Journal of Clinical Outcomes Management

A high salt intake is an important risk factor for atherosclerosis, even in the absence of hypertension, a large study from Sweden concludes.

jirkaejc/Getty Images

The study, including more than 10,000 individuals between the ages of 50 and 64 years from the Swedish Cardiopulmonary bioImage Study, showed a significant link between dietary salt intake and the risk for atherosclerotic lesions in the coronary and carotid arteries, even in participants with normal blood pressure and without known cardiovascular disease.

The finding suggests that salt could be a damaging factor in its own right before the development of hypertension, the authors write. The results were published online in European Heart Journal Open.

It has been known for a long time that salt is linked to hypertension, but the role that salt plays in atherosclerosis has not been examined, first author Jonas Wuopio, MD, Karolinska Institutet, Huddinge, and Clinical Research Center, Falun, Uppsala University, both in Sweden, told this news organization.

“Hardly anyone looks at changes in the arteries’ calcification, the atherosclerotic plaques and the association with salt intake,” Dr. Wuopio said. “We had this exclusive data from our cohort, so we wanted to use it to close this knowledge gap.”

The analysis included 10,788 adults aged 50-64 years, (average age, 58 years; 52% women) who underwent a coronary computed tomography angiography (CCTA) scan. The estimated 24-hour sodium excretion was used to measure sodium intake.

CCTA was used to obtain 3-D images of the coronary arteries to measure the degree of coronary artery calcium as well as detect stenosis in the coronary arteries. Participants also had an ultrasound of the carotid arteries.

After adjusting for age, sex, and study site (the study was done at Uppsala and Malmö, Sweden), the researchers found that rising salt consumption was linked with increasing atherosclerosis in a linear fashion in both the coronary and carotid arteries.

Each 1,000 mg rise in sodium excretion was associated with a 9% increased occurrence of carotid plaque (odds ratio, 1.09; P < .001; confidence interval, 1.06-1.12), a higher coronary artery calcium score (OR, 1.16; P < .001; CI, 1.12-1.19), and a 17% increased occurrence of coronary artery stenosis (OR, 1.17; P < .001; CI, 1.13-1.20).

The association was abolished, though, after adjusting for blood pressure, they note. Their “interpretation is that the increase in blood pressure from sodium intake, even below the level that currently defines arterial hypertension, is an important factor that mediates the interplay between salt intake and the atherosclerotic process,” they write. “As we observed an association in individuals with normal blood pressure, one possible explanation for these findings is that the detrimental pathological processes begin already prior to the development of hypertension,” they note, although they caution that no causal relationships can be gleaned from this cross-sectional study.

They also reported no sign of a “J-curve”; participants with the lowest levels of sodium excretion had the lowest occurrence of both coronary and carotid atherosclerosis, which contradicts findings in some studies that found very low sodium linked to increased cardiovascular disease–related events.

“There have been some controversies among researchers regarding very low intake, where some say very low salt intake can increase the risk of cardiovascular disease, but we could not find this in this study,” Dr. Wuopio said.

“Our study is confirming that excess salt is not a good thing, but the fact that it is linked to atherosclerosis, even in the absence of hypertension, was a bit of a surprise,” he said.

“I will be telling my patients to follow the advice given by the World Health Organization and other medical societies, to limit your intake of salt to approximately 1 teaspoon, even if your blood pressure is normal.”


 

Time to scrutinize salt’s role in atherosclerosis

In an accompanying editorial, Maciej Banach, MD, Medical University of Lodz, and Stanislaw Surma, MD, Faculty of Medical Sciences in Katowice, both in Poland, write that excessive dietary salt intake is a well-documented cardiovascular risk factor, and that the association is explained in most studies by increased blood pressure.

“We should look more extensively on the role of dietary salt, as it affects many pathological mechanisms, by which, especially with the coexistence of other risk factors, atherosclerosis may progress very fast,” they write.

“The results of the study shed new light on the direct relationship between excessive dietary salt intake and the risk of ASCVD [atherosclerotic cardiovascular disease], indicating that salt intake might be a risk factor for atherosclerosis even prior to the development of hypertension,” they conclude.
 

Confirmatory and novel

“Nobody questions the fact that high blood pressure is a powerful risk factor for atherosclerotic disease, but not all studies have suggested that, at least at significantly higher levels of sodium intake, that high salt intake tracks with risk for atherosclerotic disease,” Alon Gitig, MD, assistant professor and director of cardiology, Mount Sinai Doctors-Westchester, Yonkers, New York, told this news organization.

Most of the studies of salt intake in the diet are based on patient self-reports via food frequency questionnaires, which can give a general idea of salt intake, but are often not totally accurate, Dr. Gitig said.

“Here, they measured sodium in the urine and estimated the 24-hour salt intake from that, which is slightly novel,” he said.

Everybody knows that high blood pressure is associated with future cardiovascular disease risk, but what many don’t realize is that that risk starts to increase slightly but significantly above a blood pressure that is already in the range of 115 mm Hg/75 mm Hg, he said.

“The lower you can get your blood pressure down, to around 115-120, the lower your risk for cardiovascular disease,” Dr. Gitig said.

It is possible for most people to lower blood pressure through attention to diet, restricting sodium, performing cardio and weight training exercises, and maintaining a healthy weight, he said.

An example of a cardiovascular health diet is the Dietary Approaches to Stop Hypertension (DASH) diet.

“The DASH diet, consisting of 9 servings of fruits and vegetables a day with few refined carbs, flour and sugar, has been shown in a randomized trial to dramatically reduce blood pressure. There are two reasons for that. One is that the fruits and vegetables have many phytonutrients that are good for arteries. The other is that a large proportion of U.S. adults have insulin resistance, which leads to high blood pressure.  

“The more fruits and vegetables and healthy animal products, and less sugar and flour, the more you are going to improve your insulin resistance, so you can bring your blood pressure down that way,” Dr. Gitig said.

The study was funded by the Swedish Heart-Lung Foundation, the Knut and Alice Wallenberg Foundation, the Swedish Research Council and Vinnova (Sweden’s Innovation agency), the University of Gothenburg and Sahlgrenska University Hospital, the Karolinska Institutet and Stockholm County Council, the Linköping University and University Hospital, the Lund University and Skane University Hospital, the Umea University and University Hospital, and the Uppsala University and University Hospital. Dr. Wuopio and Dr. Gitig report no relevant financial relationships. Dr. Banach reports financial relationships with Adamed, Amgen, Daichii Sankyo, Esperion, KrKa, NewAmsterdam, Polpharma, Novartis, Pfizer, Sanofi, Teva, Viatris, and CMDO at Longevity Group (LU). Dr. Surma reports a financial relationship with Sanofi and Novartis.

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

A high salt intake is an important risk factor for atherosclerosis, even in the absence of hypertension, a large study from Sweden concludes.

jirkaejc/Getty Images

The study, including more than 10,000 individuals between the ages of 50 and 64 years from the Swedish Cardiopulmonary bioImage Study, showed a significant link between dietary salt intake and the risk for atherosclerotic lesions in the coronary and carotid arteries, even in participants with normal blood pressure and without known cardiovascular disease.

The finding suggests that salt could be a damaging factor in its own right before the development of hypertension, the authors write. The results were published online in European Heart Journal Open.

It has been known for a long time that salt is linked to hypertension, but the role that salt plays in atherosclerosis has not been examined, first author Jonas Wuopio, MD, Karolinska Institutet, Huddinge, and Clinical Research Center, Falun, Uppsala University, both in Sweden, told this news organization.

“Hardly anyone looks at changes in the arteries’ calcification, the atherosclerotic plaques and the association with salt intake,” Dr. Wuopio said. “We had this exclusive data from our cohort, so we wanted to use it to close this knowledge gap.”

The analysis included 10,788 adults aged 50-64 years, (average age, 58 years; 52% women) who underwent a coronary computed tomography angiography (CCTA) scan. The estimated 24-hour sodium excretion was used to measure sodium intake.

CCTA was used to obtain 3-D images of the coronary arteries to measure the degree of coronary artery calcium as well as detect stenosis in the coronary arteries. Participants also had an ultrasound of the carotid arteries.

After adjusting for age, sex, and study site (the study was done at Uppsala and Malmö, Sweden), the researchers found that rising salt consumption was linked with increasing atherosclerosis in a linear fashion in both the coronary and carotid arteries.

Each 1,000 mg rise in sodium excretion was associated with a 9% increased occurrence of carotid plaque (odds ratio, 1.09; P < .001; confidence interval, 1.06-1.12), a higher coronary artery calcium score (OR, 1.16; P < .001; CI, 1.12-1.19), and a 17% increased occurrence of coronary artery stenosis (OR, 1.17; P < .001; CI, 1.13-1.20).

The association was abolished, though, after adjusting for blood pressure, they note. Their “interpretation is that the increase in blood pressure from sodium intake, even below the level that currently defines arterial hypertension, is an important factor that mediates the interplay between salt intake and the atherosclerotic process,” they write. “As we observed an association in individuals with normal blood pressure, one possible explanation for these findings is that the detrimental pathological processes begin already prior to the development of hypertension,” they note, although they caution that no causal relationships can be gleaned from this cross-sectional study.

They also reported no sign of a “J-curve”; participants with the lowest levels of sodium excretion had the lowest occurrence of both coronary and carotid atherosclerosis, which contradicts findings in some studies that found very low sodium linked to increased cardiovascular disease–related events.

“There have been some controversies among researchers regarding very low intake, where some say very low salt intake can increase the risk of cardiovascular disease, but we could not find this in this study,” Dr. Wuopio said.

“Our study is confirming that excess salt is not a good thing, but the fact that it is linked to atherosclerosis, even in the absence of hypertension, was a bit of a surprise,” he said.

“I will be telling my patients to follow the advice given by the World Health Organization and other medical societies, to limit your intake of salt to approximately 1 teaspoon, even if your blood pressure is normal.”


 

Time to scrutinize salt’s role in atherosclerosis

In an accompanying editorial, Maciej Banach, MD, Medical University of Lodz, and Stanislaw Surma, MD, Faculty of Medical Sciences in Katowice, both in Poland, write that excessive dietary salt intake is a well-documented cardiovascular risk factor, and that the association is explained in most studies by increased blood pressure.

“We should look more extensively on the role of dietary salt, as it affects many pathological mechanisms, by which, especially with the coexistence of other risk factors, atherosclerosis may progress very fast,” they write.

“The results of the study shed new light on the direct relationship between excessive dietary salt intake and the risk of ASCVD [atherosclerotic cardiovascular disease], indicating that salt intake might be a risk factor for atherosclerosis even prior to the development of hypertension,” they conclude.
 

Confirmatory and novel

“Nobody questions the fact that high blood pressure is a powerful risk factor for atherosclerotic disease, but not all studies have suggested that, at least at significantly higher levels of sodium intake, that high salt intake tracks with risk for atherosclerotic disease,” Alon Gitig, MD, assistant professor and director of cardiology, Mount Sinai Doctors-Westchester, Yonkers, New York, told this news organization.

Most of the studies of salt intake in the diet are based on patient self-reports via food frequency questionnaires, which can give a general idea of salt intake, but are often not totally accurate, Dr. Gitig said.

“Here, they measured sodium in the urine and estimated the 24-hour salt intake from that, which is slightly novel,” he said.

Everybody knows that high blood pressure is associated with future cardiovascular disease risk, but what many don’t realize is that that risk starts to increase slightly but significantly above a blood pressure that is already in the range of 115 mm Hg/75 mm Hg, he said.

“The lower you can get your blood pressure down, to around 115-120, the lower your risk for cardiovascular disease,” Dr. Gitig said.

It is possible for most people to lower blood pressure through attention to diet, restricting sodium, performing cardio and weight training exercises, and maintaining a healthy weight, he said.

An example of a cardiovascular health diet is the Dietary Approaches to Stop Hypertension (DASH) diet.

“The DASH diet, consisting of 9 servings of fruits and vegetables a day with few refined carbs, flour and sugar, has been shown in a randomized trial to dramatically reduce blood pressure. There are two reasons for that. One is that the fruits and vegetables have many phytonutrients that are good for arteries. The other is that a large proportion of U.S. adults have insulin resistance, which leads to high blood pressure.  

“The more fruits and vegetables and healthy animal products, and less sugar and flour, the more you are going to improve your insulin resistance, so you can bring your blood pressure down that way,” Dr. Gitig said.

The study was funded by the Swedish Heart-Lung Foundation, the Knut and Alice Wallenberg Foundation, the Swedish Research Council and Vinnova (Sweden’s Innovation agency), the University of Gothenburg and Sahlgrenska University Hospital, the Karolinska Institutet and Stockholm County Council, the Linköping University and University Hospital, the Lund University and Skane University Hospital, the Umea University and University Hospital, and the Uppsala University and University Hospital. Dr. Wuopio and Dr. Gitig report no relevant financial relationships. Dr. Banach reports financial relationships with Adamed, Amgen, Daichii Sankyo, Esperion, KrKa, NewAmsterdam, Polpharma, Novartis, Pfizer, Sanofi, Teva, Viatris, and CMDO at Longevity Group (LU). Dr. Surma reports a financial relationship with Sanofi and Novartis.

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

A high salt intake is an important risk factor for atherosclerosis, even in the absence of hypertension, a large study from Sweden concludes.

jirkaejc/Getty Images

The study, including more than 10,000 individuals between the ages of 50 and 64 years from the Swedish Cardiopulmonary bioImage Study, showed a significant link between dietary salt intake and the risk for atherosclerotic lesions in the coronary and carotid arteries, even in participants with normal blood pressure and without known cardiovascular disease.

The finding suggests that salt could be a damaging factor in its own right before the development of hypertension, the authors write. The results were published online in European Heart Journal Open.

It has been known for a long time that salt is linked to hypertension, but the role that salt plays in atherosclerosis has not been examined, first author Jonas Wuopio, MD, Karolinska Institutet, Huddinge, and Clinical Research Center, Falun, Uppsala University, both in Sweden, told this news organization.

“Hardly anyone looks at changes in the arteries’ calcification, the atherosclerotic plaques and the association with salt intake,” Dr. Wuopio said. “We had this exclusive data from our cohort, so we wanted to use it to close this knowledge gap.”

The analysis included 10,788 adults aged 50-64 years, (average age, 58 years; 52% women) who underwent a coronary computed tomography angiography (CCTA) scan. The estimated 24-hour sodium excretion was used to measure sodium intake.

CCTA was used to obtain 3-D images of the coronary arteries to measure the degree of coronary artery calcium as well as detect stenosis in the coronary arteries. Participants also had an ultrasound of the carotid arteries.

After adjusting for age, sex, and study site (the study was done at Uppsala and Malmö, Sweden), the researchers found that rising salt consumption was linked with increasing atherosclerosis in a linear fashion in both the coronary and carotid arteries.

Each 1,000 mg rise in sodium excretion was associated with a 9% increased occurrence of carotid plaque (odds ratio, 1.09; P < .001; confidence interval, 1.06-1.12), a higher coronary artery calcium score (OR, 1.16; P < .001; CI, 1.12-1.19), and a 17% increased occurrence of coronary artery stenosis (OR, 1.17; P < .001; CI, 1.13-1.20).

The association was abolished, though, after adjusting for blood pressure, they note. Their “interpretation is that the increase in blood pressure from sodium intake, even below the level that currently defines arterial hypertension, is an important factor that mediates the interplay between salt intake and the atherosclerotic process,” they write. “As we observed an association in individuals with normal blood pressure, one possible explanation for these findings is that the detrimental pathological processes begin already prior to the development of hypertension,” they note, although they caution that no causal relationships can be gleaned from this cross-sectional study.

They also reported no sign of a “J-curve”; participants with the lowest levels of sodium excretion had the lowest occurrence of both coronary and carotid atherosclerosis, which contradicts findings in some studies that found very low sodium linked to increased cardiovascular disease–related events.

“There have been some controversies among researchers regarding very low intake, where some say very low salt intake can increase the risk of cardiovascular disease, but we could not find this in this study,” Dr. Wuopio said.

“Our study is confirming that excess salt is not a good thing, but the fact that it is linked to atherosclerosis, even in the absence of hypertension, was a bit of a surprise,” he said.

“I will be telling my patients to follow the advice given by the World Health Organization and other medical societies, to limit your intake of salt to approximately 1 teaspoon, even if your blood pressure is normal.”


 

Time to scrutinize salt’s role in atherosclerosis

In an accompanying editorial, Maciej Banach, MD, Medical University of Lodz, and Stanislaw Surma, MD, Faculty of Medical Sciences in Katowice, both in Poland, write that excessive dietary salt intake is a well-documented cardiovascular risk factor, and that the association is explained in most studies by increased blood pressure.

“We should look more extensively on the role of dietary salt, as it affects many pathological mechanisms, by which, especially with the coexistence of other risk factors, atherosclerosis may progress very fast,” they write.

“The results of the study shed new light on the direct relationship between excessive dietary salt intake and the risk of ASCVD [atherosclerotic cardiovascular disease], indicating that salt intake might be a risk factor for atherosclerosis even prior to the development of hypertension,” they conclude.
 

Confirmatory and novel

“Nobody questions the fact that high blood pressure is a powerful risk factor for atherosclerotic disease, but not all studies have suggested that, at least at significantly higher levels of sodium intake, that high salt intake tracks with risk for atherosclerotic disease,” Alon Gitig, MD, assistant professor and director of cardiology, Mount Sinai Doctors-Westchester, Yonkers, New York, told this news organization.

Most of the studies of salt intake in the diet are based on patient self-reports via food frequency questionnaires, which can give a general idea of salt intake, but are often not totally accurate, Dr. Gitig said.

“Here, they measured sodium in the urine and estimated the 24-hour salt intake from that, which is slightly novel,” he said.

Everybody knows that high blood pressure is associated with future cardiovascular disease risk, but what many don’t realize is that that risk starts to increase slightly but significantly above a blood pressure that is already in the range of 115 mm Hg/75 mm Hg, he said.

