notes,” said another physician. “If physicians write lousy notes that say they did things they didn’t do, that fail to actually state a diagnosis and a plan (and they often do), that is the doc’s problem, not the patient’s.”

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

When the long-awaited news of a Food and Drug Administration–approved vaccine came on Dec. 11, 2020, my first thought was that I would wait. I can manage a few more months of Zooming for work, my household is down to two people, I’m not at high risk of dying from COVID, and my husband is not going to be vaccinated any time soon, so a change in my status wouldn’t “free” me. I would rather have “my” vaccine go to a 70-year-old ICU janitor or a bus driver.

South_agency/Getty Images

The weeks have gone by. I expected there would be kinks, but it has now been a month – one in which COVID rates have soared, and hospitalizations and deaths have risen to unmanageable numbers in some places. Still, vaccines remain in freezers – people are dying while vials of prevention sit unused. I began to think that, when my “turn” came, the better thing was to be vaccinated. We need to have a large segment of the population vaccinated to squelch this virus, and it’s become much less clear to me that, if I yield my turn, it will go into the arm of a bus driver. The process has not been fair, and there are moments of media outrage when one group gets vaccinated before another, so perhaps we have reached point where the goal should not be to get the vaccine into the exact right person in the exact right order, but to get the vaccine into arms according to the protocol that has already been set. Anyone who does not end up in a hospital bed is doing the system a favor.

Mahmood Jahromi, MD, a psychiatrist in private practice in Towson, Md., described the process of vaccination as being similar to a bottleneck traffic jam. “Yes, one must be courteous to the car trying to but in, but no, don’t jam the glue because you are excessively kind. Let the traffic police do their job. When your name is called, go ahead and take it. The system needs to know people are accepting the vaccine, not by begging the authorities to be called ahead of others, but with respect for what is already designed.”

On Friday, Jan. 8, I received information on how to get vaccinated – it seems my “turn” has arrived. An email from the board of physicians informed me that I am in the “1A” category and included a link to sign up for a vaccine in Baltimore – vaccinations would be given until Jan. 29, Mondays to Thursdays from 10 a.m. to 4 p.m. and Fridays from 10 a.m. to 1 p.m. There are no weekend or evening hours, and one might think there would be enough urgency to call for this. The Maryland Psychiatric Society sent out a notice that Sheppard Pratt would be offering vaccines to all behavioral health providers in the state of Maryland during a 2-day clinic. I heard from others that health care workers can now get vaccinated at the Cow Palace (how great is that?) at the Maryland State Fairgrounds and another link was sent for those in Howard County, between Baltimore and Washington.

As I discussed this with colleagues, a couple of issues came up – the most common was one of not wanting to get the vaccine yet because there are others who need it more. Others voiced concern about a vaccine where the long-term effects remain unknown: Is this vaccine safe, might it spur autoimmune problems in the months or years to come? Is it safe for women who plan to become pregnant? Some have insisted it is safe. They say “follow the science” and have dismissed the skepticism. To my read, it makes perfect sense to be wary, but COVID spreads silently and it kills.

With a vaccine where so many are reluctant to get it, including many health care workers, Sue Kim, MD, a psychiatrist in private practice in Lutherville, Md., noted that she has concerns about the safety of the vaccine. “Getting it now is both altruistic and selfish, but letting others go first is also altruistic and selfish. In the meantime, if I get sick, I was too smart for my own good. How do you weigh this ethically?”

My personal feelings have been influenced by a few things. An article in the New York Times highlighted how New York City vaccinated 5 million people for smallpox in just 2 weeks in 1947. I am frustrated knowing that, a month after approval of the first vaccine, only 7 million people have received it in the entire United States. In that time period, millions have contracted COVID and thousands have died. Closer to home, a 45-year-old psychiatrist in Maryland died of COVID, and I have heard more stories about younger people with long-haul neurologic and vascular symptoms. The risk of COVID is feeling higher than it did, and the fact that the first vaccine was authorized after the election somehow makes me feel that it might be safer. Had it been approved right before, I would have worried – perhaps wrongly – that the authorization was a political maneuver, not one based on science.

As we think about what is best for ourselves, our families, our patients, and society as a whole, I believe that those who want the vaccine but don’t feel they should take their place in line before others who are higher risk must ask if it makes sense to wait. Each state is different. While Houston Methodist Hospital is reportedly giving its health care workers a $500 bonus to get the vaccine, Gov. Andrew Cuomo of New York announced that hospitals would be fined $100,000 if they don’t use all of their vaccines within 7 days of receipt and $1 million if they vaccinate anyone out of order. Gov. Cuomo later broadened who could be vaccinated to prevent wasting the vaccine, but there remains an element of being damned if you do and damned if you don’t.

Paul Nestadt, MD, a psychiatrist at Johns Hopkins University, Baltimore, noted that one distribution site initially had to waste unused vaccine when people did not come for their appointments. A waiting list was created for people who could come right away if called to prevent this waste. “To me, this only highlighted that the tier system, while a good idea, does not need to be written in stone. The goal needs to be getting shots in arms, building herd immunity. If there are two arms in front of you, shoot the health care worker or those who are vulnerable. But if there is a healthy arm in reach, it should get any shot made available.”

I registered to be vaccinated. Maryland is still vaccinating only health care workers and people in long-term care facilities – senior citizens and essential workers are not yet eligible. In Baltimore, vaccinations are available Mondays to Thursdays from 10 a.m. to 4 p.m. and on Fridays from 10 a.m. to 1 p.m. There are no options for early morning or weekend times, but there are slots still available for the coming week. As of this writing, there are 6,100 Marylanders dead, and more than 1,800 COVID patients in hospital beds, and our governor, Larry Hogan, has commercials to “Mask On Maryland” and “Wear the Damn Mask.” I’ll offer some changes: “Wake Up, World” and “Offer the Damn Shot.”

Dr. Miller is coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University, 2016). She is assistant professor of psychiatry and behavioral sciences at Johns Hopkins University, both in Baltimore. Dr. Miller has no disclosures.

When the long-awaited news of a Food and Drug Administration–approved vaccine came on Dec. 11, 2020, my first thought was that I would wait. I can manage a few more months of Zooming for work, my household is down to two people, I’m not at high risk of dying from COVID, and my husband is not going to be vaccinated any time soon, so a change in my status wouldn’t “free” me. I would rather have “my” vaccine go to a 70-year-old ICU janitor or a bus driver.

South_agency/Getty Images

The weeks have gone by. I expected there would be kinks, but it has now been a month – one in which COVID rates have soared, and hospitalizations and deaths have risen to unmanageable numbers in some places. Still, vaccines remain in freezers – people are dying while vials of prevention sit unused. I began to think that, when my “turn” came, the better thing was to be vaccinated. We need to have a large segment of the population vaccinated to squelch this virus, and it’s become much less clear to me that, if I yield my turn, it will go into the arm of a bus driver. The process has not been fair, and there are moments of media outrage when one group gets vaccinated before another, so perhaps we have reached point where the goal should not be to get the vaccine into the exact right person in the exact right order, but to get the vaccine into arms according to the protocol that has already been set. Anyone who does not end up in a hospital bed is doing the system a favor.

Mahmood Jahromi, MD, a psychiatrist in private practice in Towson, Md., described the process of vaccination as being similar to a bottleneck traffic jam. “Yes, one must be courteous to the car trying to but in, but no, don’t jam the glue because you are excessively kind. Let the traffic police do their job. When your name is called, go ahead and take it. The system needs to know people are accepting the vaccine, not by begging the authorities to be called ahead of others, but with respect for what is already designed.”

On Friday, Jan. 8, I received information on how to get vaccinated – it seems my “turn” has arrived. An email from the board of physicians informed me that I am in the “1A” category and included a link to sign up for a vaccine in Baltimore – vaccinations would be given until Jan. 29, Mondays to Thursdays from 10 a.m. to 4 p.m. and Fridays from 10 a.m. to 1 p.m. There are no weekend or evening hours, and one might think there would be enough urgency to call for this. The Maryland Psychiatric Society sent out a notice that Sheppard Pratt would be offering vaccines to all behavioral health providers in the state of Maryland during a 2-day clinic. I heard from others that health care workers can now get vaccinated at the Cow Palace (how great is that?) at the Maryland State Fairgrounds and another link was sent for those in Howard County, between Baltimore and Washington.

As I discussed this with colleagues, a couple of issues came up – the most common was one of not wanting to get the vaccine yet because there are others who need it more. Others voiced concern about a vaccine where the long-term effects remain unknown: Is this vaccine safe, might it spur autoimmune problems in the months or years to come? Is it safe for women who plan to become pregnant? Some have insisted it is safe. They say “follow the science” and have dismissed the skepticism. To my read, it makes perfect sense to be wary, but COVID spreads silently and it kills.

With a vaccine where so many are reluctant to get it, including many health care workers, Sue Kim, MD, a psychiatrist in private practice in Lutherville, Md., noted that she has concerns about the safety of the vaccine. “Getting it now is both altruistic and selfish, but letting others go first is also altruistic and selfish. In the meantime, if I get sick, I was too smart for my own good. How do you weigh this ethically?”

My personal feelings have been influenced by a few things. An article in the New York Times highlighted how New York City vaccinated 5 million people for smallpox in just 2 weeks in 1947. I am frustrated knowing that, a month after approval of the first vaccine, only 7 million people have received it in the entire United States. In that time period, millions have contracted COVID and thousands have died. Closer to home, a 45-year-old psychiatrist in Maryland died of COVID, and I have heard more stories about younger people with long-haul neurologic and vascular symptoms. The risk of COVID is feeling higher than it did, and the fact that the first vaccine was authorized after the election somehow makes me feel that it might be safer. Had it been approved right before, I would have worried – perhaps wrongly – that the authorization was a political maneuver, not one based on science.

As we think about what is best for ourselves, our families, our patients, and society as a whole, I believe that those who want the vaccine but don’t feel they should take their place in line before others who are higher risk must ask if it makes sense to wait. Each state is different. While Houston Methodist Hospital is reportedly giving its health care workers a $500 bonus to get the vaccine, Gov. Andrew Cuomo of New York announced that hospitals would be fined $100,000 if they don’t use all of their vaccines within 7 days of receipt and $1 million if they vaccinate anyone out of order. Gov. Cuomo later broadened who could be vaccinated to prevent wasting the vaccine, but there remains an element of being damned if you do and damned if you don’t.

