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Drug Overdose Suicide Rates: Down, But Also Up
Who is most at risk of suicide by drug overdose? Has that changed in recent years? Researchers at the National Institute on Drug Abuse analyzed data from 2001 to 2019 from the Centers for Disease Control and Prevention’s National Vital Statistics System to find out.
On the whole, they say, intentional overdose deaths have declined. But suicide rates increased in certain subgroups: young adults (aged 15-24 years), older adults (aged 75-84 years), and non-Hispanic Black women. Rates among women were “consistently higher” than those of men. The highest rates were observed in women aged 45 to 64 years.
Monday was the worst day, and the weekends had the lowest rates. The researchers say social factors, such as more social interactions on the weekend and reluctance about starting the workweek, could be factors.
Seasonally, the numbers ran true to the pattern seen in previous studies: The lowest rates occurred in December and highest in late spring and summer. Perhaps the “collective optimism” of the holiday season and social interactions exert protective effects against suicidality, the researchers suggest.
Factors also may include biological changes. In this study, the researchers found a positive linear relationship between daylength, which varies by latitude, and intentional overdose deaths for both sexes. Daylength is associated with mu opioid receptor (MOR) availability that might underlie seasonal variations in mood, they posit. MORs are the main target of opioid drugs; the researchers cite a study that found altered MOR expression in postmortem brains of suicide victims.
They note some limitations of their study, one being that, in 2019, 5% of overdose deaths had undetermined intent. Improving classifications of overdose deaths is needed, they say.
Moreover, the trends might have changed during the pandemic, as provisional mortality data indicate decreases in deaths by suicides, but also an approximate 30% increase in overall overdose deaths.
“This research underscores the importance of external support structures and environmental factors in determining a person’s suicide risk,” said Emily B. Einstein, PhD, chief of the National Institute on Drug Abuse’s Science Policy Branch and an author on the study. “The risk of intentional overdoses, and suicide risk in general, is not static. This is crucial for clinicians to keep in mind, as they may need to assess patients’ suicide risk frequently rather than at one point in time. It is also important for friends and family members of people who may be at an increased risk of suicide, and for those people themselves, so that they can be aware of the greatest periods of risk and seek help when needed.”
Sources: https://www.nih.gov/news-events/news-releases/suicides-drug-overdose-increased-among-young-people-elderly-people-black-women-despite-overall-downward-tren
Han B, Compton WM, Einstein EB, et al. Intentional drug overdose deaths in the United States. Am J Psychiatry. doi:10.1176/appi.ajp.2021.21060604
Who is most at risk of suicide by drug overdose? Has that changed in recent years? Researchers at the National Institute on Drug Abuse analyzed data from 2001 to 2019 from the Centers for Disease Control and Prevention’s National Vital Statistics System to find out.
On the whole, they say, intentional overdose deaths have declined. But suicide rates increased in certain subgroups: young adults (aged 15-24 years), older adults (aged 75-84 years), and non-Hispanic Black women. Rates among women were “consistently higher” than those of men. The highest rates were observed in women aged 45 to 64 years.
Monday was the worst day, and the weekends had the lowest rates. The researchers say social factors, such as more social interactions on the weekend and reluctance about starting the workweek, could be factors.
Seasonally, the numbers ran true to the pattern seen in previous studies: The lowest rates occurred in December and highest in late spring and summer. Perhaps the “collective optimism” of the holiday season and social interactions exert protective effects against suicidality, the researchers suggest.
Factors also may include biological changes. In this study, the researchers found a positive linear relationship between daylength, which varies by latitude, and intentional overdose deaths for both sexes. Daylength is associated with mu opioid receptor (MOR) availability that might underlie seasonal variations in mood, they posit. MORs are the main target of opioid drugs; the researchers cite a study that found altered MOR expression in postmortem brains of suicide victims.
They note some limitations of their study, one being that, in 2019, 5% of overdose deaths had undetermined intent. Improving classifications of overdose deaths is needed, they say.
Moreover, the trends might have changed during the pandemic, as provisional mortality data indicate decreases in deaths by suicides, but also an approximate 30% increase in overall overdose deaths.
“This research underscores the importance of external support structures and environmental factors in determining a person’s suicide risk,” said Emily B. Einstein, PhD, chief of the National Institute on Drug Abuse’s Science Policy Branch and an author on the study. “The risk of intentional overdoses, and suicide risk in general, is not static. This is crucial for clinicians to keep in mind, as they may need to assess patients’ suicide risk frequently rather than at one point in time. It is also important for friends and family members of people who may be at an increased risk of suicide, and for those people themselves, so that they can be aware of the greatest periods of risk and seek help when needed.”
