A new study finds that patients with screen-detected lung cancer are at increased risk for a second primary lung cancer diagnosis, with about half occurring within 6 months of the first diagnosis. More than 80% of second primary cancers diagnosed within 2 years were stage 1, compared with about 25% when diagnosed more than 5 years later.

“With the growing adoption of lung cancer screening, more patients are being diagnosed with early-stage lung cancers and are able to achieve excellent long-term survival. After lung cancer diagnosis, these patients remain at high risk of developing a second primary lung cancer. The incidence, timing, and survival of second primary lung cancers is not well understood, particularly in a patient population with initial primary lung cancers detected via lung cancer screening,” said Alexandra Potter, who is a study coauthor.

The results were presented by Chi-Fu Jeffrey Yang, MD, at a press conference held at the World Conference on Lung Cancer sponsored by the International Association for the Study of Lung Cancer. Dr. Yang is a thoracic surgeon at Massachusetts General Hospital, Boston.

A 2012 study analyzed data from the SEER database and found that lung cancer survivors had a four- to sixfold increase in the risk of developing a second primary lung cancer, compared with the risk of lung cancer in the general population after adjusting for sex, age, race, and calendar year. “That study demonstrated that second primary lung cancers are an important risk among lung cancer survivors. However, it did not evaluate patients diagnosed with initial lung cancers detected via lung cancer screening. Thus, the incidence, timing, characteristics, and survival of lung cancers diagnosed among patients diagnosed with initial lung cancers detected via lung cancer screening remain unknown,” said Ms. Potter, who is a research assistant at Massachusetts General Hospital and president of the American Lung Cancer Screening Initiative.

To address that question, the researchers used data from the National Lung Screening Trial, which compared low-dose computed tomography to chest x-ray and found that the former led to a 15%-20% lower risk of death. The new analysis included 1,405 patients who were diagnosed with stage I-III lung cancer and treated between 2002 and 2009. Of these patients, 5.8% went on to be diagnosed with a second primary lung cancer, at a rate of 1%-2% per year. Of the second lung cancers, 54.9% were synchronous, occurring within 6 months of the diagnosis, and 45.1% were metachronous, occurring later than 6 months; 65% of synchronous secondary cancers and 81% of metachronous cancers were diagnosed at stage I; 24% of synchronous and 14% of metachronous were stage III (P = .25). The median time to diagnosis of metachronous lung cancers was 2.7 years, and 27% of the second primary tumors were diagnosed 4 or more years after the first diagnosis.

Among those with synchronous tumors, 5- and 10-year survival rates were 55.2% and 39.5%. The rates were 90.0% and 30.8% among metachronous tumors, respectively. Ms. Potter emphasized that most patients with second primary cancer were diagnosed at stage I, suggesting that it is very possible to catch these cancers early. But patients who were diagnosed with a second primary tumor 4 or more years after their first diagnosis had a greater likelihood of later-stage second cancer. Medical societies generally recommend CT screening surveillance every 6 months for 2 years following a lung cancer diagnosis, then annually thereafter. The greater frequency of later-stage cancer detected after 4 years suggests that surveillance may be flagging as time goes on. “These data highlight the importance of lifelong follow up after initial lung cancer diagnosis,” said Ms. Potter.

She also emphasized the importance of smoking cessation and ongoing abstinence following a diagnosis of lung cancer. “About 70% of patients in the NLST who developed second primary lung cancer currently smoked at the time of entry into the trial. Smoking cessation can help reduce patients’ risk of developing second primary lung cancers,” she said. Ms. Potter has no relevant financial disclosures.

A new study finds that patients with screen-detected lung cancer are at increased risk for a second primary lung cancer diagnosis, with about half occurring within 6 months of the first diagnosis. More than 80% of second primary cancers diagnosed within 2 years were stage 1, compared with about 25% when diagnosed more than 5 years later.

“With the growing adoption of lung cancer screening, more patients are being diagnosed with early-stage lung cancers and are able to achieve excellent long-term survival. After lung cancer diagnosis, these patients remain at high risk of developing a second primary lung cancer. The incidence, timing, and survival of second primary lung cancers is not well understood, particularly in a patient population with initial primary lung cancers detected via lung cancer screening,” said Alexandra Potter, who is a study coauthor.

The results were presented by Chi-Fu Jeffrey Yang, MD, at a press conference held at the World Conference on Lung Cancer sponsored by the International Association for the Study of Lung Cancer. Dr. Yang is a thoracic surgeon at Massachusetts General Hospital, Boston.

A 2012 study analyzed data from the SEER database and found that lung cancer survivors had a four- to sixfold increase in the risk of developing a second primary lung cancer, compared with the risk of lung cancer in the general population after adjusting for sex, age, race, and calendar year. “That study demonstrated that second primary lung cancers are an important risk among lung cancer survivors. However, it did not evaluate patients diagnosed with initial lung cancers detected via lung cancer screening. Thus, the incidence, timing, characteristics, and survival of lung cancers diagnosed among patients diagnosed with initial lung cancers detected via lung cancer screening remain unknown,” said Ms. Potter, who is a research assistant at Massachusetts General Hospital and president of the American Lung Cancer Screening Initiative.

To address that question, the researchers used data from the National Lung Screening Trial, which compared low-dose computed tomography to chest x-ray and found that the former led to a 15%-20% lower risk of death. The new analysis included 1,405 patients who were diagnosed with stage I-III lung cancer and treated between 2002 and 2009. Of these patients, 5.8% went on to be diagnosed with a second primary lung cancer, at a rate of 1%-2% per year. Of the second lung cancers, 54.9% were synchronous, occurring within 6 months of the diagnosis, and 45.1% were metachronous, occurring later than 6 months; 65% of synchronous secondary cancers and 81% of metachronous cancers were diagnosed at stage I; 24% of synchronous and 14% of metachronous were stage III (P = .25). The median time to diagnosis of metachronous lung cancers was 2.7 years, and 27% of the second primary tumors were diagnosed 4 or more years after the first diagnosis.

Among those with synchronous tumors, 5- and 10-year survival rates were 55.2% and 39.5%. The rates were 90.0% and 30.8% among metachronous tumors, respectively. Ms. Potter emphasized that most patients with second primary cancer were diagnosed at stage I, suggesting that it is very possible to catch these cancers early. But patients who were diagnosed with a second primary tumor 4 or more years after their first diagnosis had a greater likelihood of later-stage second cancer. Medical societies generally recommend CT screening surveillance every 6 months for 2 years following a lung cancer diagnosis, then annually thereafter. The greater frequency of later-stage cancer detected after 4 years suggests that surveillance may be flagging as time goes on. “These data highlight the importance of lifelong follow up after initial lung cancer diagnosis,” said Ms. Potter.

She also emphasized the importance of smoking cessation and ongoing abstinence following a diagnosis of lung cancer. “About 70% of patients in the NLST who developed second primary lung cancer currently smoked at the time of entry into the trial. Smoking cessation can help reduce patients’ risk of developing second primary lung cancers,” she said. Ms. Potter has no relevant financial disclosures.

A new study finds that patients with screen-detected lung cancer are at increased risk for a second primary lung cancer diagnosis, with about half occurring within 6 months of the first diagnosis. More than 80% of second primary cancers diagnosed within 2 years were stage 1, compared with about 25% when diagnosed more than 5 years later.

“With the growing adoption of lung cancer screening, more patients are being diagnosed with early-stage lung cancers and are able to achieve excellent long-term survival. After lung cancer diagnosis, these patients remain at high risk of developing a second primary lung cancer. The incidence, timing, and survival of second primary lung cancers is not well understood, particularly in a patient population with initial primary lung cancers detected via lung cancer screening,” said Alexandra Potter, who is a study coauthor.

The results were presented by Chi-Fu Jeffrey Yang, MD, at a press conference held at the World Conference on Lung Cancer sponsored by the International Association for the Study of Lung Cancer. Dr. Yang is a thoracic surgeon at Massachusetts General Hospital, Boston.

A 2012 study analyzed data from the SEER database and found that lung cancer survivors had a four- to sixfold increase in the risk of developing a second primary lung cancer, compared with the risk of lung cancer in the general population after adjusting for sex, age, race, and calendar year. “That study demonstrated that second primary lung cancers are an important risk among lung cancer survivors. However, it did not evaluate patients diagnosed with initial lung cancers detected via lung cancer screening. Thus, the incidence, timing, characteristics, and survival of lung cancers diagnosed among patients diagnosed with initial lung cancers detected via lung cancer screening remain unknown,” said Ms. Potter, who is a research assistant at Massachusetts General Hospital and president of the American Lung Cancer Screening Initiative.

To address that question, the researchers used data from the National Lung Screening Trial, which compared low-dose computed tomography to chest x-ray and found that the former led to a 15%-20% lower risk of death. The new analysis included 1,405 patients who were diagnosed with stage I-III lung cancer and treated between 2002 and 2009. Of these patients, 5.8% went on to be diagnosed with a second primary lung cancer, at a rate of 1%-2% per year. Of the second lung cancers, 54.9% were synchronous, occurring within 6 months of the diagnosis, and 45.1% were metachronous, occurring later than 6 months; 65% of synchronous secondary cancers and 81% of metachronous cancers were diagnosed at stage I; 24% of synchronous and 14% of metachronous were stage III (P = .25). The median time to diagnosis of metachronous lung cancers was 2.7 years, and 27% of the second primary tumors were diagnosed 4 or more years after the first diagnosis.

Among those with synchronous tumors, 5- and 10-year survival rates were 55.2% and 39.5%. The rates were 90.0% and 30.8% among metachronous tumors, respectively. Ms. Potter emphasized that most patients with second primary cancer were diagnosed at stage I, suggesting that it is very possible to catch these cancers early. But patients who were diagnosed with a second primary tumor 4 or more years after their first diagnosis had a greater likelihood of later-stage second cancer. Medical societies generally recommend CT screening surveillance every 6 months for 2 years following a lung cancer diagnosis, then annually thereafter. The greater frequency of later-stage cancer detected after 4 years suggests that surveillance may be flagging as time goes on. “These data highlight the importance of lifelong follow up after initial lung cancer diagnosis,” said Ms. Potter.

She also emphasized the importance of smoking cessation and ongoing abstinence following a diagnosis of lung cancer. “About 70% of patients in the NLST who developed second primary lung cancer currently smoked at the time of entry into the trial. Smoking cessation can help reduce patients’ risk of developing second primary lung cancers,” she said. Ms. Potter has no relevant financial disclosures.

Early improvement of left ventricular ejection fraction (LVEF) after transcatheter aortic valve replacement (TAVR) is associated with improved all-cause and cardiac death at 5 years in patients with severe aortic stenosis and LVEF less than 50%, new research shows.

Further analyses revealed a significant interaction by sex, with the mortality benefit largely in women.

“It’s absolutely fascinating,” senior author Sammy Elmariah, MD, Massachusetts General Hospital, Boston, said of the finding. “We know that women are more likely to have concentric hypertrophy, that they have lesser degrees of fibrosis, and smaller ventricles, and, of course, they’re in general less affected by coronary artery disease and MIs [myocardial infarctions]. All of those things in my mind, at least that’s what I assumed ahead of time, would make it more likely for women’s hearts to recover.”

“But that’s actually not what we found,” he continued. “We didn’t see a difference between the sexes in terms of likelihood of recovery. But what we saw is that the survival benefit, that associates with improvement in EF, was almost completely driven by women. So women really seem to be reaping that benefit in a manner that is unique and very different from what we saw in men.”

Dr. Elmariah noted that the reason for this benefit is unclear but points to the differences in biology for LV remodeling. “Clearly there are several details there that warrant further attention and more research.”

Suzanne J. Baron, MD, director of interventional cardiology research at Lahey Hospital and Medical Center, Burlington, Mass., said in an email that the finding of a substantial long-term survival benefit was “a bit surprising.”

Several studies have suggested that women may derive a greater benefit from TAVR versus surgical aortic valve replacement, and meta-analyses have demonstrated short and intermediate-term survival after TAVR is better in women, compared with in men, she pointed out. However, the mediating mechanism for this finding has never been clearly elucidated.

“Certainly, the sex differences in LVEF improvement after TAVR observed in this study, which could be related to sex differences in LV remodeling and LV mass regression, may now give us a clue as to why these sex-specific survival differences after TAVR persist,” Dr. Baron said.
 

More data amassed

Previous research in smaller cohorts with follow-up out to 1 year have shown an association between early LVEF improvement after TAVR and better survival. This includes a 2013 study by the investigators in high-risk patients in PARTNER-1 and a separate 2016 study in patients in the CoreValve extreme and high surgical risk trials.

Now, with longer follow-up amassed, the investigators examined data from 659 high- or intermediate-risk patients with severe stenosis and LVEF less than 50% who underwent transfemoral TAVR in the PARTNER 1, 2, and S3 trials and registries between July 2007 and April 2015.

Their mean age was 82.4 years, 71% were men, and 89.7% were White individuals. During the study period, 55.6% of the cohort died.

As reported in JAMA Cardiology, 32.8% of patients had early LVEF improvement, defined as an increase of at least 10% percentage points at 30 days after TAVR (mean change, 16.4%).

This compares with about 50%-60% of patients in the earlier studies, likely owing to the relatively higher baseline LVEF, especially in the intermediate-risk cohort, the authors suggested.

Independent predictors of lower likelihood of early LVEF improvement were previous MI, diabetes, cancer, higher baseline LVEF, larger LV end-diastolic diameter, and larger aortic valve area (AVA), whereas higher body mass index and higher stroke volume index predicted greater likelihood of LV recovery.

At 5 years, patients with versus without improved early LV improvement had lower risks of all-cause death (50.0% vs. 58.4%; P = .04) and cardiac death (29.5% vs. 38.1%; P = .05).

In multivariable analyses, each 5%-point increase in LVEF after TAVR was associated with a 6% lower risk of all-cause death (hazard ratio [HR], 0.94; P = .04) and 10% lower risk of cardiac death (HR, 0.90; P = .02).

Restricted cubic spline analysis demonstrated an inflection point above a 10% change in LVEF beyond which there was a steep decline in all-cause mortality with increasing degree of LVEF improvement.

There were no significant differences in rehospitalization, New York Heart Association functional class, or Kansas City Cardiomyopathy Questionnaire score at 5 years in patients with and without early LVEF improvement.

“I think what this really gets to is what is the reason behind the LV dysfunction in the first place,” said Dr. Elmariah, soon to be joining the University of California, San Francisco. “We know that TAVR cures aortic stenosis, so if the LV dysfunction is primarily related to the valve itself, hopefully those patients are going to recover.”

On the other hand, if the patient has LV dysfunction because of a prior myocardial infarction or cardiomyopathy and then developed aortic stenosis, “you can treat the aortic stenosis but the heart is still diseased from whatever process was affecting it previously and so it’s not likely to recover in those scenarios,” he added.

The results can be used for counseling patients and highlight the need to optimize goal-directed medical therapy in those with valvular heart disease, Dr. Elmariah suggested.

“Often, patients with aortic stenosis are on miniscule doses of many of the heart failure agents because people are worried about the hemodynamic consequences and they’re worried that patients won’t tolerate these medications,” he said. “But it’s very important for us to aggressively try to treat the heart failure that is affecting these patients in order to hopefully increase the chances that their left ventricles will recover and, hopefully, that they will have improved survival.”

Dr. Baron said that “this study clearly demonstrates that patients with reduced LVEF and severe aortic stenosis can benefit from TAVR and that early improvement in LVEF is an important prognostic marker for this population.”

In Dr. Baron and colleagues’ earlier analysis of 11,000 patients who underwent TAVR as part of the transcatheter valve therapy registry, only low aortic valve gradient but not LV dysfunction was associated with higher adjusted 1-year mortality. Asked about the finding, she noted that patients were evaluated based on LV function at baseline and not for a difference in outcomes based on LVEF improvement after TAVR.

“As such, I think that these two studies are actually complementary,” Dr. Baron said. “Together, they suggest that a low LVEF should not preclude a patient from receiving TAVR and if the patient does experience a 10% increase in LVEF after TAVR, then their 5-year prognosis is improved.”

Dr. Elmariah reports grants from the American Heart Association, National Institutes of Health, Edwards Lifesciences, Medtronic, and Svelte Medical and has received consulting fees from Medtronic and AstraZeneca. Coauthor disclosures are listed in the paper. The PARTNER trials and registries and this analysis were supported by Edwards Lifesciences. Edwards was involved in the design and conduct of the study including collection, management, analysis, and interpretation of the data. Dr. Baron reports receiving research grant funding from Abiomed and Boston Scientific; consulting/medical advisory board fees from Boston Scientific, Shockwave and Biotronik; and speaking honoraria from Medtronic and Zoll.

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

Early improvement of left ventricular ejection fraction (LVEF) after transcatheter aortic valve replacement (TAVR) is associated with improved all-cause and cardiac death at 5 years in patients with severe aortic stenosis and LVEF less than 50%, new research shows.

Further analyses revealed a significant interaction by sex, with the mortality benefit largely in women.

“It’s absolutely fascinating,” senior author Sammy Elmariah, MD, Massachusetts General Hospital, Boston, said of the finding. “We know that women are more likely to have concentric hypertrophy, that they have lesser degrees of fibrosis, and smaller ventricles, and, of course, they’re in general less affected by coronary artery disease and MIs [myocardial infarctions]. All of those things in my mind, at least that’s what I assumed ahead of time, would make it more likely for women’s hearts to recover.”

“But that’s actually not what we found,” he continued. “We didn’t see a difference between the sexes in terms of likelihood of recovery. But what we saw is that the survival benefit, that associates with improvement in EF, was almost completely driven by women. So women really seem to be reaping that benefit in a manner that is unique and very different from what we saw in men.”