“The lower you can get your blood pressure down, to around 115-120, the lower your risk for cardiovascular disease,” Dr. Gitig said.

It is possible for most people to lower blood pressure through attention to diet, restricting sodium, performing cardio and weight training exercises, and maintaining a healthy weight, he said.

An example of a cardiovascular health diet is the Dietary Approaches to Stop Hypertension (DASH) diet.

“The DASH diet, consisting of 9 servings of fruits and vegetables a day with few refined carbs, flour and sugar, has been shown in a randomized trial to dramatically reduce blood pressure. There are two reasons for that. One is that the fruits and vegetables have many phytonutrients that are good for arteries. The other is that a large proportion of U.S. adults have insulin resistance, which leads to high blood pressure.  

“The more fruits and vegetables and healthy animal products, and less sugar and flour, the more you are going to improve your insulin resistance, so you can bring your blood pressure down that way,” Dr. Gitig said.

The study was funded by the Swedish Heart-Lung Foundation, the Knut and Alice Wallenberg Foundation, the Swedish Research Council and Vinnova (Sweden’s Innovation agency), the University of Gothenburg and Sahlgrenska University Hospital, the Karolinska Institutet and Stockholm County Council, the Linköping University and University Hospital, the Lund University and Skane University Hospital, the Umea University and University Hospital, and the Uppsala University and University Hospital. Dr. Wuopio and Dr. Gitig report no relevant financial relationships. Dr. Banach reports financial relationships with Adamed, Amgen, Daichii Sankyo, Esperion, KrKa, NewAmsterdam, Polpharma, Novartis, Pfizer, Sanofi, Teva, Viatris, and CMDO at Longevity Group (LU). Dr. Surma reports a financial relationship with Sanofi and Novartis.

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

Investigators have identified four blood biomarkers that could potentially be used to predict, diagnose, and monitor treatment response for posttraumatic stress disorder.

“More accurate means of predicting or screening for PTSD could help to overcome the disorder by identifying individuals at high risk of developing PTSD and providing them with early intervention or prevention strategies,” said study investigator Stacy-Ann Miller, MS.

She also noted that the biomarkers could be used to monitor treatment for PTSD, identify subtypes of PTSD, and lead to a new understanding of the mechanisms underlying PTSD.

The findings were presented at Discover BMB, the annual meeting of the American Society for Biochemistry and Molecular Biology.
 

Toward better clinical assessment

The findings originated from research conducted by the Department of Defense–initiated PTSD Systems Biology Consortium. The consortium’s goals include developing a reproducible panel of blood-based biomarkers with high sensitivity and specificity for PTSD diagnosis and is made up of about 45 researchers, led by Marti Jett, PhD, Charles Marmar, MD, and Francis J. Doyle III, PhD.

The researchers analyzed blood samples from 1,000 active-duty Army personnel from the 101st Airborne at Fort Campbell, Ky. Participants were assessed before and after deployment to Afghanistan in February 2014 and are referred to as the Fort Campbell Cohort (FCC). Participants’ age ranged from 25 to 30 and approximately 6% were female.

Investigators collected blood samples from the service members and looked for four biomarkers: glycolytic ratio, arginine, serotonin, and glutamate. The team then divided the participants into four groups – those with PTSD (PTSD Checklist score above 30), those who were subthreshold for PTSD (PTSD Checklist score 15-30), those who had high resilience, and those who had low levels of resilience.

The resilience groups were determined based on answers to the Generalized Anxiety Disorder Questionnaire, Patient Health Questionnaire, Pittsburgh Sleep Quality Index, Intensive Combat Exposure (DRRI-D), the number of deployments, whether they had moderate or severe traumatic brain injury, and scores on the Alcohol Use Disorders Identification Test.

Those who scored in the high range at current or prior time points or who were PTSD/subthreshold at prior time points were placed in the low resilience group.

Ms. Miller noted that those in the PTSD group had more severe symptoms than those in the PTSD subthreshold group based on the longitudinal clinical assessment at 3-6 months, 5 years, and longer post deployment. The low resilience group had a much higher rate of PTSD post deployment than the high resilience group.

Investigators found participants with PTSD or subthreshold PTSD had significantly higher glycolic ratios and lower arginine than those with high resilience. They also found that those with PTSD had significantly lower serotonin and higher glutamate levels versus those with high resilience. These associations were independent of factors such as sex, age, body mass index, smoking, and caffeine consumption.

Ms. Miller said that the study results require further validation by the consortium’s labs and third-party labs.

“We are also interested in determining the most appropriate time to screen soldiers for PTSD, as it has been noted that the time period where we see the most psychological issues is around 2-3 months post return from deployment and when the soldier is preparing for their next assignment, perhaps a next deployment,” she said.

She added that previous studies have identified several promising biomarkers of PTSD. “However, like much of the research data, the study sample was comprised mainly of combat-exposed males. With more women serving on the front lines, the military faces new challenges in how combat affects females in the military,” including sex-specific biomarkers that will improve clinical assessment for female soldiers.

Eventually, the team would also like to be able to apply their research to the civilian population experiencing PTSD.

“Our research is anticipated to be useful in helping the medical provider select appropriate therapeutic interventions,” Ms. Miller said.

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

Investigators have identified four blood biomarkers that could potentially be used to predict, diagnose, and monitor treatment response for posttraumatic stress disorder.

“More accurate means of predicting or screening for PTSD could help to overcome the disorder by identifying individuals at high risk of developing PTSD and providing them with early intervention or prevention strategies,” said study investigator Stacy-Ann Miller, MS.

She also noted that the biomarkers could be used to monitor treatment for PTSD, identify subtypes of PTSD, and lead to a new understanding of the mechanisms underlying PTSD.

The findings were presented at Discover BMB, the annual meeting of the American Society for Biochemistry and Molecular Biology.
 

Toward better clinical assessment

The findings originated from research conducted by the Department of Defense–initiated PTSD Systems Biology Consortium. The consortium’s goals include developing a reproducible panel of blood-based biomarkers with high sensitivity and specificity for PTSD diagnosis and is made up of about 45 researchers, led by Marti Jett, PhD, Charles Marmar, MD, and Francis J. Doyle III, PhD.

The researchers analyzed blood samples from 1,000 active-duty Army personnel from the 101st Airborne at Fort Campbell, Ky. Participants were assessed before and after deployment to Afghanistan in February 2014 and are referred to as the Fort Campbell Cohort (FCC). Participants’ age ranged from 25 to 30 and approximately 6% were female.

Investigators collected blood samples from the service members and looked for four biomarkers: glycolytic ratio, arginine, serotonin, and glutamate. The team then divided the participants into four groups – those with PTSD (PTSD Checklist score above 30), those who were subthreshold for PTSD (PTSD Checklist score 15-30), those who had high resilience, and those who had low levels of resilience.

The resilience groups were determined based on answers to the Generalized Anxiety Disorder Questionnaire, Patient Health Questionnaire, Pittsburgh Sleep Quality Index, Intensive Combat Exposure (DRRI-D), the number of deployments, whether they had moderate or severe traumatic brain injury, and scores on the Alcohol Use Disorders Identification Test.

Those who scored in the high range at current or prior time points or who were PTSD/subthreshold at prior time points were placed in the low resilience group.

Ms. Miller noted that those in the PTSD group had more severe symptoms than those in the PTSD subthreshold group based on the longitudinal clinical assessment at 3-6 months, 5 years, and longer post deployment. The low resilience group had a much higher rate of PTSD post deployment than the high resilience group.

Investigators found participants with PTSD or subthreshold PTSD had significantly higher glycolic ratios and lower arginine than those with high resilience. They also found that those with PTSD had significantly lower serotonin and higher glutamate levels versus those with high resilience. These associations were independent of factors such as sex, age, body mass index, smoking, and caffeine consumption.

Ms. Miller said that the study results require further validation by the consortium’s labs and third-party labs.

“We are also interested in determining the most appropriate time to screen soldiers for PTSD, as it has been noted that the time period where we see the most psychological issues is around 2-3 months post return from deployment and when the soldier is preparing for their next assignment, perhaps a next deployment,” she said.

She added that previous studies have identified several promising biomarkers of PTSD. “However, like much of the research data, the study sample was comprised mainly of combat-exposed males. With more women serving on the front lines, the military faces new challenges in how combat affects females in the military,” including sex-specific biomarkers that will improve clinical assessment for female soldiers.

Eventually, the team would also like to be able to apply their research to the civilian population experiencing PTSD.

“Our research is anticipated to be useful in helping the medical provider select appropriate therapeutic interventions,” Ms. Miller said.

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

Investigators have identified four blood biomarkers that could potentially be used to predict, diagnose, and monitor treatment response for posttraumatic stress disorder.

“More accurate means of predicting or screening for PTSD could help to overcome the disorder by identifying individuals at high risk of developing PTSD and providing them with early intervention or prevention strategies,” said study investigator Stacy-Ann Miller, MS.

She also noted that the biomarkers could be used to monitor treatment for PTSD, identify subtypes of PTSD, and lead to a new understanding of the mechanisms underlying PTSD.

The findings were presented at Discover BMB, the annual meeting of the American Society for Biochemistry and Molecular Biology.
 

Toward better clinical assessment

The findings originated from research conducted by the Department of Defense–initiated PTSD Systems Biology Consortium. The consortium’s goals include developing a reproducible panel of blood-based biomarkers with high sensitivity and specificity for PTSD diagnosis and is made up of about 45 researchers, led by Marti Jett, PhD, Charles Marmar, MD, and Francis J. Doyle III, PhD.

The researchers analyzed blood samples from 1,000 active-duty Army personnel from the 101st Airborne at Fort Campbell, Ky. Participants were assessed before and after deployment to Afghanistan in February 2014 and are referred to as the Fort Campbell Cohort (FCC). Participants’ age ranged from 25 to 30 and approximately 6% were female.

Investigators collected blood samples from the service members and looked for four biomarkers: glycolytic ratio, arginine, serotonin, and glutamate. The team then divided the participants into four groups – those with PTSD (PTSD Checklist score above 30), those who were subthreshold for PTSD (PTSD Checklist score 15-30), those who had high resilience, and those who had low levels of resilience.

The resilience groups were determined based on answers to the Generalized Anxiety Disorder Questionnaire, Patient Health Questionnaire, Pittsburgh Sleep Quality Index, Intensive Combat Exposure (DRRI-D), the number of deployments, whether they had moderate or severe traumatic brain injury, and scores on the Alcohol Use Disorders Identification Test.

Those who scored in the high range at current or prior time points or who were PTSD/subthreshold at prior time points were placed in the low resilience group.

Ms. Miller noted that those in the PTSD group had more severe symptoms than those in the PTSD subthreshold group based on the longitudinal clinical assessment at 3-6 months, 5 years, and longer post deployment. The low resilience group had a much higher rate of PTSD post deployment than the high resilience group.

Investigators found participants with PTSD or subthreshold PTSD had significantly higher glycolic ratios and lower arginine than those with high resilience. They also found that those with PTSD had significantly lower serotonin and higher glutamate levels versus those with high resilience. These associations were independent of factors such as sex, age, body mass index, smoking, and caffeine consumption.

Ms. Miller said that the study results require further validation by the consortium’s labs and third-party labs.

“We are also interested in determining the most appropriate time to screen soldiers for PTSD, as it has been noted that the time period where we see the most psychological issues is around 2-3 months post return from deployment and when the soldier is preparing for their next assignment, perhaps a next deployment,” she said.

She added that previous studies have identified several promising biomarkers of PTSD. “However, like much of the research data, the study sample was comprised mainly of combat-exposed males. With more women serving on the front lines, the military faces new challenges in how combat affects females in the military,” including sex-specific biomarkers that will improve clinical assessment for female soldiers.

Eventually, the team would also like to be able to apply their research to the civilian population experiencing PTSD.

“Our research is anticipated to be useful in helping the medical provider select appropriate therapeutic interventions,” Ms. Miller said.

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

Processed and ultraprocessed food consumption has been shown to increase the risk for various cancers. A new analysis suggests that replacing even a small amount of such foods with an equal amount of minimally processed options may reduce that risk.

Using data from more than 450,000 participants, the dietary substitution analysis found that swapping out just 10% of processed foods with minimally processed foods significantly lowered the risk for cancer overall by 4% as well as the risk for several cancer types, including esophageal squamous cell carcinoma by 43% and hepatocellular carcinoma by 23%.

Making this substitution with ultraprocessed foods also appeared to lower cancer risk but often to a lesser degree. For instance, swapping 10% of ultraprocessed foods for minimally processed foods lowered the overall cancer risk by just 1%, the risk of hepatocellular carcinoma by 27%, and the risk of esophageal squamous cell carcinoma by 20%.

Overall, “this study suggests that the replacement of processed and ultraprocessed foods and drinks with an equal amount of minimally processed foods might reduce the risk of various cancer types,” Nathalie Kliemann, PhD, from the World Health Organization’s International Agency for Research on Cancer, Lyon, France, and colleagues concluded.

The findings were published in The Lancet Planetary Health.

Processed and ultraprocessed foods tend to have high-energy density and low nutritional value, and some epidemiological evidence indicates a possible link between consuming ultraprocessed food and cancer outcomes.

Dr. Kliemann and colleagues, for instance, recently published a study showing a link between ultraprocessed food consumption and increased risk for cancer, particularly ovarian cancer, as well as increased risk of dying from cancer. That study of nearly 200,000 middle-aged adults in the UK Biobank database showed that, for each 10 percentage point increase in the consumption of ultraprocessed foods, there was a 2% increase in the overall incidence of cancer and a 19% increase in ovarian cancer incidence.

However, conflicting reports exist, and research exploring associations between processed foods and cancer remains limited.

The researchers wanted to better understand the potential association between the degree of food processing and risk for cancer in a larger cohort of individuals.

The investigators performed a dietary substitution analysis using data from more than 450,000 participants from the European Prospective Investigation into Cancer and Nutrition (EPIC) study and looking at 25 anatomical sites. EPIC study participants, who had no cancer diagnoses prior to enrollment, were identified between March 1991 and July 2001. Of the 450,111 included in the analysis, 47,573 were diagnosed with cancer during a mean follow-up of 14.1 years. Mean age at recruitment was 51 years, and mean BMI was 25.3 kg/m².

Food items were classified according to their level of processing using the NOVA classification system: minimally or nonprocessed foods (NOVA 1), processed culinary ingredients (NOVA 2), processed foods (NOVA 3), and ultraprocessed foods (NOVA 4). The investigators highlighted comparisons between NOVA 1 and NOVA 3 and between NOVA 1 and NOVA 4.

The analysis revealed that swapping out just 10% of processed foods with minimally processed foods significantly lowered the risk for cancer overall (hazard ratio, 0.96) as well as for esophageal squamous cell carcinoma (HR, 0.57), hepatocellular carcinoma (HR, 0.77), head and neck cancers (HR, 0.80), colon cancer (HR, 0,88), rectal cancer (HR, 0.90), and postmenopausal breast cancer (HR, 0.93)

Swapping 10% of ultraprocessed foods for minimally processed foods lowered the risk of cancer overall only slightly (HR, 0.99) as well as the risk for various cancer types, including hepatocellular carcinoma (HR, 0.73), head and neck cancers (HR, 0.80), esophageal adenocarcinoma (HR, 0.80), and colon cancer (HR, 0.93).

The authors noted several limitations to the analysis, perhaps most notably that intake of ultraprocessed foods contributed to about 32% of total daily energy intake among study participants, but today that percentage could be nearly double across European countries.

“This discrepancy might explain the fewer significant associations observed between ultraprocessed foods and cancer risk than in processed foods and cancer risk,” the authors suggested.

The findings are “broadly in line with current evidence,” but the authors also noted some inconsistencies. For example, the current study showed a positive association between processed food consumption and risk for colorectal cancer and postmenopausal breast cancer, whereas other studies have not.

Overall, though, the authors concluded that increased consumption of minimally processed and fresh foods was associated with reduced overall risk for cancer and risk for specific cancers, and increased consumption of processed and ultraprocessed foods was associated with increased cancer risks.

This study “is the largest study investigating these associations between food processing and cancer risk and therefore has greater power to detect differences in populations, potentially explaining why we found overall more significant results for different cancer sites than other cohorts,” Dr. Kliemann and colleagues wrote.

This study was funded by Cancer Research UK, the French National Cancer Institute, and World Cancer Research Fund International. The authors declared no competing interests.

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

Processed and ultraprocessed food consumption has been shown to increase the risk for various cancers. A new analysis suggests that replacing even a small amount of such foods with an equal amount of minimally processed options may reduce that risk.

Using data from more than 450,000 participants, the dietary substitution analysis found that swapping out just 10% of processed foods with minimally processed foods significantly lowered the risk for cancer overall by 4% as well as the risk for several cancer types, including esophageal squamous cell carcinoma by 43% and hepatocellular carcinoma by 23%.

Making this substitution with ultraprocessed foods also appeared to lower cancer risk but often to a lesser degree. For instance, swapping 10% of ultraprocessed foods for minimally processed foods lowered the overall cancer risk by just 1%, the risk of hepatocellular carcinoma by 27%, and the risk of esophageal squamous cell carcinoma by 20%.

Overall, “this study suggests that the replacement of processed and ultraprocessed foods and drinks with an equal amount of minimally processed foods might reduce the risk of various cancer types,” Nathalie Kliemann, PhD, from the World Health Organization’s International Agency for Research on Cancer, Lyon, France, and colleagues concluded.

The findings were published in The Lancet Planetary Health.

Processed and ultraprocessed foods tend to have high-energy density and low nutritional value, and some epidemiological evidence indicates a possible link between consuming ultraprocessed food and cancer outcomes.

Dr. Kliemann and colleagues, for instance, recently published a study showing a link between ultraprocessed food consumption and increased risk for cancer, particularly ovarian cancer, as well as increased risk of dying from cancer. That study of nearly 200,000 middle-aged adults in the UK Biobank database showed that, for each 10 percentage point increase in the consumption of ultraprocessed foods, there was a 2% increase in the overall incidence of cancer and a 19% increase in ovarian cancer incidence.