Paul Nestadt, MD, a psychiatrist at Johns Hopkins University, Baltimore, noted that one distribution site initially had to waste unused vaccine when people did not come for their appointments. A waiting list was created for people who could come right away if called to prevent this waste. “To me, this only highlighted that the tier system, while a good idea, does not need to be written in stone. The goal needs to be getting shots in arms, building herd immunity. If there are two arms in front of you, shoot the health care worker or those who are vulnerable. But if there is a healthy arm in reach, it should get any shot made available.”

I registered to be vaccinated. Maryland is still vaccinating only health care workers and people in long-term care facilities – senior citizens and essential workers are not yet eligible. In Baltimore, vaccinations are available Mondays to Thursdays from 10 a.m. to 4 p.m. and on Fridays from 10 a.m. to 1 p.m. There are no options for early morning or weekend times, but there are slots still available for the coming week. As of this writing, there are 6,100 Marylanders dead, and more than 1,800 COVID patients in hospital beds, and our governor, Larry Hogan, has commercials to “Mask On Maryland” and “Wear the Damn Mask.” I’ll offer some changes: “Wake Up, World” and “Offer the Damn Shot.”

Dr. Miller is coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University, 2016). She is assistant professor of psychiatry and behavioral sciences at Johns Hopkins University, both in Baltimore. Dr. Miller has no disclosures.

When the long-awaited news of a Food and Drug Administration–approved vaccine came on Dec. 11, 2020, my first thought was that I would wait. I can manage a few more months of Zooming for work, my household is down to two people, I’m not at high risk of dying from COVID, and my husband is not going to be vaccinated any time soon, so a change in my status wouldn’t “free” me. I would rather have “my” vaccine go to a 70-year-old ICU janitor or a bus driver.

South_agency/Getty Images

The weeks have gone by. I expected there would be kinks, but it has now been a month – one in which COVID rates have soared, and hospitalizations and deaths have risen to unmanageable numbers in some places. Still, vaccines remain in freezers – people are dying while vials of prevention sit unused. I began to think that, when my “turn” came, the better thing was to be vaccinated. We need to have a large segment of the population vaccinated to squelch this virus, and it’s become much less clear to me that, if I yield my turn, it will go into the arm of a bus driver. The process has not been fair, and there are moments of media outrage when one group gets vaccinated before another, so perhaps we have reached point where the goal should not be to get the vaccine into the exact right person in the exact right order, but to get the vaccine into arms according to the protocol that has already been set. Anyone who does not end up in a hospital bed is doing the system a favor.

Mahmood Jahromi, MD, a psychiatrist in private practice in Towson, Md., described the process of vaccination as being similar to a bottleneck traffic jam. “Yes, one must be courteous to the car trying to but in, but no, don’t jam the glue because you are excessively kind. Let the traffic police do their job. When your name is called, go ahead and take it. The system needs to know people are accepting the vaccine, not by begging the authorities to be called ahead of others, but with respect for what is already designed.”

On Friday, Jan. 8, I received information on how to get vaccinated – it seems my “turn” has arrived. An email from the board of physicians informed me that I am in the “1A” category and included a link to sign up for a vaccine in Baltimore – vaccinations would be given until Jan. 29, Mondays to Thursdays from 10 a.m. to 4 p.m. and Fridays from 10 a.m. to 1 p.m. There are no weekend or evening hours, and one might think there would be enough urgency to call for this. The Maryland Psychiatric Society sent out a notice that Sheppard Pratt would be offering vaccines to all behavioral health providers in the state of Maryland during a 2-day clinic. I heard from others that health care workers can now get vaccinated at the Cow Palace (how great is that?) at the Maryland State Fairgrounds and another link was sent for those in Howard County, between Baltimore and Washington.

As I discussed this with colleagues, a couple of issues came up – the most common was one of not wanting to get the vaccine yet because there are others who need it more. Others voiced concern about a vaccine where the long-term effects remain unknown: Is this vaccine safe, might it spur autoimmune problems in the months or years to come? Is it safe for women who plan to become pregnant? Some have insisted it is safe. They say “follow the science” and have dismissed the skepticism. To my read, it makes perfect sense to be wary, but COVID spreads silently and it kills.

With a vaccine where so many are reluctant to get it, including many health care workers, Sue Kim, MD, a psychiatrist in private practice in Lutherville, Md., noted that she has concerns about the safety of the vaccine. “Getting it now is both altruistic and selfish, but letting others go first is also altruistic and selfish. In the meantime, if I get sick, I was too smart for my own good. How do you weigh this ethically?”

My personal feelings have been influenced by a few things. An article in the New York Times highlighted how New York City vaccinated 5 million people for smallpox in just 2 weeks in 1947. I am frustrated knowing that, a month after approval of the first vaccine, only 7 million people have received it in the entire United States. In that time period, millions have contracted COVID and thousands have died. Closer to home, a 45-year-old psychiatrist in Maryland died of COVID, and I have heard more stories about younger people with long-haul neurologic and vascular symptoms. The risk of COVID is feeling higher than it did, and the fact that the first vaccine was authorized after the election somehow makes me feel that it might be safer. Had it been approved right before, I would have worried – perhaps wrongly – that the authorization was a political maneuver, not one based on science.

As we think about what is best for ourselves, our families, our patients, and society as a whole, I believe that those who want the vaccine but don’t feel they should take their place in line before others who are higher risk must ask if it makes sense to wait. Each state is different. While Houston Methodist Hospital is reportedly giving its health care workers a $500 bonus to get the vaccine, Gov. Andrew Cuomo of New York announced that hospitals would be fined $100,000 if they don’t use all of their vaccines within 7 days of receipt and $1 million if they vaccinate anyone out of order. Gov. Cuomo later broadened who could be vaccinated to prevent wasting the vaccine, but there remains an element of being damned if you do and damned if you don’t.

Paul Nestadt, MD, a psychiatrist at Johns Hopkins University, Baltimore, noted that one distribution site initially had to waste unused vaccine when people did not come for their appointments. A waiting list was created for people who could come right away if called to prevent this waste. “To me, this only highlighted that the tier system, while a good idea, does not need to be written in stone. The goal needs to be getting shots in arms, building herd immunity. If there are two arms in front of you, shoot the health care worker or those who are vulnerable. But if there is a healthy arm in reach, it should get any shot made available.”

I registered to be vaccinated. Maryland is still vaccinating only health care workers and people in long-term care facilities – senior citizens and essential workers are not yet eligible. In Baltimore, vaccinations are available Mondays to Thursdays from 10 a.m. to 4 p.m. and on Fridays from 10 a.m. to 1 p.m. There are no options for early morning or weekend times, but there are slots still available for the coming week. As of this writing, there are 6,100 Marylanders dead, and more than 1,800 COVID patients in hospital beds, and our governor, Larry Hogan, has commercials to “Mask On Maryland” and “Wear the Damn Mask.” I’ll offer some changes: “Wake Up, World” and “Offer the Damn Shot.”

Dr. Miller is coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University, 2016). She is assistant professor of psychiatry and behavioral sciences at Johns Hopkins University, both in Baltimore. Dr. Miller has no disclosures.

A newly updated expert consensus from the American College of Cardiology for management of heart failure with reduced ejection fraction includes several new guideline-directed medical therapies among other substantial changes relative to its 2017 predecessor.

The advances in treatment of heart failure with reduced ejection fraction (HFrEF) have resulted in a substantial increase in complexity in reaching treatment goals, according to the authors of the new guidance. Structured similarly to the 2017 ACC Expert Consensus Decision Pathway, the update accommodates a series of practical tips to bring all patients on board with the newer as well as the established therapies with lifesaving potential.

The potential return from implementing these recommendations is not trivial. Relative to an ACE inhibitor and a beta-blocker alone, optimal implementation of the current guideline-directed medical therapies (GDMT) “can extend medical survival by more than 6 years,” according to Gregg C. Fonarow, MD, chief of cardiology at the University of California, Los Angeles.

A member of the writing committee for the 2021 update, Dr. Fonarow explained that the consensus pathway is more than a list of therapies and recommended doses. The detailed advice on how to overcome the barriers to GDMT is meant to close the substantial gap between current practice and unmet opportunities for inhibiting HFrEF progression.

“Optimal GDMT among HFrEF patients is distressingly low, due in part to the number and complexity of medications that now constitute GDMT,” said the chair of the writing committee, Thomas M. Maddox, MD, executive director, Healthcare Innovation Lab, BJC HealthCare/Washington University, St. Louis. Like Dr. Fonarow, Dr. Maddox emphasized that the importance of the update for the practical strategies it offers to place patients on optimal care.

SOURCE: Maddox TM et al. J Am Coll Cardiol. 2021 Jan 11. doi: 10.1016/j.jacc.2020.11.022.

A newly updated expert consensus from the American College of Cardiology for management of heart failure with reduced ejection fraction includes several new guideline-directed medical therapies among other substantial changes relative to its 2017 predecessor.

The advances in treatment of heart failure with reduced ejection fraction (HFrEF) have resulted in a substantial increase in complexity in reaching treatment goals, according to the authors of the new guidance. Structured similarly to the 2017 ACC Expert Consensus Decision Pathway, the update accommodates a series of practical tips to bring all patients on board with the newer as well as the established therapies with lifesaving potential.

The potential return from implementing these recommendations is not trivial. Relative to an ACE inhibitor and a beta-blocker alone, optimal implementation of the current guideline-directed medical therapies (GDMT) “can extend medical survival by more than 6 years,” according to Gregg C. Fonarow, MD, chief of cardiology at the University of California, Los Angeles.

A member of the writing committee for the 2021 update, Dr. Fonarow explained that the consensus pathway is more than a list of therapies and recommended doses. The detailed advice on how to overcome the barriers to GDMT is meant to close the substantial gap between current practice and unmet opportunities for inhibiting HFrEF progression.

“Optimal GDMT among HFrEF patients is distressingly low, due in part to the number and complexity of medications that now constitute GDMT,” said the chair of the writing committee, Thomas M. Maddox, MD, executive director, Healthcare Innovation Lab, BJC HealthCare/Washington University, St. Louis. Like Dr. Fonarow, Dr. Maddox emphasized that the importance of the update for the practical strategies it offers to place patients on optimal care.

SOURCE: Maddox TM et al. J Am Coll Cardiol. 2021 Jan 11. doi: 10.1016/j.jacc.2020.11.022.