Dr. Elmariah noted that the reason for this benefit is unclear but points to the differences in biology for LV remodeling. “Clearly there are several details there that warrant further attention and more research.”

Suzanne J. Baron, MD, director of interventional cardiology research at Lahey Hospital and Medical Center, Burlington, Mass., said in an email that the finding of a substantial long-term survival benefit was “a bit surprising.”

Several studies have suggested that women may derive a greater benefit from TAVR versus surgical aortic valve replacement, and meta-analyses have demonstrated short and intermediate-term survival after TAVR is better in women, compared with in men, she pointed out. However, the mediating mechanism for this finding has never been clearly elucidated.

“Certainly, the sex differences in LVEF improvement after TAVR observed in this study, which could be related to sex differences in LV remodeling and LV mass regression, may now give us a clue as to why these sex-specific survival differences after TAVR persist,” Dr. Baron said.
 

More data amassed

Previous research in smaller cohorts with follow-up out to 1 year have shown an association between early LVEF improvement after TAVR and better survival. This includes a 2013 study by the investigators in high-risk patients in PARTNER-1 and a separate 2016 study in patients in the CoreValve extreme and high surgical risk trials.

Now, with longer follow-up amassed, the investigators examined data from 659 high- or intermediate-risk patients with severe stenosis and LVEF less than 50% who underwent transfemoral TAVR in the PARTNER 1, 2, and S3 trials and registries between July 2007 and April 2015.

Their mean age was 82.4 years, 71% were men, and 89.7% were White individuals. During the study period, 55.6% of the cohort died.

As reported in JAMA Cardiology, 32.8% of patients had early LVEF improvement, defined as an increase of at least 10% percentage points at 30 days after TAVR (mean change, 16.4%).

This compares with about 50%-60% of patients in the earlier studies, likely owing to the relatively higher baseline LVEF, especially in the intermediate-risk cohort, the authors suggested.

Independent predictors of lower likelihood of early LVEF improvement were previous MI, diabetes, cancer, higher baseline LVEF, larger LV end-diastolic diameter, and larger aortic valve area (AVA), whereas higher body mass index and higher stroke volume index predicted greater likelihood of LV recovery.

At 5 years, patients with versus without improved early LV improvement had lower risks of all-cause death (50.0% vs. 58.4%; P = .04) and cardiac death (29.5% vs. 38.1%; P = .05).

In multivariable analyses, each 5%-point increase in LVEF after TAVR was associated with a 6% lower risk of all-cause death (hazard ratio [HR], 0.94; P = .04) and 10% lower risk of cardiac death (HR, 0.90; P = .02).

Restricted cubic spline analysis demonstrated an inflection point above a 10% change in LVEF beyond which there was a steep decline in all-cause mortality with increasing degree of LVEF improvement.

There were no significant differences in rehospitalization, New York Heart Association functional class, or Kansas City Cardiomyopathy Questionnaire score at 5 years in patients with and without early LVEF improvement.

“I think what this really gets to is what is the reason behind the LV dysfunction in the first place,” said Dr. Elmariah, soon to be joining the University of California, San Francisco. “We know that TAVR cures aortic stenosis, so if the LV dysfunction is primarily related to the valve itself, hopefully those patients are going to recover.”

On the other hand, if the patient has LV dysfunction because of a prior myocardial infarction or cardiomyopathy and then developed aortic stenosis, “you can treat the aortic stenosis but the heart is still diseased from whatever process was affecting it previously and so it’s not likely to recover in those scenarios,” he added.

The results can be used for counseling patients and highlight the need to optimize goal-directed medical therapy in those with valvular heart disease, Dr. Elmariah suggested.

“Often, patients with aortic stenosis are on miniscule doses of many of the heart failure agents because people are worried about the hemodynamic consequences and they’re worried that patients won’t tolerate these medications,” he said. “But it’s very important for us to aggressively try to treat the heart failure that is affecting these patients in order to hopefully increase the chances that their left ventricles will recover and, hopefully, that they will have improved survival.”

Dr. Baron said that “this study clearly demonstrates that patients with reduced LVEF and severe aortic stenosis can benefit from TAVR and that early improvement in LVEF is an important prognostic marker for this population.”

In Dr. Baron and colleagues’ earlier analysis of 11,000 patients who underwent TAVR as part of the transcatheter valve therapy registry, only low aortic valve gradient but not LV dysfunction was associated with higher adjusted 1-year mortality. Asked about the finding, she noted that patients were evaluated based on LV function at baseline and not for a difference in outcomes based on LVEF improvement after TAVR.

“As such, I think that these two studies are actually complementary,” Dr. Baron said. “Together, they suggest that a low LVEF should not preclude a patient from receiving TAVR and if the patient does experience a 10% increase in LVEF after TAVR, then their 5-year prognosis is improved.”

Dr. Elmariah reports grants from the American Heart Association, National Institutes of Health, Edwards Lifesciences, Medtronic, and Svelte Medical and has received consulting fees from Medtronic and AstraZeneca. Coauthor disclosures are listed in the paper. The PARTNER trials and registries and this analysis were supported by Edwards Lifesciences. Edwards was involved in the design and conduct of the study including collection, management, analysis, and interpretation of the data. Dr. Baron reports receiving research grant funding from Abiomed and Boston Scientific; consulting/medical advisory board fees from Boston Scientific, Shockwave and Biotronik; and speaking honoraria from Medtronic and Zoll.

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

Early improvement of left ventricular ejection fraction (LVEF) after transcatheter aortic valve replacement (TAVR) is associated with improved all-cause and cardiac death at 5 years in patients with severe aortic stenosis and LVEF less than 50%, new research shows.

Further analyses revealed a significant interaction by sex, with the mortality benefit largely in women.

“It’s absolutely fascinating,” senior author Sammy Elmariah, MD, Massachusetts General Hospital, Boston, said of the finding. “We know that women are more likely to have concentric hypertrophy, that they have lesser degrees of fibrosis, and smaller ventricles, and, of course, they’re in general less affected by coronary artery disease and MIs [myocardial infarctions]. All of those things in my mind, at least that’s what I assumed ahead of time, would make it more likely for women’s hearts to recover.”

“But that’s actually not what we found,” he continued. “We didn’t see a difference between the sexes in terms of likelihood of recovery. But what we saw is that the survival benefit, that associates with improvement in EF, was almost completely driven by women. So women really seem to be reaping that benefit in a manner that is unique and very different from what we saw in men.”

Dr. Elmariah noted that the reason for this benefit is unclear but points to the differences in biology for LV remodeling. “Clearly there are several details there that warrant further attention and more research.”

Suzanne J. Baron, MD, director of interventional cardiology research at Lahey Hospital and Medical Center, Burlington, Mass., said in an email that the finding of a substantial long-term survival benefit was “a bit surprising.”

Several studies have suggested that women may derive a greater benefit from TAVR versus surgical aortic valve replacement, and meta-analyses have demonstrated short and intermediate-term survival after TAVR is better in women, compared with in men, she pointed out. However, the mediating mechanism for this finding has never been clearly elucidated.

“Certainly, the sex differences in LVEF improvement after TAVR observed in this study, which could be related to sex differences in LV remodeling and LV mass regression, may now give us a clue as to why these sex-specific survival differences after TAVR persist,” Dr. Baron said.
 

More data amassed

Previous research in smaller cohorts with follow-up out to 1 year have shown an association between early LVEF improvement after TAVR and better survival. This includes a 2013 study by the investigators in high-risk patients in PARTNER-1 and a separate 2016 study in patients in the CoreValve extreme and high surgical risk trials.

Now, with longer follow-up amassed, the investigators examined data from 659 high- or intermediate-risk patients with severe stenosis and LVEF less than 50% who underwent transfemoral TAVR in the PARTNER 1, 2, and S3 trials and registries between July 2007 and April 2015.

Their mean age was 82.4 years, 71% were men, and 89.7% were White individuals. During the study period, 55.6% of the cohort died.

As reported in JAMA Cardiology, 32.8% of patients had early LVEF improvement, defined as an increase of at least 10% percentage points at 30 days after TAVR (mean change, 16.4%).

This compares with about 50%-60% of patients in the earlier studies, likely owing to the relatively higher baseline LVEF, especially in the intermediate-risk cohort, the authors suggested.

Independent predictors of lower likelihood of early LVEF improvement were previous MI, diabetes, cancer, higher baseline LVEF, larger LV end-diastolic diameter, and larger aortic valve area (AVA), whereas higher body mass index and higher stroke volume index predicted greater likelihood of LV recovery.

At 5 years, patients with versus without improved early LV improvement had lower risks of all-cause death (50.0% vs. 58.4%; P = .04) and cardiac death (29.5% vs. 38.1%; P = .05).

In multivariable analyses, each 5%-point increase in LVEF after TAVR was associated with a 6% lower risk of all-cause death (hazard ratio [HR], 0.94; P = .04) and 10% lower risk of cardiac death (HR, 0.90; P = .02).

Restricted cubic spline analysis demonstrated an inflection point above a 10% change in LVEF beyond which there was a steep decline in all-cause mortality with increasing degree of LVEF improvement.

There were no significant differences in rehospitalization, New York Heart Association functional class, or Kansas City Cardiomyopathy Questionnaire score at 5 years in patients with and without early LVEF improvement.

“I think what this really gets to is what is the reason behind the LV dysfunction in the first place,” said Dr. Elmariah, soon to be joining the University of California, San Francisco. “We know that TAVR cures aortic stenosis, so if the LV dysfunction is primarily related to the valve itself, hopefully those patients are going to recover.”

On the other hand, if the patient has LV dysfunction because of a prior myocardial infarction or cardiomyopathy and then developed aortic stenosis, “you can treat the aortic stenosis but the heart is still diseased from whatever process was affecting it previously and so it’s not likely to recover in those scenarios,” he added.

The results can be used for counseling patients and highlight the need to optimize goal-directed medical therapy in those with valvular heart disease, Dr. Elmariah suggested.

“Often, patients with aortic stenosis are on miniscule doses of many of the heart failure agents because people are worried about the hemodynamic consequences and they’re worried that patients won’t tolerate these medications,” he said. “But it’s very important for us to aggressively try to treat the heart failure that is affecting these patients in order to hopefully increase the chances that their left ventricles will recover and, hopefully, that they will have improved survival.”

Dr. Baron said that “this study clearly demonstrates that patients with reduced LVEF and severe aortic stenosis can benefit from TAVR and that early improvement in LVEF is an important prognostic marker for this population.”

In Dr. Baron and colleagues’ earlier analysis of 11,000 patients who underwent TAVR as part of the transcatheter valve therapy registry, only low aortic valve gradient but not LV dysfunction was associated with higher adjusted 1-year mortality. Asked about the finding, she noted that patients were evaluated based on LV function at baseline and not for a difference in outcomes based on LVEF improvement after TAVR.

“As such, I think that these two studies are actually complementary,” Dr. Baron said. “Together, they suggest that a low LVEF should not preclude a patient from receiving TAVR and if the patient does experience a 10% increase in LVEF after TAVR, then their 5-year prognosis is improved.”

Dr. Elmariah reports grants from the American Heart Association, National Institutes of Health, Edwards Lifesciences, Medtronic, and Svelte Medical and has received consulting fees from Medtronic and AstraZeneca. Coauthor disclosures are listed in the paper. The PARTNER trials and registries and this analysis were supported by Edwards Lifesciences. Edwards was involved in the design and conduct of the study including collection, management, analysis, and interpretation of the data. Dr. Baron reports receiving research grant funding from Abiomed and Boston Scientific; consulting/medical advisory board fees from Boston Scientific, Shockwave and Biotronik; and speaking honoraria from Medtronic and Zoll.

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

Screening for atrial fibrillation with wearable devices is cost effective, when compared with either no screening or screening using traditional methods, a new study concludes.

“Undiagnosed atrial fibrillation (AFib) is an important cause of stroke. Screening for AFib using wrist-worn wearable devices may prevent strokes, but their cost effectiveness is unknown,” write Wanyi Chen, PhD, from Massachusetts General Hospital, Boston, and colleagues, in JAMA Health Forum.

The investigators used a microsimulation decision-analytic model to evaluate the cost effectiveness of these devices to screen for undiagnosed AFib.

The model comprised 30 million simulated individuals with an age, sex, and comorbidity profile matching the United States population aged 65 years or older.

The model looked at eight AFib screening strategies: six using wrist-worn wearable devices (either watch or band photoplethysmography with or without watch or band electrocardiography) and two using traditional modalities (that is, pulse palpation and 12-lead electrocardiogram) versus no screening.

The primary outcome was the incremental cost effectiveness ratio, defined as U.S. dollars per quality-adjusted life-year (QALY). Secondary outcomes included rates of stroke and major bleeding.

In the model, the mean age was 72.5 years and 50% were women.

All 6 screening strategies using wrist-worn wearable devices were estimated to be more cost effective than no screening. The model showed that the range of QALYs gained, compared with no screening, was 226 to 957 per 100,000 individuals.

The wrist-worn devices were also associated with greater relative benefit than screening using traditional modalities, as the range of QALYs gained, compared with no screening, was –116 to 93 per 100,000 individuals.

Compared with no screening, screening with wrist-worn wearable devices was associated with a reduction in stroke incidence by 20 to 23 per 100,000 person-years but an increase in major bleeding by 20 to 44 per 100,000 person years.

Overall, the preferred strategy for screening was wearable photoplethysmography, followed by wearable electrocardiography with patch monitor confirmation. This strategy had an incremental cost effectiveness ratio of $57,894 per QALY, “meeting the acceptability threshold of $100,000 per QALY,” the authors write.

The cost effectiveness of screening was consistent across multiple clinically relevant scenarios, including screening a general population aged 50 years or older with risk factors for stroke, the authors report.

“When deployed within specific AFib screening pathways, wearable devices are likely to be an important component of cost-effective AFib screening,” the investigators conclude.

Study based on modeled data

“This study is the first simulation of various screening strategies for atrial fibrillation using wearable devices and suggests that wearable devices, in particular wrist-worn wearables, in an elderly population, [are] estimated to be cost-effective,” Emma Svennberg, MD, PhD, from the Karolinska University Hospital, Stockholm, told this news organization.

“I find this study interesting, as the adoption of wearables amongst individuals is high and increasing, hence many wearers will screen themselves for arrhythmias (even if health care recommendations are discordant), and the potential costs for society have been unknown,” said Dr. Svennberg, who was not part of this study.

“Of course, no study is without its flaws, and here one must note that the study is based on modeled data alone and not RCTs of the wearable screening strategies ... hence true clinical outcome data is missing,” Dr. Svennberg added.

The large STROKESTOP study, on which she was the lead investigator, “presented data based on true clinical outcomes at ESC 2021 (European Society of Cardiology) and showed cost effectiveness,” Dr. Svennberg said.

The study authors report financial relationships with Bristol Myers Squibb, Fitbit, Medtronic, Pfizer, UpToDate, American Heart Association, IBM, Bayer AG, Novartis, MyoKardia, Boehringer Ingelheim, Heart Rhythm Society, Avania Consulting, Apple, Premier, the National Institutes of Health, Invitae, Blackstone Life Sciences, Flatiron, and Value Analytics Labs. Dr. Svennberg reports no relevant financial relationships.

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

Screening for atrial fibrillation with wearable devices is cost effective, when compared with either no screening or screening using traditional methods, a new study concludes.

“Undiagnosed atrial fibrillation (AFib) is an important cause of stroke. Screening for AFib using wrist-worn wearable devices may prevent strokes, but their cost effectiveness is unknown,” write Wanyi Chen, PhD, from Massachusetts General Hospital, Boston, and colleagues, in JAMA Health Forum.

The investigators used a microsimulation decision-analytic model to evaluate the cost effectiveness of these devices to screen for undiagnosed AFib.

The model comprised 30 million simulated individuals with an age, sex, and comorbidity profile matching the United States population aged 65 years or older.

The model looked at eight AFib screening strategies: six using wrist-worn wearable devices (either watch or band photoplethysmography with or without watch or band electrocardiography) and two using traditional modalities (that is, pulse palpation and 12-lead electrocardiogram) versus no screening.

The primary outcome was the incremental cost effectiveness ratio, defined as U.S. dollars per quality-adjusted life-year (QALY). Secondary outcomes included rates of stroke and major bleeding.

In the model, the mean age was 72.5 years and 50% were women.

All 6 screening strategies using wrist-worn wearable devices were estimated to be more cost effective than no screening. The model showed that the range of QALYs gained, compared with no screening, was 226 to 957 per 100,000 individuals.

The wrist-worn devices were also associated with greater relative benefit than screening using traditional modalities, as the range of QALYs gained, compared with no screening, was –116 to 93 per 100,000 individuals.

Compared with no screening, screening with wrist-worn wearable devices was associated with a reduction in stroke incidence by 20 to 23 per 100,000 person-years but an increase in major bleeding by 20 to 44 per 100,000 person years.

Overall, the preferred strategy for screening was wearable photoplethysmography, followed by wearable electrocardiography with patch monitor confirmation. This strategy had an incremental cost effectiveness ratio of $57,894 per QALY, “meeting the acceptability threshold of $100,000 per QALY,” the authors write.

The cost effectiveness of screening was consistent across multiple clinically relevant scenarios, including screening a general population aged 50 years or older with risk factors for stroke, the authors report.

“When deployed within specific AFib screening pathways, wearable devices are likely to be an important component of cost-effective AFib screening,” the investigators conclude.

Study based on modeled data

“This study is the first simulation of various screening strategies for atrial fibrillation using wearable devices and suggests that wearable devices, in particular wrist-worn wearables, in an elderly population, [are] estimated to be cost-effective,” Emma Svennberg, MD, PhD, from the Karolinska University Hospital, Stockholm, told this news organization.

“I find this study interesting, as the adoption of wearables amongst individuals is high and increasing, hence many wearers will screen themselves for arrhythmias (even if health care recommendations are discordant), and the potential costs for society have been unknown,” said Dr. Svennberg, who was not part of this study.