However, conflicting reports exist, and research exploring associations between processed foods and cancer remains limited.

The researchers wanted to better understand the potential association between the degree of food processing and risk for cancer in a larger cohort of individuals.

The investigators performed a dietary substitution analysis using data from more than 450,000 participants from the European Prospective Investigation into Cancer and Nutrition (EPIC) study and looking at 25 anatomical sites. EPIC study participants, who had no cancer diagnoses prior to enrollment, were identified between March 1991 and July 2001. Of the 450,111 included in the analysis, 47,573 were diagnosed with cancer during a mean follow-up of 14.1 years. Mean age at recruitment was 51 years, and mean BMI was 25.3 kg/m².

Food items were classified according to their level of processing using the NOVA classification system: minimally or nonprocessed foods (NOVA 1), processed culinary ingredients (NOVA 2), processed foods (NOVA 3), and ultraprocessed foods (NOVA 4). The investigators highlighted comparisons between NOVA 1 and NOVA 3 and between NOVA 1 and NOVA 4.

The analysis revealed that swapping out just 10% of processed foods with minimally processed foods significantly lowered the risk for cancer overall (hazard ratio, 0.96) as well as for esophageal squamous cell carcinoma (HR, 0.57), hepatocellular carcinoma (HR, 0.77), head and neck cancers (HR, 0.80), colon cancer (HR, 0,88), rectal cancer (HR, 0.90), and postmenopausal breast cancer (HR, 0.93)

Swapping 10% of ultraprocessed foods for minimally processed foods lowered the risk of cancer overall only slightly (HR, 0.99) as well as the risk for various cancer types, including hepatocellular carcinoma (HR, 0.73), head and neck cancers (HR, 0.80), esophageal adenocarcinoma (HR, 0.80), and colon cancer (HR, 0.93).

The authors noted several limitations to the analysis, perhaps most notably that intake of ultraprocessed foods contributed to about 32% of total daily energy intake among study participants, but today that percentage could be nearly double across European countries.

“This discrepancy might explain the fewer significant associations observed between ultraprocessed foods and cancer risk than in processed foods and cancer risk,” the authors suggested.

The findings are “broadly in line with current evidence,” but the authors also noted some inconsistencies. For example, the current study showed a positive association between processed food consumption and risk for colorectal cancer and postmenopausal breast cancer, whereas other studies have not.

Overall, though, the authors concluded that increased consumption of minimally processed and fresh foods was associated with reduced overall risk for cancer and risk for specific cancers, and increased consumption of processed and ultraprocessed foods was associated with increased cancer risks.

This study “is the largest study investigating these associations between food processing and cancer risk and therefore has greater power to detect differences in populations, potentially explaining why we found overall more significant results for different cancer sites than other cohorts,” Dr. Kliemann and colleagues wrote.

This study was funded by Cancer Research UK, the French National Cancer Institute, and World Cancer Research Fund International. The authors declared no competing interests.

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

Processed and ultraprocessed food consumption has been shown to increase the risk for various cancers. A new analysis suggests that replacing even a small amount of such foods with an equal amount of minimally processed options may reduce that risk.

Using data from more than 450,000 participants, the dietary substitution analysis found that swapping out just 10% of processed foods with minimally processed foods significantly lowered the risk for cancer overall by 4% as well as the risk for several cancer types, including esophageal squamous cell carcinoma by 43% and hepatocellular carcinoma by 23%.

Making this substitution with ultraprocessed foods also appeared to lower cancer risk but often to a lesser degree. For instance, swapping 10% of ultraprocessed foods for minimally processed foods lowered the overall cancer risk by just 1%, the risk of hepatocellular carcinoma by 27%, and the risk of esophageal squamous cell carcinoma by 20%.

Overall, “this study suggests that the replacement of processed and ultraprocessed foods and drinks with an equal amount of minimally processed foods might reduce the risk of various cancer types,” Nathalie Kliemann, PhD, from the World Health Organization’s International Agency for Research on Cancer, Lyon, France, and colleagues concluded.

The findings were published in The Lancet Planetary Health.

Processed and ultraprocessed foods tend to have high-energy density and low nutritional value, and some epidemiological evidence indicates a possible link between consuming ultraprocessed food and cancer outcomes.

Dr. Kliemann and colleagues, for instance, recently published a study showing a link between ultraprocessed food consumption and increased risk for cancer, particularly ovarian cancer, as well as increased risk of dying from cancer. That study of nearly 200,000 middle-aged adults in the UK Biobank database showed that, for each 10 percentage point increase in the consumption of ultraprocessed foods, there was a 2% increase in the overall incidence of cancer and a 19% increase in ovarian cancer incidence.

However, conflicting reports exist, and research exploring associations between processed foods and cancer remains limited.

The researchers wanted to better understand the potential association between the degree of food processing and risk for cancer in a larger cohort of individuals.

The investigators performed a dietary substitution analysis using data from more than 450,000 participants from the European Prospective Investigation into Cancer and Nutrition (EPIC) study and looking at 25 anatomical sites. EPIC study participants, who had no cancer diagnoses prior to enrollment, were identified between March 1991 and July 2001. Of the 450,111 included in the analysis, 47,573 were diagnosed with cancer during a mean follow-up of 14.1 years. Mean age at recruitment was 51 years, and mean BMI was 25.3 kg/m².

Food items were classified according to their level of processing using the NOVA classification system: minimally or nonprocessed foods (NOVA 1), processed culinary ingredients (NOVA 2), processed foods (NOVA 3), and ultraprocessed foods (NOVA 4). The investigators highlighted comparisons between NOVA 1 and NOVA 3 and between NOVA 1 and NOVA 4.

The analysis revealed that swapping out just 10% of processed foods with minimally processed foods significantly lowered the risk for cancer overall (hazard ratio, 0.96) as well as for esophageal squamous cell carcinoma (HR, 0.57), hepatocellular carcinoma (HR, 0.77), head and neck cancers (HR, 0.80), colon cancer (HR, 0,88), rectal cancer (HR, 0.90), and postmenopausal breast cancer (HR, 0.93)

Swapping 10% of ultraprocessed foods for minimally processed foods lowered the risk of cancer overall only slightly (HR, 0.99) as well as the risk for various cancer types, including hepatocellular carcinoma (HR, 0.73), head and neck cancers (HR, 0.80), esophageal adenocarcinoma (HR, 0.80), and colon cancer (HR, 0.93).

The authors noted several limitations to the analysis, perhaps most notably that intake of ultraprocessed foods contributed to about 32% of total daily energy intake among study participants, but today that percentage could be nearly double across European countries.

“This discrepancy might explain the fewer significant associations observed between ultraprocessed foods and cancer risk than in processed foods and cancer risk,” the authors suggested.

The findings are “broadly in line with current evidence,” but the authors also noted some inconsistencies. For example, the current study showed a positive association between processed food consumption and risk for colorectal cancer and postmenopausal breast cancer, whereas other studies have not.

Overall, though, the authors concluded that increased consumption of minimally processed and fresh foods was associated with reduced overall risk for cancer and risk for specific cancers, and increased consumption of processed and ultraprocessed foods was associated with increased cancer risks.

This study “is the largest study investigating these associations between food processing and cancer risk and therefore has greater power to detect differences in populations, potentially explaining why we found overall more significant results for different cancer sites than other cohorts,” Dr. Kliemann and colleagues wrote.

This study was funded by Cancer Research UK, the French National Cancer Institute, and World Cancer Research Fund International. The authors declared no competing interests.

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

Researchers have found for the first time that COVID infection has crossed the placenta and caused brain damage in two newborns, according to a study published online today in Pediatrics .

One of the infants died at 13 months and the other remained in hospice care at time of manuscript submission.

Lead author Merline Benny, MD, with the division of neonatology, department of pediatrics at University of Miami, and colleagues briefed reporters today ahead of the release.

Zelda Calvert

“This is a first,” said senior author Shahnaz Duara, MD, medical director of the Neonatal Intensive Care Unit at Holtz Children’s Hospital, Miami, explaining it is the first study to confirm cross-placental SARS-CoV-2 transmission leading to brain injury in a newborn.
 

Both infants negative for the virus at birth

The two infants were admitted in the early days of the pandemic in the Delta wave to the neonatal ICU at Holtz Children’s Hospital at University of Miami/Jackson Memorial Medical Center.

Both infants tested negative for the virus at birth, but had significantly elevated SARS-CoV-2 antibodies in their blood, indicating that either antibodies crossed the placenta, or the virus crossed and the immune response was the baby’s.

Dr. Benny explained that the researchers have seen, to this point, more than 700 mother/infant pairs in whom the mother tested positive for COVID in Jackson hospital.

Most who tested positive for COVID were asymptomatic and most of the mothers and infants left the hospital without complications.

“However, (these) two babies had a very unusual clinical picture,” Dr. Benny said.

Those infants were born to mothers who became COVID positive in the second trimester and delivered a few weeks later.

Seizures started on day 1 of life

The babies began to seize from the first day of life. They had profound low tone (hypotonia) in their clinical exam, Dr. Benny explained.

“We had absolutely no good explanation for the early seizures and the degree of brain injury we saw,” Dr. Duara said.

Dr. Benny said that as their bodies grew, they had very small head circumference. Unlike some babies born with the Zika virus, these babies were not microcephalic at birth. Brain imaging on the two babies indicated significant brain atrophy, and neurodevelopment exams showed significant delay.

Discussions began with the center’s multidisciplinary team including neurologists, pathologists, neuroradiologists, and obstetricians who cared for both the mothers and the babies.

The experts examined the placentas and found some characteristic COVID changes and presence of the COVID virus. This was accompanied by increased markers for inflammation and a severe reduction in a hormone critical for placental health and brain development.

Examining the infant’s autopsy findings further raised suspicions of maternal transmission, something that had not been documented before.

Coauthor Ali G. Saad, MD, pediatric and perinatal pathology director at Miami, said, “I have seen literally thousands of brains in autopsies over the last 14 years, and this was the most dramatic case of leukoencephalopathy or loss of white matter in a patient with no significant reason. That’s what triggered the investigation.”
 

Mothers had very different presentations

Coauthor Michael J. Paidas, MD, with the department of obstetrics, gynecology, and reproductive sciences at Miami, pointed out that the circumstances of the two mothers, who were in their 20s, were very different.

One mother delivered at 32 weeks and had a very severe COVID presentation and spent a month in the intensive care unit. The team decided to deliver the child to save the mother, Dr. Paidas said.

In contrast, the other mother had asymptomatic COVID infection in the second trimester and delivered at full term.

He said one of the early suspicions in the babies’ presentations was hypoxic ischemic encephalopathy. “But it wasn’t lack of blood flow to the placenta that caused this,” he said. “As best we can tell, it was the viral infection.”
 

Instances are rare

The researchers emphasized that these instances are rare and have not been seen before or since the period of this study to their knowledge.

Dr. Duara said, “This is something we want to alert the medical community to more than the general public. We do not want the lay public to be panicked. We’re trying to understand what made these two pregnancies different, so we can direct research towards protecting vulnerable babies.”

Previous data have indicated a relatively benign status in infants who test negative for the COVID virus after birth. Dr. Benny added that COVID vaccination has been found safe in pregnancy and both vaccination and breastfeeding can help passage of antibodies to the infant and help protect the baby. Because these cases happened in the early days of the pandemic, no vaccines were available.

Dr. Paidas received funding from BioIncept to study hypoxic-ischemic encephalopathy with Preimplantation Factor, is a scientific advisory board member, and has stock options. Dr. Paidas and coauthor Dr. Jayakumar are coinventors of SPIKENET, University of Miami, patent pending 2023. The other authors have no conflicts of interest to disclose.

Researchers have found for the first time that COVID infection has crossed the placenta and caused brain damage in two newborns, according to a study published online today in Pediatrics .

One of the infants died at 13 months and the other remained in hospice care at time of manuscript submission.

Lead author Merline Benny, MD, with the division of neonatology, department of pediatrics at University of Miami, and colleagues briefed reporters today ahead of the release.

Zelda Calvert

“This is a first,” said senior author Shahnaz Duara, MD, medical director of the Neonatal Intensive Care Unit at Holtz Children’s Hospital, Miami, explaining it is the first study to confirm cross-placental SARS-CoV-2 transmission leading to brain injury in a newborn.
 

Both infants negative for the virus at birth

The two infants were admitted in the early days of the pandemic in the Delta wave to the neonatal ICU at Holtz Children’s Hospital at University of Miami/Jackson Memorial Medical Center.

Both infants tested negative for the virus at birth, but had significantly elevated SARS-CoV-2 antibodies in their blood, indicating that either antibodies crossed the placenta, or the virus crossed and the immune response was the baby’s.

Dr. Benny explained that the researchers have seen, to this point, more than 700 mother/infant pairs in whom the mother tested positive for COVID in Jackson hospital.

Most who tested positive for COVID were asymptomatic and most of the mothers and infants left the hospital without complications.

“However, (these) two babies had a very unusual clinical picture,” Dr. Benny said.

Those infants were born to mothers who became COVID positive in the second trimester and delivered a few weeks later.

Seizures started on day 1 of life

The babies began to seize from the first day of life. They had profound low tone (hypotonia) in their clinical exam, Dr. Benny explained.

“We had absolutely no good explanation for the early seizures and the degree of brain injury we saw,” Dr. Duara said.

Dr. Benny said that as their bodies grew, they had very small head circumference. Unlike some babies born with the Zika virus, these babies were not microcephalic at birth. Brain imaging on the two babies indicated significant brain atrophy, and neurodevelopment exams showed significant delay.

Discussions began with the center’s multidisciplinary team including neurologists, pathologists, neuroradiologists, and obstetricians who cared for both the mothers and the babies.

The experts examined the placentas and found some characteristic COVID changes and presence of the COVID virus. This was accompanied by increased markers for inflammation and a severe reduction in a hormone critical for placental health and brain development.

Examining the infant’s autopsy findings further raised suspicions of maternal transmission, something that had not been documented before.

Coauthor Ali G. Saad, MD, pediatric and perinatal pathology director at Miami, said, “I have seen literally thousands of brains in autopsies over the last 14 years, and this was the most dramatic case of leukoencephalopathy or loss of white matter in a patient with no significant reason. That’s what triggered the investigation.”
 

Mothers had very different presentations

Coauthor Michael J. Paidas, MD, with the department of obstetrics, gynecology, and reproductive sciences at Miami, pointed out that the circumstances of the two mothers, who were in their 20s, were very different.

One mother delivered at 32 weeks and had a very severe COVID presentation and spent a month in the intensive care unit. The team decided to deliver the child to save the mother, Dr. Paidas said.

In contrast, the other mother had asymptomatic COVID infection in the second trimester and delivered at full term.

He said one of the early suspicions in the babies’ presentations was hypoxic ischemic encephalopathy. “But it wasn’t lack of blood flow to the placenta that caused this,” he said. “As best we can tell, it was the viral infection.”
 

Instances are rare

The researchers emphasized that these instances are rare and have not been seen before or since the period of this study to their knowledge.

Dr. Duara said, “This is something we want to alert the medical community to more than the general public. We do not want the lay public to be panicked. We’re trying to understand what made these two pregnancies different, so we can direct research towards protecting vulnerable babies.”

Previous data have indicated a relatively benign status in infants who test negative for the COVID virus after birth. Dr. Benny added that COVID vaccination has been found safe in pregnancy and both vaccination and breastfeeding can help passage of antibodies to the infant and help protect the baby. Because these cases happened in the early days of the pandemic, no vaccines were available.

Dr. Paidas received funding from BioIncept to study hypoxic-ischemic encephalopathy with Preimplantation Factor, is a scientific advisory board member, and has stock options. Dr. Paidas and coauthor Dr. Jayakumar are coinventors of SPIKENET, University of Miami, patent pending 2023. The other authors have no conflicts of interest to disclose.

Researchers have found for the first time that COVID infection has crossed the placenta and caused brain damage in two newborns, according to a study published online today in Pediatrics .

One of the infants died at 13 months and the other remained in hospice care at time of manuscript submission.

Lead author Merline Benny, MD, with the division of neonatology, department of pediatrics at University of Miami, and colleagues briefed reporters today ahead of the release.

Zelda Calvert

“This is a first,” said senior author Shahnaz Duara, MD, medical director of the Neonatal Intensive Care Unit at Holtz Children’s Hospital, Miami, explaining it is the first study to confirm cross-placental SARS-CoV-2 transmission leading to brain injury in a newborn.
 

Both infants negative for the virus at birth

The two infants were admitted in the early days of the pandemic in the Delta wave to the neonatal ICU at Holtz Children’s Hospital at University of Miami/Jackson Memorial Medical Center.

Both infants tested negative for the virus at birth, but had significantly elevated SARS-CoV-2 antibodies in their blood, indicating that either antibodies crossed the placenta, or the virus crossed and the immune response was the baby’s.

Dr. Benny explained that the researchers have seen, to this point, more than 700 mother/infant pairs in whom the mother tested positive for COVID in Jackson hospital.

Most who tested positive for COVID were asymptomatic and most of the mothers and infants left the hospital without complications.

“However, (these) two babies had a very unusual clinical picture,” Dr. Benny said.

Those infants were born to mothers who became COVID positive in the second trimester and delivered a few weeks later.

Seizures started on day 1 of life

The babies began to seize from the first day of life. They had profound low tone (hypotonia) in their clinical exam, Dr. Benny explained.

“We had absolutely no good explanation for the early seizures and the degree of brain injury we saw,” Dr. Duara said.

Dr. Benny said that as their bodies grew, they had very small head circumference. Unlike some babies born with the Zika virus, these babies were not microcephalic at birth. Brain imaging on the two babies indicated significant brain atrophy, and neurodevelopment exams showed significant delay.

Discussions began with the center’s multidisciplinary team including neurologists, pathologists, neuroradiologists, and obstetricians who cared for both the mothers and the babies.