A newly updated expert consensus from the American College of Cardiology for management of heart failure with reduced ejection fraction includes several new guideline-directed medical therapies among other substantial changes relative to its 2017 predecessor.

The advances in treatment of heart failure with reduced ejection fraction (HFrEF) have resulted in a substantial increase in complexity in reaching treatment goals, according to the authors of the new guidance. Structured similarly to the 2017 ACC Expert Consensus Decision Pathway, the update accommodates a series of practical tips to bring all patients on board with the newer as well as the established therapies with lifesaving potential.

The potential return from implementing these recommendations is not trivial. Relative to an ACE inhibitor and a beta-blocker alone, optimal implementation of the current guideline-directed medical therapies (GDMT) “can extend medical survival by more than 6 years,” according to Gregg C. Fonarow, MD, chief of cardiology at the University of California, Los Angeles.

A member of the writing committee for the 2021 update, Dr. Fonarow explained that the consensus pathway is more than a list of therapies and recommended doses. The detailed advice on how to overcome the barriers to GDMT is meant to close the substantial gap between current practice and unmet opportunities for inhibiting HFrEF progression.

“Optimal GDMT among HFrEF patients is distressingly low, due in part to the number and complexity of medications that now constitute GDMT,” said the chair of the writing committee, Thomas M. Maddox, MD, executive director, Healthcare Innovation Lab, BJC HealthCare/Washington University, St. Louis. Like Dr. Fonarow, Dr. Maddox emphasized that the importance of the update for the practical strategies it offers to place patients on optimal care.

SOURCE: Maddox TM et al. J Am Coll Cardiol. 2021 Jan 11. doi: 10.1016/j.jacc.2020.11.022.

People who have brown fat detected on imaging seem to be at reduced risk of cardiac and metabolic conditions, ranging from type 2 diabetes to hypertension and coronary artery disease, with a notably strong effect in people with obesity, according to a new study of more than 52,000 individuals who had PET/CT scans as part of cancer evaluation.

Although this has been studied for decades in newborns and animals, only in the past decade have scientists appreciated that some adults have brown fat, typically around the neck and shoulders.

The new study, by far the largest of its kind in humans, appears to confirm the health benefits of brown fat suggested by previous studies, Tobias Becher, MD, and colleagues from The Rockefeller University, New York, wrote in their article published online Jan. 4 in Nature Medicine.

“Our study indicates an important contribution of brown adipose tissue to cardiometabolic health and suggests ... [it] has therapeutic potential in humans,” they stated.

But Caroline M. Apovian, MD, Center for Weight Management and Wellness, Brigham and Women’s Hospital, Boston, is more cautious in her interpretation of the findings.

“It’s nice to see that what we believe about this is correct, and it’s great to see that with obesity and more brown fat there is reduced diabetes and hypertension, but it’s only an association,” she said in an interview.

“This is a good study, but I don’t think we have an understanding of exactly why some people have more brown fat than others, how white fat becomes brown fat, the role of therapeutics, or if it’s important to try to create more brown fat.

“We don’t know if it’s a matter of exercise or something like living in a colder environment, so we need to find out whether or not brown fat is, for instance, a genetic issue, and if it is, if there is a way to increase it in humans,” she added.

And the fact that the study included patients with or being screened for cancer is one of the most important limitations of the study, Dr. Apovian noted.
 

Brown fat detected in 10% of participants

Contrary to white fat, which stores energy, brown fat is thermogenic, activated by cold conditions, and instead burns energy. And although animal studies have shown a link between brown fat and improvements in glucose and lipid homeostasis, the effects of brown fat in humans are not well understood.

Dr. Becher and colleagues explained that large-scale studies of brown fat have been practically impossible because the tissue only shows up on medical imaging and it would be unethical to expose people to radiation just to study brown fat.  

But they realized that, across the street from their lab, many thousands of people visit Memorial Sloan Kettering Cancer Center each year to undergo PET/CT scans for cancer evaluation.

Because radiologists routinely take note when brown adipose tissue is detected to prevent its misinterpretation as a tumor, the information was readily available with the scan data.

“We realized this could be a valuable resource to get us started with looking at brown fat at a population scale,” Dr. Becher said in a press statement from The Rockefeller University.

So they reviewed 134,529 PET/CT scans from 52,487 individuals attending Memorial Sloan Kettering between June 2009 and March 2018 for indications ranging from cancer diagnosis to treatment or surveillance.

Participants were classified by the presence or absence of brown adipose tissue and researchers were able to use electronic health records to comprehensively examine associations between brown fat and rates of disease.

Overall, brown adipose tissue was identified in 5,070 (9.7%) of patients, with higher rates of brown fat among women than men (13.8% vs. 4.9%; P < .0001) and reduced rates with advancing age (P < .0001), as has been observed in previous studies.

The researchers noted, however, that this rate of around 10% of people having brown fat is likely an underestimate because the patients had been instructed to avoid cold exposure, exercise, and caffeine – all of which are thought to increase brown adipose tissue – prior to having their scans.
 

Does brown fat mitigate some harms of obesity?

Among those with brown fat, the rate of type 2 diabetes was 4.6% compared with 9.5% in those with no detected brown fat (P < .0001), and in a multivariate analysis, the odds ratio (OR) for type 2 diabetes in the presence of brown fat was 0.44.

The occurrence of coronary artery disease was significantly lower in those with brown fat (OR, 0.68; P = .0002), as was cerebrovascular disease (OR, 0.77; P = .0317), heart failure (OR, 0.62; P = .0043), and hypertension (OR, 0.85; P = .0014).

Brown fat also was associated with notable improvements in glucose, triglycerides, and HDL-C levels (all P < .0001), while no differences were seen in measures of LDL-Cs or total cholesterol.

Leukocyte and platelet counts were significantly decreased in individuals with brown fat (both P < .0001).

The findings “suggest potential roles for brown adipose beyond regulation of lipid and glucose metabolism,” the authors wrote.

Most notably, the effects were more pronounced in people with obesity. For example, the prevalence of type 2 diabetes in those with obesity and brown fat was less than half the rate in those with obesity without brown fat (7.5% vs. 20.3%; P < .0001).

This could indicate that brown adipose tissue “might play a role in mitigating the deleterious effects of obesity,” the researchers stated.

“Future research should aim to improve our understanding of brown adipose tissue regulation in humans and to develop mechanisms to safely modulate [its activity],” they concluded.

The study received funding from the American Diabetes Association, the Sinsheimer Foundation, and the National Center for Advancing Translational Sciences of the U.S. Department of Health & Human Services. The authors and Dr. Apovian have reported no relevant financial relationships.

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

People who have brown fat detected on imaging seem to be at reduced risk of cardiac and metabolic conditions, ranging from type 2 diabetes to hypertension and coronary artery disease, with a notably strong effect in people with obesity, according to a new study of more than 52,000 individuals who had PET/CT scans as part of cancer evaluation.

Although this has been studied for decades in newborns and animals, only in the past decade have scientists appreciated that some adults have brown fat, typically around the neck and shoulders.

The new study, by far the largest of its kind in humans, appears to confirm the health benefits of brown fat suggested by previous studies, Tobias Becher, MD, and colleagues from The Rockefeller University, New York, wrote in their article published online Jan. 4 in Nature Medicine.

“Our study indicates an important contribution of brown adipose tissue to cardiometabolic health and suggests ... [it] has therapeutic potential in humans,” they stated.

But Caroline M. Apovian, MD, Center for Weight Management and Wellness, Brigham and Women’s Hospital, Boston, is more cautious in her interpretation of the findings.

“It’s nice to see that what we believe about this is correct, and it’s great to see that with obesity and more brown fat there is reduced diabetes and hypertension, but it’s only an association,” she said in an interview.

“This is a good study, but I don’t think we have an understanding of exactly why some people have more brown fat than others, how white fat becomes brown fat, the role of therapeutics, or if it’s important to try to create more brown fat.

“We don’t know if it’s a matter of exercise or something like living in a colder environment, so we need to find out whether or not brown fat is, for instance, a genetic issue, and if it is, if there is a way to increase it in humans,” she added.

And the fact that the study included patients with or being screened for cancer is one of the most important limitations of the study, Dr. Apovian noted.
 

Brown fat detected in 10% of participants

Contrary to white fat, which stores energy, brown fat is thermogenic, activated by cold conditions, and instead burns energy. And although animal studies have shown a link between brown fat and improvements in glucose and lipid homeostasis, the effects of brown fat in humans are not well understood.

Dr. Becher and colleagues explained that large-scale studies of brown fat have been practically impossible because the tissue only shows up on medical imaging and it would be unethical to expose people to radiation just to study brown fat.  

But they realized that, across the street from their lab, many thousands of people visit Memorial Sloan Kettering Cancer Center each year to undergo PET/CT scans for cancer evaluation.

Because radiologists routinely take note when brown adipose tissue is detected to prevent its misinterpretation as a tumor, the information was readily available with the scan data.

“We realized this could be a valuable resource to get us started with looking at brown fat at a population scale,” Dr. Becher said in a press statement from The Rockefeller University.

So they reviewed 134,529 PET/CT scans from 52,487 individuals attending Memorial Sloan Kettering between June 2009 and March 2018 for indications ranging from cancer diagnosis to treatment or surveillance.

Participants were classified by the presence or absence of brown adipose tissue and researchers were able to use electronic health records to comprehensively examine associations between brown fat and rates of disease.

Overall, brown adipose tissue was identified in 5,070 (9.7%) of patients, with higher rates of brown fat among women than men (13.8% vs. 4.9%; P < .0001) and reduced rates with advancing age (P < .0001), as has been observed in previous studies.

The researchers noted, however, that this rate of around 10% of people having brown fat is likely an underestimate because the patients had been instructed to avoid cold exposure, exercise, and caffeine – all of which are thought to increase brown adipose tissue – prior to having their scans.
 

Does brown fat mitigate some harms of obesity?

Among those with brown fat, the rate of type 2 diabetes was 4.6% compared with 9.5% in those with no detected brown fat (P < .0001), and in a multivariate analysis, the odds ratio (OR) for type 2 diabetes in the presence of brown fat was 0.44.

The occurrence of coronary artery disease was significantly lower in those with brown fat (OR, 0.68; P = .0002), as was cerebrovascular disease (OR, 0.77; P = .0317), heart failure (OR, 0.62; P = .0043), and hypertension (OR, 0.85; P = .0014).