“Of course, no study is without its flaws, and here one must note that the study is based on modeled data alone and not RCTs of the wearable screening strategies ... hence true clinical outcome data is missing,” Dr. Svennberg added.

The large STROKESTOP study, on which she was the lead investigator, “presented data based on true clinical outcomes at ESC 2021 (European Society of Cardiology) and showed cost effectiveness,” Dr. Svennberg said.

The study authors report financial relationships with Bristol Myers Squibb, Fitbit, Medtronic, Pfizer, UpToDate, American Heart Association, IBM, Bayer AG, Novartis, MyoKardia, Boehringer Ingelheim, Heart Rhythm Society, Avania Consulting, Apple, Premier, the National Institutes of Health, Invitae, Blackstone Life Sciences, Flatiron, and Value Analytics Labs. Dr. Svennberg reports no relevant financial relationships.

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

Screening for atrial fibrillation with wearable devices is cost effective, when compared with either no screening or screening using traditional methods, a new study concludes.

“Undiagnosed atrial fibrillation (AFib) is an important cause of stroke. Screening for AFib using wrist-worn wearable devices may prevent strokes, but their cost effectiveness is unknown,” write Wanyi Chen, PhD, from Massachusetts General Hospital, Boston, and colleagues, in JAMA Health Forum.

The investigators used a microsimulation decision-analytic model to evaluate the cost effectiveness of these devices to screen for undiagnosed AFib.

The model comprised 30 million simulated individuals with an age, sex, and comorbidity profile matching the United States population aged 65 years or older.

The model looked at eight AFib screening strategies: six using wrist-worn wearable devices (either watch or band photoplethysmography with or without watch or band electrocardiography) and two using traditional modalities (that is, pulse palpation and 12-lead electrocardiogram) versus no screening.

The primary outcome was the incremental cost effectiveness ratio, defined as U.S. dollars per quality-adjusted life-year (QALY). Secondary outcomes included rates of stroke and major bleeding.

In the model, the mean age was 72.5 years and 50% were women.

All 6 screening strategies using wrist-worn wearable devices were estimated to be more cost effective than no screening. The model showed that the range of QALYs gained, compared with no screening, was 226 to 957 per 100,000 individuals.

The wrist-worn devices were also associated with greater relative benefit than screening using traditional modalities, as the range of QALYs gained, compared with no screening, was –116 to 93 per 100,000 individuals.

Compared with no screening, screening with wrist-worn wearable devices was associated with a reduction in stroke incidence by 20 to 23 per 100,000 person-years but an increase in major bleeding by 20 to 44 per 100,000 person years.

Overall, the preferred strategy for screening was wearable photoplethysmography, followed by wearable electrocardiography with patch monitor confirmation. This strategy had an incremental cost effectiveness ratio of $57,894 per QALY, “meeting the acceptability threshold of $100,000 per QALY,” the authors write.

The cost effectiveness of screening was consistent across multiple clinically relevant scenarios, including screening a general population aged 50 years or older with risk factors for stroke, the authors report.

“When deployed within specific AFib screening pathways, wearable devices are likely to be an important component of cost-effective AFib screening,” the investigators conclude.

Study based on modeled data

“This study is the first simulation of various screening strategies for atrial fibrillation using wearable devices and suggests that wearable devices, in particular wrist-worn wearables, in an elderly population, [are] estimated to be cost-effective,” Emma Svennberg, MD, PhD, from the Karolinska University Hospital, Stockholm, told this news organization.

“I find this study interesting, as the adoption of wearables amongst individuals is high and increasing, hence many wearers will screen themselves for arrhythmias (even if health care recommendations are discordant), and the potential costs for society have been unknown,” said Dr. Svennberg, who was not part of this study.

“Of course, no study is without its flaws, and here one must note that the study is based on modeled data alone and not RCTs of the wearable screening strategies ... hence true clinical outcome data is missing,” Dr. Svennberg added.

The large STROKESTOP study, on which she was the lead investigator, “presented data based on true clinical outcomes at ESC 2021 (European Society of Cardiology) and showed cost effectiveness,” Dr. Svennberg said.

The study authors report financial relationships with Bristol Myers Squibb, Fitbit, Medtronic, Pfizer, UpToDate, American Heart Association, IBM, Bayer AG, Novartis, MyoKardia, Boehringer Ingelheim, Heart Rhythm Society, Avania Consulting, Apple, Premier, the National Institutes of Health, Invitae, Blackstone Life Sciences, Flatiron, and Value Analytics Labs. Dr. Svennberg reports no relevant financial relationships.

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

Patients with psoriasis and psoriatic arthritis who belong to underserved groups may not be getting the health care they need because of lack of access, a study based on national registry data suggests.

“Using the All of Us dataset, we identified lower rates of psoriasis and psoriatic arthritis in participants with skin of color, lower education levels, and no health insurance,” lead author Megan M. Tran said in her oral presentation at the annual meeting of the Society for Investigative Dermatology.

“This suggests psoriasis and psoriatic arthritis underdiagnosis in these underserved populations, possibly due to limited dermatologic care access,” added Ms. Tran, a second-year medical student at Brown University in Providence, R.I.

Ms. Tran and colleagues used the ongoing National Institutes of Health All of Us Research Program registry that contains a large proportion of participants from groups in the United States who have historically been underrepresented in biomedical research, she said in her talk. 

Of the 329,038 participants with data in version 5 (released this past March) of the All of Us database, 150,158 (45.6%) had skin of color, and 251,597 (76.5%) had available electronic health records (EHRs).
 

Underserved groups need better access to health care

Linking data from EHRs, surveys, and physical measurements at enrollment, the researchers used several variables to estimate psoriasis and psoriatic arthritis (PsA) prevalence, and they used multivariate logistic regression to adjust for the variables. They found:

• Twenty-two percent of patients with psoriasis had PsA. Odds of psoriasis and PsA were lower among Black (psoriasis odds ratio [OR], 0.32, 95% confidence interval [CI], 0.28-0.36; PsA OR, 0.20, 95% CI, 0.15-0.26) and Hispanic participants (psoriasis OR, 0.77, 95% CI, 0.71-0.84; PsA OR, 0.74, 95% CI, 0.61-0.89) compared with White participants.
• Psoriasis prevalence increased linearly with age (topping off at age 70 and older [OR, 3.35, 95% CI, 2.91-3.88], with 18-29 years as the reference). The same trend was found with PsA (70 years and above [OR, 4.41, 95% CI, 3.07-6.55] compared with those aged 18-29 years).  
• Psoriasis prevalence increased linearly with body mass index (BMI 40 and above [OR, 1.71, 95% CI, 1.54-1.90], with 20-24.9 as the reference). The same trend was found with PsA (BMI 40 and above [OR, 2.09, 95% CI, 1.68-2.59], with 20-24.9 as the reference).  
• Former smokers were at increased risk for disease, compared with people who had never smoked (psoriasis OR, 1.30, 95% CI, 1.22-1.39; PsA OR, 2.15, 95% CI, 1.33-3.78).
• Lower odds were found in uninsured adults (psoriasis OR, 0.43, 95% CI, 0.35-0.52; PsA OR, 0.37, 95% CI, 0.22-0.58) compared with those who were insured, and in those with less than a high school degree (psoriasis OR, 0.72, 95% CI, 0.63-0.82; PsA OR, 0.65, 95% CI, 0.47-0.87) compared with those with a college degree.

“The All of Us research program has demonstrated to be a valuable resource to gain unique dermatologic insights on diverse participant populations,” Ms. Tran said.

“There needs to be improvement in access to quality dermatologic care, as this may help to reduce underdiagnosis of psoriasis and psoriatic arthritis,” she added. Access can be increased  in various ways, including “outreach to underserved communities, equitable distribution of resources, and increased awareness of clinical variations in skin of color.”

Laura Korb Ferris, MD, PhD, professor of dermatology and director of clinical trials for the department of dermatology at University of Pittsburgh Medical Center, said the study is interesting.

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

Patients with psoriasis and psoriatic arthritis who belong to underserved groups may not be getting the health care they need because of lack of access, a study based on national registry data suggests.

“Using the All of Us dataset, we identified lower rates of psoriasis and psoriatic arthritis in participants with skin of color, lower education levels, and no health insurance,” lead author Megan M. Tran said in her oral presentation at the annual meeting of the Society for Investigative Dermatology.

“This suggests psoriasis and psoriatic arthritis underdiagnosis in these underserved populations, possibly due to limited dermatologic care access,” added Ms. Tran, a second-year medical student at Brown University in Providence, R.I.

Ms. Tran and colleagues used the ongoing National Institutes of Health All of Us Research Program registry that contains a large proportion of participants from groups in the United States who have historically been underrepresented in biomedical research, she said in her talk. 

Of the 329,038 participants with data in version 5 (released this past March) of the All of Us database, 150,158 (45.6%) had skin of color, and 251,597 (76.5%) had available electronic health records (EHRs).
 

Underserved groups need better access to health care

Linking data from EHRs, surveys, and physical measurements at enrollment, the researchers used several variables to estimate psoriasis and psoriatic arthritis (PsA) prevalence, and they used multivariate logistic regression to adjust for the variables. They found:

• Twenty-two percent of patients with psoriasis had PsA. Odds of psoriasis and PsA were lower among Black (psoriasis odds ratio [OR], 0.32, 95% confidence interval [CI], 0.28-0.36; PsA OR, 0.20, 95% CI, 0.15-0.26) and Hispanic participants (psoriasis OR, 0.77, 95% CI, 0.71-0.84; PsA OR, 0.74, 95% CI, 0.61-0.89) compared with White participants.
• Psoriasis prevalence increased linearly with age (topping off at age 70 and older [OR, 3.35, 95% CI, 2.91-3.88], with 18-29 years as the reference). The same trend was found with PsA (70 years and above [OR, 4.41, 95% CI, 3.07-6.55] compared with those aged 18-29 years).  
• Psoriasis prevalence increased linearly with body mass index (BMI 40 and above [OR, 1.71, 95% CI, 1.54-1.90], with 20-24.9 as the reference). The same trend was found with PsA (BMI 40 and above [OR, 2.09, 95% CI, 1.68-2.59], with 20-24.9 as the reference).  
• Former smokers were at increased risk for disease, compared with people who had never smoked (psoriasis OR, 1.30, 95% CI, 1.22-1.39; PsA OR, 2.15, 95% CI, 1.33-3.78).
• Lower odds were found in uninsured adults (psoriasis OR, 0.43, 95% CI, 0.35-0.52; PsA OR, 0.37, 95% CI, 0.22-0.58) compared with those who were insured, and in those with less than a high school degree (psoriasis OR, 0.72, 95% CI, 0.63-0.82; PsA OR, 0.65, 95% CI, 0.47-0.87) compared with those with a college degree.

“The All of Us research program has demonstrated to be a valuable resource to gain unique dermatologic insights on diverse participant populations,” Ms. Tran said.

“There needs to be improvement in access to quality dermatologic care, as this may help to reduce underdiagnosis of psoriasis and psoriatic arthritis,” she added. Access can be increased  in various ways, including “outreach to underserved communities, equitable distribution of resources, and increased awareness of clinical variations in skin of color.”

Laura Korb Ferris, MD, PhD, professor of dermatology and director of clinical trials for the department of dermatology at University of Pittsburgh Medical Center, said the study is interesting.

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

Patients with psoriasis and psoriatic arthritis who belong to underserved groups may not be getting the health care they need because of lack of access, a study based on national registry data suggests.

“Using the All of Us dataset, we identified lower rates of psoriasis and psoriatic arthritis in participants with skin of color, lower education levels, and no health insurance,” lead author Megan M. Tran said in her oral presentation at the annual meeting of the Society for Investigative Dermatology.

“This suggests psoriasis and psoriatic arthritis underdiagnosis in these underserved populations, possibly due to limited dermatologic care access,” added Ms. Tran, a second-year medical student at Brown University in Providence, R.I.

Ms. Tran and colleagues used the ongoing National Institutes of Health All of Us Research Program registry that contains a large proportion of participants from groups in the United States who have historically been underrepresented in biomedical research, she said in her talk. 

Of the 329,038 participants with data in version 5 (released this past March) of the All of Us database, 150,158 (45.6%) had skin of color, and 251,597 (76.5%) had available electronic health records (EHRs).
 

Underserved groups need better access to health care

Linking data from EHRs, surveys, and physical measurements at enrollment, the researchers used several variables to estimate psoriasis and psoriatic arthritis (PsA) prevalence, and they used multivariate logistic regression to adjust for the variables. They found:

• Twenty-two percent of patients with psoriasis had PsA. Odds of psoriasis and PsA were lower among Black (psoriasis odds ratio [OR], 0.32, 95% confidence interval [CI], 0.28-0.36; PsA OR, 0.20, 95% CI, 0.15-0.26) and Hispanic participants (psoriasis OR, 0.77, 95% CI, 0.71-0.84; PsA OR, 0.74, 95% CI, 0.61-0.89) compared with White participants.
• Psoriasis prevalence increased linearly with age (topping off at age 70 and older [OR, 3.35, 95% CI, 2.91-3.88], with 18-29 years as the reference). The same trend was found with PsA (70 years and above [OR, 4.41, 95% CI, 3.07-6.55] compared with those aged 18-29 years).  
• Psoriasis prevalence increased linearly with body mass index (BMI 40 and above [OR, 1.71, 95% CI, 1.54-1.90], with 20-24.9 as the reference). The same trend was found with PsA (BMI 40 and above [OR, 2.09, 95% CI, 1.68-2.59], with 20-24.9 as the reference).  
• Former smokers were at increased risk for disease, compared with people who had never smoked (psoriasis OR, 1.30, 95% CI, 1.22-1.39; PsA OR, 2.15, 95% CI, 1.33-3.78).
• Lower odds were found in uninsured adults (psoriasis OR, 0.43, 95% CI, 0.35-0.52; PsA OR, 0.37, 95% CI, 0.22-0.58) compared with those who were insured, and in those with less than a high school degree (psoriasis OR, 0.72, 95% CI, 0.63-0.82; PsA OR, 0.65, 95% CI, 0.47-0.87) compared with those with a college degree.

“The All of Us research program has demonstrated to be a valuable resource to gain unique dermatologic insights on diverse participant populations,” Ms. Tran said.

“There needs to be improvement in access to quality dermatologic care, as this may help to reduce underdiagnosis of psoriasis and psoriatic arthritis,” she added. Access can be increased  in various ways, including “outreach to underserved communities, equitable distribution of resources, and increased awareness of clinical variations in skin of color.”

Laura Korb Ferris, MD, PhD, professor of dermatology and director of clinical trials for the department of dermatology at University of Pittsburgh Medical Center, said the study is interesting.

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

Dietary salt substitutes not only lower blood pressure but also have a clear impact on hard clinical endpoints, lowering the risk of myocardial infarction (MI), stroke, and death from all causes and cardiovascular disease (CVD), a meta-analysis shows.

jirkaejc/Getty Images

The blood pressure–mediated protective effects of salt substitutes on CVD and death are likely to apply to the roughly 1.28 billion people around the world who have high blood pressure, the researchers say.

“These findings are unlikely to reflect the play of chance and support the adoption of salt substitutes in clinical practice and public health policy as a strategy to reduce dietary sodium intake, increase dietary potassium intake, lower blood pressure, and prevent major cardiovascular events,” they write.

The study was published online  in Heart.
 

Strong support for landmark study

In salt substitutes, a proportion of sodium chloride is replaced with potassium chloride. They are known to help lower blood pressure, but less is known about their impact on hard clinical endpoints, Maoyi Tian, PhD, with Harbin Medical University, China, and the George Institute for Global Health, Sydney, and colleagues note in their article.

In the landmark Salt Substitute and Stroke Study (SSaSS), salt substitutes cut the risk of MI, stroke, and early death, as reported previously by this news organization.

But SSaSS was conducted in China, and it was unclear whether these benefits would apply to people in other parts of the world.

To investigate, Dr. Tian and colleagues pooled data from 21 relevant parallel-group, step-wedge, or cluster randomized controlled trials published through August 2021, with 31,949 participants. The trials were conducted in Europe, the Western Pacific Region, the Americas, and South East Asia and reported the effect of a salt substitute on blood pressure or clinical outcomes.

A meta-analysis of blood pressure data from 19 trials that included 29,528 participants showed that salt substitutes lowered systolic blood pressure (SBP) by 4.61 mm Hg (95% confidence interval, −6.07 to −3.14) and diastolic blood pressure (DBP) by 1.61 mm Hg (95% CI, −2.42 to −0.79).

The proportion of sodium chloride in the salt substitutes varied from 33% to 75%; the proportion of potassium ranged from 25% to 65%.

Each 10% lower proportion of sodium chloride in the salt substitute was associated with a 1.53 mm Hg (95% CI, −3.02 to −0.03; P = .045) greater reduction in SBP and a 0.95 mm Hg (95% CI, −1.78 to −0.12; P = .025) greater reduction in DBP.

Reductions in blood pressure appeared consistent, irrespective of country, age, sex, history of high blood pressure, weight, baseline blood pressure, and baseline levels of urinary sodium and potassium.

Clear benefit on hard outcomes

Pooled data on clinical outcomes from five trials that included 24,306 participants, mostly from the SSaSS, showed clear protective effects of salt substitutes on total mortality (risk ratio, 0.89; 95% CI, 0.85-0.94), CV mortality (RR, 0.87; 95% CI, 0.81-0.94), and CV events (RR, 0.89; 95% CI, 0.85-0.94).

Dr. Tian and colleagues say that “broader population use of salt substitute is supported by the absence of any detectable adverse effect of salt substitutes on hyperkalemia in this review.”