The experts examined the placentas and found some characteristic COVID changes and presence of the COVID virus. This was accompanied by increased markers for inflammation and a severe reduction in a hormone critical for placental health and brain development.

Examining the infant’s autopsy findings further raised suspicions of maternal transmission, something that had not been documented before.

Coauthor Ali G. Saad, MD, pediatric and perinatal pathology director at Miami, said, “I have seen literally thousands of brains in autopsies over the last 14 years, and this was the most dramatic case of leukoencephalopathy or loss of white matter in a patient with no significant reason. That’s what triggered the investigation.”
 

Mothers had very different presentations

Coauthor Michael J. Paidas, MD, with the department of obstetrics, gynecology, and reproductive sciences at Miami, pointed out that the circumstances of the two mothers, who were in their 20s, were very different.

One mother delivered at 32 weeks and had a very severe COVID presentation and spent a month in the intensive care unit. The team decided to deliver the child to save the mother, Dr. Paidas said.

In contrast, the other mother had asymptomatic COVID infection in the second trimester and delivered at full term.

He said one of the early suspicions in the babies’ presentations was hypoxic ischemic encephalopathy. “But it wasn’t lack of blood flow to the placenta that caused this,” he said. “As best we can tell, it was the viral infection.”
 

Instances are rare

The researchers emphasized that these instances are rare and have not been seen before or since the period of this study to their knowledge.

Dr. Duara said, “This is something we want to alert the medical community to more than the general public. We do not want the lay public to be panicked. We’re trying to understand what made these two pregnancies different, so we can direct research towards protecting vulnerable babies.”

Previous data have indicated a relatively benign status in infants who test negative for the COVID virus after birth. Dr. Benny added that COVID vaccination has been found safe in pregnancy and both vaccination and breastfeeding can help passage of antibodies to the infant and help protect the baby. Because these cases happened in the early days of the pandemic, no vaccines were available.

Dr. Paidas received funding from BioIncept to study hypoxic-ischemic encephalopathy with Preimplantation Factor, is a scientific advisory board member, and has stock options. Dr. Paidas and coauthor Dr. Jayakumar are coinventors of SPIKENET, University of Miami, patent pending 2023. The other authors have no conflicts of interest to disclose.

The patient’s recurrent indurated nodules under her arms and other intertriginous areas, often draining pus, are consistent with a diagnosis of hidradenitis suppurativa (HS).

HS is a chronic inflammatory and suppurative skin condition that primarily involves the sweat glands.¹ The most commonly affected sites are intertriginous areas that include the axillae, groin, and perianal and inframammary regions.² Prevalence of this disorder ranges from 0.05% to 4.1% of the population with an onset from puberty to adulthood, usually at around 40 years of age.³ Its incidence is twice as high in women as men and is more common in Black individuals.^4,5

While its pathogenesis is not fully understood, it’s believed that excess proliferation of keratinocytes contributes to occlusion, leading to plugging of hair follicle ducts. Hormones, smoking, and obesity may contribute to and exacerbate HS. Intertriginous areas are prone to friction, leading to inflammation and further clogging.

The inflammation evolves into a chronic foreign body-type granulomatous inflammation with the potential for rupture, tunneling, and draining sinuses, which, although malodorous, are sterile, separating HS from an infected abscess.⁵ The result is thick, dense, scarred tissue.

The diagnosis is clinical in nature, with the history and physical exam distinguishing it from other skin disorders. In addition to the recurring physical pain, there is the emotional distress and self-consciousness about the drainage, odor, and scarring. This particular patient said that she avoided wearing sleeveless shirts due to the lesions’ appearance.

Treatment is multifactorial. Smoking and obesity are contributory factors, so smoking cessation and weight loss are recommended. For very mild HS, topical clindamycin 1% twice daily may suffice, but usually, due to the amount of inflammation, oral antibiotics are the initial therapy. (The use of antibiotics is for their anti-inflammatory component, as the nodules and unruptured tracts are sterile.)

Doxycycline 100 mg twice daily is the usual starting systemic antibiotic. In more severe or resistant cases, a combination of clindamycin and rifampin 300 mg each twice daily is used. (Worth noting: Rifampin interacts with oral contraceptives and many of these patients are women of reproductive age.) Treatment length is usually long (10 to 12 weeks) and recurrence is common.³

Spironolactone 100 mg daily and metformin 1000 mg extended release daily, which reduces insulin resistance, may be helpful. Intralesional injections of 10 mg/mL of triamcinolone in sterile saline can relieve the painful inflamed tracts. Referral for biologic agents, including infliximab, may be needed in severe cases that do not respond to other measures. Although invasive, wide debridement of the diseased tissue can reduce the disease burden.⁶

This particular patient said that she’d stopped smoking 3 years earlier and would work on losing weight. She was prescribed topical clindamycin 1% lotion twice daily along with oral clindamycin and rifampin dosed as above for 3 months. She declined metformin and intralesional injections. At a follow-up appointment 3 weeks later, she was pleased with the decrease in inflammation and had only 1 remaining tender area of fluctuance. She again declined injections and planned to continue on her oral and topical antibiotics.

‌

Photo courtesy of Daniel Stulberg, MD, FAAFP. Text courtesy of Derissa F. Raynold, MD, and Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, Western Michigan University Homer Stryker, MD School of Medicine, Kalamazoo.

The patient’s recurrent indurated nodules under her arms and other intertriginous areas, often draining pus, are consistent with a diagnosis of hidradenitis suppurativa (HS).

HS is a chronic inflammatory and suppurative skin condition that primarily involves the sweat glands.¹ The most commonly affected sites are intertriginous areas that include the axillae, groin, and perianal and inframammary regions.² Prevalence of this disorder ranges from 0.05% to 4.1% of the population with an onset from puberty to adulthood, usually at around 40 years of age.³ Its incidence is twice as high in women as men and is more common in Black individuals.^4,5

While its pathogenesis is not fully understood, it’s believed that excess proliferation of keratinocytes contributes to occlusion, leading to plugging of hair follicle ducts. Hormones, smoking, and obesity may contribute to and exacerbate HS. Intertriginous areas are prone to friction, leading to inflammation and further clogging.

The inflammation evolves into a chronic foreign body-type granulomatous inflammation with the potential for rupture, tunneling, and draining sinuses, which, although malodorous, are sterile, separating HS from an infected abscess.⁵ The result is thick, dense, scarred tissue.

The diagnosis is clinical in nature, with the history and physical exam distinguishing it from other skin disorders. In addition to the recurring physical pain, there is the emotional distress and self-consciousness about the drainage, odor, and scarring. This particular patient said that she avoided wearing sleeveless shirts due to the lesions’ appearance.

Treatment is multifactorial. Smoking and obesity are contributory factors, so smoking cessation and weight loss are recommended. For very mild HS, topical clindamycin 1% twice daily may suffice, but usually, due to the amount of inflammation, oral antibiotics are the initial therapy. (The use of antibiotics is for their anti-inflammatory component, as the nodules and unruptured tracts are sterile.)

Doxycycline 100 mg twice daily is the usual starting systemic antibiotic. In more severe or resistant cases, a combination of clindamycin and rifampin 300 mg each twice daily is used. (Worth noting: Rifampin interacts with oral contraceptives and many of these patients are women of reproductive age.) Treatment length is usually long (10 to 12 weeks) and recurrence is common.³

Spironolactone 100 mg daily and metformin 1000 mg extended release daily, which reduces insulin resistance, may be helpful. Intralesional injections of 10 mg/mL of triamcinolone in sterile saline can relieve the painful inflamed tracts. Referral for biologic agents, including infliximab, may be needed in severe cases that do not respond to other measures. Although invasive, wide debridement of the diseased tissue can reduce the disease burden.⁶

This particular patient said that she’d stopped smoking 3 years earlier and would work on losing weight. She was prescribed topical clindamycin 1% lotion twice daily along with oral clindamycin and rifampin dosed as above for 3 months. She declined metformin and intralesional injections. At a follow-up appointment 3 weeks later, she was pleased with the decrease in inflammation and had only 1 remaining tender area of fluctuance. She again declined injections and planned to continue on her oral and topical antibiotics.

‌

Photo courtesy of Daniel Stulberg, MD, FAAFP. Text courtesy of Derissa F. Raynold, MD, and Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, Western Michigan University Homer Stryker, MD School of Medicine, Kalamazoo.

The patient’s recurrent indurated nodules under her arms and other intertriginous areas, often draining pus, are consistent with a diagnosis of hidradenitis suppurativa (HS).

HS is a chronic inflammatory and suppurative skin condition that primarily involves the sweat glands.¹ The most commonly affected sites are intertriginous areas that include the axillae, groin, and perianal and inframammary regions.² Prevalence of this disorder ranges from 0.05% to 4.1% of the population with an onset from puberty to adulthood, usually at around 40 years of age.³ Its incidence is twice as high in women as men and is more common in Black individuals.^4,5

While its pathogenesis is not fully understood, it’s believed that excess proliferation of keratinocytes contributes to occlusion, leading to plugging of hair follicle ducts. Hormones, smoking, and obesity may contribute to and exacerbate HS. Intertriginous areas are prone to friction, leading to inflammation and further clogging.

The inflammation evolves into a chronic foreign body-type granulomatous inflammation with the potential for rupture, tunneling, and draining sinuses, which, although malodorous, are sterile, separating HS from an infected abscess.⁵ The result is thick, dense, scarred tissue.

The diagnosis is clinical in nature, with the history and physical exam distinguishing it from other skin disorders. In addition to the recurring physical pain, there is the emotional distress and self-consciousness about the drainage, odor, and scarring. This particular patient said that she avoided wearing sleeveless shirts due to the lesions’ appearance.

Treatment is multifactorial. Smoking and obesity are contributory factors, so smoking cessation and weight loss are recommended. For very mild HS, topical clindamycin 1% twice daily may suffice, but usually, due to the amount of inflammation, oral antibiotics are the initial therapy. (The use of antibiotics is for their anti-inflammatory component, as the nodules and unruptured tracts are sterile.)

Doxycycline 100 mg twice daily is the usual starting systemic antibiotic. In more severe or resistant cases, a combination of clindamycin and rifampin 300 mg each twice daily is used. (Worth noting: Rifampin interacts with oral contraceptives and many of these patients are women of reproductive age.) Treatment length is usually long (10 to 12 weeks) and recurrence is common.³

Spironolactone 100 mg daily and metformin 1000 mg extended release daily, which reduces insulin resistance, may be helpful. Intralesional injections of 10 mg/mL of triamcinolone in sterile saline can relieve the painful inflamed tracts. Referral for biologic agents, including infliximab, may be needed in severe cases that do not respond to other measures. Although invasive, wide debridement of the diseased tissue can reduce the disease burden.⁶

This particular patient said that she’d stopped smoking 3 years earlier and would work on losing weight. She was prescribed topical clindamycin 1% lotion twice daily along with oral clindamycin and rifampin dosed as above for 3 months. She declined metformin and intralesional injections. At a follow-up appointment 3 weeks later, she was pleased with the decrease in inflammation and had only 1 remaining tender area of fluctuance. She again declined injections and planned to continue on her oral and topical antibiotics.

‌

Photo courtesy of Daniel Stulberg, MD, FAAFP. Text courtesy of Derissa F. Raynold, MD, and Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, Western Michigan University Homer Stryker, MD School of Medicine, Kalamazoo.

A mindfulness-based cognitive therapy self-help (MBCT-SH) intervention in which patients were supported by a trained practitioner led to better clinical outcomes at lower cost than practitioner-supported cognitive-behavioral therapy self-help (CBT-SH), new research shows.

The findings suggest that “offering practitioner-supported MBCT-SH as an intervention for mild to moderate depression would improve outcomes and save money compared with practitioner-supported CBT-SH,” noted the investigators, led by Clara Strauss, PhD, DClinPsy, with the University of Sussex School of Psychology in England.

Practitioner-supported CBT-SH is recommended in U.K. national treatment guidelines for mild to moderate depression. However, some patients’ conditions don’t respond, and dropout rates are high.

The Low-Intensity Guided Help Through Mindfulness (LIGHTMind) trial tested practitioner-supported MBCT-SH as an alternative.

The findings have “important implications” for the more than 100,000 people currently offered CBT-SH for depression in the Improving Access to Psychological Therapies (IAPT) program each year and in publicly funded services elsewhere, the researchers noted.

If translated into routine practice, “this would see many more people recovering from depression while costing health services less money,” they added.

The study was published online in JAMA Psychiatry .
 

Practice changing?

The trial included 410 adults (mean age, 32 years; 62% women) with mild to moderate depression who were recruited from 10 publicly funded psychological therapy services in England as part of the IAPT program.

Participants were given one of two established self-help workbooks – The Mindful Way Workbook: An 8-Week Program to Free Yourself from Depression and Emotional Distress, written by the pioneers of MBCT, or Overcoming Depression and Low Mood, 3rd Edition: A Five Areas Approach, which is a CBT-SH program widely used in IAPT.

Use of the self-help books was supported by six structured phone or in-person sessions with a trained psychological well-being practitioner.

The primary outcome was depression symptom severity at 16 weeks, which was determined on the basis of Patient Health Questionnaire 9 (PHQ-9) score.

At 16 weeks following randomization, MBCT-SH led to significantly greater reductions in depression symptom severity compared with CBT-SH (mean PHQ-9 score, 7.2 vs. 8.6; between-group difference, 1.5 points; P = .009; d = −0.36).

MBCT-SH also had superior effects on anxiety symptom severity at 16 weeks.

At the 42-week follow-up, between-group effects on depression and anxiety symptom severity remained in the hypothesized direction but were nonsignificant.

This could be due in part by the greater postintervention psychological therapy accessed by participants in the CBT-SH group, the investigators noted.

Practitioner-supported MBCT-SH was more cost-effective than supported CBT-SH.

On average, the CBT-SH intervention cost health services £526 ($631) more per participant than the MBCT-SH intervention over the 42-week follow-up. The probability of MBCT-SH being cost-effective compared with CBT-SH exceeded 95%, the researchers noted.
 

Useful model for the United States

Commenting for this news organization, Zindel Segal, PhD, professor of psychology, University of Toronto, Scarborough, cautioned against making too much of the differences between the groups, because CBT-SH “trended positive and had a pretty healthy effect size, it just never reached significance.

“I wouldn’t say mindfulness drastically outperformed cognitive therapy. But cognitive therapy is a robust treatment in its own right, and so doing a little bit better is significant,” Dr. Segal said.

He also noted that, appropriately, the trial enrolled adults who were experiencing moderate depression and were not acutely ill. “That’s one of the rationales for self-help compared to providing patients with a more resource-intensive group treatment.

“If you look at the needs of people with moderate depression, what you find is that for cognitive therapy to work, negative thoughts and feelings need to be pervasive in order to make use of the techniques,” Dr. Segal explained.

“With mindfulness, you don’t need any to have constant negative thoughts or feelings. Anything that arises in your experience serves as grist for mill in terms of concentration and focus,” Dr. Segal said.

He also noted that mindfulness-based intervention is “more optimized” for people who are experiencing some measure of recovery or remission.

“It’s well suited for that, as it trends towards the wellness spectrum. But for people who might have greater levels of acuity or severity, cognitive-behavioral therapy might be indicated,” said Dr. Segal.

He also said the U.K. study findings are relevant to U.S. patients with depression.

“While it’s not disseminated in the same way through any kind of national program, the self-help books that are used are widely available, and the support that people were offered, either in person, telephone, or email, could be easily delivered. This would be a very useful model,” Dr. Segal said.

The LIGHTMind trial was funded by the National Institute for Health and Care Research and the Brighton and Sussex Clinical Trials Unit. Dr. Strauss has received grants from Headspace, is research lead for Sussex Mindfulness Centre, and has been chief investigator on National Institute for Health and Care Research. Dr. Segal is one of the authors of the MBCT-SH workbooks used in the study.
 

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

A mindfulness-based cognitive therapy self-help (MBCT-SH) intervention in which patients were supported by a trained practitioner led to better clinical outcomes at lower cost than practitioner-supported cognitive-behavioral therapy self-help (CBT-SH), new research shows.

The findings suggest that “offering practitioner-supported MBCT-SH as an intervention for mild to moderate depression would improve outcomes and save money compared with practitioner-supported CBT-SH,” noted the investigators, led by Clara Strauss, PhD, DClinPsy, with the University of Sussex School of Psychology in England.

Practitioner-supported CBT-SH is recommended in U.K. national treatment guidelines for mild to moderate depression. However, some patients’ conditions don’t respond, and dropout rates are high.

The Low-Intensity Guided Help Through Mindfulness (LIGHTMind) trial tested practitioner-supported MBCT-SH as an alternative.

The findings have “important implications” for the more than 100,000 people currently offered CBT-SH for depression in the Improving Access to Psychological Therapies (IAPT) program each year and in publicly funded services elsewhere, the researchers noted.

If translated into routine practice, “this would see many more people recovering from depression while costing health services less money,” they added.

The study was published online in JAMA Psychiatry .
 

Practice changing?

The trial included 410 adults (mean age, 32 years; 62% women) with mild to moderate depression who were recruited from 10 publicly funded psychological therapy services in England as part of the IAPT program.

Participants were given one of two established self-help workbooks – The Mindful Way Workbook: An 8-Week Program to Free Yourself from Depression and Emotional Distress, written by the pioneers of MBCT, or Overcoming Depression and Low Mood, 3rd Edition: A Five Areas Approach, which is a CBT-SH program widely used in IAPT.

Use of the self-help books was supported by six structured phone or in-person sessions with a trained psychological well-being practitioner.

The primary outcome was depression symptom severity at 16 weeks, which was determined on the basis of Patient Health Questionnaire 9 (PHQ-9) score.

At 16 weeks following randomization, MBCT-SH led to significantly greater reductions in depression symptom severity compared with CBT-SH (mean PHQ-9 score, 7.2 vs. 8.6; between-group difference, 1.5 points; P = .009; d = −0.36).