Brown fat also was associated with notable improvements in glucose, triglycerides, and HDL-C levels (all P < .0001), while no differences were seen in measures of LDL-Cs or total cholesterol.

Leukocyte and platelet counts were significantly decreased in individuals with brown fat (both P < .0001).

The findings “suggest potential roles for brown adipose beyond regulation of lipid and glucose metabolism,” the authors wrote.

Most notably, the effects were more pronounced in people with obesity. For example, the prevalence of type 2 diabetes in those with obesity and brown fat was less than half the rate in those with obesity without brown fat (7.5% vs. 20.3%; P < .0001).

This could indicate that brown adipose tissue “might play a role in mitigating the deleterious effects of obesity,” the researchers stated.

“Future research should aim to improve our understanding of brown adipose tissue regulation in humans and to develop mechanisms to safely modulate [its activity],” they concluded.

The study received funding from the American Diabetes Association, the Sinsheimer Foundation, and the National Center for Advancing Translational Sciences of the U.S. Department of Health & Human Services. The authors and Dr. Apovian have reported no relevant financial relationships.

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

People who have brown fat detected on imaging seem to be at reduced risk of cardiac and metabolic conditions, ranging from type 2 diabetes to hypertension and coronary artery disease, with a notably strong effect in people with obesity, according to a new study of more than 52,000 individuals who had PET/CT scans as part of cancer evaluation.

Although this has been studied for decades in newborns and animals, only in the past decade have scientists appreciated that some adults have brown fat, typically around the neck and shoulders.

The new study, by far the largest of its kind in humans, appears to confirm the health benefits of brown fat suggested by previous studies, Tobias Becher, MD, and colleagues from The Rockefeller University, New York, wrote in their article published online Jan. 4 in Nature Medicine.

“Our study indicates an important contribution of brown adipose tissue to cardiometabolic health and suggests ... [it] has therapeutic potential in humans,” they stated.

But Caroline M. Apovian, MD, Center for Weight Management and Wellness, Brigham and Women’s Hospital, Boston, is more cautious in her interpretation of the findings.

“It’s nice to see that what we believe about this is correct, and it’s great to see that with obesity and more brown fat there is reduced diabetes and hypertension, but it’s only an association,” she said in an interview.

“This is a good study, but I don’t think we have an understanding of exactly why some people have more brown fat than others, how white fat becomes brown fat, the role of therapeutics, or if it’s important to try to create more brown fat.

“We don’t know if it’s a matter of exercise or something like living in a colder environment, so we need to find out whether or not brown fat is, for instance, a genetic issue, and if it is, if there is a way to increase it in humans,” she added.

And the fact that the study included patients with or being screened for cancer is one of the most important limitations of the study, Dr. Apovian noted.
 

Brown fat detected in 10% of participants

Contrary to white fat, which stores energy, brown fat is thermogenic, activated by cold conditions, and instead burns energy. And although animal studies have shown a link between brown fat and improvements in glucose and lipid homeostasis, the effects of brown fat in humans are not well understood.

Dr. Becher and colleagues explained that large-scale studies of brown fat have been practically impossible because the tissue only shows up on medical imaging and it would be unethical to expose people to radiation just to study brown fat.  

But they realized that, across the street from their lab, many thousands of people visit Memorial Sloan Kettering Cancer Center each year to undergo PET/CT scans for cancer evaluation.

Because radiologists routinely take note when brown adipose tissue is detected to prevent its misinterpretation as a tumor, the information was readily available with the scan data.

“We realized this could be a valuable resource to get us started with looking at brown fat at a population scale,” Dr. Becher said in a press statement from The Rockefeller University.

So they reviewed 134,529 PET/CT scans from 52,487 individuals attending Memorial Sloan Kettering between June 2009 and March 2018 for indications ranging from cancer diagnosis to treatment or surveillance.

Participants were classified by the presence or absence of brown adipose tissue and researchers were able to use electronic health records to comprehensively examine associations between brown fat and rates of disease.

Overall, brown adipose tissue was identified in 5,070 (9.7%) of patients, with higher rates of brown fat among women than men (13.8% vs. 4.9%; P < .0001) and reduced rates with advancing age (P < .0001), as has been observed in previous studies.

The researchers noted, however, that this rate of around 10% of people having brown fat is likely an underestimate because the patients had been instructed to avoid cold exposure, exercise, and caffeine – all of which are thought to increase brown adipose tissue – prior to having their scans.
 

Does brown fat mitigate some harms of obesity?

Among those with brown fat, the rate of type 2 diabetes was 4.6% compared with 9.5% in those with no detected brown fat (P < .0001), and in a multivariate analysis, the odds ratio (OR) for type 2 diabetes in the presence of brown fat was 0.44.

The occurrence of coronary artery disease was significantly lower in those with brown fat (OR, 0.68; P = .0002), as was cerebrovascular disease (OR, 0.77; P = .0317), heart failure (OR, 0.62; P = .0043), and hypertension (OR, 0.85; P = .0014).

Brown fat also was associated with notable improvements in glucose, triglycerides, and HDL-C levels (all P < .0001), while no differences were seen in measures of LDL-Cs or total cholesterol.

Leukocyte and platelet counts were significantly decreased in individuals with brown fat (both P < .0001).

The findings “suggest potential roles for brown adipose beyond regulation of lipid and glucose metabolism,” the authors wrote.

Most notably, the effects were more pronounced in people with obesity. For example, the prevalence of type 2 diabetes in those with obesity and brown fat was less than half the rate in those with obesity without brown fat (7.5% vs. 20.3%; P < .0001).

This could indicate that brown adipose tissue “might play a role in mitigating the deleterious effects of obesity,” the researchers stated.

“Future research should aim to improve our understanding of brown adipose tissue regulation in humans and to develop mechanisms to safely modulate [its activity],” they concluded.

The study received funding from the American Diabetes Association, the Sinsheimer Foundation, and the National Center for Advancing Translational Sciences of the U.S. Department of Health & Human Services. The authors and Dr. Apovian have reported no relevant financial relationships.

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

The American College of Cardiology has released a new expert consensus decision pathway to provide practical guidance on same-day discharge after percutaneous coronary intervention (PCI).

“There’s been a lot of interest in people wanting to start these programs, so we thought this is an ideal topic for a consensus pathway that will help programs that want to implement these things – give them kind of a road map for how to do that,” writing committee chair Sunil Rao, MD, Duke University Medical Center, Durham, N.C., said.

Although the document reviews the evidence supporting same-day discharge much like a guideline, the focus is on implementation, he said in an interview. It features a checklist of patient- and systems-specific considerations along with key definitions and a series of clinical scenarios showing the rationale for same-day discharge or overnight monitoring.

The checklist can be used for anyone presenting for an elective PCI or for ad hoc cases that flow directly from the diagnostic cath lab and make up about 80% of procedures. It is not applicable for those presenting with ST-elevation myocardial infarction (STEMI) or non-STEMI, but can be used for staged procedures performed after their index PCI, according to the report, published online Jan. 7 in the Journal of the American College of Cardiology.

When establishing a new same-day discharge program, the basic approach can be distilled down to the “three Ps”– the patient, the procedure, and the program – Dr. Rao explained. The patient has to be the right patient, be willing to go home that night, and have some kind of support structure at home in case they run into trouble. The procedure itself should be without complications and the recovery unremarkable, with a stable access site and a return to baseline mental status and ambulation. Finally, “this all has to take place in the context of a program with buy-in from the different stakeholders,” he said.

The report points out that the need for administrative buy-in “should not be underestimated” and recommends physician-champions meet with staff administrators to present the data on PCI utility and safety and to communicate the need for staff to complete the checklist.

Implementing the checklist also requires buy-in from nurses and other team members who may be tasked with educating patients on issues like access site complications and ensuring they receive relevant discharge information, a loading dose of a P2Y12 inhibitor, and appropriate prescriptions.

“If you’re only going to observe the patient for 6 hours, you’ve got to make sure that they’re on all the secondary prevention medications and the referral to cardiac rehabilitation takes place,” Dr. Rao said. “So I think that, in a funny way, the implementation of same-day discharge allows us to actually focus a little bit more on these kinds of postprocedure aspects that I think we were taking for granted a little bit when patients were being observed overnight.”

The checklist is detailed but was designed so it can be tailored to the needs of individual institutions, writing committee member Connie N. Hess, MD, MHS, University of Colorado at Denver, Aurora, pointed out.

“At every level there is a lot of variance in institutional resources or even a patient’s resources,” she said. “So we didn’t want to seem too prescriptive.”

Some institutions, for example, may feel strongly that accessibility to a caregiver means someone staying in the house who can monitor the patient’s access site and call 911 if need be, whereas others may define it as having a neighbor who’s easy to reach by phone, Dr. Hess noted in an interview.

Exactly when the last patient can be eligible for same-day discharge may also vary between urban and rural settings where patients may drive hours for their care. The built-in flexibility also allows institutions to incorporate their own preexisting documents into the checklist.

“I don’t think the hospital buy-in is necessarily the hard part because there is a clear monetary benefit as long as you can show that it’s done safely and you’re not harming patients, which I think has been done,” Dr. Hess said. “I think then the next level down, you have the provider buy-in and that may be where there might be a little bit more work depending on the preexisting culture.”

Part of the hesitancy may reflect a generational gap, whereby younger interventionalists who trained in programs with same-day discharge may be more willing to support the checklist.

“This actually parallels radial artery access where data exists on its benefits but it’s not used,” Dr. Hess said. “And I think a lot of this has to do with provider comfort levels with sending patients home and just not necessarily knowing how to implement a program at their institution.”

Both Dr. Rao and Dr. Hess pointed out that uptake of same-day discharge PCI is low in the United States, compared with other part of the world, including the United Kingdom, with estimates at about 16%-20% of PCIs.

That said, the timing of the new expert consensus document is “fortuitous,” Dr. Rao noted. Since work on the document began 2 years ago, the Centers for Medicare & Medicaid Services’ greenlit reimbursement for PCI performed in an ambulatory surgical center and the pandemic walloped U.S. hospitals. “I think those two things really do highlight the importance of a document like this.”

“A potential advantage of the same-day discharge program is that you won’t be exposing patients to the hospital setting where COVID is a problem, and you’ll keep your beds open for the COVID patients that really do need it,” he said.

The ability to go home without an overnight stay may also encourage some patients to seek care. “Patients with cardiovascular disease really need to understand that you may be stable at one point but then obviously can become unstable, and we don’t want people to stay away from the hospital because they are worried about being admitted,” Dr. Rao said.