Sources: https://www.nih.gov/news-events/news-releases/suicides-drug-overdose-increased-among-young-people-elderly-people-black-women-despite-overall-downward-tren
Han B, Compton WM, Einstein EB, et al. Intentional drug overdose deaths in the United States. Am J Psychiatry. doi:10.1176/appi.ajp.2021.21060604
Who is most at risk of suicide by drug overdose? Has that changed in recent years? Researchers at the National Institute on Drug Abuse analyzed data from 2001 to 2019 from the Centers for Disease Control and Prevention’s National Vital Statistics System to find out.
On the whole, they say, intentional overdose deaths have declined. But suicide rates increased in certain subgroups: young adults (aged 15-24 years), older adults (aged 75-84 years), and non-Hispanic Black women. Rates among women were “consistently higher” than those of men. The highest rates were observed in women aged 45 to 64 years.
Monday was the worst day, and the weekends had the lowest rates. The researchers say social factors, such as more social interactions on the weekend and reluctance about starting the workweek, could be factors.
Seasonally, the numbers ran true to the pattern seen in previous studies: The lowest rates occurred in December and highest in late spring and summer. Perhaps the “collective optimism” of the holiday season and social interactions exert protective effects against suicidality, the researchers suggest.
Factors also may include biological changes. In this study, the researchers found a positive linear relationship between daylength, which varies by latitude, and intentional overdose deaths for both sexes. Daylength is associated with mu opioid receptor (MOR) availability that might underlie seasonal variations in mood, they posit. MORs are the main target of opioid drugs; the researchers cite a study that found altered MOR expression in postmortem brains of suicide victims.
They note some limitations of their study, one being that, in 2019, 5% of overdose deaths had undetermined intent. Improving classifications of overdose deaths is needed, they say.
Moreover, the trends might have changed during the pandemic, as provisional mortality data indicate decreases in deaths by suicides, but also an approximate 30% increase in overall overdose deaths.
“This research underscores the importance of external support structures and environmental factors in determining a person’s suicide risk,” said Emily B. Einstein, PhD, chief of the National Institute on Drug Abuse’s Science Policy Branch and an author on the study. “The risk of intentional overdoses, and suicide risk in general, is not static. This is crucial for clinicians to keep in mind, as they may need to assess patients’ suicide risk frequently rather than at one point in time. It is also important for friends and family members of people who may be at an increased risk of suicide, and for those people themselves, so that they can be aware of the greatest periods of risk and seek help when needed.”
Sources: https://www.nih.gov/news-events/news-releases/suicides-drug-overdose-increased-among-young-people-elderly-people-black-women-despite-overall-downward-tren
Han B, Compton WM, Einstein EB, et al. Intentional drug overdose deaths in the United States. Am J Psychiatry. doi:10.1176/appi.ajp.2021.21060604
Lung cancer now a growing public health threat
, according to estimates of lung cancer incident cases, deaths, and their age-standardized rates.
The findings, based on recently released data from GLOBOCAN 2020 projected to the year 2050, suggest that the lung cancer epidemic will continue to unfold, according to Rajesh Sharma, PhD, et al., in a study published in the International Journal of Clinical Oncology. GLOBOCAN 2020 is an online database produced by the International Agency for Research on Cancer. It provides global cancer statistics from 185 countries for 36 cancer types.
The increase in lung cancer, the leading cancer worldwide in terms of deaths, is generally attributed to increases in cigarette smoking, Sharma et al. wrote. They point out that, while cigarette smoking is expected to have peaked in industrialized countries in the latter half of the twentieth century, the tobacco smoking epidemic is unfolding in regions of Asia and Africa with concomitant increases in lung cancer burden in several countries. Smoking is the most significant lung cancer risk factor, followed by air pollution (especially particulate matter, passive smoking, and occupational exposure to radon and asbestos).
The authors investigated bivariate associations between smoking prevalence and age-standardized rates of lung cancer, and projected lung cancer incident cases and deaths to 2050. They also looked at mortality-to-incidence, considered to be a proxy indicator of 5-year survival, and at human development index, a measure including life expectancy at birth, years of schooling, and standard of living. The results, they state, are expected to aid in policy formulation to combat the lung cancer burden at global, regional, and national levels.