MBCT-SH also had superior effects on anxiety symptom severity at 16 weeks.

At the 42-week follow-up, between-group effects on depression and anxiety symptom severity remained in the hypothesized direction but were nonsignificant.

This could be due in part by the greater postintervention psychological therapy accessed by participants in the CBT-SH group, the investigators noted.

Practitioner-supported MBCT-SH was more cost-effective than supported CBT-SH.

On average, the CBT-SH intervention cost health services £526 ($631) more per participant than the MBCT-SH intervention over the 42-week follow-up. The probability of MBCT-SH being cost-effective compared with CBT-SH exceeded 95%, the researchers noted.
 

Useful model for the United States

Commenting for this news organization, Zindel Segal, PhD, professor of psychology, University of Toronto, Scarborough, cautioned against making too much of the differences between the groups, because CBT-SH “trended positive and had a pretty healthy effect size, it just never reached significance.

“I wouldn’t say mindfulness drastically outperformed cognitive therapy. But cognitive therapy is a robust treatment in its own right, and so doing a little bit better is significant,” Dr. Segal said.

He also noted that, appropriately, the trial enrolled adults who were experiencing moderate depression and were not acutely ill. “That’s one of the rationales for self-help compared to providing patients with a more resource-intensive group treatment.

“If you look at the needs of people with moderate depression, what you find is that for cognitive therapy to work, negative thoughts and feelings need to be pervasive in order to make use of the techniques,” Dr. Segal explained.

“With mindfulness, you don’t need any to have constant negative thoughts or feelings. Anything that arises in your experience serves as grist for mill in terms of concentration and focus,” Dr. Segal said.

He also noted that mindfulness-based intervention is “more optimized” for people who are experiencing some measure of recovery or remission.

“It’s well suited for that, as it trends towards the wellness spectrum. But for people who might have greater levels of acuity or severity, cognitive-behavioral therapy might be indicated,” said Dr. Segal.

He also said the U.K. study findings are relevant to U.S. patients with depression.

“While it’s not disseminated in the same way through any kind of national program, the self-help books that are used are widely available, and the support that people were offered, either in person, telephone, or email, could be easily delivered. This would be a very useful model,” Dr. Segal said.

The LIGHTMind trial was funded by the National Institute for Health and Care Research and the Brighton and Sussex Clinical Trials Unit. Dr. Strauss has received grants from Headspace, is research lead for Sussex Mindfulness Centre, and has been chief investigator on National Institute for Health and Care Research. Dr. Segal is one of the authors of the MBCT-SH workbooks used in the study.
 

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

A mindfulness-based cognitive therapy self-help (MBCT-SH) intervention in which patients were supported by a trained practitioner led to better clinical outcomes at lower cost than practitioner-supported cognitive-behavioral therapy self-help (CBT-SH), new research shows.

The findings suggest that “offering practitioner-supported MBCT-SH as an intervention for mild to moderate depression would improve outcomes and save money compared with practitioner-supported CBT-SH,” noted the investigators, led by Clara Strauss, PhD, DClinPsy, with the University of Sussex School of Psychology in England.

Practitioner-supported CBT-SH is recommended in U.K. national treatment guidelines for mild to moderate depression. However, some patients’ conditions don’t respond, and dropout rates are high.

The Low-Intensity Guided Help Through Mindfulness (LIGHTMind) trial tested practitioner-supported MBCT-SH as an alternative.

The findings have “important implications” for the more than 100,000 people currently offered CBT-SH for depression in the Improving Access to Psychological Therapies (IAPT) program each year and in publicly funded services elsewhere, the researchers noted.

If translated into routine practice, “this would see many more people recovering from depression while costing health services less money,” they added.

The study was published online in JAMA Psychiatry .
 

Practice changing?

The trial included 410 adults (mean age, 32 years; 62% women) with mild to moderate depression who were recruited from 10 publicly funded psychological therapy services in England as part of the IAPT program.

Participants were given one of two established self-help workbooks – The Mindful Way Workbook: An 8-Week Program to Free Yourself from Depression and Emotional Distress, written by the pioneers of MBCT, or Overcoming Depression and Low Mood, 3rd Edition: A Five Areas Approach, which is a CBT-SH program widely used in IAPT.

Use of the self-help books was supported by six structured phone or in-person sessions with a trained psychological well-being practitioner.

The primary outcome was depression symptom severity at 16 weeks, which was determined on the basis of Patient Health Questionnaire 9 (PHQ-9) score.

At 16 weeks following randomization, MBCT-SH led to significantly greater reductions in depression symptom severity compared with CBT-SH (mean PHQ-9 score, 7.2 vs. 8.6; between-group difference, 1.5 points; P = .009; d = −0.36).

MBCT-SH also had superior effects on anxiety symptom severity at 16 weeks.

At the 42-week follow-up, between-group effects on depression and anxiety symptom severity remained in the hypothesized direction but were nonsignificant.

This could be due in part by the greater postintervention psychological therapy accessed by participants in the CBT-SH group, the investigators noted.

Practitioner-supported MBCT-SH was more cost-effective than supported CBT-SH.

On average, the CBT-SH intervention cost health services £526 ($631) more per participant than the MBCT-SH intervention over the 42-week follow-up. The probability of MBCT-SH being cost-effective compared with CBT-SH exceeded 95%, the researchers noted.
 

Useful model for the United States

Commenting for this news organization, Zindel Segal, PhD, professor of psychology, University of Toronto, Scarborough, cautioned against making too much of the differences between the groups, because CBT-SH “trended positive and had a pretty healthy effect size, it just never reached significance.

“I wouldn’t say mindfulness drastically outperformed cognitive therapy. But cognitive therapy is a robust treatment in its own right, and so doing a little bit better is significant,” Dr. Segal said.

He also noted that, appropriately, the trial enrolled adults who were experiencing moderate depression and were not acutely ill. “That’s one of the rationales for self-help compared to providing patients with a more resource-intensive group treatment.

“If you look at the needs of people with moderate depression, what you find is that for cognitive therapy to work, negative thoughts and feelings need to be pervasive in order to make use of the techniques,” Dr. Segal explained.

“With mindfulness, you don’t need any to have constant negative thoughts or feelings. Anything that arises in your experience serves as grist for mill in terms of concentration and focus,” Dr. Segal said.

He also noted that mindfulness-based intervention is “more optimized” for people who are experiencing some measure of recovery or remission.

“It’s well suited for that, as it trends towards the wellness spectrum. But for people who might have greater levels of acuity or severity, cognitive-behavioral therapy might be indicated,” said Dr. Segal.

He also said the U.K. study findings are relevant to U.S. patients with depression.

“While it’s not disseminated in the same way through any kind of national program, the self-help books that are used are widely available, and the support that people were offered, either in person, telephone, or email, could be easily delivered. This would be a very useful model,” Dr. Segal said.

The LIGHTMind trial was funded by the National Institute for Health and Care Research and the Brighton and Sussex Clinical Trials Unit. Dr. Strauss has received grants from Headspace, is research lead for Sussex Mindfulness Centre, and has been chief investigator on National Institute for Health and Care Research. Dr. Segal is one of the authors of the MBCT-SH workbooks used in the study.
 

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

The youngest patient with cannabis-induced psychosis (CIP) whom Karen Randall, DO, has treated was a 7-year-old boy. She remembers the screaming, the yelling, the uncontrollable rage.

Dr. Randall is an emergency medicine physician at Southern Colorado Emergency Medicine Associates, a group practice in Pueblo, Colo. She treats youth for cannabis-related medical problems in the emergency department an average of two or three times per shift, she said.

Colorado legalized the recreational use of cannabis for adults older than 21 in 2012. Since then, Dr. Randall said, she has noticed an uptick in cannabis use among youth, as well as an increase in CIP, a syndrome that can be indistinguishable from other psychiatric disorders such as schizophrenia in the emergency department. But the two conditions require different approaches to care.

“You can’t differentiate unless you know the patient,” Dr. Randall said in an interview.

In 2019, 37% of high school students in the United States reported ever using marijuana, and 22% reported use in the past 30 days. Rates remained steady in 2020 following increases in 2018 and 2019, according to the Centers for Disease Control and Prevention.

The CDC also found that 8% of 8th graders, 19% of 10th graders, and 22% of 12th graders reported vaping marijuana in the past year.

Clinicians in states where recreational marijuana has been legalized say they have noticed an increase in young patients with psychiatric problems – especially after consumption of cannabis products in high doses. But CIP can be tricky to distinguish from psychoses of other causes, such as schizophrenia or bipolar disorder, which often begin to present in adolescence.
 

How to differentiate

CIP is characterized by delusions and hallucinations and sometimes anxiety, disorganized thoughts, paranoia, dissociation, and changes in mood and behavior. Symptoms typically last for a couple hours and do not require specific treatment, although they can persist, depending on a patient’s tolerance and the dose of tetrahydrocannabinol (THC) they have consumed. Research suggests that the higher the dose and concentration of the drug consumed, the more likely a person will develop symptoms of psychosis.

Diagnosis requires gathering information on previous bipolar disorder or schizophrenia diagnosis, prescriptions for mental illness indications, whether there is a family history of mental illness, and whether the patient recently started using marijuana. In some cases, marijuana use might exacerbate or unmask mental illness.

If symptoms of CIP resolve, and usually they do, clinicians can recommend that patients abstain from cannabis going forward, and psychosis would not need further treatment, according to Divya Singh, MD, a psychiatrist at Banner Behavioral Health Hospital in Scottsdale, Ariz., where recreational cannabis became legal in 2020.

“When I have limited information, especially in the first couple of days, I err on the side of safety,” Dr. Singh said.

Psychosis is the combination of symptoms, including delusions, hallucinations, and disorganized behavior, but it is not a disorder in itself. Rather, it is the primary symptom of schizophrenia and other chronic psychiatric illnesses.

Schizophrenia can be diagnosed only after a patient presents with signs of disturbance for at least 6 months, according to guidelines in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Dr. Singh said a diagnosis of schizophrenia cannot be made in a one-off interaction.

If the patient is younger than 24 years and has no family history of mental illness, a full recovery is likely if the patient abstains from marijuana, he said. But if the patient does have a family history, “the chances of them having a full-blown mental illness is very high,” Dr. Singh said.

If a patient reports that he or she has recently started using marijuana and was previously diagnosed with bipolar disorder or schizophrenia, Dr. Singh said he generally prescribes medications such as lithium or quetiapine and refers the patient to services such as cognitive-behavioral therapy. He also advises against continuing use of cannabis.

“Cannabis can result in people requiring a higher dose of medication than they took before,” Dr. Singh said. “If they were stable on 600 mg of lithium before, they might need more and may never be able to lower the dose in some cases, even after the acute episode.”
 

The science of cannabis

As of March 2023, 21 states and the District of Columbia permit the recreational use of marijuana, according to the Congressional Research Service. Thirty-seven states and the District of Columbia allow medicinal use of marijuana, and 10 states allow “limited access to medical cannabis,” defined as low-THC cannabis or cannabidiol (CBD) oil.

THC is the main psychoactive compound in cannabis. It creates a high feeling after binding with receptors in the brain that control pain and mood. CBD is another chemical found in cannabis, but it does not create a high.

Some research suggests cannabinoids may help reduce anxiety, reduce inflammation, relieve pain, control nausea, reduce cancer cells, slow the growth of tumor cells, relax tight muscles, and stimulate appetite.

The drug also carries risks, according to Mayo Clinic. Use of marijuana is linked to mental health problems in teens and adults, such as depression, social anxiety, and temporary psychosis, and long-lasting mental disorders, such as schizophrenia.

In the worst cases, CIP can persist for weeks or months – long after a negative drug test – and sometimes does not subside at all, according to Ken Finn, MD, president and founder of Springs Rehabilitation, PC, a pain medicine practice in Colorado Springs, Colo.

Dr. Finn, the co–vice president of the International Academy on the Science and Impact of Cannabis, which opposes making the drug more accessible, said educating health care providers is an urgent need.

Studies are mixed on whether the legalization of cannabis has led to more cases of CIP.

A 2021 study found that experiences of psychosis among users of cannabis jumped 2.5-fold between 2001 and 2013. But a study published earlier this year of more than 63 million medical claims from 2003 to 2017 found no statistically significant difference in rates of psychosis-related diagnoses or prescribed antipsychotics in states that have legalized medical or recreational cannabis compared with states where cannabis is still illegal. However, a secondary analysis did find that rates of psychosis-related diagnoses increased significantly among men, people aged 55-64 years, and Asian adults in states where recreational marijuana has been legalized.

Complicating matters, researchers say, is the question of causality. Cannabis may exacerbate or trigger psychosis, but people with an underlying psychological illness may also be more likely to use cannabis.

Dr. Finn said clinicians in Colorado and other states with legalization laws are seeing more patients with CIP. As more states consider legalizing recreational marijuana, he expects the data will reflect what doctors experience on the ground.

Cannabis-induced “psychosis is complicated and likely underdiagnosed,” Dr. Finn said.
 

Talking to teens

Clinicians outside the emergency department can play a role in aiding young people at risk for CIP. Primary care physicians, for instance, might explain to young patients that the brain only becomes fully developed at roughly age 26, after which the long-term health consequences of using cannabis become less likely. According to the CDC, using cannabis before age 18 can change how the brain builds connections and can impair attention, memory, and learning.

Dr. Singh takes a harm reduction approach when he engages with a patient who is forthcoming about substance use.

“If I see an 18-year-old, I tell them to abstain,” he said. “I tell them if they are ever going to use it, to use it after 26.”

Clinicians also should understand dosages to provide the optimal guidance to their patients who use cannabis.

“People often have no idea how much cannabis they are taking,” especially when using vape cartridges, Dr. Singh said. “If you don’t know, you can’t tell patients about the harms – and if you tell them the wrong information, they will write you off.”

Dr. Singh said he advises his patients to avoid using cannabis vapes or dabbing pens. Both can contain much higher levels of THC than dried flower or edible forms of the drug. He also says patients should stick with low concentrations and use products that contain CBD, which some studies have shown has a protective effect against CIP, although other studies have found that CBD can induce anxiety.

He also tells patients to buy from legal dispensaries and to avoid buying street products that may have methamphetamine or fentanyl mixed in.

Despite the risks, Dr. Singh said legalization can reduce the stigma associated with cannabis use and may prompt patients to be honest with their clinicians. Dr. Singh recalled a 28-year-old patient who was using cannabis to alleviate her arthritic pain. She also was taking a transplant medication, which carried potential side effects of delirium, generalized anxiety disorder, and hallucinosis. After doubling her THC dose, the patient experienced severe anxiety and paranoia.

Dr. Singh’s patient paid him a visit and asked for help. Dr. Singh told her to reduce the dose and to keep track of how she felt. If she continued to feel anxious and paranoid, he recommended that she switch to CBD instead.

“I think education and knowledge is liberating,” Dr. Singh said. “Legalization and frank conversations help people understand how to use a product – and right now, I think that’s lacking.”
 

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

The youngest patient with cannabis-induced psychosis (CIP) whom Karen Randall, DO, has treated was a 7-year-old boy. She remembers the screaming, the yelling, the uncontrollable rage.

Dr. Randall is an emergency medicine physician at Southern Colorado Emergency Medicine Associates, a group practice in Pueblo, Colo. She treats youth for cannabis-related medical problems in the emergency department an average of two or three times per shift, she said.

Colorado legalized the recreational use of cannabis for adults older than 21 in 2012. Since then, Dr. Randall said, she has noticed an uptick in cannabis use among youth, as well as an increase in CIP, a syndrome that can be indistinguishable from other psychiatric disorders such as schizophrenia in the emergency department. But the two conditions require different approaches to care.

“You can’t differentiate unless you know the patient,” Dr. Randall said in an interview.

In 2019, 37% of high school students in the United States reported ever using marijuana, and 22% reported use in the past 30 days. Rates remained steady in 2020 following increases in 2018 and 2019, according to the Centers for Disease Control and Prevention.

The CDC also found that 8% of 8th graders, 19% of 10th graders, and 22% of 12th graders reported vaping marijuana in the past year.

Clinicians in states where recreational marijuana has been legalized say they have noticed an increase in young patients with psychiatric problems – especially after consumption of cannabis products in high doses. But CIP can be tricky to distinguish from psychoses of other causes, such as schizophrenia or bipolar disorder, which often begin to present in adolescence.
 

How to differentiate

CIP is characterized by delusions and hallucinations and sometimes anxiety, disorganized thoughts, paranoia, dissociation, and changes in mood and behavior. Symptoms typically last for a couple hours and do not require specific treatment, although they can persist, depending on a patient’s tolerance and the dose of tetrahydrocannabinol (THC) they have consumed. Research suggests that the higher the dose and concentration of the drug consumed, the more likely a person will develop symptoms of psychosis.

Diagnosis requires gathering information on previous bipolar disorder or schizophrenia diagnosis, prescriptions for mental illness indications, whether there is a family history of mental illness, and whether the patient recently started using marijuana. In some cases, marijuana use might exacerbate or unmask mental illness.

If symptoms of CIP resolve, and usually they do, clinicians can recommend that patients abstain from cannabis going forward, and psychosis would not need further treatment, according to Divya Singh, MD, a psychiatrist at Banner Behavioral Health Hospital in Scottsdale, Ariz., where recreational cannabis became legal in 2020.

“When I have limited information, especially in the first couple of days, I err on the side of safety,” Dr. Singh said.

Psychosis is the combination of symptoms, including delusions, hallucinations, and disorganized behavior, but it is not a disorder in itself. Rather, it is the primary symptom of schizophrenia and other chronic psychiatric illnesses.

Schizophrenia can be diagnosed only after a patient presents with signs of disturbance for at least 6 months, according to guidelines in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Dr. Singh said a diagnosis of schizophrenia cannot be made in a one-off interaction.

If the patient is younger than 24 years and has no family history of mental illness, a full recovery is likely if the patient abstains from marijuana, he said. But if the patient does have a family history, “the chances of them having a full-blown mental illness is very high,” Dr. Singh said.