Dr. Rao and Dr. Hess report no relevant conflicts of interest.

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

The American College of Cardiology has released a new expert consensus decision pathway to provide practical guidance on same-day discharge after percutaneous coronary intervention (PCI).

“There’s been a lot of interest in people wanting to start these programs, so we thought this is an ideal topic for a consensus pathway that will help programs that want to implement these things – give them kind of a road map for how to do that,” writing committee chair Sunil Rao, MD, Duke University Medical Center, Durham, N.C., said.

Although the document reviews the evidence supporting same-day discharge much like a guideline, the focus is on implementation, he said in an interview. It features a checklist of patient- and systems-specific considerations along with key definitions and a series of clinical scenarios showing the rationale for same-day discharge or overnight monitoring.

The checklist can be used for anyone presenting for an elective PCI or for ad hoc cases that flow directly from the diagnostic cath lab and make up about 80% of procedures. It is not applicable for those presenting with ST-elevation myocardial infarction (STEMI) or non-STEMI, but can be used for staged procedures performed after their index PCI, according to the report, published online Jan. 7 in the Journal of the American College of Cardiology.

When establishing a new same-day discharge program, the basic approach can be distilled down to the “three Ps”– the patient, the procedure, and the program – Dr. Rao explained. The patient has to be the right patient, be willing to go home that night, and have some kind of support structure at home in case they run into trouble. The procedure itself should be without complications and the recovery unremarkable, with a stable access site and a return to baseline mental status and ambulation. Finally, “this all has to take place in the context of a program with buy-in from the different stakeholders,” he said.

The report points out that the need for administrative buy-in “should not be underestimated” and recommends physician-champions meet with staff administrators to present the data on PCI utility and safety and to communicate the need for staff to complete the checklist.

Implementing the checklist also requires buy-in from nurses and other team members who may be tasked with educating patients on issues like access site complications and ensuring they receive relevant discharge information, a loading dose of a P2Y12 inhibitor, and appropriate prescriptions.

“If you’re only going to observe the patient for 6 hours, you’ve got to make sure that they’re on all the secondary prevention medications and the referral to cardiac rehabilitation takes place,” Dr. Rao said. “So I think that, in a funny way, the implementation of same-day discharge allows us to actually focus a little bit more on these kinds of postprocedure aspects that I think we were taking for granted a little bit when patients were being observed overnight.”

The checklist is detailed but was designed so it can be tailored to the needs of individual institutions, writing committee member Connie N. Hess, MD, MHS, University of Colorado at Denver, Aurora, pointed out.

“At every level there is a lot of variance in institutional resources or even a patient’s resources,” she said. “So we didn’t want to seem too prescriptive.”

Some institutions, for example, may feel strongly that accessibility to a caregiver means someone staying in the house who can monitor the patient’s access site and call 911 if need be, whereas others may define it as having a neighbor who’s easy to reach by phone, Dr. Hess noted in an interview.

Exactly when the last patient can be eligible for same-day discharge may also vary between urban and rural settings where patients may drive hours for their care. The built-in flexibility also allows institutions to incorporate their own preexisting documents into the checklist.

“I don’t think the hospital buy-in is necessarily the hard part because there is a clear monetary benefit as long as you can show that it’s done safely and you’re not harming patients, which I think has been done,” Dr. Hess said. “I think then the next level down, you have the provider buy-in and that may be where there might be a little bit more work depending on the preexisting culture.”

Part of the hesitancy may reflect a generational gap, whereby younger interventionalists who trained in programs with same-day discharge may be more willing to support the checklist.

“This actually parallels radial artery access where data exists on its benefits but it’s not used,” Dr. Hess said. “And I think a lot of this has to do with provider comfort levels with sending patients home and just not necessarily knowing how to implement a program at their institution.”

Both Dr. Rao and Dr. Hess pointed out that uptake of same-day discharge PCI is low in the United States, compared with other part of the world, including the United Kingdom, with estimates at about 16%-20% of PCIs.

That said, the timing of the new expert consensus document is “fortuitous,” Dr. Rao noted. Since work on the document began 2 years ago, the Centers for Medicare & Medicaid Services’ greenlit reimbursement for PCI performed in an ambulatory surgical center and the pandemic walloped U.S. hospitals. “I think those two things really do highlight the importance of a document like this.”

“A potential advantage of the same-day discharge program is that you won’t be exposing patients to the hospital setting where COVID is a problem, and you’ll keep your beds open for the COVID patients that really do need it,” he said.

The ability to go home without an overnight stay may also encourage some patients to seek care. “Patients with cardiovascular disease really need to understand that you may be stable at one point but then obviously can become unstable, and we don’t want people to stay away from the hospital because they are worried about being admitted,” Dr. Rao said.

Dr. Rao and Dr. Hess report no relevant conflicts of interest.

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

The American College of Cardiology has released a new expert consensus decision pathway to provide practical guidance on same-day discharge after percutaneous coronary intervention (PCI).

“There’s been a lot of interest in people wanting to start these programs, so we thought this is an ideal topic for a consensus pathway that will help programs that want to implement these things – give them kind of a road map for how to do that,” writing committee chair Sunil Rao, MD, Duke University Medical Center, Durham, N.C., said.

Although the document reviews the evidence supporting same-day discharge much like a guideline, the focus is on implementation, he said in an interview. It features a checklist of patient- and systems-specific considerations along with key definitions and a series of clinical scenarios showing the rationale for same-day discharge or overnight monitoring.

The checklist can be used for anyone presenting for an elective PCI or for ad hoc cases that flow directly from the diagnostic cath lab and make up about 80% of procedures. It is not applicable for those presenting with ST-elevation myocardial infarction (STEMI) or non-STEMI, but can be used for staged procedures performed after their index PCI, according to the report, published online Jan. 7 in the Journal of the American College of Cardiology.

When establishing a new same-day discharge program, the basic approach can be distilled down to the “three Ps”– the patient, the procedure, and the program – Dr. Rao explained. The patient has to be the right patient, be willing to go home that night, and have some kind of support structure at home in case they run into trouble. The procedure itself should be without complications and the recovery unremarkable, with a stable access site and a return to baseline mental status and ambulation. Finally, “this all has to take place in the context of a program with buy-in from the different stakeholders,” he said.

The report points out that the need for administrative buy-in “should not be underestimated” and recommends physician-champions meet with staff administrators to present the data on PCI utility and safety and to communicate the need for staff to complete the checklist.

Implementing the checklist also requires buy-in from nurses and other team members who may be tasked with educating patients on issues like access site complications and ensuring they receive relevant discharge information, a loading dose of a P2Y12 inhibitor, and appropriate prescriptions.

“If you’re only going to observe the patient for 6 hours, you’ve got to make sure that they’re on all the secondary prevention medications and the referral to cardiac rehabilitation takes place,” Dr. Rao said. “So I think that, in a funny way, the implementation of same-day discharge allows us to actually focus a little bit more on these kinds of postprocedure aspects that I think we were taking for granted a little bit when patients were being observed overnight.”

The checklist is detailed but was designed so it can be tailored to the needs of individual institutions, writing committee member Connie N. Hess, MD, MHS, University of Colorado at Denver, Aurora, pointed out.

“At every level there is a lot of variance in institutional resources or even a patient’s resources,” she said. “So we didn’t want to seem too prescriptive.”

Some institutions, for example, may feel strongly that accessibility to a caregiver means someone staying in the house who can monitor the patient’s access site and call 911 if need be, whereas others may define it as having a neighbor who’s easy to reach by phone, Dr. Hess noted in an interview.

Exactly when the last patient can be eligible for same-day discharge may also vary between urban and rural settings where patients may drive hours for their care. The built-in flexibility also allows institutions to incorporate their own preexisting documents into the checklist.

“I don’t think the hospital buy-in is necessarily the hard part because there is a clear monetary benefit as long as you can show that it’s done safely and you’re not harming patients, which I think has been done,” Dr. Hess said. “I think then the next level down, you have the provider buy-in and that may be where there might be a little bit more work depending on the preexisting culture.”

Part of the hesitancy may reflect a generational gap, whereby younger interventionalists who trained in programs with same-day discharge may be more willing to support the checklist.

“This actually parallels radial artery access where data exists on its benefits but it’s not used,” Dr. Hess said. “And I think a lot of this has to do with provider comfort levels with sending patients home and just not necessarily knowing how to implement a program at their institution.”

Both Dr. Rao and Dr. Hess pointed out that uptake of same-day discharge PCI is low in the United States, compared with other part of the world, including the United Kingdom, with estimates at about 16%-20% of PCIs.

That said, the timing of the new expert consensus document is “fortuitous,” Dr. Rao noted. Since work on the document began 2 years ago, the Centers for Medicare & Medicaid Services’ greenlit reimbursement for PCI performed in an ambulatory surgical center and the pandemic walloped U.S. hospitals. “I think those two things really do highlight the importance of a document like this.”

“A potential advantage of the same-day discharge program is that you won’t be exposing patients to the hospital setting where COVID is a problem, and you’ll keep your beds open for the COVID patients that really do need it,” he said.

The ability to go home without an overnight stay may also encourage some patients to seek care. “Patients with cardiovascular disease really need to understand that you may be stable at one point but then obviously can become unstable, and we don’t want people to stay away from the hospital because they are worried about being admitted,” Dr. Rao said.

Dr. Rao and Dr. Hess report no relevant conflicts of interest.

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

Background: There have been advances in perioperative care and technology for adults, but at the same time the patient population is increasingly medically complex. We do not know the current mortality risk of noncardiac surgery in adults.

Nine events were independently associated with postoperative death, but the top three – major bleeding, myocardial injury after noncardiac surgery (MINS), and sepsis – accounted for 45% of the attributable fraction. These, on average, occurred within 1-6 days after surgery. The other events (infection, kidney injury with dialysis, stroke, venous thromboembolism, new atrial fibrillation, and congestive heart failure) constituted less than 3% of the attributable fraction. Findings suggest that closer monitoring in the hospital and post discharge might improve survival after noncardiac surgery.

Limitations for hospitalists include that patients were younger and less medically complex than our typically comanaged patients: More than half of patients were aged 45-64, less than 10% had chronic kidney disease stage 3b or greater, and only 20% had diabetes mellitus.