Tobacco smoking prevalence was 21.9% worldwide in 2016, with tobacco smoking prevalence exceeding 25% in 57/149 countries. It was high in European countries with 5 of the top-10 countries among the 149 countries within Europe. Prevalence was greater than 10% in all European countries. Notably, 11/33 countries in Africa had a smoking prevalence less than 10%.
Analysis showed 2.21 million new lung cancer cases and 1.8 million deaths attributed to lung cancer worldwide in 2020, with males accounting for about two-thirds of the burden. The analysis projection for 2050 was for 3.8 million incident cases of lung cancer and 3.2 million lung cancer deaths globally. In 2050, lung cancer cases and deaths are projected to be more than 100,000 in 10/21 regions, led by Eastern Asia, projected to record 1.7 million incident cases and 1.5 million deaths.
The burden of lung cancer in regions of Asia and Africa is expected to increase at least twofold from 2020 to 2050, surpassing European regions that are expected to have the smallest increases. Also, while incident cases will remain much higher in Northern America than in Southeastern Asia and South-Central Asia, the number of lives lost is projected to be similar. The age-specific incidence and death rates rose with age such that the oldest age groups had the highest age-specific rates. With the human development index, mortality-to-incidence showed a negative correlation.
The authors wrote that worsening smoking and pollution levels in developing countries may push the future lung cancer burden much higher than these projections. Unless reversed, cases and death will grow unabated.
“Countering the burden of lung cancer also requires curtailment of other risk factors such as air pollution and exposure to carcinogens,” the authors wrote.
This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. The authors stated that they have no conflicts of interest.
, according to estimates of lung cancer incident cases, deaths, and their age-standardized rates.
The findings, based on recently released data from GLOBOCAN 2020 projected to the year 2050, suggest that the lung cancer epidemic will continue to unfold, according to Rajesh Sharma, PhD, et al., in a study published in the International Journal of Clinical Oncology. GLOBOCAN 2020 is an online database produced by the International Agency for Research on Cancer. It provides global cancer statistics from 185 countries for 36 cancer types.
The increase in lung cancer, the leading cancer worldwide in terms of deaths, is generally attributed to increases in cigarette smoking, Sharma et al. wrote. They point out that, while cigarette smoking is expected to have peaked in industrialized countries in the latter half of the twentieth century, the tobacco smoking epidemic is unfolding in regions of Asia and Africa with concomitant increases in lung cancer burden in several countries. Smoking is the most significant lung cancer risk factor, followed by air pollution (especially particulate matter, passive smoking, and occupational exposure to radon and asbestos).
The authors investigated bivariate associations between smoking prevalence and age-standardized rates of lung cancer, and projected lung cancer incident cases and deaths to 2050. They also looked at mortality-to-incidence, considered to be a proxy indicator of 5-year survival, and at human development index, a measure including life expectancy at birth, years of schooling, and standard of living. The results, they state, are expected to aid in policy formulation to combat the lung cancer burden at global, regional, and national levels.
Tobacco smoking prevalence was 21.9% worldwide in 2016, with tobacco smoking prevalence exceeding 25% in 57/149 countries. It was high in European countries with 5 of the top-10 countries among the 149 countries within Europe. Prevalence was greater than 10% in all European countries. Notably, 11/33 countries in Africa had a smoking prevalence less than 10%.
Analysis showed 2.21 million new lung cancer cases and 1.8 million deaths attributed to lung cancer worldwide in 2020, with males accounting for about two-thirds of the burden. The analysis projection for 2050 was for 3.8 million incident cases of lung cancer and 3.2 million lung cancer deaths globally. In 2050, lung cancer cases and deaths are projected to be more than 100,000 in 10/21 regions, led by Eastern Asia, projected to record 1.7 million incident cases and 1.5 million deaths.
The burden of lung cancer in regions of Asia and Africa is expected to increase at least twofold from 2020 to 2050, surpassing European regions that are expected to have the smallest increases. Also, while incident cases will remain much higher in Northern America than in Southeastern Asia and South-Central Asia, the number of lives lost is projected to be similar. The age-specific incidence and death rates rose with age such that the oldest age groups had the highest age-specific rates. With the human development index, mortality-to-incidence showed a negative correlation.
The authors wrote that worsening smoking and pollution levels in developing countries may push the future lung cancer burden much higher than these projections. Unless reversed, cases and death will grow unabated.
“Countering the burden of lung cancer also requires curtailment of other risk factors such as air pollution and exposure to carcinogens,” the authors wrote.
This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. The authors stated that they have no conflicts of interest.