If a patient reports that he or she has recently started using marijuana and was previously diagnosed with bipolar disorder or schizophrenia, Dr. Singh said he generally prescribes medications such as lithium or quetiapine and refers the patient to services such as cognitive-behavioral therapy. He also advises against continuing use of cannabis.

“Cannabis can result in people requiring a higher dose of medication than they took before,” Dr. Singh said. “If they were stable on 600 mg of lithium before, they might need more and may never be able to lower the dose in some cases, even after the acute episode.”
 

The science of cannabis

As of March 2023, 21 states and the District of Columbia permit the recreational use of marijuana, according to the Congressional Research Service. Thirty-seven states and the District of Columbia allow medicinal use of marijuana, and 10 states allow “limited access to medical cannabis,” defined as low-THC cannabis or cannabidiol (CBD) oil.

THC is the main psychoactive compound in cannabis. It creates a high feeling after binding with receptors in the brain that control pain and mood. CBD is another chemical found in cannabis, but it does not create a high.

Some research suggests cannabinoids may help reduce anxiety, reduce inflammation, relieve pain, control nausea, reduce cancer cells, slow the growth of tumor cells, relax tight muscles, and stimulate appetite.

The drug also carries risks, according to Mayo Clinic. Use of marijuana is linked to mental health problems in teens and adults, such as depression, social anxiety, and temporary psychosis, and long-lasting mental disorders, such as schizophrenia.

In the worst cases, CIP can persist for weeks or months – long after a negative drug test – and sometimes does not subside at all, according to Ken Finn, MD, president and founder of Springs Rehabilitation, PC, a pain medicine practice in Colorado Springs, Colo.

Dr. Finn, the co–vice president of the International Academy on the Science and Impact of Cannabis, which opposes making the drug more accessible, said educating health care providers is an urgent need.

Studies are mixed on whether the legalization of cannabis has led to more cases of CIP.

A 2021 study found that experiences of psychosis among users of cannabis jumped 2.5-fold between 2001 and 2013. But a study published earlier this year of more than 63 million medical claims from 2003 to 2017 found no statistically significant difference in rates of psychosis-related diagnoses or prescribed antipsychotics in states that have legalized medical or recreational cannabis compared with states where cannabis is still illegal. However, a secondary analysis did find that rates of psychosis-related diagnoses increased significantly among men, people aged 55-64 years, and Asian adults in states where recreational marijuana has been legalized.

Complicating matters, researchers say, is the question of causality. Cannabis may exacerbate or trigger psychosis, but people with an underlying psychological illness may also be more likely to use cannabis.

Dr. Finn said clinicians in Colorado and other states with legalization laws are seeing more patients with CIP. As more states consider legalizing recreational marijuana, he expects the data will reflect what doctors experience on the ground.

Cannabis-induced “psychosis is complicated and likely underdiagnosed,” Dr. Finn said.
 

Talking to teens

Clinicians outside the emergency department can play a role in aiding young people at risk for CIP. Primary care physicians, for instance, might explain to young patients that the brain only becomes fully developed at roughly age 26, after which the long-term health consequences of using cannabis become less likely. According to the CDC, using cannabis before age 18 can change how the brain builds connections and can impair attention, memory, and learning.

Dr. Singh takes a harm reduction approach when he engages with a patient who is forthcoming about substance use.

“If I see an 18-year-old, I tell them to abstain,” he said. “I tell them if they are ever going to use it, to use it after 26.”

Clinicians also should understand dosages to provide the optimal guidance to their patients who use cannabis.

“People often have no idea how much cannabis they are taking,” especially when using vape cartridges, Dr. Singh said. “If you don’t know, you can’t tell patients about the harms – and if you tell them the wrong information, they will write you off.”

Dr. Singh said he advises his patients to avoid using cannabis vapes or dabbing pens. Both can contain much higher levels of THC than dried flower or edible forms of the drug. He also says patients should stick with low concentrations and use products that contain CBD, which some studies have shown has a protective effect against CIP, although other studies have found that CBD can induce anxiety.

He also tells patients to buy from legal dispensaries and to avoid buying street products that may have methamphetamine or fentanyl mixed in.

Despite the risks, Dr. Singh said legalization can reduce the stigma associated with cannabis use and may prompt patients to be honest with their clinicians. Dr. Singh recalled a 28-year-old patient who was using cannabis to alleviate her arthritic pain. She also was taking a transplant medication, which carried potential side effects of delirium, generalized anxiety disorder, and hallucinosis. After doubling her THC dose, the patient experienced severe anxiety and paranoia.

Dr. Singh’s patient paid him a visit and asked for help. Dr. Singh told her to reduce the dose and to keep track of how she felt. If she continued to feel anxious and paranoid, he recommended that she switch to CBD instead.

“I think education and knowledge is liberating,” Dr. Singh said. “Legalization and frank conversations help people understand how to use a product – and right now, I think that’s lacking.”
 

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

The youngest patient with cannabis-induced psychosis (CIP) whom Karen Randall, DO, has treated was a 7-year-old boy. She remembers the screaming, the yelling, the uncontrollable rage.

Dr. Randall is an emergency medicine physician at Southern Colorado Emergency Medicine Associates, a group practice in Pueblo, Colo. She treats youth for cannabis-related medical problems in the emergency department an average of two or three times per shift, she said.

Colorado legalized the recreational use of cannabis for adults older than 21 in 2012. Since then, Dr. Randall said, she has noticed an uptick in cannabis use among youth, as well as an increase in CIP, a syndrome that can be indistinguishable from other psychiatric disorders such as schizophrenia in the emergency department. But the two conditions require different approaches to care.

“You can’t differentiate unless you know the patient,” Dr. Randall said in an interview.

In 2019, 37% of high school students in the United States reported ever using marijuana, and 22% reported use in the past 30 days. Rates remained steady in 2020 following increases in 2018 and 2019, according to the Centers for Disease Control and Prevention.

The CDC also found that 8% of 8th graders, 19% of 10th graders, and 22% of 12th graders reported vaping marijuana in the past year.

Clinicians in states where recreational marijuana has been legalized say they have noticed an increase in young patients with psychiatric problems – especially after consumption of cannabis products in high doses. But CIP can be tricky to distinguish from psychoses of other causes, such as schizophrenia or bipolar disorder, which often begin to present in adolescence.
 

How to differentiate

CIP is characterized by delusions and hallucinations and sometimes anxiety, disorganized thoughts, paranoia, dissociation, and changes in mood and behavior. Symptoms typically last for a couple hours and do not require specific treatment, although they can persist, depending on a patient’s tolerance and the dose of tetrahydrocannabinol (THC) they have consumed. Research suggests that the higher the dose and concentration of the drug consumed, the more likely a person will develop symptoms of psychosis.

Diagnosis requires gathering information on previous bipolar disorder or schizophrenia diagnosis, prescriptions for mental illness indications, whether there is a family history of mental illness, and whether the patient recently started using marijuana. In some cases, marijuana use might exacerbate or unmask mental illness.

If symptoms of CIP resolve, and usually they do, clinicians can recommend that patients abstain from cannabis going forward, and psychosis would not need further treatment, according to Divya Singh, MD, a psychiatrist at Banner Behavioral Health Hospital in Scottsdale, Ariz., where recreational cannabis became legal in 2020.

“When I have limited information, especially in the first couple of days, I err on the side of safety,” Dr. Singh said.

Psychosis is the combination of symptoms, including delusions, hallucinations, and disorganized behavior, but it is not a disorder in itself. Rather, it is the primary symptom of schizophrenia and other chronic psychiatric illnesses.

Schizophrenia can be diagnosed only after a patient presents with signs of disturbance for at least 6 months, according to guidelines in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Dr. Singh said a diagnosis of schizophrenia cannot be made in a one-off interaction.

If the patient is younger than 24 years and has no family history of mental illness, a full recovery is likely if the patient abstains from marijuana, he said. But if the patient does have a family history, “the chances of them having a full-blown mental illness is very high,” Dr. Singh said.

If a patient reports that he or she has recently started using marijuana and was previously diagnosed with bipolar disorder or schizophrenia, Dr. Singh said he generally prescribes medications such as lithium or quetiapine and refers the patient to services such as cognitive-behavioral therapy. He also advises against continuing use of cannabis.

“Cannabis can result in people requiring a higher dose of medication than they took before,” Dr. Singh said. “If they were stable on 600 mg of lithium before, they might need more and may never be able to lower the dose in some cases, even after the acute episode.”
 

The science of cannabis

As of March 2023, 21 states and the District of Columbia permit the recreational use of marijuana, according to the Congressional Research Service. Thirty-seven states and the District of Columbia allow medicinal use of marijuana, and 10 states allow “limited access to medical cannabis,” defined as low-THC cannabis or cannabidiol (CBD) oil.

THC is the main psychoactive compound in cannabis. It creates a high feeling after binding with receptors in the brain that control pain and mood. CBD is another chemical found in cannabis, but it does not create a high.

Some research suggests cannabinoids may help reduce anxiety, reduce inflammation, relieve pain, control nausea, reduce cancer cells, slow the growth of tumor cells, relax tight muscles, and stimulate appetite.

The drug also carries risks, according to Mayo Clinic. Use of marijuana is linked to mental health problems in teens and adults, such as depression, social anxiety, and temporary psychosis, and long-lasting mental disorders, such as schizophrenia.

In the worst cases, CIP can persist for weeks or months – long after a negative drug test – and sometimes does not subside at all, according to Ken Finn, MD, president and founder of Springs Rehabilitation, PC, a pain medicine practice in Colorado Springs, Colo.

Dr. Finn, the co–vice president of the International Academy on the Science and Impact of Cannabis, which opposes making the drug more accessible, said educating health care providers is an urgent need.

Studies are mixed on whether the legalization of cannabis has led to more cases of CIP.

A 2021 study found that experiences of psychosis among users of cannabis jumped 2.5-fold between 2001 and 2013. But a study published earlier this year of more than 63 million medical claims from 2003 to 2017 found no statistically significant difference in rates of psychosis-related diagnoses or prescribed antipsychotics in states that have legalized medical or recreational cannabis compared with states where cannabis is still illegal. However, a secondary analysis did find that rates of psychosis-related diagnoses increased significantly among men, people aged 55-64 years, and Asian adults in states where recreational marijuana has been legalized.

Complicating matters, researchers say, is the question of causality. Cannabis may exacerbate or trigger psychosis, but people with an underlying psychological illness may also be more likely to use cannabis.

Dr. Finn said clinicians in Colorado and other states with legalization laws are seeing more patients with CIP. As more states consider legalizing recreational marijuana, he expects the data will reflect what doctors experience on the ground.

Cannabis-induced “psychosis is complicated and likely underdiagnosed,” Dr. Finn said.
 

Talking to teens

Clinicians outside the emergency department can play a role in aiding young people at risk for CIP. Primary care physicians, for instance, might explain to young patients that the brain only becomes fully developed at roughly age 26, after which the long-term health consequences of using cannabis become less likely. According to the CDC, using cannabis before age 18 can change how the brain builds connections and can impair attention, memory, and learning.

Dr. Singh takes a harm reduction approach when he engages with a patient who is forthcoming about substance use.

“If I see an 18-year-old, I tell them to abstain,” he said. “I tell them if they are ever going to use it, to use it after 26.”

Clinicians also should understand dosages to provide the optimal guidance to their patients who use cannabis.

“People often have no idea how much cannabis they are taking,” especially when using vape cartridges, Dr. Singh said. “If you don’t know, you can’t tell patients about the harms – and if you tell them the wrong information, they will write you off.”

Dr. Singh said he advises his patients to avoid using cannabis vapes or dabbing pens. Both can contain much higher levels of THC than dried flower or edible forms of the drug. He also says patients should stick with low concentrations and use products that contain CBD, which some studies have shown has a protective effect against CIP, although other studies have found that CBD can induce anxiety.

He also tells patients to buy from legal dispensaries and to avoid buying street products that may have methamphetamine or fentanyl mixed in.

Despite the risks, Dr. Singh said legalization can reduce the stigma associated with cannabis use and may prompt patients to be honest with their clinicians. Dr. Singh recalled a 28-year-old patient who was using cannabis to alleviate her arthritic pain. She also was taking a transplant medication, which carried potential side effects of delirium, generalized anxiety disorder, and hallucinosis. After doubling her THC dose, the patient experienced severe anxiety and paranoia.

Dr. Singh’s patient paid him a visit and asked for help. Dr. Singh told her to reduce the dose and to keep track of how she felt. If she continued to feel anxious and paranoid, he recommended that she switch to CBD instead.

“I think education and knowledge is liberating,” Dr. Singh said. “Legalization and frank conversations help people understand how to use a product – and right now, I think that’s lacking.”
 

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

A magnesium-rich diet has been linked to better brain health, an outcome that may help lower dementia risk, new research suggests.

Investigators studied more than 6,000 cognitively healthy individuals, aged 40-73, and found that those who consumed more than 550 mg of magnesium daily had a brain age approximately 1 year younger by age 55 years, compared with a person who consumed a normal magnesium intake (~360 mg per day).

“This research highlights the potential benefits of a diet high in magnesium and the role it plays in promoting good brain health,” lead author Khawlah Alateeq, a PhD candidate in neuroscience at Australian National University’s National Centre for Epidemiology and Population Health, said in an interview.

Clinicians “can use [the findings] to counsel patients on the benefits of increasing magnesium intake through a healthy diet and monitoring magnesium levels to prevent deficiencies,” she stated.

The study was published online  in the European Journal of Nutrition.
 

Promising target

The researchers were motivated to conduct the study because of “the growing concern over the increasing prevalence of dementia,” Ms. Alateeq said.

“Since there is no cure for dementia, and the development of pharmacological treatment for dementia has been unsuccessful over the last 30 years, prevention has been suggested as an effective approach to address the issue,” she added.

Nutrition, Ms. Alateeq said, is a “modifiable risk factor that can influence brain health and is highly amenable to scalable and cost-effective interventions.” It represents “a promising target” for risk reduction at a population level.

Previous research shows individuals with lower magnesium levels are at higher risk for AD, while those with higher dietary magnesium intake may be at lower risk of progressing from normal aging to cognitive impairment.

Most previous studies, however, included participants older than age 60 years, and it’s “unclear when the neuroprotective effects of dietary magnesium become detectable,” the researchers note.

Moreover, dietary patterns change and fluctuate, potentially leading to changes in magnesium intake over time. These changes may have as much impact as absolute magnesium at any point in time.

In light of the “current lack of understanding of when and to what extent dietary magnesium exerts its protective effects on the brain,” the researchers examined the association between magnesium trajectories over time, brain matter, and white matter lesions.

They also examined the association between magnesium and several different blood pressure measures (mean arterial pressure, systolic blood pressure, diastolic blood pressure, and pulse pressure).

Since cardiovascular health, neurodegeneration, and brain shrinkage patterns differ between men and women, the researchers stratified their analyses by sex.
 

Brain volume differences

The researchers analyzed the dietary magnesium intake of 6,001 individuals (mean age, 55.3 years) selected from the UK Biobank – a prospective cohort study of participants aged 37-73 at baseline, who were assessed between 2005 and 2023.

For the current study, only participants with baseline DBP and SBP measurements and structural MRI scans were included. Participants were also required to be free of neurologic disorders and to have an available record of dietary magnesium intake.

Covariates included age, sex, education, health conditions, smoking status, body mass index, amount of physical activity, smoking status, and alcohol intake.

Over a 16-month period, participants completed an online questionnaire five times. Their responses were used to calculate daily magnesium intake. Foods of particular interest included leafy green vegetables, legumes, nuts, seeds, and whole grains, all of which are magnesium rich.

They used latent class analysis (LCA) to “identify mutually exclusive subgroup (classes) of magnesium intake trajectory separately for men and women.”

Men had a slightly higher prevalence of BP medication and diabetes, compared with women, and postmenopausal women had a higher prevalence of BP medication and diabetes, compared with premenopausal women.

Compared with lower baseline magnesium intake, higher baseline dietary intake of magnesium was associated with larger brain volumes in several regions in both men and women.

The latent class analysis identified three classes of magnesium intake:

Association, not causation

Yuko Hara, PhD, director of Aging and Prevention, Alzheimer’s Drug Discovery Foundation, noted that the study is observational and therefore shows an association, not causation.

“People eating a high-magnesium diet may also be eating a brain-healthy diet and getting high levels of nutrients/minerals other than magnesium alone,” suggested Dr. Hara, who was not involved with the study.

She noted that many foods are good sources of magnesium, including spinach, almonds, cashews, legumes, yogurt, brown rice, and avocados.

“Eating a brain-healthy diet (for example, the Mediterranean diet) is one of the Seven Steps to Protect Your Cognitive Vitality that ADDF’s Cognitive Vitality promotes,” she said.

Open Access funding was enabled and organized by the Council of Australian University Librarians and its Member Institutions. Ms. Alateeq, her co-authors, and Dr. Hara declare no relevant financial relationships.

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

A magnesium-rich diet has been linked to better brain health, an outcome that may help lower dementia risk, new research suggests.

Investigators studied more than 6,000 cognitively healthy individuals, aged 40-73, and found that those who consumed more than 550 mg of magnesium daily had a brain age approximately 1 year younger by age 55 years, compared with a person who consumed a normal magnesium intake (~360 mg per day).

“This research highlights the potential benefits of a diet high in magnesium and the role it plays in promoting good brain health,” lead author Khawlah Alateeq, a PhD candidate in neuroscience at Australian National University’s National Centre for Epidemiology and Population Health, said in an interview.

Clinicians “can use [the findings] to counsel patients on the benefits of increasing magnesium intake through a healthy diet and monitoring magnesium levels to prevent deficiencies,” she stated.

The study was published online  in the European Journal of Nutrition.
 

Promising target

The researchers were motivated to conduct the study because of “the growing concern over the increasing prevalence of dementia,” Ms. Alateeq said.