Bottom line: Postoperative and postdischarge bleeding, myocardial injury after noncardiac surgery, and sepsis are major risk factors for 30-day mortality in adults undergoing noncardiac surgery. Closer postoperative monitoring for these conditions should be explored.

Citation: The Vision Study Investigators (Spence J et al.) Association between complications and death within 30 days after noncardiac surgery. CMAJ. 2019 Jul 29;191(30):E830-7.

Dr. Brouillette is a med-peds hospitalist at Maine Medical Center in Portland.

Background: There have been advances in perioperative care and technology for adults, but at the same time the patient population is increasingly medically complex. We do not know the current mortality risk of noncardiac surgery in adults.

Nine events were independently associated with postoperative death, but the top three – major bleeding, myocardial injury after noncardiac surgery (MINS), and sepsis – accounted for 45% of the attributable fraction. These, on average, occurred within 1-6 days after surgery. The other events (infection, kidney injury with dialysis, stroke, venous thromboembolism, new atrial fibrillation, and congestive heart failure) constituted less than 3% of the attributable fraction. Findings suggest that closer monitoring in the hospital and post discharge might improve survival after noncardiac surgery.

Limitations for hospitalists include that patients were younger and less medically complex than our typically comanaged patients: More than half of patients were aged 45-64, less than 10% had chronic kidney disease stage 3b or greater, and only 20% had diabetes mellitus.

Bottom line: Postoperative and postdischarge bleeding, myocardial injury after noncardiac surgery, and sepsis are major risk factors for 30-day mortality in adults undergoing noncardiac surgery. Closer postoperative monitoring for these conditions should be explored.

Citation: The Vision Study Investigators (Spence J et al.) Association between complications and death within 30 days after noncardiac surgery. CMAJ. 2019 Jul 29;191(30):E830-7.

Dr. Brouillette is a med-peds hospitalist at Maine Medical Center in Portland.

Background: There have been advances in perioperative care and technology for adults, but at the same time the patient population is increasingly medically complex. We do not know the current mortality risk of noncardiac surgery in adults.

Nine events were independently associated with postoperative death, but the top three – major bleeding, myocardial injury after noncardiac surgery (MINS), and sepsis – accounted for 45% of the attributable fraction. These, on average, occurred within 1-6 days after surgery. The other events (infection, kidney injury with dialysis, stroke, venous thromboembolism, new atrial fibrillation, and congestive heart failure) constituted less than 3% of the attributable fraction. Findings suggest that closer monitoring in the hospital and post discharge might improve survival after noncardiac surgery.

Limitations for hospitalists include that patients were younger and less medically complex than our typically comanaged patients: More than half of patients were aged 45-64, less than 10% had chronic kidney disease stage 3b or greater, and only 20% had diabetes mellitus.

Bottom line: Postoperative and postdischarge bleeding, myocardial injury after noncardiac surgery, and sepsis are major risk factors for 30-day mortality in adults undergoing noncardiac surgery. Closer postoperative monitoring for these conditions should be explored.

Citation: The Vision Study Investigators (Spence J et al.) Association between complications and death within 30 days after noncardiac surgery. CMAJ. 2019 Jul 29;191(30):E830-7.

Dr. Brouillette is a med-peds hospitalist at Maine Medical Center in Portland.

Heavy alcohol use in adolescence is linked to disruptions in white-matter integrity, new research suggests.

Highwaystarz-Photography/Thinkstock

In a case-control study of more than 400 participants, the association was more pronounced in younger adolescents and in the anterior and middle corpus callosum, which serve the interhemispheric integration of frontal networking and communication.

The results provide clinicians with yet another reason to ask adolescents about their alcohol use, said investigator Adolf Pfefferbaum, MD, Center for Health Sciences, SRI International, Menlo Park, Calif., and professor emeritus at Stanford (Calif.) University.

However, when questioning adolescents about their alcohol use, “sometimes it’s better to ask: ‘How much alcohol do you drink?’ ” instead of just asking if they drink, Dr. Pfefferbaum said in an interview. That’s because they may be more willing to answer the first question honestly.

It’s also important for clinicians to nonjudgmentally tell teens there is evidence “that heavy drinking is bad for their brain,” he added.

The findings were published online Dec. 30, 2020, in JAMA Psychiatry.
 

Fractional anisotropy

Adolescence is a critical period of physiological and social maturation accompanied by significant structural, functional, and neurochemical brain changes, the investigators noted.

Diffusion tensor imaging (DTI) produces a measure called fractional anisotropy (FA), which characterizes some of these brain changes by measuring molecular water diffusion in the brain.

“FA is a measure of the integrity of brain white matter; so, the part of the brain that connects neurons with each other,” Dr. Pfefferbaum said. He added that FA decreases in diseases such as multiple sclerosis (MS), reflecting “some kind of pathology.”

Affected fiber systems include the corpus callosum, superior longitudinal fasciculus, internal and external capsule, brain stem, and cortical projection fibers. Disruption of these neural systems may degrade neural signal transmission and affect certain cognitive functions, possibly resulting in enhanced impulsivity, poor inhibitory control, and restricted working memory capacity, the researchers wrote.

FA follows an inverted U-shaped pattern. “The natural trajectory is to increase from infancy up to middle adolescence and then, as we get older, from about age 25 to 30 years, starts to go down. Our brains are starting to show signs of aging a bit by then,” said Dr. Pfefferbaum.

The current analysis assessed 451 adolescents (228 boys and 223 girls) from the NCANDA study, for whom researchers had four years of longitudinal DTI data. All were aged 12- 21 years at baseline.

The NCANDA cohort was recruited across five U.S. sites. Participants are assessed yearly on psychobiologic measures, including brain maturation. The cohort, which did not have any significant substance abuse upon entry, is balanced in terms of gender and ethnicity.

The investigators quantified the developmental change of white-matter (WM) integrity within each individual as the slope of FA over visits. They also examined altered developmental trajectories associated with drinking onset during adolescence and the differential alcohol associations by age with specific regional WM fiber tracts.

Researchers assessed drinking on a scale of 1-4, based on the youth-adjusted Cahalan score. The scale considers quantity and frequency to classify drinking levels based on past-year self-reported patterns.
 

Altered trajectory

Results showed that 291 participants (37.2%) remained at no to low drinking levels (youth-adjusted Cahalan score, 0) throughout the time points examined, and 160 (20.5%) were classified as heavy drinkers for at least two consecutive visits (youth-adjusted Cahalan score >1).

Among the no to low drinkers, 48.4% were boys with a mean age of 16.5 years and 51.2% were girls with a mean age of 16.5 years. About two thirds of the group (66%) were White.

Among heavy drinkers, 53.8% were boys with a mean age of 20.1 years and 46.3% were girls with a mean age of 20.5 years. In this group, 88.8% were White.

The investigators did not analyze moderate drinkers or those who initiated heavy drinking for only one visit.

The findings also showed that heavy drinkers exhibited significant reduction of whole-brain FA. The slopes of the 78 heavy drinkers were significantly more negative than the 78 matched no to low drinkers (mean, –0.0013 vs. 0.0001; P = .008).

“The concept of the slopes is really important here because it’s the trajectory that seems to be the most sensitive measure,” Dr. Pfefferbaum said. “Probably what’s happening is the exposure to alcohol is interfering with the normal myelination and normal development of the adolescent’s white matter.”

The no to low drinkers had relatively stable FA measures across all visits.

A reduction in FA was significantly linked to heavy drinking. An analysis of 63 youth who transitioned from being a no to low drinker to a heavy drinker showed that before the transition, they had significantly increased FA over visits (95% CI of slope, 0.0011-0.0024; P < .001). In addition, their corresponding slopes were not different from other no to low drinkers of the same age range.

However, this group’s FA declined significantly after they reported heavy drinking, resulting in slopes significantly below zero (95% CI of slope, –0.0036 to –0.0014; P < .001) and that were lower than the no to low participants of the same age range.

The findings of this unique before-and-after assessment “bring us one step closer to causality,” and further illustrates that heavy drinking in adolescence affects WM integrity, Dr. Pfefferbaum said.
 

Potential markers

None of the slope measures correlated with number of visits or use of tobacco or cannabis. The association of alcohol with the slope measures was more apparent in the younger cohort (<19 years).

“The effects were seen more readily in younger adolescents because they are the ones who are still progressing along this normal developmental trajectory,” Dr. Pfefferbaum noted. “In a sense, the younger you are when you’re exposed to alcohol, probably the more vulnerable you are.”

Previous studies have suggested that damage in WM tracts is associated with heightened neural reactivity to alcohol cues in adults with alcohol use disorder. Given this evidence, the greater WM degradation at younger versus older ages might help explain why adolescents who initiate early drinking are more likely to develop addiction later in life, the investigators wrote.

Of the five major fiber tracts, only the commissural fibers (corpus callosum) showed a significant association with alcohol. The researchers noted that WM volume shrinkage and callosal demyelination are two of the most prominent markers in adult alcoholism and are potential markers in adolescent alcohol abuse.

Upon further extending the analysis to the four subregions of the corpus callosum, the investigators found that only the anterior and middle callosal regions (genu and body) showed significant age-alcohol interactions.

This could be a result of the timing of fiber myelination in these regions of the brain, compared with others, Dr. Pfefferbaum said.

He noted that these fibers connect the left and right part of the anterior regions of the brain, especially the frontal lobes, which are particularly vulnerable to the effects of alcohol. “It may well be that we have this interaction of the developmental time and the sensitivity of the frontal parts of the brain.”
 

Cognitive effects?

Although the researchers did not find any sex effects, Dr. Pfefferbaum stressed that this doesn’t mean they do not exist. “We just may not have the power to see them,” he said.

The study did not look specifically at binge drinkers, defined as consuming five drinks in 2 hours for men and four drinks in 2 hours for women. Dr. Pfefferbaum noted that it is difficult to get “good quantification” of binge drinking. “We don’t have a fine enough grain analysis to separate that out,” he said.

Asked whether the altered FA trajectory in heavy drinkers affects cognition, Dr. Pfefferbaum said “those studies are still in progress,” with results hopefully available within about a year.

Dr. Pfefferbaum said he and his colleagues are continuing to follow these adolescents and hope to see if the altered FA trajectory in heavy drinkers returns to normal, adding: “The real question now is: If they stop heavy drinking, will they get back on track?”

This study is believed to be the first to suggest in vivo differential vulnerability in WM microstructure with respect to age, the authors note.