They note, however, that all of the trials took “pragmatic steps to exclude participants at elevated risk of hyperkalemia, seeking to exclude those with chronic kidney disease or using medications that elevate serum potassium.”

Offering perspective on the study, Harlan Krumholz, MD, with Yale New Haven Hospital and Yale School of Medicine, both in New Haven, Conn., said it provides “useful information by bringing together the trial evidence on salt substitutes. The evidence is dominated by the SSaSS, but the others add context.”

Dr. Krumholz said that at this point, he thinks salt substitutes “could be included in recommendations to patients.”

“SSaSS was conducted in villages in China, so that is where the evidence is strongest and most relevant, but this is a low-cost and seemingly safe strategy that could be tried by anyone without contraindications, such as kidney disease or taking a potassium-sparing medication or potassium supplement,” Dr. Krumholz told this news organization.

Johanna Contreras, MD, heart failure and transplant cardiologist at the Mount Sinai Hospital, New York, agrees that in the absence of contraindications, salt substitutes should be recommended.

“Americans put salt on everything and don’t even think about it. The salt substitutes are very helpful,” Dr. Contreras said in an interview.

“People who don’t have high blood pressure should limit salt intake, because what we have seen is that if you have high blood pressure in your family – even if you don’t have high blood pressure in your 20s or 30s – you’re likely to develop high blood pressure,” Dr. Contreras said.

“Therefore, it’s wise early on to start protecting yourself and using low salt and salt substitutes,” she added.

The study had no specific funding. Dr. Tian, Dr. Krumholz, and Dr. Contreras have disclosed no relevant financial relationships.

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

Dietary salt substitutes not only lower blood pressure but also have a clear impact on hard clinical endpoints, lowering the risk of myocardial infarction (MI), stroke, and death from all causes and cardiovascular disease (CVD), a meta-analysis shows.

jirkaejc/Getty Images

The blood pressure–mediated protective effects of salt substitutes on CVD and death are likely to apply to the roughly 1.28 billion people around the world who have high blood pressure, the researchers say.

“These findings are unlikely to reflect the play of chance and support the adoption of salt substitutes in clinical practice and public health policy as a strategy to reduce dietary sodium intake, increase dietary potassium intake, lower blood pressure, and prevent major cardiovascular events,” they write.

The study was published online  in Heart.
 

Strong support for landmark study

In salt substitutes, a proportion of sodium chloride is replaced with potassium chloride. They are known to help lower blood pressure, but less is known about their impact on hard clinical endpoints, Maoyi Tian, PhD, with Harbin Medical University, China, and the George Institute for Global Health, Sydney, and colleagues note in their article.

In the landmark Salt Substitute and Stroke Study (SSaSS), salt substitutes cut the risk of MI, stroke, and early death, as reported previously by this news organization.

But SSaSS was conducted in China, and it was unclear whether these benefits would apply to people in other parts of the world.

To investigate, Dr. Tian and colleagues pooled data from 21 relevant parallel-group, step-wedge, or cluster randomized controlled trials published through August 2021, with 31,949 participants. The trials were conducted in Europe, the Western Pacific Region, the Americas, and South East Asia and reported the effect of a salt substitute on blood pressure or clinical outcomes.

A meta-analysis of blood pressure data from 19 trials that included 29,528 participants showed that salt substitutes lowered systolic blood pressure (SBP) by 4.61 mm Hg (95% confidence interval, −6.07 to −3.14) and diastolic blood pressure (DBP) by 1.61 mm Hg (95% CI, −2.42 to −0.79).

The proportion of sodium chloride in the salt substitutes varied from 33% to 75%; the proportion of potassium ranged from 25% to 65%.

Each 10% lower proportion of sodium chloride in the salt substitute was associated with a 1.53 mm Hg (95% CI, −3.02 to −0.03; P = .045) greater reduction in SBP and a 0.95 mm Hg (95% CI, −1.78 to −0.12; P = .025) greater reduction in DBP.

Reductions in blood pressure appeared consistent, irrespective of country, age, sex, history of high blood pressure, weight, baseline blood pressure, and baseline levels of urinary sodium and potassium.

Clear benefit on hard outcomes

Pooled data on clinical outcomes from five trials that included 24,306 participants, mostly from the SSaSS, showed clear protective effects of salt substitutes on total mortality (risk ratio, 0.89; 95% CI, 0.85-0.94), CV mortality (RR, 0.87; 95% CI, 0.81-0.94), and CV events (RR, 0.89; 95% CI, 0.85-0.94).

Dr. Tian and colleagues say that “broader population use of salt substitute is supported by the absence of any detectable adverse effect of salt substitutes on hyperkalemia in this review.”

They note, however, that all of the trials took “pragmatic steps to exclude participants at elevated risk of hyperkalemia, seeking to exclude those with chronic kidney disease or using medications that elevate serum potassium.”

Offering perspective on the study, Harlan Krumholz, MD, with Yale New Haven Hospital and Yale School of Medicine, both in New Haven, Conn., said it provides “useful information by bringing together the trial evidence on salt substitutes. The evidence is dominated by the SSaSS, but the others add context.”

Dr. Krumholz said that at this point, he thinks salt substitutes “could be included in recommendations to patients.”

“SSaSS was conducted in villages in China, so that is where the evidence is strongest and most relevant, but this is a low-cost and seemingly safe strategy that could be tried by anyone without contraindications, such as kidney disease or taking a potassium-sparing medication or potassium supplement,” Dr. Krumholz told this news organization.

Johanna Contreras, MD, heart failure and transplant cardiologist at the Mount Sinai Hospital, New York, agrees that in the absence of contraindications, salt substitutes should be recommended.

“Americans put salt on everything and don’t even think about it. The salt substitutes are very helpful,” Dr. Contreras said in an interview.

“People who don’t have high blood pressure should limit salt intake, because what we have seen is that if you have high blood pressure in your family – even if you don’t have high blood pressure in your 20s or 30s – you’re likely to develop high blood pressure,” Dr. Contreras said.

“Therefore, it’s wise early on to start protecting yourself and using low salt and salt substitutes,” she added.

The study had no specific funding. Dr. Tian, Dr. Krumholz, and Dr. Contreras have disclosed no relevant financial relationships.

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

Dietary salt substitutes not only lower blood pressure but also have a clear impact on hard clinical endpoints, lowering the risk of myocardial infarction (MI), stroke, and death from all causes and cardiovascular disease (CVD), a meta-analysis shows.

jirkaejc/Getty Images

The blood pressure–mediated protective effects of salt substitutes on CVD and death are likely to apply to the roughly 1.28 billion people around the world who have high blood pressure, the researchers say.

“These findings are unlikely to reflect the play of chance and support the adoption of salt substitutes in clinical practice and public health policy as a strategy to reduce dietary sodium intake, increase dietary potassium intake, lower blood pressure, and prevent major cardiovascular events,” they write.

The study was published online  in Heart.
 

Strong support for landmark study

In salt substitutes, a proportion of sodium chloride is replaced with potassium chloride. They are known to help lower blood pressure, but less is known about their impact on hard clinical endpoints, Maoyi Tian, PhD, with Harbin Medical University, China, and the George Institute for Global Health, Sydney, and colleagues note in their article.

In the landmark Salt Substitute and Stroke Study (SSaSS), salt substitutes cut the risk of MI, stroke, and early death, as reported previously by this news organization.

But SSaSS was conducted in China, and it was unclear whether these benefits would apply to people in other parts of the world.

To investigate, Dr. Tian and colleagues pooled data from 21 relevant parallel-group, step-wedge, or cluster randomized controlled trials published through August 2021, with 31,949 participants. The trials were conducted in Europe, the Western Pacific Region, the Americas, and South East Asia and reported the effect of a salt substitute on blood pressure or clinical outcomes.

A meta-analysis of blood pressure data from 19 trials that included 29,528 participants showed that salt substitutes lowered systolic blood pressure (SBP) by 4.61 mm Hg (95% confidence interval, −6.07 to −3.14) and diastolic blood pressure (DBP) by 1.61 mm Hg (95% CI, −2.42 to −0.79).

The proportion of sodium chloride in the salt substitutes varied from 33% to 75%; the proportion of potassium ranged from 25% to 65%.

Each 10% lower proportion of sodium chloride in the salt substitute was associated with a 1.53 mm Hg (95% CI, −3.02 to −0.03; P = .045) greater reduction in SBP and a 0.95 mm Hg (95% CI, −1.78 to −0.12; P = .025) greater reduction in DBP.

Reductions in blood pressure appeared consistent, irrespective of country, age, sex, history of high blood pressure, weight, baseline blood pressure, and baseline levels of urinary sodium and potassium.

Clear benefit on hard outcomes

Pooled data on clinical outcomes from five trials that included 24,306 participants, mostly from the SSaSS, showed clear protective effects of salt substitutes on total mortality (risk ratio, 0.89; 95% CI, 0.85-0.94), CV mortality (RR, 0.87; 95% CI, 0.81-0.94), and CV events (RR, 0.89; 95% CI, 0.85-0.94).

Dr. Tian and colleagues say that “broader population use of salt substitute is supported by the absence of any detectable adverse effect of salt substitutes on hyperkalemia in this review.”

They note, however, that all of the trials took “pragmatic steps to exclude participants at elevated risk of hyperkalemia, seeking to exclude those with chronic kidney disease or using medications that elevate serum potassium.”

Offering perspective on the study, Harlan Krumholz, MD, with Yale New Haven Hospital and Yale School of Medicine, both in New Haven, Conn., said it provides “useful information by bringing together the trial evidence on salt substitutes. The evidence is dominated by the SSaSS, but the others add context.”

Dr. Krumholz said that at this point, he thinks salt substitutes “could be included in recommendations to patients.”

“SSaSS was conducted in villages in China, so that is where the evidence is strongest and most relevant, but this is a low-cost and seemingly safe strategy that could be tried by anyone without contraindications, such as kidney disease or taking a potassium-sparing medication or potassium supplement,” Dr. Krumholz told this news organization.

Johanna Contreras, MD, heart failure and transplant cardiologist at the Mount Sinai Hospital, New York, agrees that in the absence of contraindications, salt substitutes should be recommended.

“Americans put salt on everything and don’t even think about it. The salt substitutes are very helpful,” Dr. Contreras said in an interview.

“People who don’t have high blood pressure should limit salt intake, because what we have seen is that if you have high blood pressure in your family – even if you don’t have high blood pressure in your 20s or 30s – you’re likely to develop high blood pressure,” Dr. Contreras said.

“Therefore, it’s wise early on to start protecting yourself and using low salt and salt substitutes,” she added.

The study had no specific funding. Dr. Tian, Dr. Krumholz, and Dr. Contreras have disclosed no relevant financial relationships.

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

The battle was just beginning for Le Roy Torres and his wife, Rosie, when the Army captain returned to Texas in 2008, already starting to suffer from the toxic substances he’d inhaled from the 10-acre burn pit at Camp Anaconda in Balad, Iraq.

Along the way, Le Roy would lose the job he loved as a Texas state trooper and take his fight all the way to a Supreme Court victory. He would be rushed to the emergency room hundreds of times, be denied health benefits by the Department of Veterans Affairs for years, attempt suicide, and seek experimental cures for the damage done to his lungs and brain.

Amid all that, Le Roy and Rosie founded an organization to help others and push Congress to fix the laws that allowed the suffering of veterans to go on, and ultimately enlist people like comedian and activist Jon Stewart, who helped them win a dramatic showdown in the Senate last week.

Their struggle will never really be over. But the Torreses’ campaign to make sure no other veterans experience what they had to ends Aug. 10, when they are set to join President Joe Biden as he signs a law to guarantee that 3.5 million American warriors exposed to similar hazards can get care.

“I mean, to think that 13 years ago we were walking the halls [of Congress] — it’s really emotional,” Rosie said recently, halting to collect herself and wipe back tears, “because I think of all the people that died along the way.”

The bill provides a new entitlement program for veterans who served in a combat zone in the past 32 years. If they are diagnosed with any of 23 conditions identified in the legislation — ranging from specific cancers to breathing ailments — they would be deemed automatically eligible for health coverage. The Congressional Budget Office estimated the new benefits would cost $280 billion over the next 10 years.

Most veterans — nearly 80% — who start experiencing symptoms after leaving the service get denied what’s known as a service connection when they seek help from the VA. The system has been designed to disbelieve them, the veterans complain. They must prove their breathing problems or cancers came from the toxic trash smoke they breathed overseas, which is extremely difficult.

When Le Roy returned home from Balad Air Base — the second-largest U.S. post in Iraq and where the military incinerated tons of debris daily, including plastic, ammunition, and medical waste — he was already sick. He was rushed to the hospital a few weeks later with a severe respiratory infection.

He had expected to keep working as a state trooper, but by 2010 it was clear he couldn’t perform all the duties because of his illness. When he asked for a different job with the Texas Department of Public Safety, he was denied. He was told he had to resign if he wanted to apply for medical retirement. The retirement request was then rejected. So he sued and eventually took the case to the Supreme Court, which in June ruled that states were not immune from such lawsuits by service members.

In those early years, the military and VA doctors couldn’t say what caused his breathing problems and splitting headaches. As with other victims of toxic exposure, diagnoses proved to be difficult. Some doctors suggested the problems weren’t real — a pronouncement often encountered by other vets whose claims are denied.

Like so many others, Rosie turned to the internet for information she couldn’t get from the VA, where she had worked for 23 years. She discovered a Facebook group that she would use as the basis for a new advocacy group, Burn Pits 360.

Le Roy was ultimately diagnosed with constrictive bronchiolitis, fibrosis of the lungs, and toxic encephalopathy. He eventually got his benefits in early 2013. By then, the family was deep in debt.

For years he lived with the reality that the military he had served for 23 years refused to answer his needs, and the police force he loved didn’t seem to care.

“It’s something that we have now learned is known as moral injury and compound loss,” Rosie said.

As a man, he began to wonder how he could provide for his family, if he was any use to anyone, she added. “So then that led to him attempting to take his life.”

It also led the couple and parents of three to beseech Congress to fix the problems. They started walking the halls in the Capitol. Success there was not any easier.

“We came to Capitol Hill and just handed out information we had printed about burn pit exposure,” Le Roy said at his last visit to the Hill in June, an oxygen tube strung under his nose.

“There were a lot of doors shut in our face,” Rosie said.

While making little progress in Congress, they built Burn Pits 360 into an advocacy group and a clearinghouse to help other veterans similarly frustrated by a system that seemed to be failing them.

The breakthrough for Rosie began when she saw Stewart and 9/11 survivors’ advocate John Feal winning a similar battle to make Congress fully fund health and compensation programs for responders of the Sept. 11, 2001, terror attacks. She recalls reading up on the toxic substances in the dust and smoke that spewed from the collapsed twin towers and discovering they were remarkably similar to the poisons inhaled by troops near the waste fires that were also set ablaze with jet fuel.

She called Feal. Feal called Stewart, and by February 2019 the four of them were meeting on Capitol Hill with lawmakers, including Sen. Kirsten Gillibrand (D-N.Y.), one of the authors of the 9/11 legislation.

The key, they decided in those first meetings, was to remove the obstacles for the most common illnesses and eliminate the burden of proof on ill former soldiers. Gillibrand’s office wrote that bill, along with Rep. Raul Ruiz (D-Calif.), who championed it in the House.

Related Links

• Senate GOP Puts Up Roadblocks to Bipartisan House Bill for Veterans’ Burn Pit Care
• Doctors Found Jet Fuel in Veteran’s Lungs. He Can’t Get Full Benefits.
• Role Reversal: Covid Increases Ranks of Child Caregivers

Ultimately, that bill became the heart of the measure that passed, known as the PACT Act and named for a soldier who died from cancer linked to his service.

“Our bill was the first federal presumption for burn pits coverage ever. And that was all because of Rosie and Le Roy,” said Gillibrand.

But just as with the 9/11 legislation, many in Congress weren’t that interested.

“It’s about money, and nobody likes to spend money,” Gillibrand said. “Congress never wants to accept the fact that treating these veterans and addressing their health care is the cost of war.”

Weeks ago, the bill appeared ready to glide through. It passed both the House and Senate but needed another vote to fix a technical legislative issue. Then on July 27, Sen. Pat Toomey (R-Pa.), who opposed the measure, unexpectedly persuaded 25 of his Republican colleagues who had supported the bill to vote against it, claiming that because the bill made the spending mandatory — not subject to the annual whims of Congress — Democrats would spend $400 billion elsewhere in the budget. Democrats countered that the money Toomey cited is already being spent and, regardless of how it’s categorized, it’s still up to Congress to appropriate it.

Rosie and veterans who had come to the Capitol that day to celebrate instead had to dig in one more time, with Stewart bringing the high-wattage attention that led the Republicans to reconsider. On Aug. 2, most Republicans decided to agree with the Democrats, and the bill passed 86 to 11.

Rosie said it never would have happened without Feal and Stewart. Stewart said it was all about Rosie, bringing together veterans in a way that Congress couldn’t ignore.

“She’s the reason I’m doing it, her and Le Roy,” Stewart said, standing outside the Capitol with Rosie the day before the vote.

Stewart, the Torreses, and untold other veterans tempered their joy with the warning that it will be a hard journey making the new program work with a VA that already has a massive backlog. The legislation has provisions to create facilities and bring in private doctors, but some vets remain dubious.

Iraq War veteran Brian Alvarado of Long Beach, California, was diagnosed with neck and throat cancer soon after returning from Iraq in 2006. He had been assigned to patrol one of the many burn pits. He eats and breathes through tubes and struggles to keep weight on. Radiation and a tracheostomy have left his voice almost inaudible.

“You can pass laws, but it all boils down to the VA. How are they going to implement the changes? The claims, the compensation, the treatment,” he asked in June. “And how long will it take?”

For the time being, though, Rosie said that even more than a visit to the White House, she was looking forward to going back to Texas and her family.