“Since there is no cure for dementia, and the development of pharmacological treatment for dementia has been unsuccessful over the last 30 years, prevention has been suggested as an effective approach to address the issue,” she added.

Nutrition, Ms. Alateeq said, is a “modifiable risk factor that can influence brain health and is highly amenable to scalable and cost-effective interventions.” It represents “a promising target” for risk reduction at a population level.

Previous research shows individuals with lower magnesium levels are at higher risk for AD, while those with higher dietary magnesium intake may be at lower risk of progressing from normal aging to cognitive impairment.

Most previous studies, however, included participants older than age 60 years, and it’s “unclear when the neuroprotective effects of dietary magnesium become detectable,” the researchers note.

Moreover, dietary patterns change and fluctuate, potentially leading to changes in magnesium intake over time. These changes may have as much impact as absolute magnesium at any point in time.

In light of the “current lack of understanding of when and to what extent dietary magnesium exerts its protective effects on the brain,” the researchers examined the association between magnesium trajectories over time, brain matter, and white matter lesions.

They also examined the association between magnesium and several different blood pressure measures (mean arterial pressure, systolic blood pressure, diastolic blood pressure, and pulse pressure).

Since cardiovascular health, neurodegeneration, and brain shrinkage patterns differ between men and women, the researchers stratified their analyses by sex.
 

Brain volume differences

The researchers analyzed the dietary magnesium intake of 6,001 individuals (mean age, 55.3 years) selected from the UK Biobank – a prospective cohort study of participants aged 37-73 at baseline, who were assessed between 2005 and 2023.

For the current study, only participants with baseline DBP and SBP measurements and structural MRI scans were included. Participants were also required to be free of neurologic disorders and to have an available record of dietary magnesium intake.

Covariates included age, sex, education, health conditions, smoking status, body mass index, amount of physical activity, smoking status, and alcohol intake.

Over a 16-month period, participants completed an online questionnaire five times. Their responses were used to calculate daily magnesium intake. Foods of particular interest included leafy green vegetables, legumes, nuts, seeds, and whole grains, all of which are magnesium rich.

They used latent class analysis (LCA) to “identify mutually exclusive subgroup (classes) of magnesium intake trajectory separately for men and women.”

Men had a slightly higher prevalence of BP medication and diabetes, compared with women, and postmenopausal women had a higher prevalence of BP medication and diabetes, compared with premenopausal women.

Compared with lower baseline magnesium intake, higher baseline dietary intake of magnesium was associated with larger brain volumes in several regions in both men and women.

The latent class analysis identified three classes of magnesium intake:

Association, not causation

Yuko Hara, PhD, director of Aging and Prevention, Alzheimer’s Drug Discovery Foundation, noted that the study is observational and therefore shows an association, not causation.

“People eating a high-magnesium diet may also be eating a brain-healthy diet and getting high levels of nutrients/minerals other than magnesium alone,” suggested Dr. Hara, who was not involved with the study.

She noted that many foods are good sources of magnesium, including spinach, almonds, cashews, legumes, yogurt, brown rice, and avocados.

“Eating a brain-healthy diet (for example, the Mediterranean diet) is one of the Seven Steps to Protect Your Cognitive Vitality that ADDF’s Cognitive Vitality promotes,” she said.

Open Access funding was enabled and organized by the Council of Australian University Librarians and its Member Institutions. Ms. Alateeq, her co-authors, and Dr. Hara declare no relevant financial relationships.

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

A magnesium-rich diet has been linked to better brain health, an outcome that may help lower dementia risk, new research suggests.

Investigators studied more than 6,000 cognitively healthy individuals, aged 40-73, and found that those who consumed more than 550 mg of magnesium daily had a brain age approximately 1 year younger by age 55 years, compared with a person who consumed a normal magnesium intake (~360 mg per day).

“This research highlights the potential benefits of a diet high in magnesium and the role it plays in promoting good brain health,” lead author Khawlah Alateeq, a PhD candidate in neuroscience at Australian National University’s National Centre for Epidemiology and Population Health, said in an interview.

Clinicians “can use [the findings] to counsel patients on the benefits of increasing magnesium intake through a healthy diet and monitoring magnesium levels to prevent deficiencies,” she stated.

The study was published online  in the European Journal of Nutrition.
 

Promising target

The researchers were motivated to conduct the study because of “the growing concern over the increasing prevalence of dementia,” Ms. Alateeq said.

“Since there is no cure for dementia, and the development of pharmacological treatment for dementia has been unsuccessful over the last 30 years, prevention has been suggested as an effective approach to address the issue,” she added.

Nutrition, Ms. Alateeq said, is a “modifiable risk factor that can influence brain health and is highly amenable to scalable and cost-effective interventions.” It represents “a promising target” for risk reduction at a population level.

Previous research shows individuals with lower magnesium levels are at higher risk for AD, while those with higher dietary magnesium intake may be at lower risk of progressing from normal aging to cognitive impairment.

Most previous studies, however, included participants older than age 60 years, and it’s “unclear when the neuroprotective effects of dietary magnesium become detectable,” the researchers note.

Moreover, dietary patterns change and fluctuate, potentially leading to changes in magnesium intake over time. These changes may have as much impact as absolute magnesium at any point in time.

In light of the “current lack of understanding of when and to what extent dietary magnesium exerts its protective effects on the brain,” the researchers examined the association between magnesium trajectories over time, brain matter, and white matter lesions.

They also examined the association between magnesium and several different blood pressure measures (mean arterial pressure, systolic blood pressure, diastolic blood pressure, and pulse pressure).

Since cardiovascular health, neurodegeneration, and brain shrinkage patterns differ between men and women, the researchers stratified their analyses by sex.
 

Brain volume differences

The researchers analyzed the dietary magnesium intake of 6,001 individuals (mean age, 55.3 years) selected from the UK Biobank – a prospective cohort study of participants aged 37-73 at baseline, who were assessed between 2005 and 2023.

For the current study, only participants with baseline DBP and SBP measurements and structural MRI scans were included. Participants were also required to be free of neurologic disorders and to have an available record of dietary magnesium intake.

Covariates included age, sex, education, health conditions, smoking status, body mass index, amount of physical activity, smoking status, and alcohol intake.

Over a 16-month period, participants completed an online questionnaire five times. Their responses were used to calculate daily magnesium intake. Foods of particular interest included leafy green vegetables, legumes, nuts, seeds, and whole grains, all of which are magnesium rich.

They used latent class analysis (LCA) to “identify mutually exclusive subgroup (classes) of magnesium intake trajectory separately for men and women.”

Men had a slightly higher prevalence of BP medication and diabetes, compared with women, and postmenopausal women had a higher prevalence of BP medication and diabetes, compared with premenopausal women.

Compared with lower baseline magnesium intake, higher baseline dietary intake of magnesium was associated with larger brain volumes in several regions in both men and women.

The latent class analysis identified three classes of magnesium intake:

Association, not causation

Yuko Hara, PhD, director of Aging and Prevention, Alzheimer’s Drug Discovery Foundation, noted that the study is observational and therefore shows an association, not causation.

“People eating a high-magnesium diet may also be eating a brain-healthy diet and getting high levels of nutrients/minerals other than magnesium alone,” suggested Dr. Hara, who was not involved with the study.

She noted that many foods are good sources of magnesium, including spinach, almonds, cashews, legumes, yogurt, brown rice, and avocados.

“Eating a brain-healthy diet (for example, the Mediterranean diet) is one of the Seven Steps to Protect Your Cognitive Vitality that ADDF’s Cognitive Vitality promotes,” she said.

Open Access funding was enabled and organized by the Council of Australian University Librarians and its Member Institutions. Ms. Alateeq, her co-authors, and Dr. Hara declare no relevant financial relationships.

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

Investigators found that simultaneous infection with adeno-associated virus type 2 (AAV2) and certain other viruses is associated with the outbreak of mysterious pediatric hepatitis cases worldwide.

Coinfection with AAV2 and a human adenovirus (HAdV), in particular, appears to leave some children more vulnerable to this acute hepatitis of unknown origin, researchers reported in three studies published online in Nature. Coinfection with Epstein-Barr virus (EBV), herpes, and enterovirus also were found. Adeno-associated viruses are not considered pathogenic on their own and require a “helper” virus for productive infection.

“I am quite confident that we have identified the key viruses involved because we used a comprehensive metagenomic sequencing approach to look for potential infections from any virus or non-viral pathogen,” Charles Chiu, MD, PhD, senior author and professor of laboratory medicine and medicine/infectious diseases at the University of California, San Francisco, said in an interview.

Dr. Chiu and colleagues propose that lockdowns and social isolation during the COVID-19 pandemic left more children susceptible. A major aspect of immunity in childhood is the adaptive immune response – both cell-mediated and humoral – shaped in part by exposure to viruses and other pathogens early in life, Dr. Chiu said.

“Due to COVID-19, a large population of children did not experience this, so it is possible once restrictions were lifted, they were suddenly exposed over a short period of time to multiple viruses that, in a poorly trained immune system, would have increased their risk of developing severe disease,” he said.

This theory has been popular, especially because cases of unexplained acute hepatitis peaked during the height of the COVID-19 pandemic when isolation was common, William F. Balistreri, MD, who was not affiliated with the study, told this news organization. Dr. Balistreri is professor of pediatrics and director emeritus of the Pediatric Liver Care Center at Cincinnati Children’s Hospital Medical Center.
 

Identifying the culprits

Determining what factors might be involved was the main aim of the etiology study by Dr. Chiu and colleagues published online  in Nature.

The journal simultaneously published a genomic study confirming the presence of AAV2 and other suspected viruses and a genomic and laboratory study further corroborating the results.

More than 1,000 children worldwide had been diagnosed with unexplained acute pediatric hepatitis as of August 2022. In the United States, there have been 358 cases, including 22 in which the child required a liver transplant and 13 in which the child died.

This new form of hepatitis, first detected in October 2021, does not fit into existing classifications of types A through E, so some researchers refer to the condition as acute non–A-E hepatitis of unknown etiology.

The investigators started with an important clue based on previous research: the role adenovirus might play. Dr. Chiu and colleagues assessed 27 blood, stool, and other samples from 16 affected children who each previously tested positive for adenoviruses. The researchers included cases of the condition identified up until May 22, 2022. The median age was 3 years, and approximately half were boys.

They compared viruses present in these children with those in 113 controls without the mysterious hepatitis. The control group consisted of 15 children who were hospitalized with a nonhepatitis inflammatory condition, 27 with a noninflammatory condition, 30 with acute hepatitis of known origin, 12 with acute gastroenteritis and an HAdV-positive stool sample, and 11 with acute gastroenteritis and an HAdV-negative stool sample, as well as 18 blood donors. The median age was 7 years.

The researchers assessed samples using multiple technologies, including metagenomic sequencing, tiling multiplex polymerase chain reaction (PCR) amplicon sequencing, metagenomic sequencing with probe capture viral enrichment, and virus-specific PCR. Many of these advanced techniques were not even available 5-10 years ago, Dr. Chiu said.
 

Key findings

Blood samples were available for 14 of the 16 children with acute hepatitis of unknown origin. Among this study group, AAV2 was found in 13 (93%). No other adeno-associated viruses were found. HAdV was detected in all 14 children: HAdV-41 in 11 children and HAdV-40, HAdV-2, and an untypeable strain in one child each. This finding was not intuitive because HAdVs are not commonly associated with hepatitis, according to the study.

AAV2 was much less common in the control group. For example, it was found in none of the children with hepatitis of known origin and in only four children (3.5%) with acute gastroenteritis and HAdV-positive stool. Of note, neither AAV2 nor HAdV-41 was detected among the 30 pediatric controls with acute hepatitis of defined etiology nor 42 of the hospitalized children without hepatitis, the researchers wrote.

In the search for other viruses in the study group, metagenomic sequencing detected EBV, also known as human herpesvirus (HHV)–4, in two children, cytomegalovirus (CMV) in one child, and HAdV type C in one child.

Analysis of whole blood revealed enterovirus A71 in one patient. HAdV type C also was detected in one child on the basis of a nasopharyngeal swab, and picobirnavirus was found in a stool sample from another patient.

Researchers conducted virus-specific PCR tests on both patient groups to identify additional viruses that may be associated with the unexplained acute hepatitis. EBV/HHV-4 was detected in 11 children (79%) in the study group vs. in 1 child (0.88%) in the control group. HHV-6 was detected in seven children (50%) in the study group, compared with one case in the control group. CMV was not detected in any of the children in the study group versus vs. two children (1.8%) in the control group.

“Although we found significant differences in the relative proportions of EBV and HHV-6 in cases compared to controls, we do not believe that these viruses are the primary cause of acute severe hepatitis,” the researchers wrote. The viral load of the two herpes viruses were very low, so the positive results could represent integrated proviral DNA rather than bona fide low-level herpesvirus. In addition, herpesvirus can be reactivated by an inflammatory condition.

“Nevertheless, it is striking that among the 16 cases (in the study group), dual, triple, or quadruple infections with AAV2, adenovirus, and one or both herpesviruses were detected in whole blood from at least 12 cases (75%),” the researchers wrote.
 

Management of suspected hepatitis

The study’s key messages for parents and health care providers “are awareness and reassurance,” Dr. Balistreri said in an interview.

Vigilance also is warranted if a child develops prodromal symptoms including respiratory and/or gastrointestinal signs such as nausea, vomiting, diarrhea, and abdomen pain, he said. If jaundice or scleral icterus is noted, then hepatitis should be suspected.

Some patients need hospitalization and quickly recover. In very rare instances, the inflammation may progress to liver failure and transplantation, Dr. Balistreri said.

“Reassurance is based on the good news that most children with acute hepatitis get better. If a case arises, it is good practice to keep the child well hydrated, offer a normal diet, and avoid medications that may be cleared by the liver,” Dr. Balistreri added.

“Of course, COVID-19 vaccination is strongly suggested,” he said.

Some existing treatments could help against unexplained acute hepatitis, Dr. Chiu said. “The findings suggest that antiviral therapy might be effective in these cases.”

Cidofovir can be effective against adenovirus, according to a report in The Lancet . Similarly, ganciclovir or valganciclovir may have activity against EBV/HHV-4 or HHV-6, Dr. Chiu said. “However, antiviral therapy is not available for AAV2.”

The three studies published in Nature “offer compelling evidence, from disparate centers, of a linkage of outbreak cases to infection by AAV2,” Dr. Balistreri said. The studies also suggest that liver injury was related to abnormal immune responses. This is an important clinical distinction, indicating a potential therapeutic approach to future cases – immunosuppression rather than anti-adenoviral agents, he said.

“We await further studies of this important concept,” Dr. Balistreri said.

Many unanswered questions remain about the condition’s etiology, he added. Is there a synergy or shared susceptibility related to SARS-CoV-2? Is the COVID-19 virus helping to trigger these infections, or does it increase the risk once infected? Also, are other epigenetic factors or viruses involved?
 

Moving forward

The next steps in the research could go beyond identifying presence of these different viruses and determining which one(s) are contributing the most to the acute pediatric hepatitis, Dr. Chiu said.

The researchers also would like to test early results from the United Kingdom that identified a potential association of acute severe hepatitis with the presence of human leukocyte antigen genotype DRB1*04:01, he added.

They also might investigate other unintended potential clinical consequences of the COVID-19 pandemic, including long COVID and resurgence of infections from other viruses, such as respiratory syncytial virus, influenza, and enterovirus D68.

The study was supported by the Centers for Disease Control and Prevention, the National Institutes of Health, the Department of Homeland Security, and other grants. Dr. Chiu is a founder of Delve Bio and on the scientific advisory board for Delve Bio, Mammoth Biosciences, BiomeSense, and Poppy Health. Dr. Balistreri had no relevant disclosures.
 

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

Investigators found that simultaneous infection with adeno-associated virus type 2 (AAV2) and certain other viruses is associated with the outbreak of mysterious pediatric hepatitis cases worldwide.

Coinfection with AAV2 and a human adenovirus (HAdV), in particular, appears to leave some children more vulnerable to this acute hepatitis of unknown origin, researchers reported in three studies published online in Nature. Coinfection with Epstein-Barr virus (EBV), herpes, and enterovirus also were found. Adeno-associated viruses are not considered pathogenic on their own and require a “helper” virus for productive infection.

“I am quite confident that we have identified the key viruses involved because we used a comprehensive metagenomic sequencing approach to look for potential infections from any virus or non-viral pathogen,” Charles Chiu, MD, PhD, senior author and professor of laboratory medicine and medicine/infectious diseases at the University of California, San Francisco, said in an interview.

Dr. Chiu and colleagues propose that lockdowns and social isolation during the COVID-19 pandemic left more children susceptible. A major aspect of immunity in childhood is the adaptive immune response – both cell-mediated and humoral – shaped in part by exposure to viruses and other pathogens early in life, Dr. Chiu said.

“Due to COVID-19, a large population of children did not experience this, so it is possible once restrictions were lifted, they were suddenly exposed over a short period of time to multiple viruses that, in a poorly trained immune system, would have increased their risk of developing severe disease,” he said.

This theory has been popular, especially because cases of unexplained acute hepatitis peaked during the height of the COVID-19 pandemic when isolation was common, William F. Balistreri, MD, who was not affiliated with the study, told this news organization. Dr. Balistreri is professor of pediatrics and director emeritus of the Pediatric Liver Care Center at Cincinnati Children’s Hospital Medical Center.
 

Identifying the culprits

Determining what factors might be involved was the main aim of the etiology study by Dr. Chiu and colleagues published online  in Nature.

The journal simultaneously published a genomic study confirming the presence of AAV2 and other suspected viruses and a genomic and laboratory study further corroborating the results.

More than 1,000 children worldwide had been diagnosed with unexplained acute pediatric hepatitis as of August 2022. In the United States, there have been 358 cases, including 22 in which the child required a liver transplant and 13 in which the child died.

This new form of hepatitis, first detected in October 2021, does not fit into existing classifications of types A through E, so some researchers refer to the condition as acute non–A-E hepatitis of unknown etiology.