In addition to asking teens about their alcohol use, the clinician’s role should be to “counsel and refer,” said Dr. Pfefferbaum. He also suggested accessing resources from the National Institute on Alcohol Abuse and Alcoholism.
 

Important data, but several limitations

In an interview, Oscar G. Bukstein, MD, MPH, medical director of outpatient psychiatry service at Boston Children’s Hospital, and professor of psychiatry at Harvard Medical School, also in Boston, said the findings provide further evidence that alcohol affects the maturing brain.

This study, and others that have examined cannabis use, “show that you have a dynamically growing brain with certain sections, particularly in this case the anterior and middle corpus callosum, that mature later [and] that are more likely to be affected by early alcohol use,” said Dr. Bukstein, who was not involved with the research.

He stressed the importance of determining the mechanism involved and noted some study limitations. For example, the DTI technology used may “already be out of date,” he said.

Using older technology may have prevented finding an impact of heavy drinking on parts of the brain other than the anterior and middle corpus callosum, Dr. Bukstein noted.

Newer technology might provide “a finer-grain nonlinear voxel-wise analysis,” although using more updated scanning techniques may not have detected additional differences in study groups, he added.

Dr. Bukstein also noted that there were limitations: The study did not have “gradations,” but only looked at heavy drinking and no to low drinking. “You’d like to find out about kids who are somewhere in the middle.” It also didn’t determine a “cutoff” where deleterious effects of alcohol on the brain begin, Dr. Bukstein added.

Additionally, the study didn’t look at brain development outcomes in children with conditions such as depression and ADHD that are known to lead to substance use – something a larger study may have been able to do, he said.

Dr. Bukstein noted that a newer and much larger study, the Adolescent Brain Cognitive Development study, has begun assessing kids for risk factors such as substance use, starting at age 10 years.

The study was funded by grants from NIAAA and by the National Institute on Drug Abuse, the National Institute of Mental Health, the National Institute of Child Health and Human Development, and the Stanford Institute for Human-Centered Artificial Intelligence–AWS Cloud Credits for Research. Dr. Pfefferbaum reported receiving an NIAAA grant during the conduct of the study. Dr. Bukstein disclosed no relevant financial relationships.

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

Heavy alcohol use in adolescence is linked to disruptions in white-matter integrity, new research suggests.

Highwaystarz-Photography/Thinkstock

In a case-control study of more than 400 participants, the association was more pronounced in younger adolescents and in the anterior and middle corpus callosum, which serve the interhemispheric integration of frontal networking and communication.

The results provide clinicians with yet another reason to ask adolescents about their alcohol use, said investigator Adolf Pfefferbaum, MD, Center for Health Sciences, SRI International, Menlo Park, Calif., and professor emeritus at Stanford (Calif.) University.

However, when questioning adolescents about their alcohol use, “sometimes it’s better to ask: ‘How much alcohol do you drink?’ ” instead of just asking if they drink, Dr. Pfefferbaum said in an interview. That’s because they may be more willing to answer the first question honestly.

It’s also important for clinicians to nonjudgmentally tell teens there is evidence “that heavy drinking is bad for their brain,” he added.

The findings were published online Dec. 30, 2020, in JAMA Psychiatry.
 

Fractional anisotropy

Adolescence is a critical period of physiological and social maturation accompanied by significant structural, functional, and neurochemical brain changes, the investigators noted.

Diffusion tensor imaging (DTI) produces a measure called fractional anisotropy (FA), which characterizes some of these brain changes by measuring molecular water diffusion in the brain.

“FA is a measure of the integrity of brain white matter; so, the part of the brain that connects neurons with each other,” Dr. Pfefferbaum said. He added that FA decreases in diseases such as multiple sclerosis (MS), reflecting “some kind of pathology.”

Affected fiber systems include the corpus callosum, superior longitudinal fasciculus, internal and external capsule, brain stem, and cortical projection fibers. Disruption of these neural systems may degrade neural signal transmission and affect certain cognitive functions, possibly resulting in enhanced impulsivity, poor inhibitory control, and restricted working memory capacity, the researchers wrote.

FA follows an inverted U-shaped pattern. “The natural trajectory is to increase from infancy up to middle adolescence and then, as we get older, from about age 25 to 30 years, starts to go down. Our brains are starting to show signs of aging a bit by then,” said Dr. Pfefferbaum.

The current analysis assessed 451 adolescents (228 boys and 223 girls) from the NCANDA study, for whom researchers had four years of longitudinal DTI data. All were aged 12- 21 years at baseline.

The NCANDA cohort was recruited across five U.S. sites. Participants are assessed yearly on psychobiologic measures, including brain maturation. The cohort, which did not have any significant substance abuse upon entry, is balanced in terms of gender and ethnicity.

The investigators quantified the developmental change of white-matter (WM) integrity within each individual as the slope of FA over visits. They also examined altered developmental trajectories associated with drinking onset during adolescence and the differential alcohol associations by age with specific regional WM fiber tracts.

Researchers assessed drinking on a scale of 1-4, based on the youth-adjusted Cahalan score. The scale considers quantity and frequency to classify drinking levels based on past-year self-reported patterns.
 

Altered trajectory

Results showed that 291 participants (37.2%) remained at no to low drinking levels (youth-adjusted Cahalan score, 0) throughout the time points examined, and 160 (20.5%) were classified as heavy drinkers for at least two consecutive visits (youth-adjusted Cahalan score >1).

Among the no to low drinkers, 48.4% were boys with a mean age of 16.5 years and 51.2% were girls with a mean age of 16.5 years. About two thirds of the group (66%) were White.

Among heavy drinkers, 53.8% were boys with a mean age of 20.1 years and 46.3% were girls with a mean age of 20.5 years. In this group, 88.8% were White.

The investigators did not analyze moderate drinkers or those who initiated heavy drinking for only one visit.

The findings also showed that heavy drinkers exhibited significant reduction of whole-brain FA. The slopes of the 78 heavy drinkers were significantly more negative than the 78 matched no to low drinkers (mean, –0.0013 vs. 0.0001; P = .008).

“The concept of the slopes is really important here because it’s the trajectory that seems to be the most sensitive measure,” Dr. Pfefferbaum said. “Probably what’s happening is the exposure to alcohol is interfering with the normal myelination and normal development of the adolescent’s white matter.”

The no to low drinkers had relatively stable FA measures across all visits.

A reduction in FA was significantly linked to heavy drinking. An analysis of 63 youth who transitioned from being a no to low drinker to a heavy drinker showed that before the transition, they had significantly increased FA over visits (95% CI of slope, 0.0011-0.0024; P < .001). In addition, their corresponding slopes were not different from other no to low drinkers of the same age range.

However, this group’s FA declined significantly after they reported heavy drinking, resulting in slopes significantly below zero (95% CI of slope, –0.0036 to –0.0014; P < .001) and that were lower than the no to low participants of the same age range.

The findings of this unique before-and-after assessment “bring us one step closer to causality,” and further illustrates that heavy drinking in adolescence affects WM integrity, Dr. Pfefferbaum said.
 

Potential markers

None of the slope measures correlated with number of visits or use of tobacco or cannabis. The association of alcohol with the slope measures was more apparent in the younger cohort (<19 years).

“The effects were seen more readily in younger adolescents because they are the ones who are still progressing along this normal developmental trajectory,” Dr. Pfefferbaum noted. “In a sense, the younger you are when you’re exposed to alcohol, probably the more vulnerable you are.”

Previous studies have suggested that damage in WM tracts is associated with heightened neural reactivity to alcohol cues in adults with alcohol use disorder. Given this evidence, the greater WM degradation at younger versus older ages might help explain why adolescents who initiate early drinking are more likely to develop addiction later in life, the investigators wrote.

Of the five major fiber tracts, only the commissural fibers (corpus callosum) showed a significant association with alcohol. The researchers noted that WM volume shrinkage and callosal demyelination are two of the most prominent markers in adult alcoholism and are potential markers in adolescent alcohol abuse.

Upon further extending the analysis to the four subregions of the corpus callosum, the investigators found that only the anterior and middle callosal regions (genu and body) showed significant age-alcohol interactions.

This could be a result of the timing of fiber myelination in these regions of the brain, compared with others, Dr. Pfefferbaum said.

He noted that these fibers connect the left and right part of the anterior regions of the brain, especially the frontal lobes, which are particularly vulnerable to the effects of alcohol. “It may well be that we have this interaction of the developmental time and the sensitivity of the frontal parts of the brain.”
 

Cognitive effects?

Although the researchers did not find any sex effects, Dr. Pfefferbaum stressed that this doesn’t mean they do not exist. “We just may not have the power to see them,” he said.

The study did not look specifically at binge drinkers, defined as consuming five drinks in 2 hours for men and four drinks in 2 hours for women. Dr. Pfefferbaum noted that it is difficult to get “good quantification” of binge drinking. “We don’t have a fine enough grain analysis to separate that out,” he said.

Asked whether the altered FA trajectory in heavy drinkers affects cognition, Dr. Pfefferbaum said “those studies are still in progress,” with results hopefully available within about a year.

Dr. Pfefferbaum said he and his colleagues are continuing to follow these adolescents and hope to see if the altered FA trajectory in heavy drinkers returns to normal, adding: “The real question now is: If they stop heavy drinking, will they get back on track?”

This study is believed to be the first to suggest in vivo differential vulnerability in WM microstructure with respect to age, the authors note.

In addition to asking teens about their alcohol use, the clinician’s role should be to “counsel and refer,” said Dr. Pfefferbaum. He also suggested accessing resources from the National Institute on Alcohol Abuse and Alcoholism.
 

Important data, but several limitations

In an interview, Oscar G. Bukstein, MD, MPH, medical director of outpatient psychiatry service at Boston Children’s Hospital, and professor of psychiatry at Harvard Medical School, also in Boston, said the findings provide further evidence that alcohol affects the maturing brain.

This study, and others that have examined cannabis use, “show that you have a dynamically growing brain with certain sections, particularly in this case the anterior and middle corpus callosum, that mature later [and] that are more likely to be affected by early alcohol use,” said Dr. Bukstein, who was not involved with the research.

He stressed the importance of determining the mechanism involved and noted some study limitations. For example, the DTI technology used may “already be out of date,” he said.

Using older technology may have prevented finding an impact of heavy drinking on parts of the brain other than the anterior and middle corpus callosum, Dr. Bukstein noted.

Newer technology might provide “a finer-grain nonlinear voxel-wise analysis,” although using more updated scanning techniques may not have detected additional differences in study groups, he added.