“You know, I lost 13 years away from my children, with trips to the hospital, coming to D.C.,” she said. “It means I can go home.”

Le Roy and Rosie can also reflect that as painful as this path has been, 3.5 million veterans are guaranteed a backstop because of this law, and thousands of veterans and active-duty service members who work for state and local governments now have recourse if they are fired after being injured at war.

“It is good to know that so many people will be helped,” Le Roy said from his home in Robstown, Texas. “It does help.”

KHN reporter Heidi de Marco contributed to this article.

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

The battle was just beginning for Le Roy Torres and his wife, Rosie, when the Army captain returned to Texas in 2008, already starting to suffer from the toxic substances he’d inhaled from the 10-acre burn pit at Camp Anaconda in Balad, Iraq.

Along the way, Le Roy would lose the job he loved as a Texas state trooper and take his fight all the way to a Supreme Court victory. He would be rushed to the emergency room hundreds of times, be denied health benefits by the Department of Veterans Affairs for years, attempt suicide, and seek experimental cures for the damage done to his lungs and brain.

Amid all that, Le Roy and Rosie founded an organization to help others and push Congress to fix the laws that allowed the suffering of veterans to go on, and ultimately enlist people like comedian and activist Jon Stewart, who helped them win a dramatic showdown in the Senate last week.

Their struggle will never really be over. But the Torreses’ campaign to make sure no other veterans experience what they had to ends Aug. 10, when they are set to join President Joe Biden as he signs a law to guarantee that 3.5 million American warriors exposed to similar hazards can get care.

“I mean, to think that 13 years ago we were walking the halls [of Congress] — it’s really emotional,” Rosie said recently, halting to collect herself and wipe back tears, “because I think of all the people that died along the way.”

The bill provides a new entitlement program for veterans who served in a combat zone in the past 32 years. If they are diagnosed with any of 23 conditions identified in the legislation — ranging from specific cancers to breathing ailments — they would be deemed automatically eligible for health coverage. The Congressional Budget Office estimated the new benefits would cost $280 billion over the next 10 years.

Most veterans — nearly 80% — who start experiencing symptoms after leaving the service get denied what’s known as a service connection when they seek help from the VA. The system has been designed to disbelieve them, the veterans complain. They must prove their breathing problems or cancers came from the toxic trash smoke they breathed overseas, which is extremely difficult.

When Le Roy returned home from Balad Air Base — the second-largest U.S. post in Iraq and where the military incinerated tons of debris daily, including plastic, ammunition, and medical waste — he was already sick. He was rushed to the hospital a few weeks later with a severe respiratory infection.

He had expected to keep working as a state trooper, but by 2010 it was clear he couldn’t perform all the duties because of his illness. When he asked for a different job with the Texas Department of Public Safety, he was denied. He was told he had to resign if he wanted to apply for medical retirement. The retirement request was then rejected. So he sued and eventually took the case to the Supreme Court, which in June ruled that states were not immune from such lawsuits by service members.

In those early years, the military and VA doctors couldn’t say what caused his breathing problems and splitting headaches. As with other victims of toxic exposure, diagnoses proved to be difficult. Some doctors suggested the problems weren’t real — a pronouncement often encountered by other vets whose claims are denied.

Like so many others, Rosie turned to the internet for information she couldn’t get from the VA, where she had worked for 23 years. She discovered a Facebook group that she would use as the basis for a new advocacy group, Burn Pits 360.

Le Roy was ultimately diagnosed with constrictive bronchiolitis, fibrosis of the lungs, and toxic encephalopathy. He eventually got his benefits in early 2013. By then, the family was deep in debt.

For years he lived with the reality that the military he had served for 23 years refused to answer his needs, and the police force he loved didn’t seem to care.

“It’s something that we have now learned is known as moral injury and compound loss,” Rosie said.

As a man, he began to wonder how he could provide for his family, if he was any use to anyone, she added. “So then that led to him attempting to take his life.”

It also led the couple and parents of three to beseech Congress to fix the problems. They started walking the halls in the Capitol. Success there was not any easier.

“We came to Capitol Hill and just handed out information we had printed about burn pit exposure,” Le Roy said at his last visit to the Hill in June, an oxygen tube strung under his nose.

“There were a lot of doors shut in our face,” Rosie said.

While making little progress in Congress, they built Burn Pits 360 into an advocacy group and a clearinghouse to help other veterans similarly frustrated by a system that seemed to be failing them.

The breakthrough for Rosie began when she saw Stewart and 9/11 survivors’ advocate John Feal winning a similar battle to make Congress fully fund health and compensation programs for responders of the Sept. 11, 2001, terror attacks. She recalls reading up on the toxic substances in the dust and smoke that spewed from the collapsed twin towers and discovering they were remarkably similar to the poisons inhaled by troops near the waste fires that were also set ablaze with jet fuel.

She called Feal. Feal called Stewart, and by February 2019 the four of them were meeting on Capitol Hill with lawmakers, including Sen. Kirsten Gillibrand (D-N.Y.), one of the authors of the 9/11 legislation.

The key, they decided in those first meetings, was to remove the obstacles for the most common illnesses and eliminate the burden of proof on ill former soldiers. Gillibrand’s office wrote that bill, along with Rep. Raul Ruiz (D-Calif.), who championed it in the House.

Related Links

• Senate GOP Puts Up Roadblocks to Bipartisan House Bill for Veterans’ Burn Pit Care
• Doctors Found Jet Fuel in Veteran’s Lungs. He Can’t Get Full Benefits.
• Role Reversal: Covid Increases Ranks of Child Caregivers

Ultimately, that bill became the heart of the measure that passed, known as the PACT Act and named for a soldier who died from cancer linked to his service.

“Our bill was the first federal presumption for burn pits coverage ever. And that was all because of Rosie and Le Roy,” said Gillibrand.

But just as with the 9/11 legislation, many in Congress weren’t that interested.

“It’s about money, and nobody likes to spend money,” Gillibrand said. “Congress never wants to accept the fact that treating these veterans and addressing their health care is the cost of war.”

Weeks ago, the bill appeared ready to glide through. It passed both the House and Senate but needed another vote to fix a technical legislative issue. Then on July 27, Sen. Pat Toomey (R-Pa.), who opposed the measure, unexpectedly persuaded 25 of his Republican colleagues who had supported the bill to vote against it, claiming that because the bill made the spending mandatory — not subject to the annual whims of Congress — Democrats would spend $400 billion elsewhere in the budget. Democrats countered that the money Toomey cited is already being spent and, regardless of how it’s categorized, it’s still up to Congress to appropriate it.

Rosie and veterans who had come to the Capitol that day to celebrate instead had to dig in one more time, with Stewart bringing the high-wattage attention that led the Republicans to reconsider. On Aug. 2, most Republicans decided to agree with the Democrats, and the bill passed 86 to 11.

Rosie said it never would have happened without Feal and Stewart. Stewart said it was all about Rosie, bringing together veterans in a way that Congress couldn’t ignore.

“She’s the reason I’m doing it, her and Le Roy,” Stewart said, standing outside the Capitol with Rosie the day before the vote.

Stewart, the Torreses, and untold other veterans tempered their joy with the warning that it will be a hard journey making the new program work with a VA that already has a massive backlog. The legislation has provisions to create facilities and bring in private doctors, but some vets remain dubious.

Iraq War veteran Brian Alvarado of Long Beach, California, was diagnosed with neck and throat cancer soon after returning from Iraq in 2006. He had been assigned to patrol one of the many burn pits. He eats and breathes through tubes and struggles to keep weight on. Radiation and a tracheostomy have left his voice almost inaudible.

“You can pass laws, but it all boils down to the VA. How are they going to implement the changes? The claims, the compensation, the treatment,” he asked in June. “And how long will it take?”

For the time being, though, Rosie said that even more than a visit to the White House, she was looking forward to going back to Texas and her family.

“You know, I lost 13 years away from my children, with trips to the hospital, coming to D.C.,” she said. “It means I can go home.”

Le Roy and Rosie can also reflect that as painful as this path has been, 3.5 million veterans are guaranteed a backstop because of this law, and thousands of veterans and active-duty service members who work for state and local governments now have recourse if they are fired after being injured at war.

“It is good to know that so many people will be helped,” Le Roy said from his home in Robstown, Texas. “It does help.”

KHN reporter Heidi de Marco contributed to this article.

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

The battle was just beginning for Le Roy Torres and his wife, Rosie, when the Army captain returned to Texas in 2008, already starting to suffer from the toxic substances he’d inhaled from the 10-acre burn pit at Camp Anaconda in Balad, Iraq.

Along the way, Le Roy would lose the job he loved as a Texas state trooper and take his fight all the way to a Supreme Court victory. He would be rushed to the emergency room hundreds of times, be denied health benefits by the Department of Veterans Affairs for years, attempt suicide, and seek experimental cures for the damage done to his lungs and brain.

Amid all that, Le Roy and Rosie founded an organization to help others and push Congress to fix the laws that allowed the suffering of veterans to go on, and ultimately enlist people like comedian and activist Jon Stewart, who helped them win a dramatic showdown in the Senate last week.

Their struggle will never really be over. But the Torreses’ campaign to make sure no other veterans experience what they had to ends Aug. 10, when they are set to join President Joe Biden as he signs a law to guarantee that 3.5 million American warriors exposed to similar hazards can get care.

“I mean, to think that 13 years ago we were walking the halls [of Congress] — it’s really emotional,” Rosie said recently, halting to collect herself and wipe back tears, “because I think of all the people that died along the way.”

The bill provides a new entitlement program for veterans who served in a combat zone in the past 32 years. If they are diagnosed with any of 23 conditions identified in the legislation — ranging from specific cancers to breathing ailments — they would be deemed automatically eligible for health coverage. The Congressional Budget Office estimated the new benefits would cost $280 billion over the next 10 years.

Most veterans — nearly 80% — who start experiencing symptoms after leaving the service get denied what’s known as a service connection when they seek help from the VA. The system has been designed to disbelieve them, the veterans complain. They must prove their breathing problems or cancers came from the toxic trash smoke they breathed overseas, which is extremely difficult.

When Le Roy returned home from Balad Air Base — the second-largest U.S. post in Iraq and where the military incinerated tons of debris daily, including plastic, ammunition, and medical waste — he was already sick. He was rushed to the hospital a few weeks later with a severe respiratory infection.

He had expected to keep working as a state trooper, but by 2010 it was clear he couldn’t perform all the duties because of his illness. When he asked for a different job with the Texas Department of Public Safety, he was denied. He was told he had to resign if he wanted to apply for medical retirement. The retirement request was then rejected. So he sued and eventually took the case to the Supreme Court, which in June ruled that states were not immune from such lawsuits by service members.

In those early years, the military and VA doctors couldn’t say what caused his breathing problems and splitting headaches. As with other victims of toxic exposure, diagnoses proved to be difficult. Some doctors suggested the problems weren’t real — a pronouncement often encountered by other vets whose claims are denied.

Like so many others, Rosie turned to the internet for information she couldn’t get from the VA, where she had worked for 23 years. She discovered a Facebook group that she would use as the basis for a new advocacy group, Burn Pits 360.

Le Roy was ultimately diagnosed with constrictive bronchiolitis, fibrosis of the lungs, and toxic encephalopathy. He eventually got his benefits in early 2013. By then, the family was deep in debt.

For years he lived with the reality that the military he had served for 23 years refused to answer his needs, and the police force he loved didn’t seem to care.

“It’s something that we have now learned is known as moral injury and compound loss,” Rosie said.

As a man, he began to wonder how he could provide for his family, if he was any use to anyone, she added. “So then that led to him attempting to take his life.”

It also led the couple and parents of three to beseech Congress to fix the problems. They started walking the halls in the Capitol. Success there was not any easier.

“We came to Capitol Hill and just handed out information we had printed about burn pit exposure,” Le Roy said at his last visit to the Hill in June, an oxygen tube strung under his nose.

“There were a lot of doors shut in our face,” Rosie said.

While making little progress in Congress, they built Burn Pits 360 into an advocacy group and a clearinghouse to help other veterans similarly frustrated by a system that seemed to be failing them.

The breakthrough for Rosie began when she saw Stewart and 9/11 survivors’ advocate John Feal winning a similar battle to make Congress fully fund health and compensation programs for responders of the Sept. 11, 2001, terror attacks. She recalls reading up on the toxic substances in the dust and smoke that spewed from the collapsed twin towers and discovering they were remarkably similar to the poisons inhaled by troops near the waste fires that were also set ablaze with jet fuel.

She called Feal. Feal called Stewart, and by February 2019 the four of them were meeting on Capitol Hill with lawmakers, including Sen. Kirsten Gillibrand (D-N.Y.), one of the authors of the 9/11 legislation.

The key, they decided in those first meetings, was to remove the obstacles for the most common illnesses and eliminate the burden of proof on ill former soldiers. Gillibrand’s office wrote that bill, along with Rep. Raul Ruiz (D-Calif.), who championed it in the House.

Related Links

• Senate GOP Puts Up Roadblocks to Bipartisan House Bill for Veterans’ Burn Pit Care
• Doctors Found Jet Fuel in Veteran’s Lungs. He Can’t Get Full Benefits.
• Role Reversal: Covid Increases Ranks of Child Caregivers

Ultimately, that bill became the heart of the measure that passed, known as the PACT Act and named for a soldier who died from cancer linked to his service.

“Our bill was the first federal presumption for burn pits coverage ever. And that was all because of Rosie and Le Roy,” said Gillibrand.

But just as with the 9/11 legislation, many in Congress weren’t that interested.

“It’s about money, and nobody likes to spend money,” Gillibrand said. “Congress never wants to accept the fact that treating these veterans and addressing their health care is the cost of war.”

Weeks ago, the bill appeared ready to glide through. It passed both the House and Senate but needed another vote to fix a technical legislative issue. Then on July 27, Sen. Pat Toomey (R-Pa.), who opposed the measure, unexpectedly persuaded 25 of his Republican colleagues who had supported the bill to vote against it, claiming that because the bill made the spending mandatory — not subject to the annual whims of Congress — Democrats would spend $400 billion elsewhere in the budget. Democrats countered that the money Toomey cited is already being spent and, regardless of how it’s categorized, it’s still up to Congress to appropriate it.

Rosie and veterans who had come to the Capitol that day to celebrate instead had to dig in one more time, with Stewart bringing the high-wattage attention that led the Republicans to reconsider. On Aug. 2, most Republicans decided to agree with the Democrats, and the bill passed 86 to 11.

Rosie said it never would have happened without Feal and Stewart. Stewart said it was all about Rosie, bringing together veterans in a way that Congress couldn’t ignore.

“She’s the reason I’m doing it, her and Le Roy,” Stewart said, standing outside the Capitol with Rosie the day before the vote.

Stewart, the Torreses, and untold other veterans tempered their joy with the warning that it will be a hard journey making the new program work with a VA that already has a massive backlog. The legislation has provisions to create facilities and bring in private doctors, but some vets remain dubious.

Iraq War veteran Brian Alvarado of Long Beach, California, was diagnosed with neck and throat cancer soon after returning from Iraq in 2006. He had been assigned to patrol one of the many burn pits. He eats and breathes through tubes and struggles to keep weight on. Radiation and a tracheostomy have left his voice almost inaudible.

“You can pass laws, but it all boils down to the VA. How are they going to implement the changes? The claims, the compensation, the treatment,” he asked in June. “And how long will it take?”

For the time being, though, Rosie said that even more than a visit to the White House, she was looking forward to going back to Texas and her family.

“You know, I lost 13 years away from my children, with trips to the hospital, coming to D.C.,” she said. “It means I can go home.”

Le Roy and Rosie can also reflect that as painful as this path has been, 3.5 million veterans are guaranteed a backstop because of this law, and thousands of veterans and active-duty service members who work for state and local governments now have recourse if they are fired after being injured at war.

“It is good to know that so many people will be helped,” Le Roy said from his home in Robstown, Texas. “It does help.”

KHN reporter Heidi de Marco contributed to this article.

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

Patients with lung cancer now have another treatment option: If their tumors are found to carry HER2 mutations, they can now be treated with trastuzumab deruxtecan (Enhertu), a drug that specifically targets that defect.

This product is already approved for used in HER2-positive breast cancer and gastric cancer. Now it has become the first product approved by the U.S. Food and Drug Administration for use in HER2-positive lung cancer.

Clinical data welcomed by experts

Clinical data are already available from the DESTINY-Lung 01 trial, and the results were welcomed enthusiastically by experts when they were published in the New England Journal of Medicine earlier this year.

“These results establish the new standard of care for patients with NSCLC harboring HER2 mutations,” Antonio Passaro, MD, PhD, from the European Institute of Oncology IRCCS, Milan, and Solange Peters, MD, PhD, from Lausanne (Switzerland) University Hospital, wrote in an accompanying editorial.

This trial involved 91 patients, all treated with trastuzumab deruxtecan (at 6.4 mg/kg of body weight every 3 weeks). The median duration of treatment was 6.9 months, and the median follow-up was 13.1 months.

The results showed a 55% centrally confirmed objective response, and median duration of response was 9.3 months.

In addition, the investigators reported a median progression-free survival of 8.2 months and a median overall survival of almost 18 months, both of which they described as “encouraging” in this patient population.

However, the results also highlighted a problem with the drug in this patient population. Notably, 26% of patients experienced interstitial lung disease, which resulted in death in two patients. The drug was also withdrawn in 16 patients and interrupted in 8 patients because of this adverse event.

Editorialists Dr. Passaro and Dr. Peters described this finding as “a concern” and note that “the incidence of interstitial lung disease is significantly higher among patients with lung cancer than among those with breast or gastric cancers, which may indicate a role of smoking-related damage.”