, according to estimates of lung cancer incident cases, deaths, and their age-standardized rates.
The findings, based on recently released data from GLOBOCAN 2020 projected to the year 2050, suggest that the lung cancer epidemic will continue to unfold, according to Rajesh Sharma, PhD, et al., in a study published in the International Journal of Clinical Oncology. GLOBOCAN 2020 is an online database produced by the International Agency for Research on Cancer. It provides global cancer statistics from 185 countries for 36 cancer types.
The increase in lung cancer, the leading cancer worldwide in terms of deaths, is generally attributed to increases in cigarette smoking, Sharma et al. wrote. They point out that, while cigarette smoking is expected to have peaked in industrialized countries in the latter half of the twentieth century, the tobacco smoking epidemic is unfolding in regions of Asia and Africa with concomitant increases in lung cancer burden in several countries. Smoking is the most significant lung cancer risk factor, followed by air pollution (especially particulate matter, passive smoking, and occupational exposure to radon and asbestos).
The authors investigated bivariate associations between smoking prevalence and age-standardized rates of lung cancer, and projected lung cancer incident cases and deaths to 2050. They also looked at mortality-to-incidence, considered to be a proxy indicator of 5-year survival, and at human development index, a measure including life expectancy at birth, years of schooling, and standard of living. The results, they state, are expected to aid in policy formulation to combat the lung cancer burden at global, regional, and national levels.
Tobacco smoking prevalence was 21.9% worldwide in 2016, with tobacco smoking prevalence exceeding 25% in 57/149 countries. It was high in European countries with 5 of the top-10 countries among the 149 countries within Europe. Prevalence was greater than 10% in all European countries. Notably, 11/33 countries in Africa had a smoking prevalence less than 10%.
Analysis showed 2.21 million new lung cancer cases and 1.8 million deaths attributed to lung cancer worldwide in 2020, with males accounting for about two-thirds of the burden. The analysis projection for 2050 was for 3.8 million incident cases of lung cancer and 3.2 million lung cancer deaths globally. In 2050, lung cancer cases and deaths are projected to be more than 100,000 in 10/21 regions, led by Eastern Asia, projected to record 1.7 million incident cases and 1.5 million deaths.
The burden of lung cancer in regions of Asia and Africa is expected to increase at least twofold from 2020 to 2050, surpassing European regions that are expected to have the smallest increases. Also, while incident cases will remain much higher in Northern America than in Southeastern Asia and South-Central Asia, the number of lives lost is projected to be similar. The age-specific incidence and death rates rose with age such that the oldest age groups had the highest age-specific rates. With the human development index, mortality-to-incidence showed a negative correlation.
The authors wrote that worsening smoking and pollution levels in developing countries may push the future lung cancer burden much higher than these projections. Unless reversed, cases and death will grow unabated.
“Countering the burden of lung cancer also requires curtailment of other risk factors such as air pollution and exposure to carcinogens,” the authors wrote.
This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. The authors stated that they have no conflicts of interest.
FROM INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY
9/11 first responders show mutations linked to blood cancers
. These results add to concerns about the long-term health effects of that exposure and further underscore a need for screening of those exposed.
“These data demonstrate that environmental exposure to the WTC disaster site is associated with a higher burden of clonal hematopoiesis, exceeding that expected in normal aging, and establish a rationale for mutational testing of the larger WTC-exposed population,” report the authors in the study, published March 7 in Nature Medicine.
The findings come from a study of blood samples from WTC first responders, including 429 firefighters and 52 emergency medical service workers, collected between December 2013 and October 2015.
For comparisons, the authors collected blood samples from 255 firefighters from in and around Nashville, Tenn., none of whom had been exposed to the 9/11 disaster.
Genetic analysis of the samples showed that 10% of those in the WTC-exposed cohort (n = 48) had unique somatic mutations considered to likely be pathogenic, and six of those individuals carried one or more of the mutations.
After a multivariate adjustment controlling for age, sex and race/ethnicity, those among the WTC-exposed first responders had a significantly increased odds of clonal hematopoiesis versus nonexposed workers (odds ratio [OR] = 3.14; P = .0006).
The higher risk was further observed in a comparison limited only to the WTC-exposed firefighters versus nonexposed firefighters (OR = 2.93; P = .0014) after the multivariate adjustment. The greater association between WTC exposure and clonal hematopoiesis remained after the researchers controlled for smoking as well as other risk factors among the WTC-exposed group overall (OR = 3.05; P = .0015) and the firefighters-only comparison (OR = 2.78; P = .004).