Dr. Bukstein also noted that there were limitations: The study did not have “gradations,” but only looked at heavy drinking and no to low drinking. “You’d like to find out about kids who are somewhere in the middle.” It also didn’t determine a “cutoff” where deleterious effects of alcohol on the brain begin, Dr. Bukstein added.

Additionally, the study didn’t look at brain development outcomes in children with conditions such as depression and ADHD that are known to lead to substance use – something a larger study may have been able to do, he said.

Dr. Bukstein noted that a newer and much larger study, the Adolescent Brain Cognitive Development study, has begun assessing kids for risk factors such as substance use, starting at age 10 years.

The study was funded by grants from NIAAA and by the National Institute on Drug Abuse, the National Institute of Mental Health, the National Institute of Child Health and Human Development, and the Stanford Institute for Human-Centered Artificial Intelligence–AWS Cloud Credits for Research. Dr. Pfefferbaum reported receiving an NIAAA grant during the conduct of the study. Dr. Bukstein disclosed no relevant financial relationships.

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

Heavy alcohol use in adolescence is linked to disruptions in white-matter integrity, new research suggests.

Highwaystarz-Photography/Thinkstock

In a case-control study of more than 400 participants, the association was more pronounced in younger adolescents and in the anterior and middle corpus callosum, which serve the interhemispheric integration of frontal networking and communication.

The results provide clinicians with yet another reason to ask adolescents about their alcohol use, said investigator Adolf Pfefferbaum, MD, Center for Health Sciences, SRI International, Menlo Park, Calif., and professor emeritus at Stanford (Calif.) University.

However, when questioning adolescents about their alcohol use, “sometimes it’s better to ask: ‘How much alcohol do you drink?’ ” instead of just asking if they drink, Dr. Pfefferbaum said in an interview. That’s because they may be more willing to answer the first question honestly.

It’s also important for clinicians to nonjudgmentally tell teens there is evidence “that heavy drinking is bad for their brain,” he added.

The findings were published online Dec. 30, 2020, in JAMA Psychiatry.
 

Fractional anisotropy

Adolescence is a critical period of physiological and social maturation accompanied by significant structural, functional, and neurochemical brain changes, the investigators noted.

Diffusion tensor imaging (DTI) produces a measure called fractional anisotropy (FA), which characterizes some of these brain changes by measuring molecular water diffusion in the brain.

“FA is a measure of the integrity of brain white matter; so, the part of the brain that connects neurons with each other,” Dr. Pfefferbaum said. He added that FA decreases in diseases such as multiple sclerosis (MS), reflecting “some kind of pathology.”

Affected fiber systems include the corpus callosum, superior longitudinal fasciculus, internal and external capsule, brain stem, and cortical projection fibers. Disruption of these neural systems may degrade neural signal transmission and affect certain cognitive functions, possibly resulting in enhanced impulsivity, poor inhibitory control, and restricted working memory capacity, the researchers wrote.

FA follows an inverted U-shaped pattern. “The natural trajectory is to increase from infancy up to middle adolescence and then, as we get older, from about age 25 to 30 years, starts to go down. Our brains are starting to show signs of aging a bit by then,” said Dr. Pfefferbaum.

The current analysis assessed 451 adolescents (228 boys and 223 girls) from the NCANDA study, for whom researchers had four years of longitudinal DTI data. All were aged 12- 21 years at baseline.

The NCANDA cohort was recruited across five U.S. sites. Participants are assessed yearly on psychobiologic measures, including brain maturation. The cohort, which did not have any significant substance abuse upon entry, is balanced in terms of gender and ethnicity.

The investigators quantified the developmental change of white-matter (WM) integrity within each individual as the slope of FA over visits. They also examined altered developmental trajectories associated with drinking onset during adolescence and the differential alcohol associations by age with specific regional WM fiber tracts.

Researchers assessed drinking on a scale of 1-4, based on the youth-adjusted Cahalan score. The scale considers quantity and frequency to classify drinking levels based on past-year self-reported patterns.
 

Altered trajectory

Results showed that 291 participants (37.2%) remained at no to low drinking levels (youth-adjusted Cahalan score, 0) throughout the time points examined, and 160 (20.5%) were classified as heavy drinkers for at least two consecutive visits (youth-adjusted Cahalan score >1).

Among the no to low drinkers, 48.4% were boys with a mean age of 16.5 years and 51.2% were girls with a mean age of 16.5 years. About two thirds of the group (66%) were White.

Among heavy drinkers, 53.8% were boys with a mean age of 20.1 years and 46.3% were girls with a mean age of 20.5 years. In this group, 88.8% were White.

The investigators did not analyze moderate drinkers or those who initiated heavy drinking for only one visit.

The findings also showed that heavy drinkers exhibited significant reduction of whole-brain FA. The slopes of the 78 heavy drinkers were significantly more negative than the 78 matched no to low drinkers (mean, –0.0013 vs. 0.0001; P = .008).

“The concept of the slopes is really important here because it’s the trajectory that seems to be the most sensitive measure,” Dr. Pfefferbaum said. “Probably what’s happening is the exposure to alcohol is interfering with the normal myelination and normal development of the adolescent’s white matter.”

The no to low drinkers had relatively stable FA measures across all visits.

A reduction in FA was significantly linked to heavy drinking. An analysis of 63 youth who transitioned from being a no to low drinker to a heavy drinker showed that before the transition, they had significantly increased FA over visits (95% CI of slope, 0.0011-0.0024; P < .001). In addition, their corresponding slopes were not different from other no to low drinkers of the same age range.

However, this group’s FA declined significantly after they reported heavy drinking, resulting in slopes significantly below zero (95% CI of slope, –0.0036 to –0.0014; P < .001) and that were lower than the no to low participants of the same age range.

The findings of this unique before-and-after assessment “bring us one step closer to causality,” and further illustrates that heavy drinking in adolescence affects WM integrity, Dr. Pfefferbaum said.
 

Potential markers

None of the slope measures correlated with number of visits or use of tobacco or cannabis. The association of alcohol with the slope measures was more apparent in the younger cohort (<19 years).

“The effects were seen more readily in younger adolescents because they are the ones who are still progressing along this normal developmental trajectory,” Dr. Pfefferbaum noted. “In a sense, the younger you are when you’re exposed to alcohol, probably the more vulnerable you are.”

Previous studies have suggested that damage in WM tracts is associated with heightened neural reactivity to alcohol cues in adults with alcohol use disorder. Given this evidence, the greater WM degradation at younger versus older ages might help explain why adolescents who initiate early drinking are more likely to develop addiction later in life, the investigators wrote.

Of the five major fiber tracts, only the commissural fibers (corpus callosum) showed a significant association with alcohol. The researchers noted that WM volume shrinkage and callosal demyelination are two of the most prominent markers in adult alcoholism and are potential markers in adolescent alcohol abuse.

Upon further extending the analysis to the four subregions of the corpus callosum, the investigators found that only the anterior and middle callosal regions (genu and body) showed significant age-alcohol interactions.

This could be a result of the timing of fiber myelination in these regions of the brain, compared with others, Dr. Pfefferbaum said.

He noted that these fibers connect the left and right part of the anterior regions of the brain, especially the frontal lobes, which are particularly vulnerable to the effects of alcohol. “It may well be that we have this interaction of the developmental time and the sensitivity of the frontal parts of the brain.”
 

Cognitive effects?

Although the researchers did not find any sex effects, Dr. Pfefferbaum stressed that this doesn’t mean they do not exist. “We just may not have the power to see them,” he said.

The study did not look specifically at binge drinkers, defined as consuming five drinks in 2 hours for men and four drinks in 2 hours for women. Dr. Pfefferbaum noted that it is difficult to get “good quantification” of binge drinking. “We don’t have a fine enough grain analysis to separate that out,” he said.

Asked whether the altered FA trajectory in heavy drinkers affects cognition, Dr. Pfefferbaum said “those studies are still in progress,” with results hopefully available within about a year.

Dr. Pfefferbaum said he and his colleagues are continuing to follow these adolescents and hope to see if the altered FA trajectory in heavy drinkers returns to normal, adding: “The real question now is: If they stop heavy drinking, will they get back on track?”

This study is believed to be the first to suggest in vivo differential vulnerability in WM microstructure with respect to age, the authors note.

In addition to asking teens about their alcohol use, the clinician’s role should be to “counsel and refer,” said Dr. Pfefferbaum. He also suggested accessing resources from the National Institute on Alcohol Abuse and Alcoholism.
 

Important data, but several limitations

In an interview, Oscar G. Bukstein, MD, MPH, medical director of outpatient psychiatry service at Boston Children’s Hospital, and professor of psychiatry at Harvard Medical School, also in Boston, said the findings provide further evidence that alcohol affects the maturing brain.

This study, and others that have examined cannabis use, “show that you have a dynamically growing brain with certain sections, particularly in this case the anterior and middle corpus callosum, that mature later [and] that are more likely to be affected by early alcohol use,” said Dr. Bukstein, who was not involved with the research.

He stressed the importance of determining the mechanism involved and noted some study limitations. For example, the DTI technology used may “already be out of date,” he said.

Using older technology may have prevented finding an impact of heavy drinking on parts of the brain other than the anterior and middle corpus callosum, Dr. Bukstein noted.

Newer technology might provide “a finer-grain nonlinear voxel-wise analysis,” although using more updated scanning techniques may not have detected additional differences in study groups, he added.

Dr. Bukstein also noted that there were limitations: The study did not have “gradations,” but only looked at heavy drinking and no to low drinking. “You’d like to find out about kids who are somewhere in the middle.” It also didn’t determine a “cutoff” where deleterious effects of alcohol on the brain begin, Dr. Bukstein added.

Additionally, the study didn’t look at brain development outcomes in children with conditions such as depression and ADHD that are known to lead to substance use – something a larger study may have been able to do, he said.

Dr. Bukstein noted that a newer and much larger study, the Adolescent Brain Cognitive Development study, has begun assessing kids for risk factors such as substance use, starting at age 10 years.

The study was funded by grants from NIAAA and by the National Institute on Drug Abuse, the National Institute of Mental Health, the National Institute of Child Health and Human Development, and the Stanford Institute for Human-Centered Artificial Intelligence–AWS Cloud Credits for Research. Dr. Pfefferbaum reported receiving an NIAAA grant during the conduct of the study. Dr. Bukstein disclosed no relevant financial relationships.

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