They also highlighted the need for an “investigation of the clinical efficacy of a reduced dose of trastuzumab deruxtecan,” and so the dose was reduced for the DESTINY-Lung02 trial.

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

Patients with lung cancer now have another treatment option: If their tumors are found to carry HER2 mutations, they can now be treated with trastuzumab deruxtecan (Enhertu), a drug that specifically targets that defect.

This product is already approved for used in HER2-positive breast cancer and gastric cancer. Now it has become the first product approved by the U.S. Food and Drug Administration for use in HER2-positive lung cancer.

Clinical data welcomed by experts

Clinical data are already available from the DESTINY-Lung 01 trial, and the results were welcomed enthusiastically by experts when they were published in the New England Journal of Medicine earlier this year.

“These results establish the new standard of care for patients with NSCLC harboring HER2 mutations,” Antonio Passaro, MD, PhD, from the European Institute of Oncology IRCCS, Milan, and Solange Peters, MD, PhD, from Lausanne (Switzerland) University Hospital, wrote in an accompanying editorial.

This trial involved 91 patients, all treated with trastuzumab deruxtecan (at 6.4 mg/kg of body weight every 3 weeks). The median duration of treatment was 6.9 months, and the median follow-up was 13.1 months.

The results showed a 55% centrally confirmed objective response, and median duration of response was 9.3 months.

In addition, the investigators reported a median progression-free survival of 8.2 months and a median overall survival of almost 18 months, both of which they described as “encouraging” in this patient population.

However, the results also highlighted a problem with the drug in this patient population. Notably, 26% of patients experienced interstitial lung disease, which resulted in death in two patients. The drug was also withdrawn in 16 patients and interrupted in 8 patients because of this adverse event.

Editorialists Dr. Passaro and Dr. Peters described this finding as “a concern” and note that “the incidence of interstitial lung disease is significantly higher among patients with lung cancer than among those with breast or gastric cancers, which may indicate a role of smoking-related damage.”

They also highlighted the need for an “investigation of the clinical efficacy of a reduced dose of trastuzumab deruxtecan,” and so the dose was reduced for the DESTINY-Lung02 trial.

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

Patients with lung cancer now have another treatment option: If their tumors are found to carry HER2 mutations, they can now be treated with trastuzumab deruxtecan (Enhertu), a drug that specifically targets that defect.

This product is already approved for used in HER2-positive breast cancer and gastric cancer. Now it has become the first product approved by the U.S. Food and Drug Administration for use in HER2-positive lung cancer.

Clinical data welcomed by experts

Clinical data are already available from the DESTINY-Lung 01 trial, and the results were welcomed enthusiastically by experts when they were published in the New England Journal of Medicine earlier this year.

“These results establish the new standard of care for patients with NSCLC harboring HER2 mutations,” Antonio Passaro, MD, PhD, from the European Institute of Oncology IRCCS, Milan, and Solange Peters, MD, PhD, from Lausanne (Switzerland) University Hospital, wrote in an accompanying editorial.

This trial involved 91 patients, all treated with trastuzumab deruxtecan (at 6.4 mg/kg of body weight every 3 weeks). The median duration of treatment was 6.9 months, and the median follow-up was 13.1 months.

The results showed a 55% centrally confirmed objective response, and median duration of response was 9.3 months.

In addition, the investigators reported a median progression-free survival of 8.2 months and a median overall survival of almost 18 months, both of which they described as “encouraging” in this patient population.

However, the results also highlighted a problem with the drug in this patient population. Notably, 26% of patients experienced interstitial lung disease, which resulted in death in two patients. The drug was also withdrawn in 16 patients and interrupted in 8 patients because of this adverse event.

Editorialists Dr. Passaro and Dr. Peters described this finding as “a concern” and note that “the incidence of interstitial lung disease is significantly higher among patients with lung cancer than among those with breast or gastric cancers, which may indicate a role of smoking-related damage.”

They also highlighted the need for an “investigation of the clinical efficacy of a reduced dose of trastuzumab deruxtecan,” and so the dose was reduced for the DESTINY-Lung02 trial.

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

Parents are relieved when school starts up again in the fall. Kids also are eager to see their friends and go on to the next level of learning.

Or are they?

This year brings a greater mix of feelings than usual for many families.

Many parents and children have new worries: Are children going to be safe at school from COVID, bullies, and shooters? Are they going to be ready to learn at this next level after the intermittent schooling of the past 2+ pandemic years of Zoom school, home school, or no school? Are they going to be able to separate after months of closeness/entanglement? Are they going to be able to catch up academically and fit in socially?

Children may have additional worries about how they have changed over the pandemic. Will my former friends still accept me now that I am heavier, showing puberty, experiencing acne, or feeling depressed or anxious?

While most of these worries occurred in some form after other summer breaks, they may be exacerbated by the length and degree of uncertainty we have all been through.

Often, health supervision visits are happy reunions with our patients when we hear about their growth and goals. We hope that is true this year, too, but we need to be vigilant and open to discussing the worries just mentioned.

What can we do to help ease this magnified transition?

First, we need to be open to their worries. Echoing back their concerns and noting how they are understandable and common can be reassuring when families have been isolated and missing interactions that might have made this clear. Second, we can remind them of the steps that assist in any transition. Now more than ever they need to collect information by visiting the new classroom, meeting teachers, and attending open house meet-and-greets. Older students may do better by looking over textbooks or a syllabus to see what will be covered. Making an effort to meet kids and families new to the school is a kind gesture but also helps the experienced child take some initiative and feel more confident.

Setting up an organizational system for homework from the start is valuable as work gets harder and is especially important for kids with ADHD. Single-subject folders, an assignment book tracking short-term and long-term projects, a plan for a specific homework time and place, a bookbag checklist by the door, or even a homework buddy and duplicate textbooks may be needed. Any kind of active steps toward organization can reduce anxiety.

Third, adjusting to the new schedule can take time. The most important adjustment is resetting the child’s sleep-wake cycle. You can recommend a move of 1 hour per day closer to the required wake up time and a corresponding bedtime that affords at least 8 hours (for tweens and teens; 9-12 hours for younger children), then maintaining the sleep schedule within 1 hour 7 days per week. Keep phones and tablets out of the bedroom. If children over 4 (including teens) have been napping over the summer, this needs to stop. Shifting mealtimes to fit the new schedule helps. Ensuring that lights are dimmed in the evening and bright in the morning has been shown to help the brain adjust.

A “new school year” is a good time for families to set new goals. Summer is often a time of fun, freedom, and new things. Parents may need your encouragement to exert leadership after months of cutting slack for their kids during COVID. Setting new goals such as greater responsibilities, music lessons, or household rules can be balanced by higher allowance and new earned privileges. Planning things to look forward to in the new year can be a family activity with a pleasant tone rather than just evoking protest. Suggest involving everyone in brainstorming crazy, out-of-the-box ideas (large and small) without censorship at first – for instance, go on a Mars mission; have pizza for breakfast; get yoga lessons; borrow binoculars to see Saturn; have a dog party! Everyone should be heard and their creativity celebrated. The list can then be narrowed down and marked on a calendar, starting soon.

Wait, you are hearing, how do we get our child off media to achieve this? Changing the rules about media use is never easy, and more now than ever. It is not just that kids are addicted to media, but it has been their main connection to peers during the pandemic. The “information” about/from peers, cliques, bullies, and world news may also be contributing to anxiety about returning to school. They may feel that they “need to know” even though it is upsetting. You can help kids verbalize the pros and cons of media use and possible addiction for themselves. How important media is to them needs to be acknowledged but ownership of the device and the final rules about this life-altering exposure must belong to the parents.

Sharing the AAP Family Media Plan to set proportions of time for school, homework, exercise, media (less than 2 hours for nonhomework), fun, and sleep can set an objective structure for the conversation. Parents may need to change their own media habits too!

While we pediatricians may normalize worries to reassure patients and parents, we also need to be alert to children and families in need of help. Many children have developed significant anxiety, depression, or substance use during the pandemic while out of our oversight but may not bring it up. Bereavement, which affected so many families during the pandemic, may not resolve smoothly. Families may have lost support, jobs, housing, or health insurance and need help connecting with assistance. Use of screening tools can ensure these are not missed, while remembering that functional impairment (social, academic, daily living, distress) is what differentiates normal from abnormal. We may be able to counsel them ourselves or refer them.

All this may be happening for you and your family, too. It can be difficult to assist others when we are struggling ourselves. We have been called on to cope when everything has been uncertain and our patients are sad, angry, or distrustful, with no end to the stress in sight. Sharing with colleagues, taking a break, or getting help for yourself may need to be a new goal for the school year, too.

Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS. She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to MDedge News. E-mail her at [email protected].

Parents are relieved when school starts up again in the fall. Kids also are eager to see their friends and go on to the next level of learning.

Or are they?

This year brings a greater mix of feelings than usual for many families.

Many parents and children have new worries: Are children going to be safe at school from COVID, bullies, and shooters? Are they going to be ready to learn at this next level after the intermittent schooling of the past 2+ pandemic years of Zoom school, home school, or no school? Are they going to be able to separate after months of closeness/entanglement? Are they going to be able to catch up academically and fit in socially?

Children may have additional worries about how they have changed over the pandemic. Will my former friends still accept me now that I am heavier, showing puberty, experiencing acne, or feeling depressed or anxious?

While most of these worries occurred in some form after other summer breaks, they may be exacerbated by the length and degree of uncertainty we have all been through.

Often, health supervision visits are happy reunions with our patients when we hear about their growth and goals. We hope that is true this year, too, but we need to be vigilant and open to discussing the worries just mentioned.

What can we do to help ease this magnified transition?

First, we need to be open to their worries. Echoing back their concerns and noting how they are understandable and common can be reassuring when families have been isolated and missing interactions that might have made this clear. Second, we can remind them of the steps that assist in any transition. Now more than ever they need to collect information by visiting the new classroom, meeting teachers, and attending open house meet-and-greets. Older students may do better by looking over textbooks or a syllabus to see what will be covered. Making an effort to meet kids and families new to the school is a kind gesture but also helps the experienced child take some initiative and feel more confident.

Setting up an organizational system for homework from the start is valuable as work gets harder and is especially important for kids with ADHD. Single-subject folders, an assignment book tracking short-term and long-term projects, a plan for a specific homework time and place, a bookbag checklist by the door, or even a homework buddy and duplicate textbooks may be needed. Any kind of active steps toward organization can reduce anxiety.

Third, adjusting to the new schedule can take time. The most important adjustment is resetting the child’s sleep-wake cycle. You can recommend a move of 1 hour per day closer to the required wake up time and a corresponding bedtime that affords at least 8 hours (for tweens and teens; 9-12 hours for younger children), then maintaining the sleep schedule within 1 hour 7 days per week. Keep phones and tablets out of the bedroom. If children over 4 (including teens) have been napping over the summer, this needs to stop. Shifting mealtimes to fit the new schedule helps. Ensuring that lights are dimmed in the evening and bright in the morning has been shown to help the brain adjust.

A “new school year” is a good time for families to set new goals. Summer is often a time of fun, freedom, and new things. Parents may need your encouragement to exert leadership after months of cutting slack for their kids during COVID. Setting new goals such as greater responsibilities, music lessons, or household rules can be balanced by higher allowance and new earned privileges. Planning things to look forward to in the new year can be a family activity with a pleasant tone rather than just evoking protest. Suggest involving everyone in brainstorming crazy, out-of-the-box ideas (large and small) without censorship at first – for instance, go on a Mars mission; have pizza for breakfast; get yoga lessons; borrow binoculars to see Saturn; have a dog party! Everyone should be heard and their creativity celebrated. The list can then be narrowed down and marked on a calendar, starting soon.

Wait, you are hearing, how do we get our child off media to achieve this? Changing the rules about media use is never easy, and more now than ever. It is not just that kids are addicted to media, but it has been their main connection to peers during the pandemic. The “information” about/from peers, cliques, bullies, and world news may also be contributing to anxiety about returning to school. They may feel that they “need to know” even though it is upsetting. You can help kids verbalize the pros and cons of media use and possible addiction for themselves. How important media is to them needs to be acknowledged but ownership of the device and the final rules about this life-altering exposure must belong to the parents.

Sharing the AAP Family Media Plan to set proportions of time for school, homework, exercise, media (less than 2 hours for nonhomework), fun, and sleep can set an objective structure for the conversation. Parents may need to change their own media habits too!

While we pediatricians may normalize worries to reassure patients and parents, we also need to be alert to children and families in need of help. Many children have developed significant anxiety, depression, or substance use during the pandemic while out of our oversight but may not bring it up. Bereavement, which affected so many families during the pandemic, may not resolve smoothly. Families may have lost support, jobs, housing, or health insurance and need help connecting with assistance. Use of screening tools can ensure these are not missed, while remembering that functional impairment (social, academic, daily living, distress) is what differentiates normal from abnormal. We may be able to counsel them ourselves or refer them.

All this may be happening for you and your family, too. It can be difficult to assist others when we are struggling ourselves. We have been called on to cope when everything has been uncertain and our patients are sad, angry, or distrustful, with no end to the stress in sight. Sharing with colleagues, taking a break, or getting help for yourself may need to be a new goal for the school year, too.

Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS. She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to MDedge News. E-mail her at [email protected].

Parents are relieved when school starts up again in the fall. Kids also are eager to see their friends and go on to the next level of learning.

Or are they?

This year brings a greater mix of feelings than usual for many families.

Many parents and children have new worries: Are children going to be safe at school from COVID, bullies, and shooters? Are they going to be ready to learn at this next level after the intermittent schooling of the past 2+ pandemic years of Zoom school, home school, or no school? Are they going to be able to separate after months of closeness/entanglement? Are they going to be able to catch up academically and fit in socially?

Children may have additional worries about how they have changed over the pandemic. Will my former friends still accept me now that I am heavier, showing puberty, experiencing acne, or feeling depressed or anxious?

While most of these worries occurred in some form after other summer breaks, they may be exacerbated by the length and degree of uncertainty we have all been through.

Often, health supervision visits are happy reunions with our patients when we hear about their growth and goals. We hope that is true this year, too, but we need to be vigilant and open to discussing the worries just mentioned.

What can we do to help ease this magnified transition?

First, we need to be open to their worries. Echoing back their concerns and noting how they are understandable and common can be reassuring when families have been isolated and missing interactions that might have made this clear. Second, we can remind them of the steps that assist in any transition. Now more than ever they need to collect information by visiting the new classroom, meeting teachers, and attending open house meet-and-greets. Older students may do better by looking over textbooks or a syllabus to see what will be covered. Making an effort to meet kids and families new to the school is a kind gesture but also helps the experienced child take some initiative and feel more confident.

Setting up an organizational system for homework from the start is valuable as work gets harder and is especially important for kids with ADHD. Single-subject folders, an assignment book tracking short-term and long-term projects, a plan for a specific homework time and place, a bookbag checklist by the door, or even a homework buddy and duplicate textbooks may be needed. Any kind of active steps toward organization can reduce anxiety.

Third, adjusting to the new schedule can take time. The most important adjustment is resetting the child’s sleep-wake cycle. You can recommend a move of 1 hour per day closer to the required wake up time and a corresponding bedtime that affords at least 8 hours (for tweens and teens; 9-12 hours for younger children), then maintaining the sleep schedule within 1 hour 7 days per week. Keep phones and tablets out of the bedroom. If children over 4 (including teens) have been napping over the summer, this needs to stop. Shifting mealtimes to fit the new schedule helps. Ensuring that lights are dimmed in the evening and bright in the morning has been shown to help the brain adjust.

A “new school year” is a good time for families to set new goals. Summer is often a time of fun, freedom, and new things. Parents may need your encouragement to exert leadership after months of cutting slack for their kids during COVID. Setting new goals such as greater responsibilities, music lessons, or household rules can be balanced by higher allowance and new earned privileges. Planning things to look forward to in the new year can be a family activity with a pleasant tone rather than just evoking protest. Suggest involving everyone in brainstorming crazy, out-of-the-box ideas (large and small) without censorship at first – for instance, go on a Mars mission; have pizza for breakfast; get yoga lessons; borrow binoculars to see Saturn; have a dog party! Everyone should be heard and their creativity celebrated. The list can then be narrowed down and marked on a calendar, starting soon.

Wait, you are hearing, how do we get our child off media to achieve this? Changing the rules about media use is never easy, and more now than ever. It is not just that kids are addicted to media, but it has been their main connection to peers during the pandemic. The “information” about/from peers, cliques, bullies, and world news may also be contributing to anxiety about returning to school. They may feel that they “need to know” even though it is upsetting. You can help kids verbalize the pros and cons of media use and possible addiction for themselves. How important media is to them needs to be acknowledged but ownership of the device and the final rules about this life-altering exposure must belong to the parents.

Sharing the AAP Family Media Plan to set proportions of time for school, homework, exercise, media (less than 2 hours for nonhomework), fun, and sleep can set an objective structure for the conversation. Parents may need to change their own media habits too!

While we pediatricians may normalize worries to reassure patients and parents, we also need to be alert to children and families in need of help. Many children have developed significant anxiety, depression, or substance use during the pandemic while out of our oversight but may not bring it up. Bereavement, which affected so many families during the pandemic, may not resolve smoothly. Families may have lost support, jobs, housing, or health insurance and need help connecting with assistance. Use of screening tools can ensure these are not missed, while remembering that functional impairment (social, academic, daily living, distress) is what differentiates normal from abnormal. We may be able to counsel them ourselves or refer them.

All this may be happening for you and your family, too. It can be difficult to assist others when we are struggling ourselves. We have been called on to cope when everything has been uncertain and our patients are sad, angry, or distrustful, with no end to the stress in sight. Sharing with colleagues, taking a break, or getting help for yourself may need to be a new goal for the school year, too.

Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS. She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to MDedge News. E-mail her at [email protected].