The investigators started with an important clue based on previous research: the role adenovirus might play. Dr. Chiu and colleagues assessed 27 blood, stool, and other samples from 16 affected children who each previously tested positive for adenoviruses. The researchers included cases of the condition identified up until May 22, 2022. The median age was 3 years, and approximately half were boys.

They compared viruses present in these children with those in 113 controls without the mysterious hepatitis. The control group consisted of 15 children who were hospitalized with a nonhepatitis inflammatory condition, 27 with a noninflammatory condition, 30 with acute hepatitis of known origin, 12 with acute gastroenteritis and an HAdV-positive stool sample, and 11 with acute gastroenteritis and an HAdV-negative stool sample, as well as 18 blood donors. The median age was 7 years.

The researchers assessed samples using multiple technologies, including metagenomic sequencing, tiling multiplex polymerase chain reaction (PCR) amplicon sequencing, metagenomic sequencing with probe capture viral enrichment, and virus-specific PCR. Many of these advanced techniques were not even available 5-10 years ago, Dr. Chiu said.
 

Key findings

Blood samples were available for 14 of the 16 children with acute hepatitis of unknown origin. Among this study group, AAV2 was found in 13 (93%). No other adeno-associated viruses were found. HAdV was detected in all 14 children: HAdV-41 in 11 children and HAdV-40, HAdV-2, and an untypeable strain in one child each. This finding was not intuitive because HAdVs are not commonly associated with hepatitis, according to the study.

AAV2 was much less common in the control group. For example, it was found in none of the children with hepatitis of known origin and in only four children (3.5%) with acute gastroenteritis and HAdV-positive stool. Of note, neither AAV2 nor HAdV-41 was detected among the 30 pediatric controls with acute hepatitis of defined etiology nor 42 of the hospitalized children without hepatitis, the researchers wrote.

In the search for other viruses in the study group, metagenomic sequencing detected EBV, also known as human herpesvirus (HHV)–4, in two children, cytomegalovirus (CMV) in one child, and HAdV type C in one child.

Analysis of whole blood revealed enterovirus A71 in one patient. HAdV type C also was detected in one child on the basis of a nasopharyngeal swab, and picobirnavirus was found in a stool sample from another patient.

Researchers conducted virus-specific PCR tests on both patient groups to identify additional viruses that may be associated with the unexplained acute hepatitis. EBV/HHV-4 was detected in 11 children (79%) in the study group vs. in 1 child (0.88%) in the control group. HHV-6 was detected in seven children (50%) in the study group, compared with one case in the control group. CMV was not detected in any of the children in the study group versus vs. two children (1.8%) in the control group.

“Although we found significant differences in the relative proportions of EBV and HHV-6 in cases compared to controls, we do not believe that these viruses are the primary cause of acute severe hepatitis,” the researchers wrote. The viral load of the two herpes viruses were very low, so the positive results could represent integrated proviral DNA rather than bona fide low-level herpesvirus. In addition, herpesvirus can be reactivated by an inflammatory condition.

“Nevertheless, it is striking that among the 16 cases (in the study group), dual, triple, or quadruple infections with AAV2, adenovirus, and one or both herpesviruses were detected in whole blood from at least 12 cases (75%),” the researchers wrote.
 

Management of suspected hepatitis

The study’s key messages for parents and health care providers “are awareness and reassurance,” Dr. Balistreri said in an interview.

Vigilance also is warranted if a child develops prodromal symptoms including respiratory and/or gastrointestinal signs such as nausea, vomiting, diarrhea, and abdomen pain, he said. If jaundice or scleral icterus is noted, then hepatitis should be suspected.

Some patients need hospitalization and quickly recover. In very rare instances, the inflammation may progress to liver failure and transplantation, Dr. Balistreri said.

“Reassurance is based on the good news that most children with acute hepatitis get better. If a case arises, it is good practice to keep the child well hydrated, offer a normal diet, and avoid medications that may be cleared by the liver,” Dr. Balistreri added.

“Of course, COVID-19 vaccination is strongly suggested,” he said.

Some existing treatments could help against unexplained acute hepatitis, Dr. Chiu said. “The findings suggest that antiviral therapy might be effective in these cases.”

Cidofovir can be effective against adenovirus, according to a report in The Lancet . Similarly, ganciclovir or valganciclovir may have activity against EBV/HHV-4 or HHV-6, Dr. Chiu said. “However, antiviral therapy is not available for AAV2.”

The three studies published in Nature “offer compelling evidence, from disparate centers, of a linkage of outbreak cases to infection by AAV2,” Dr. Balistreri said. The studies also suggest that liver injury was related to abnormal immune responses. This is an important clinical distinction, indicating a potential therapeutic approach to future cases – immunosuppression rather than anti-adenoviral agents, he said.

“We await further studies of this important concept,” Dr. Balistreri said.

Many unanswered questions remain about the condition’s etiology, he added. Is there a synergy or shared susceptibility related to SARS-CoV-2? Is the COVID-19 virus helping to trigger these infections, or does it increase the risk once infected? Also, are other epigenetic factors or viruses involved?
 

Moving forward

The next steps in the research could go beyond identifying presence of these different viruses and determining which one(s) are contributing the most to the acute pediatric hepatitis, Dr. Chiu said.

The researchers also would like to test early results from the United Kingdom that identified a potential association of acute severe hepatitis with the presence of human leukocyte antigen genotype DRB1*04:01, he added.

They also might investigate other unintended potential clinical consequences of the COVID-19 pandemic, including long COVID and resurgence of infections from other viruses, such as respiratory syncytial virus, influenza, and enterovirus D68.

The study was supported by the Centers for Disease Control and Prevention, the National Institutes of Health, the Department of Homeland Security, and other grants. Dr. Chiu is a founder of Delve Bio and on the scientific advisory board for Delve Bio, Mammoth Biosciences, BiomeSense, and Poppy Health. Dr. Balistreri had no relevant disclosures.
 

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

Investigators found that simultaneous infection with adeno-associated virus type 2 (AAV2) and certain other viruses is associated with the outbreak of mysterious pediatric hepatitis cases worldwide.

Coinfection with AAV2 and a human adenovirus (HAdV), in particular, appears to leave some children more vulnerable to this acute hepatitis of unknown origin, researchers reported in three studies published online in Nature. Coinfection with Epstein-Barr virus (EBV), herpes, and enterovirus also were found. Adeno-associated viruses are not considered pathogenic on their own and require a “helper” virus for productive infection.

“I am quite confident that we have identified the key viruses involved because we used a comprehensive metagenomic sequencing approach to look for potential infections from any virus or non-viral pathogen,” Charles Chiu, MD, PhD, senior author and professor of laboratory medicine and medicine/infectious diseases at the University of California, San Francisco, said in an interview.

Dr. Chiu and colleagues propose that lockdowns and social isolation during the COVID-19 pandemic left more children susceptible. A major aspect of immunity in childhood is the adaptive immune response – both cell-mediated and humoral – shaped in part by exposure to viruses and other pathogens early in life, Dr. Chiu said.

“Due to COVID-19, a large population of children did not experience this, so it is possible once restrictions were lifted, they were suddenly exposed over a short period of time to multiple viruses that, in a poorly trained immune system, would have increased their risk of developing severe disease,” he said.

This theory has been popular, especially because cases of unexplained acute hepatitis peaked during the height of the COVID-19 pandemic when isolation was common, William F. Balistreri, MD, who was not affiliated with the study, told this news organization. Dr. Balistreri is professor of pediatrics and director emeritus of the Pediatric Liver Care Center at Cincinnati Children’s Hospital Medical Center.
 

Identifying the culprits

Determining what factors might be involved was the main aim of the etiology study by Dr. Chiu and colleagues published online  in Nature.

The journal simultaneously published a genomic study confirming the presence of AAV2 and other suspected viruses and a genomic and laboratory study further corroborating the results.

More than 1,000 children worldwide had been diagnosed with unexplained acute pediatric hepatitis as of August 2022. In the United States, there have been 358 cases, including 22 in which the child required a liver transplant and 13 in which the child died.

This new form of hepatitis, first detected in October 2021, does not fit into existing classifications of types A through E, so some researchers refer to the condition as acute non–A-E hepatitis of unknown etiology.

The investigators started with an important clue based on previous research: the role adenovirus might play. Dr. Chiu and colleagues assessed 27 blood, stool, and other samples from 16 affected children who each previously tested positive for adenoviruses. The researchers included cases of the condition identified up until May 22, 2022. The median age was 3 years, and approximately half were boys.

They compared viruses present in these children with those in 113 controls without the mysterious hepatitis. The control group consisted of 15 children who were hospitalized with a nonhepatitis inflammatory condition, 27 with a noninflammatory condition, 30 with acute hepatitis of known origin, 12 with acute gastroenteritis and an HAdV-positive stool sample, and 11 with acute gastroenteritis and an HAdV-negative stool sample, as well as 18 blood donors. The median age was 7 years.

The researchers assessed samples using multiple technologies, including metagenomic sequencing, tiling multiplex polymerase chain reaction (PCR) amplicon sequencing, metagenomic sequencing with probe capture viral enrichment, and virus-specific PCR. Many of these advanced techniques were not even available 5-10 years ago, Dr. Chiu said.
 

Key findings

Blood samples were available for 14 of the 16 children with acute hepatitis of unknown origin. Among this study group, AAV2 was found in 13 (93%). No other adeno-associated viruses were found. HAdV was detected in all 14 children: HAdV-41 in 11 children and HAdV-40, HAdV-2, and an untypeable strain in one child each. This finding was not intuitive because HAdVs are not commonly associated with hepatitis, according to the study.

AAV2 was much less common in the control group. For example, it was found in none of the children with hepatitis of known origin and in only four children (3.5%) with acute gastroenteritis and HAdV-positive stool. Of note, neither AAV2 nor HAdV-41 was detected among the 30 pediatric controls with acute hepatitis of defined etiology nor 42 of the hospitalized children without hepatitis, the researchers wrote.

In the search for other viruses in the study group, metagenomic sequencing detected EBV, also known as human herpesvirus (HHV)–4, in two children, cytomegalovirus (CMV) in one child, and HAdV type C in one child.

Analysis of whole blood revealed enterovirus A71 in one patient. HAdV type C also was detected in one child on the basis of a nasopharyngeal swab, and picobirnavirus was found in a stool sample from another patient.

Researchers conducted virus-specific PCR tests on both patient groups to identify additional viruses that may be associated with the unexplained acute hepatitis. EBV/HHV-4 was detected in 11 children (79%) in the study group vs. in 1 child (0.88%) in the control group. HHV-6 was detected in seven children (50%) in the study group, compared with one case in the control group. CMV was not detected in any of the children in the study group versus vs. two children (1.8%) in the control group.

“Although we found significant differences in the relative proportions of EBV and HHV-6 in cases compared to controls, we do not believe that these viruses are the primary cause of acute severe hepatitis,” the researchers wrote. The viral load of the two herpes viruses were very low, so the positive results could represent integrated proviral DNA rather than bona fide low-level herpesvirus. In addition, herpesvirus can be reactivated by an inflammatory condition.

“Nevertheless, it is striking that among the 16 cases (in the study group), dual, triple, or quadruple infections with AAV2, adenovirus, and one or both herpesviruses were detected in whole blood from at least 12 cases (75%),” the researchers wrote.
 

Management of suspected hepatitis

The study’s key messages for parents and health care providers “are awareness and reassurance,” Dr. Balistreri said in an interview.

Vigilance also is warranted if a child develops prodromal symptoms including respiratory and/or gastrointestinal signs such as nausea, vomiting, diarrhea, and abdomen pain, he said. If jaundice or scleral icterus is noted, then hepatitis should be suspected.

Some patients need hospitalization and quickly recover. In very rare instances, the inflammation may progress to liver failure and transplantation, Dr. Balistreri said.

“Reassurance is based on the good news that most children with acute hepatitis get better. If a case arises, it is good practice to keep the child well hydrated, offer a normal diet, and avoid medications that may be cleared by the liver,” Dr. Balistreri added.

“Of course, COVID-19 vaccination is strongly suggested,” he said.

Some existing treatments could help against unexplained acute hepatitis, Dr. Chiu said. “The findings suggest that antiviral therapy might be effective in these cases.”

Cidofovir can be effective against adenovirus, according to a report in The Lancet . Similarly, ganciclovir or valganciclovir may have activity against EBV/HHV-4 or HHV-6, Dr. Chiu said. “However, antiviral therapy is not available for AAV2.”

The three studies published in Nature “offer compelling evidence, from disparate centers, of a linkage of outbreak cases to infection by AAV2,” Dr. Balistreri said. The studies also suggest that liver injury was related to abnormal immune responses. This is an important clinical distinction, indicating a potential therapeutic approach to future cases – immunosuppression rather than anti-adenoviral agents, he said.

“We await further studies of this important concept,” Dr. Balistreri said.

Many unanswered questions remain about the condition’s etiology, he added. Is there a synergy or shared susceptibility related to SARS-CoV-2? Is the COVID-19 virus helping to trigger these infections, or does it increase the risk once infected? Also, are other epigenetic factors or viruses involved?
 

Moving forward

The next steps in the research could go beyond identifying presence of these different viruses and determining which one(s) are contributing the most to the acute pediatric hepatitis, Dr. Chiu said.

The researchers also would like to test early results from the United Kingdom that identified a potential association of acute severe hepatitis with the presence of human leukocyte antigen genotype DRB1*04:01, he added.

They also might investigate other unintended potential clinical consequences of the COVID-19 pandemic, including long COVID and resurgence of infections from other viruses, such as respiratory syncytial virus, influenza, and enterovirus D68.

The study was supported by the Centers for Disease Control and Prevention, the National Institutes of Health, the Department of Homeland Security, and other grants. Dr. Chiu is a founder of Delve Bio and on the scientific advisory board for Delve Bio, Mammoth Biosciences, BiomeSense, and Poppy Health. Dr. Balistreri had no relevant disclosures.
 

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

Contaminated, deadly, and blindness-causing eyedrops that were recalled earlier this year were made in India at a factory not inspected by the U.S. Food and Drug Administration, according to a new report. 

Scientists are concerned that the once-rare treatment-resistant bacteria found in the eyedrops can spread person-to-person, posing a risk of becoming a recurrent problem in the United States, The New York Times reported.

In January, EzriCare and Delsam Pharma artificial tears and ointment products were recalled after being linked to the bacterium P. aeruginosa. The bacteria have caused at least 68 infections, including three deaths and at least eight cases of blindness. The eyedrops were imported to the United States from India, and many of the cases occurred after the bacteria spread person-to-person at a long-term care facility in Connecticut, according to the Times, which cited FDA and Centers for Disease Control and Prevention lead investigator Maroya Walters, PhD.

Dr. Walters said the cases that caused death or blindness were traced to the EzriCare artificial tears product.

“It’s very hard to get rid of,” University of North Carolina at Chapel Hill infectious disease specialist David van Duin, MD, PhD, told the Times, noting that the bacteria cling to sink drains, water faucets, and other moist places. 

The FDA said it had halted the import of the recalled products and has since visited the plant in India where they were made, which is owned by Global Pharma Healthcare. In a citation to the company dated March 2, the FDA listed nearly a dozen problems, such as dirty equipment and the absence of safety procedures and tests. 

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

Contaminated, deadly, and blindness-causing eyedrops that were recalled earlier this year were made in India at a factory not inspected by the U.S. Food and Drug Administration, according to a new report. 

Scientists are concerned that the once-rare treatment-resistant bacteria found in the eyedrops can spread person-to-person, posing a risk of becoming a recurrent problem in the United States, The New York Times reported.

In January, EzriCare and Delsam Pharma artificial tears and ointment products were recalled after being linked to the bacterium P. aeruginosa. The bacteria have caused at least 68 infections, including three deaths and at least eight cases of blindness. The eyedrops were imported to the United States from India, and many of the cases occurred after the bacteria spread person-to-person at a long-term care facility in Connecticut, according to the Times, which cited FDA and Centers for Disease Control and Prevention lead investigator Maroya Walters, PhD.

Dr. Walters said the cases that caused death or blindness were traced to the EzriCare artificial tears product.

“It’s very hard to get rid of,” University of North Carolina at Chapel Hill infectious disease specialist David van Duin, MD, PhD, told the Times, noting that the bacteria cling to sink drains, water faucets, and other moist places. 

The FDA said it had halted the import of the recalled products and has since visited the plant in India where they were made, which is owned by Global Pharma Healthcare. In a citation to the company dated March 2, the FDA listed nearly a dozen problems, such as dirty equipment and the absence of safety procedures and tests. 

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

Contaminated, deadly, and blindness-causing eyedrops that were recalled earlier this year were made in India at a factory not inspected by the U.S. Food and Drug Administration, according to a new report. 

Scientists are concerned that the once-rare treatment-resistant bacteria found in the eyedrops can spread person-to-person, posing a risk of becoming a recurrent problem in the United States, The New York Times reported.

In January, EzriCare and Delsam Pharma artificial tears and ointment products were recalled after being linked to the bacterium P. aeruginosa. The bacteria have caused at least 68 infections, including three deaths and at least eight cases of blindness. The eyedrops were imported to the United States from India, and many of the cases occurred after the bacteria spread person-to-person at a long-term care facility in Connecticut, according to the Times, which cited FDA and Centers for Disease Control and Prevention lead investigator Maroya Walters, PhD.

Dr. Walters said the cases that caused death or blindness were traced to the EzriCare artificial tears product.

“It’s very hard to get rid of,” University of North Carolina at Chapel Hill infectious disease specialist David van Duin, MD, PhD, told the Times, noting that the bacteria cling to sink drains, water faucets, and other moist places. 

The FDA said it had halted the import of the recalled products and has since visited the plant in India where they were made, which is owned by Global Pharma Healthcare. In a citation to the company dated March 2, the FDA listed nearly a dozen problems, such as dirty equipment and the absence of safety procedures and tests. 

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