Clinicians’ reluctance to discuss possible harms of anal sex may be letting down a generation of young women who are unaware of the risks, two researchers from the United Kingdom write in an opinion article published in The BMJ.

Failure to discuss the subject “exposes women to missed diagnoses, futile treatments, and further harm arising from a lack of medical advice,” write Tabitha Gana, MD, and Lesley Hunt, MD, with Sheffield Teaching Hospitals NHS Foundation Trust and Northern General Hospital, both in Sheffield, United Kingdom.

In their opinion, health care professionals, particularly those in general practice, gastroenterology, and colorectal surgery, “have a duty to acknowledge changes in society around anal sex in young women and to meet these changes with open, neutral, and non-judgmental conversations to ensure that all women have the information they need to make informed choices about sex.”

Asking about anal sex is standard practice in genitourinary medicine clinics, but it’s less common in general practice and colorectal clinics, they point out.
 

No longer taboo

Anal intercourse is becoming more common among young heterosexual couples. In the United Kingdom, participation in heterosexual anal intercourse among people aged 16-24 years rose from about 13% to 29% over the last few decades, according to national survey data. 

The same thing is happening in the United States, where research suggests 30%-44% of men and women report having anal sex.

Individual motivation for anal sex varies. Young women cite pleasure, curiosity, pleasing the male partners, and coercion as factors. Up to 25% of women with experience of anal sex report they have been pressured into it at least once, Dr. Gana and Dr. Hunt say.

However, because of its association with alcohol, drug use, and multiple sex partners, anal intercourse is considered a risky sexual behavior.

It’s also associated with specific health concerns, Dr. Gana and Dr. Hunt point out. These include fecal incontinence and anal sphincter injury, which have been reported in women who engage in anal intercourse. When it comes to incontinence, women are at higher risk than men because of their different anatomy and the effects of hormones, pregnancy, and childbirth on the pelvic floor.

“Women have less robust anal sphincters and lower anal canal pressures than men, and damage caused by anal penetration is therefore more consequential,” Dr. Gana and Dr. Hunt point out.

“The pain and bleeding women report after anal sex is indicative of trauma, and risks may be increased if anal sex is coerced,” they add.

Knowledge of the underlying risk factors and taking a good history are key to effective management of anorectal disorders, they say.  

Dr. Gana and Dr. Hunt worry that clinicians may shy away from talking about anal sex, influenced by society’s taboos.

Currently, NHS patient information on anal sex considers only sexually transmitted infections, making no mention of anal trauma, incontinence, or the psychological aftermath of being coerced into anal sex.  

“It may not be just avoidance or stigma that prevents health professionals [from] talking to young women about the risks of anal sex. There is genuine concern that the message may be seen as judgmental or even misconstrued as homophobic,” Dr. Gana and Dr. Hunt write.

“However, by avoiding these discussions, we may be failing a generation of young women who are unaware of the risks,” they add.

“With better information, women who want anal sex would be able to protect themselves more effectively from possible harm, and those who agree to anal sex reluctantly to meet society’s expectations or please partners may feel better empowered to say no,” Dr. Gana and Dr. Hunt say.

This research had no specific funding. Dr. Gana and Dr. Hunt report no relevant financial relationships.

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

Clinicians’ reluctance to discuss possible harms of anal sex may be letting down a generation of young women who are unaware of the risks, two researchers from the United Kingdom write in an opinion article published in The BMJ.

Failure to discuss the subject “exposes women to missed diagnoses, futile treatments, and further harm arising from a lack of medical advice,” write Tabitha Gana, MD, and Lesley Hunt, MD, with Sheffield Teaching Hospitals NHS Foundation Trust and Northern General Hospital, both in Sheffield, United Kingdom.

In their opinion, health care professionals, particularly those in general practice, gastroenterology, and colorectal surgery, “have a duty to acknowledge changes in society around anal sex in young women and to meet these changes with open, neutral, and non-judgmental conversations to ensure that all women have the information they need to make informed choices about sex.”

Asking about anal sex is standard practice in genitourinary medicine clinics, but it’s less common in general practice and colorectal clinics, they point out.
 

No longer taboo

Anal intercourse is becoming more common among young heterosexual couples. In the United Kingdom, participation in heterosexual anal intercourse among people aged 16-24 years rose from about 13% to 29% over the last few decades, according to national survey data. 

The same thing is happening in the United States, where research suggests 30%-44% of men and women report having anal sex.

Individual motivation for anal sex varies. Young women cite pleasure, curiosity, pleasing the male partners, and coercion as factors. Up to 25% of women with experience of anal sex report they have been pressured into it at least once, Dr. Gana and Dr. Hunt say.

However, because of its association with alcohol, drug use, and multiple sex partners, anal intercourse is considered a risky sexual behavior.

It’s also associated with specific health concerns, Dr. Gana and Dr. Hunt point out. These include fecal incontinence and anal sphincter injury, which have been reported in women who engage in anal intercourse. When it comes to incontinence, women are at higher risk than men because of their different anatomy and the effects of hormones, pregnancy, and childbirth on the pelvic floor.

“Women have less robust anal sphincters and lower anal canal pressures than men, and damage caused by anal penetration is therefore more consequential,” Dr. Gana and Dr. Hunt point out.

“The pain and bleeding women report after anal sex is indicative of trauma, and risks may be increased if anal sex is coerced,” they add.

Knowledge of the underlying risk factors and taking a good history are key to effective management of anorectal disorders, they say.  

Dr. Gana and Dr. Hunt worry that clinicians may shy away from talking about anal sex, influenced by society’s taboos.

Currently, NHS patient information on anal sex considers only sexually transmitted infections, making no mention of anal trauma, incontinence, or the psychological aftermath of being coerced into anal sex.  

“It may not be just avoidance or stigma that prevents health professionals [from] talking to young women about the risks of anal sex. There is genuine concern that the message may be seen as judgmental or even misconstrued as homophobic,” Dr. Gana and Dr. Hunt write.

“However, by avoiding these discussions, we may be failing a generation of young women who are unaware of the risks,” they add.

“With better information, women who want anal sex would be able to protect themselves more effectively from possible harm, and those who agree to anal sex reluctantly to meet society’s expectations or please partners may feel better empowered to say no,” Dr. Gana and Dr. Hunt say.

This research had no specific funding. Dr. Gana and Dr. Hunt report no relevant financial relationships.

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

Clinicians’ reluctance to discuss possible harms of anal sex may be letting down a generation of young women who are unaware of the risks, two researchers from the United Kingdom write in an opinion article published in The BMJ.

Failure to discuss the subject “exposes women to missed diagnoses, futile treatments, and further harm arising from a lack of medical advice,” write Tabitha Gana, MD, and Lesley Hunt, MD, with Sheffield Teaching Hospitals NHS Foundation Trust and Northern General Hospital, both in Sheffield, United Kingdom.

In their opinion, health care professionals, particularly those in general practice, gastroenterology, and colorectal surgery, “have a duty to acknowledge changes in society around anal sex in young women and to meet these changes with open, neutral, and non-judgmental conversations to ensure that all women have the information they need to make informed choices about sex.”

Asking about anal sex is standard practice in genitourinary medicine clinics, but it’s less common in general practice and colorectal clinics, they point out.
 

No longer taboo

Anal intercourse is becoming more common among young heterosexual couples. In the United Kingdom, participation in heterosexual anal intercourse among people aged 16-24 years rose from about 13% to 29% over the last few decades, according to national survey data. 

The same thing is happening in the United States, where research suggests 30%-44% of men and women report having anal sex.

Individual motivation for anal sex varies. Young women cite pleasure, curiosity, pleasing the male partners, and coercion as factors. Up to 25% of women with experience of anal sex report they have been pressured into it at least once, Dr. Gana and Dr. Hunt say.

However, because of its association with alcohol, drug use, and multiple sex partners, anal intercourse is considered a risky sexual behavior.

It’s also associated with specific health concerns, Dr. Gana and Dr. Hunt point out. These include fecal incontinence and anal sphincter injury, which have been reported in women who engage in anal intercourse. When it comes to incontinence, women are at higher risk than men because of their different anatomy and the effects of hormones, pregnancy, and childbirth on the pelvic floor.

“Women have less robust anal sphincters and lower anal canal pressures than men, and damage caused by anal penetration is therefore more consequential,” Dr. Gana and Dr. Hunt point out.

“The pain and bleeding women report after anal sex is indicative of trauma, and risks may be increased if anal sex is coerced,” they add.

Knowledge of the underlying risk factors and taking a good history are key to effective management of anorectal disorders, they say.  

Dr. Gana and Dr. Hunt worry that clinicians may shy away from talking about anal sex, influenced by society’s taboos.

Currently, NHS patient information on anal sex considers only sexually transmitted infections, making no mention of anal trauma, incontinence, or the psychological aftermath of being coerced into anal sex.  

“It may not be just avoidance or stigma that prevents health professionals [from] talking to young women about the risks of anal sex. There is genuine concern that the message may be seen as judgmental or even misconstrued as homophobic,” Dr. Gana and Dr. Hunt write.

“However, by avoiding these discussions, we may be failing a generation of young women who are unaware of the risks,” they add.

“With better information, women who want anal sex would be able to protect themselves more effectively from possible harm, and those who agree to anal sex reluctantly to meet society’s expectations or please partners may feel better empowered to say no,” Dr. Gana and Dr. Hunt say.

This research had no specific funding. Dr. Gana and Dr. Hunt report no relevant financial relationships.

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

SAN DIEGO – In 1906, a neuroanatomist and psychiatrist named Alois Alzheimer examined the brain of a 50-year-old woman whom he had treated for paranoia, sleep and memory problems, aggression, and confusion. His autopsy revealed plaques and tangles in her brain. The most common components of these tangles are beta-amyloid peptide (A-beta) and the microtubule binding protein tau. Over the past few decades, that finding has launched many clinical development programs and dozens of clinical trials.

To date, all but one program has failed. In 2021, amidst much controversy, FDA granted accelerated approval to Biogen’s Aduhelm, which effectively clears A-beta and tau deposits from patients’ brains. The problem is that the clinical benefit is small, and uptake has been so low that the company was forced to abandon a planned postmarketing observational trial.
 

Chasing the wrong target?

At a session at the 2022 Alzheimer’s Association International Conference, Raymond J. Tesi, MD, rather forcefully refuted that approach. “Amyloid and tau therapies have had 20 years to prove themselves. We have multiple cases where we’ve been able to decrease amyloid, maybe not so much tau, but certainly amyloid, and the benefits are mild at best. So I think that the Alzheimer’s drug development community, whether you look at the NIH, whether you look at academia, whether you look at biopharma, has focused on a target that has not proven itself, and it’s time to move on,” said Dr. Tesi, who is president, CEO, and chief medical officer at INmune Bio.

Later in the session, researchers presented strategies to counter Alzheimer’s disease and other neurodegenerative conditions using strategies including modulation of metabolism and inflammation, support of brain homeostasis, and suppression of a broader range of neurotoxic proteins.

One audience member defended the potential importance of A-beta and tau, especially in astrogliosis, which is a reaction to stress by astrocytes that attempts to limit tissue damage. The questioner suggested that it was still important to measure the effect of a novel drug on A-beta and tau. “What would be the cause of the reactive astrogliosis and microglia activation, if we are not giving a damn about amyloid and tau?” he asked.

After a bit of back and forth, Dr. Tesi replied: “We both have a religious belief here, and sooner or later we’ll get the answer.”
 

A diverse clinical pipeline

The session itself focused on four companies, including Dr. Tesi’s INmune Bio, which have drugs with alternative mechanisms entering the advanced stages of clinical development. That’s good news, according to Heather Snyder, PhD, who is vice president of Medical & Scientific Relations at the Alzheimer’s Association. “One of the things that I think is really important is the diversity of what’s in the clinical pipeline, and it’s not just in the very beginning anymore. We’re seeing [companies] now reporting phase 2 [studies] and planning their next stage. That’s something that as a field we should be excited about. As we understand more and more about the biology, we’re now seeing that translating into clinical trials and we’re seeing that translate through the clinical pipeline of development,” said Dr. Snyder in an interview.

Targeting neuroinflammation

Dr. Tesi kicked off the session describing INmune Bio’s focus on neuroinflammation. The company’s drug candidate targets soluble tumor necrosis factor (TNF), which the company believes is a direct cause of Alzheimer’s disease through promotion of inflammation. He noted that TNF is a primary mediator of inflammation in rheumatoid arthritis, and patients with RA have an eightfold increased risk of developing Alzheimer’s disease, compared with the general population, while patients with RA who are taking anti-TNF medication have a 60% lower risk than the general population.

The company’s TNF inhibitor XPro is also unique in that it induces remyelination in mice, while other TNF inhibitors potentially “abuse” the brain by causing demyelination. Earlier research showed that it reduces neuroinflammation, improves nerve cell survival, and improves synaptic function. The company is conducting two phase 2 clinical trials, one in patients with mild cognitive impairment (MCI) and one in mild Alzheimer’s disease. They also use the MCI Alzheimer’s Cognitive Composite (EMACC) tool for assessing outcomes rather than the more commonly used Alzheimer’s Disease Assessment Scale-Cognitive subscale (ADAS-Cog). “ADAS-Cog is like trying to make sushi with an axe. It is designed for moderate to severe disease, and trying to use it for mild (Alzheimer’s disease) or MCI is a mistake. EMACC is purpose built for mild [AD] and MCI patients,” said Dr. Tesi.
 

Maintaining homeostatis

Next, Hans Moebius, MD, PhD, chief medical officer of Athira Pharma, described his company’s focus on the hepatocyte growth factor (HGF) receptor, also known as tyrosine kinase MET (HGF/MET). It plays an important role in brain development and homeostasis, and it is expressed at lower levels in the frontal cortex and hippocampus of patients with Alzheimer’s disease. The company’s small-molecule drug candidate boosts the HGF/MET pathway, leading to downstream neuroprotection and neurotrophic effects. It also promotes formation of new synapses.

Dr. Moebius presented the results of a phase 2 trial showing that the drug, called fosgonimeton, led to significant cognitive improvement compared with placebo. The company is conducting a phase 3 clinical trial.
 

Type 3 diabetes?

In his talk, John Didsbury, PhD, founder and CEO of T3D Therapeutics, framed Alzheimer’s disease as a disease of metabolic dysfunction. He believes alterations to glucose and lipids in the brain cause structural changes that lead to symptoms. He pointed out that the strongest genetic Alzheimer’s disease risk factor is a mutant form of the lipid transport protein APOE4.

“What we have is dysregulated glucose energy metabolism and lipid metabolism that really cause, in our mind, the structural event changes and the stress event changes – plaques, tangles, inflammation, etc. – but these events perpetuate the dysregulated metabolism. It’s a massive positive feedback loop that many have called type 3 diabetes – a brain-specific form of diabetes,” said Dr. Didsbury.

The company’s approach is to use systems biology to identify a drug target that can bypass multiple aberrant insulin signaling pathways. Its drug candidate regulates the expression of multiple genes involved in glucose metabolism. Dr. Didsbury presented interim results from a phase 2 study showing improvement over placebo.
 

Focusing on neurotoxic proteins

The final presentation of the session was by Maria Maccecchini, PhD, founder, president, and CEO of Annovis Bio. The company’s drug, buntanetap, reduces expression of a range of neurotoxic proteins. The downstream effects include restoration of axonal transport, reduction of inflammation, and protection of nerve cells. The company believes that Alzheimer’s disease results from acute and chronic stress events that lead to high levels of neurotoxic proteins, which include A-beta, tau, alpha-synuclein, and TDP43. The proteins aren’t just players in Alzheimer’s disease – they are present in abnormal levels in Parkinson’s disease and a range of other brain pathologies.

“In the brain of an Alzheimer’s and of a Parkinson’s [patient], you’re going to find all four proteins. You’ll find them in different concentrations, at different time points, in different brain areas. If you just remove one, you still have the other three that cause impairment in axonal transport, and that leads to inflammation that leads to neurodegeneration,” said Dr. Maccecchini.

The company’s drug manages to reduce levels of all four proteins by binding to a segment of messenger RNA (mRNA) shared by all of them. mRNA serves as a template for protein synthesis. Under normal conditions, the neurotoxic protein concentrations are kept low because the mRNA segment remains bound to a regulatory protein that prevents synthesis from occurring. However, when stress leads to high levels of iron, this regulatory binding protein releases the mRNA segment (along with the rest of the mRNA). The freed mRNA becomes available to the cell’s protein synthesis machinery, which starts producing high levels of neurotoxic proteins. Annovis Bio’s drug improves the ability of the regulatory protein to bind to the mRNA segment, preventing protein expression even in high-iron conditions. It works on all four neurotoxic proteins because they all have the regulatory segment in their mRNA.

The drug led to improvements in phase 2 studies of Alzheimer’s disease and Parkinson’s disease, and the company is currently recruiting for a phase 3 study in Parkinson’s disease and a phase 2/3 dose-response study in Alzheimer’s disease.
 

Combination treatments for a complex disease

Taken together, the presentations provided a snapshot of the post–A-beta/tau Alzheimer’s development world, and the future could be messy. Alzheimer’s disease and other dementias are likely to require combination treatments, according to Dr. Snyder. “This is a complex disease, not just Alzheimer’s but other dementias. It’s not going to be a single drug, a single target. It’s going to require some type of combinatorial approach, whether that be with medication and lifestyle interventions, or risk reduction, and different medications,” she said.

The latest results are good news for that approach: “We’re seeing that maturation of the science in these trials,” said Dr. Snyder.

Cheng Fang, PhD, senior vice president of research and development at Annovis Bio, agreed with that sentiment. “I believe [Alzheimer’s disease and dementia] is a very complicated disease. I always call them diseases instead of a disease because it’s a spectrum. I don’t believe one drug can cure them all, as much as I am confident in our drug. I think it’s extremely important to encourage this kind of diverse thinking,” said Dr. Fang.

Dr. Snyder has no relevant financial disclosures. Dr. Tesi, Dr. Moebius, Dr. Didsbury, Dr. Maccecchini, and Dr. Fang are employees and in some cases stockholders of their respective companies.

SAN DIEGO – In 1906, a neuroanatomist and psychiatrist named Alois Alzheimer examined the brain of a 50-year-old woman whom he had treated for paranoia, sleep and memory problems, aggression, and confusion. His autopsy revealed plaques and tangles in her brain. The most common components of these tangles are beta-amyloid peptide (A-beta) and the microtubule binding protein tau. Over the past few decades, that finding has launched many clinical development programs and dozens of clinical trials.

To date, all but one program has failed. In 2021, amidst much controversy, FDA granted accelerated approval to Biogen’s Aduhelm, which effectively clears A-beta and tau deposits from patients’ brains. The problem is that the clinical benefit is small, and uptake has been so low that the company was forced to abandon a planned postmarketing observational trial.
 

Chasing the wrong target?

At a session at the 2022 Alzheimer’s Association International Conference, Raymond J. Tesi, MD, rather forcefully refuted that approach. “Amyloid and tau therapies have had 20 years to prove themselves. We have multiple cases where we’ve been able to decrease amyloid, maybe not so much tau, but certainly amyloid, and the benefits are mild at best. So I think that the Alzheimer’s drug development community, whether you look at the NIH, whether you look at academia, whether you look at biopharma, has focused on a target that has not proven itself, and it’s time to move on,” said Dr. Tesi, who is president, CEO, and chief medical officer at INmune Bio.

Later in the session, researchers presented strategies to counter Alzheimer’s disease and other neurodegenerative conditions using strategies including modulation of metabolism and inflammation, support of brain homeostasis, and suppression of a broader range of neurotoxic proteins.

One audience member defended the potential importance of A-beta and tau, especially in astrogliosis, which is a reaction to stress by astrocytes that attempts to limit tissue damage. The questioner suggested that it was still important to measure the effect of a novel drug on A-beta and tau. “What would be the cause of the reactive astrogliosis and microglia activation, if we are not giving a damn about amyloid and tau?” he asked.

After a bit of back and forth, Dr. Tesi replied: “We both have a religious belief here, and sooner or later we’ll get the answer.”
 

A diverse clinical pipeline

The session itself focused on four companies, including Dr. Tesi’s INmune Bio, which have drugs with alternative mechanisms entering the advanced stages of clinical development. That’s good news, according to Heather Snyder, PhD, who is vice president of Medical & Scientific Relations at the Alzheimer’s Association. “One of the things that I think is really important is the diversity of what’s in the clinical pipeline, and it’s not just in the very beginning anymore. We’re seeing [companies] now reporting phase 2 [studies] and planning their next stage. That’s something that as a field we should be excited about. As we understand more and more about the biology, we’re now seeing that translating into clinical trials and we’re seeing that translate through the clinical pipeline of development,” said Dr. Snyder in an interview.

Targeting neuroinflammation

Dr. Tesi kicked off the session describing INmune Bio’s focus on neuroinflammation. The company’s drug candidate targets soluble tumor necrosis factor (TNF), which the company believes is a direct cause of Alzheimer’s disease through promotion of inflammation. He noted that TNF is a primary mediator of inflammation in rheumatoid arthritis, and patients with RA have an eightfold increased risk of developing Alzheimer’s disease, compared with the general population, while patients with RA who are taking anti-TNF medication have a 60% lower risk than the general population.

The company’s TNF inhibitor XPro is also unique in that it induces remyelination in mice, while other TNF inhibitors potentially “abuse” the brain by causing demyelination. Earlier research showed that it reduces neuroinflammation, improves nerve cell survival, and improves synaptic function. The company is conducting two phase 2 clinical trials, one in patients with mild cognitive impairment (MCI) and one in mild Alzheimer’s disease. They also use the MCI Alzheimer’s Cognitive Composite (EMACC) tool for assessing outcomes rather than the more commonly used Alzheimer’s Disease Assessment Scale-Cognitive subscale (ADAS-Cog). “ADAS-Cog is like trying to make sushi with an axe. It is designed for moderate to severe disease, and trying to use it for mild (Alzheimer’s disease) or MCI is a mistake. EMACC is purpose built for mild [AD] and MCI patients,” said Dr. Tesi.
 

Maintaining homeostatis

Next, Hans Moebius, MD, PhD, chief medical officer of Athira Pharma, described his company’s focus on the hepatocyte growth factor (HGF) receptor, also known as tyrosine kinase MET (HGF/MET). It plays an important role in brain development and homeostasis, and it is expressed at lower levels in the frontal cortex and hippocampus of patients with Alzheimer’s disease. The company’s small-molecule drug candidate boosts the HGF/MET pathway, leading to downstream neuroprotection and neurotrophic effects. It also promotes formation of new synapses.

Dr. Moebius presented the results of a phase 2 trial showing that the drug, called fosgonimeton, led to significant cognitive improvement compared with placebo. The company is conducting a phase 3 clinical trial.
 

Type 3 diabetes?

In his talk, John Didsbury, PhD, founder and CEO of T3D Therapeutics, framed Alzheimer’s disease as a disease of metabolic dysfunction. He believes alterations to glucose and lipids in the brain cause structural changes that lead to symptoms. He pointed out that the strongest genetic Alzheimer’s disease risk factor is a mutant form of the lipid transport protein APOE4.

“What we have is dysregulated glucose energy metabolism and lipid metabolism that really cause, in our mind, the structural event changes and the stress event changes – plaques, tangles, inflammation, etc. – but these events perpetuate the dysregulated metabolism. It’s a massive positive feedback loop that many have called type 3 diabetes – a brain-specific form of diabetes,” said Dr. Didsbury.

The company’s approach is to use systems biology to identify a drug target that can bypass multiple aberrant insulin signaling pathways. Its drug candidate regulates the expression of multiple genes involved in glucose metabolism. Dr. Didsbury presented interim results from a phase 2 study showing improvement over placebo.
 

Focusing on neurotoxic proteins

The final presentation of the session was by Maria Maccecchini, PhD, founder, president, and CEO of Annovis Bio. The company’s drug, buntanetap, reduces expression of a range of neurotoxic proteins. The downstream effects include restoration of axonal transport, reduction of inflammation, and protection of nerve cells. The company believes that Alzheimer’s disease results from acute and chronic stress events that lead to high levels of neurotoxic proteins, which include A-beta, tau, alpha-synuclein, and TDP43. The proteins aren’t just players in Alzheimer’s disease – they are present in abnormal levels in Parkinson’s disease and a range of other brain pathologies.

“In the brain of an Alzheimer’s and of a Parkinson’s [patient], you’re going to find all four proteins. You’ll find them in different concentrations, at different time points, in different brain areas. If you just remove one, you still have the other three that cause impairment in axonal transport, and that leads to inflammation that leads to neurodegeneration,” said Dr. Maccecchini.

The company’s drug manages to reduce levels of all four proteins by binding to a segment of messenger RNA (mRNA) shared by all of them. mRNA serves as a template for protein synthesis. Under normal conditions, the neurotoxic protein concentrations are kept low because the mRNA segment remains bound to a regulatory protein that prevents synthesis from occurring. However, when stress leads to high levels of iron, this regulatory binding protein releases the mRNA segment (along with the rest of the mRNA). The freed mRNA becomes available to the cell’s protein synthesis machinery, which starts producing high levels of neurotoxic proteins. Annovis Bio’s drug improves the ability of the regulatory protein to bind to the mRNA segment, preventing protein expression even in high-iron conditions. It works on all four neurotoxic proteins because they all have the regulatory segment in their mRNA.

The drug led to improvements in phase 2 studies of Alzheimer’s disease and Parkinson’s disease, and the company is currently recruiting for a phase 3 study in Parkinson’s disease and a phase 2/3 dose-response study in Alzheimer’s disease.
 

Combination treatments for a complex disease

Taken together, the presentations provided a snapshot of the post–A-beta/tau Alzheimer’s development world, and the future could be messy. Alzheimer’s disease and other dementias are likely to require combination treatments, according to Dr. Snyder. “This is a complex disease, not just Alzheimer’s but other dementias. It’s not going to be a single drug, a single target. It’s going to require some type of combinatorial approach, whether that be with medication and lifestyle interventions, or risk reduction, and different medications,” she said.

The latest results are good news for that approach: “We’re seeing that maturation of the science in these trials,” said Dr. Snyder.

Cheng Fang, PhD, senior vice president of research and development at Annovis Bio, agreed with that sentiment. “I believe [Alzheimer’s disease and dementia] is a very complicated disease. I always call them diseases instead of a disease because it’s a spectrum. I don’t believe one drug can cure them all, as much as I am confident in our drug. I think it’s extremely important to encourage this kind of diverse thinking,” said Dr. Fang.

Dr. Snyder has no relevant financial disclosures. Dr. Tesi, Dr. Moebius, Dr. Didsbury, Dr. Maccecchini, and Dr. Fang are employees and in some cases stockholders of their respective companies.

SAN DIEGO – In 1906, a neuroanatomist and psychiatrist named Alois Alzheimer examined the brain of a 50-year-old woman whom he had treated for paranoia, sleep and memory problems, aggression, and confusion. His autopsy revealed plaques and tangles in her brain. The most common components of these tangles are beta-amyloid peptide (A-beta) and the microtubule binding protein tau. Over the past few decades, that finding has launched many clinical development programs and dozens of clinical trials.

To date, all but one program has failed. In 2021, amidst much controversy, FDA granted accelerated approval to Biogen’s Aduhelm, which effectively clears A-beta and tau deposits from patients’ brains. The problem is that the clinical benefit is small, and uptake has been so low that the company was forced to abandon a planned postmarketing observational trial.
 

Chasing the wrong target?

At a session at the 2022 Alzheimer’s Association International Conference, Raymond J. Tesi, MD, rather forcefully refuted that approach. “Amyloid and tau therapies have had 20 years to prove themselves. We have multiple cases where we’ve been able to decrease amyloid, maybe not so much tau, but certainly amyloid, and the benefits are mild at best. So I think that the Alzheimer’s drug development community, whether you look at the NIH, whether you look at academia, whether you look at biopharma, has focused on a target that has not proven itself, and it’s time to move on,” said Dr. Tesi, who is president, CEO, and chief medical officer at INmune Bio.

Later in the session, researchers presented strategies to counter Alzheimer’s disease and other neurodegenerative conditions using strategies including modulation of metabolism and inflammation, support of brain homeostasis, and suppression of a broader range of neurotoxic proteins.

One audience member defended the potential importance of A-beta and tau, especially in astrogliosis, which is a reaction to stress by astrocytes that attempts to limit tissue damage. The questioner suggested that it was still important to measure the effect of a novel drug on A-beta and tau. “What would be the cause of the reactive astrogliosis and microglia activation, if we are not giving a damn about amyloid and tau?” he asked.

After a bit of back and forth, Dr. Tesi replied: “We both have a religious belief here, and sooner or later we’ll get the answer.”
 

A diverse clinical pipeline

The session itself focused on four companies, including Dr. Tesi’s INmune Bio, which have drugs with alternative mechanisms entering the advanced stages of clinical development. That’s good news, according to Heather Snyder, PhD, who is vice president of Medical & Scientific Relations at the Alzheimer’s Association. “One of the things that I think is really important is the diversity of what’s in the clinical pipeline, and it’s not just in the very beginning anymore. We’re seeing [companies] now reporting phase 2 [studies] and planning their next stage. That’s something that as a field we should be excited about. As we understand more and more about the biology, we’re now seeing that translating into clinical trials and we’re seeing that translate through the clinical pipeline of development,” said Dr. Snyder in an interview.

Targeting neuroinflammation

Dr. Tesi kicked off the session describing INmune Bio’s focus on neuroinflammation. The company’s drug candidate targets soluble tumor necrosis factor (TNF), which the company believes is a direct cause of Alzheimer’s disease through promotion of inflammation. He noted that TNF is a primary mediator of inflammation in rheumatoid arthritis, and patients with RA have an eightfold increased risk of developing Alzheimer’s disease, compared with the general population, while patients with RA who are taking anti-TNF medication have a 60% lower risk than the general population.

The company’s TNF inhibitor XPro is also unique in that it induces remyelination in mice, while other TNF inhibitors potentially “abuse” the brain by causing demyelination. Earlier research showed that it reduces neuroinflammation, improves nerve cell survival, and improves synaptic function. The company is conducting two phase 2 clinical trials, one in patients with mild cognitive impairment (MCI) and one in mild Alzheimer’s disease. They also use the MCI Alzheimer’s Cognitive Composite (EMACC) tool for assessing outcomes rather than the more commonly used Alzheimer’s Disease Assessment Scale-Cognitive subscale (ADAS-Cog). “ADAS-Cog is like trying to make sushi with an axe. It is designed for moderate to severe disease, and trying to use it for mild (Alzheimer’s disease) or MCI is a mistake. EMACC is purpose built for mild [AD] and MCI patients,” said Dr. Tesi.
 

Maintaining homeostatis

Next, Hans Moebius, MD, PhD, chief medical officer of Athira Pharma, described his company’s focus on the hepatocyte growth factor (HGF) receptor, also known as tyrosine kinase MET (HGF/MET). It plays an important role in brain development and homeostasis, and it is expressed at lower levels in the frontal cortex and hippocampus of patients with Alzheimer’s disease. The company’s small-molecule drug candidate boosts the HGF/MET pathway, leading to downstream neuroprotection and neurotrophic effects. It also promotes formation of new synapses.

Dr. Moebius presented the results of a phase 2 trial showing that the drug, called fosgonimeton, led to significant cognitive improvement compared with placebo. The company is conducting a phase 3 clinical trial.
 

Type 3 diabetes?

In his talk, John Didsbury, PhD, founder and CEO of T3D Therapeutics, framed Alzheimer’s disease as a disease of metabolic dysfunction. He believes alterations to glucose and lipids in the brain cause structural changes that lead to symptoms. He pointed out that the strongest genetic Alzheimer’s disease risk factor is a mutant form of the lipid transport protein APOE4.

“What we have is dysregulated glucose energy metabolism and lipid metabolism that really cause, in our mind, the structural event changes and the stress event changes – plaques, tangles, inflammation, etc. – but these events perpetuate the dysregulated metabolism. It’s a massive positive feedback loop that many have called type 3 diabetes – a brain-specific form of diabetes,” said Dr. Didsbury.

The company’s approach is to use systems biology to identify a drug target that can bypass multiple aberrant insulin signaling pathways. Its drug candidate regulates the expression of multiple genes involved in glucose metabolism. Dr. Didsbury presented interim results from a phase 2 study showing improvement over placebo.
 

Focusing on neurotoxic proteins

The final presentation of the session was by Maria Maccecchini, PhD, founder, president, and CEO of Annovis Bio. The company’s drug, buntanetap, reduces expression of a range of neurotoxic proteins. The downstream effects include restoration of axonal transport, reduction of inflammation, and protection of nerve cells. The company believes that Alzheimer’s disease results from acute and chronic stress events that lead to high levels of neurotoxic proteins, which include A-beta, tau, alpha-synuclein, and TDP43. The proteins aren’t just players in Alzheimer’s disease – they are present in abnormal levels in Parkinson’s disease and a range of other brain pathologies.

“In the brain of an Alzheimer’s and of a Parkinson’s [patient], you’re going to find all four proteins. You’ll find them in different concentrations, at different time points, in different brain areas. If you just remove one, you still have the other three that cause impairment in axonal transport, and that leads to inflammation that leads to neurodegeneration,” said Dr. Maccecchini.

The company’s drug manages to reduce levels of all four proteins by binding to a segment of messenger RNA (mRNA) shared by all of them. mRNA serves as a template for protein synthesis. Under normal conditions, the neurotoxic protein concentrations are kept low because the mRNA segment remains bound to a regulatory protein that prevents synthesis from occurring. However, when stress leads to high levels of iron, this regulatory binding protein releases the mRNA segment (along with the rest of the mRNA). The freed mRNA becomes available to the cell’s protein synthesis machinery, which starts producing high levels of neurotoxic proteins. Annovis Bio’s drug improves the ability of the regulatory protein to bind to the mRNA segment, preventing protein expression even in high-iron conditions. It works on all four neurotoxic proteins because they all have the regulatory segment in their mRNA.

The drug led to improvements in phase 2 studies of Alzheimer’s disease and Parkinson’s disease, and the company is currently recruiting for a phase 3 study in Parkinson’s disease and a phase 2/3 dose-response study in Alzheimer’s disease.
 

Combination treatments for a complex disease

Taken together, the presentations provided a snapshot of the post–A-beta/tau Alzheimer’s development world, and the future could be messy. Alzheimer’s disease and other dementias are likely to require combination treatments, according to Dr. Snyder. “This is a complex disease, not just Alzheimer’s but other dementias. It’s not going to be a single drug, a single target. It’s going to require some type of combinatorial approach, whether that be with medication and lifestyle interventions, or risk reduction, and different medications,” she said.

The latest results are good news for that approach: “We’re seeing that maturation of the science in these trials,” said Dr. Snyder.

Cheng Fang, PhD, senior vice president of research and development at Annovis Bio, agreed with that sentiment. “I believe [Alzheimer’s disease and dementia] is a very complicated disease. I always call them diseases instead of a disease because it’s a spectrum. I don’t believe one drug can cure them all, as much as I am confident in our drug. I think it’s extremely important to encourage this kind of diverse thinking,” said Dr. Fang.

Dr. Snyder has no relevant financial disclosures. Dr. Tesi, Dr. Moebius, Dr. Didsbury, Dr. Maccecchini, and Dr. Fang are employees and in some cases stockholders of their respective companies.