A history of smoking was not significantly associated with an increased risk of clonal hematopoiesis in either model.
As a risk factor for hematologic malignancy, cardiovascular events, and mortality, “clonal hematopoiesis is a concerning acquired risk not only for diseases that are already associated with WTC exposure but also as the population ages, this may exacerbate their risk profile,” Dr. Anna Nolan, coauthor of the study, and professor of medicine and environmental medicine in the division of pulmonary and critical care, New York University, said in an interview.
The most common gene mutations observed in the WTC-exposed group were those associated with myeloid malignancies, such as chronic myeloid leukemia; however, blood counts in the exposed group showed no association between exposure and mutations linked to cytopenias.
A further analysis on mice, investigating how WTC particulate matter uniquely affects DNA, surprisingly showed that just one exposure to the material was associated with clonal hematopoietic changes.
“Exposure to particulates, even at a single time point, can yield clonal mutations that may be risk for multisystem end-organ changes,” Dr. Nolan said.
While the serious health effects of WTC exposure on humans, have been extensively documented, including a study published in February showing increases in skin, prostate and thyroid cancers, clonal hematopoiesis suggests further heightened risks as the exposed population grows older, Dr. Nolan noted.
“[Clonal hematopoiesis] is a concerning acquired risk not only for diseases that are already associated with WTC exposure, but also, as the population ages, this may exacerbate their risk profile,” she said.
Due to the risk, “clinicians should be aware that WTC-exposed first responders have had a significant exposure and that they are at risk for developing several conditions.”
Commenting on this study, William K. Oh, MD, whose team at the Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, has reported in a previous study on the increased risk of prostate cancer among WTC first responders, noted that more time may be necessary to better understand the full effects of the increases in clonal hematopoiesis.
“Though these findings are of concern, there were still no differences in the cohorts in actual hematologic cancers or even cytopenias, suggesting that more time and additional DNA damaging events were needed to transform the clonal hematopoiesis findings to clinically relevant diseases,” Dr. Oh, clinical professor of medicine, said in an interview.
Nevertheless, “if a patient is found on testing to have clonal hematopoiesis, they should be screened more closely for blood disorders and cardiovascular issues than they might otherwise be, though this remains an area of active investigation,” Dr. Oh said.
Dr. Nolan had no disclosures to report. Dr. Oh is the chief medical science officer at Sema4, a genomic testing and data company.
. These results add to concerns about the long-term health effects of that exposure and further underscore a need for screening of those exposed.
“These data demonstrate that environmental exposure to the WTC disaster site is associated with a higher burden of clonal hematopoiesis, exceeding that expected in normal aging, and establish a rationale for mutational testing of the larger WTC-exposed population,” report the authors in the study, published March 7 in Nature Medicine.
The findings come from a study of blood samples from WTC first responders, including 429 firefighters and 52 emergency medical service workers, collected between December 2013 and October 2015.
For comparisons, the authors collected blood samples from 255 firefighters from in and around Nashville, Tenn., none of whom had been exposed to the 9/11 disaster.
Genetic analysis of the samples showed that 10% of those in the WTC-exposed cohort (n = 48) had unique somatic mutations considered to likely be pathogenic, and six of those individuals carried one or more of the mutations.
After a multivariate adjustment controlling for age, sex and race/ethnicity, those among the WTC-exposed first responders had a significantly increased odds of clonal hematopoiesis versus nonexposed workers (odds ratio [OR] = 3.14; P = .0006).
The higher risk was further observed in a comparison limited only to the WTC-exposed firefighters versus nonexposed firefighters (OR = 2.93; P = .0014) after the multivariate adjustment. The greater association between WTC exposure and clonal hematopoiesis remained after the researchers controlled for smoking as well as other risk factors among the WTC-exposed group overall (OR = 3.05; P = .0015) and the firefighters-only comparison (OR = 2.78; P = .004).
A history of smoking was not significantly associated with an increased risk of clonal hematopoiesis in either model.
As a risk factor for hematologic malignancy, cardiovascular events, and mortality, “clonal hematopoiesis is a concerning acquired risk not only for diseases that are already associated with WTC exposure but also as the population ages, this may exacerbate their risk profile,” Dr. Anna Nolan, coauthor of the study, and professor of medicine and environmental medicine in the division of pulmonary and critical care, New York University, said in an interview.
The most common gene mutations observed in the WTC-exposed group were those associated with myeloid malignancies, such as chronic myeloid leukemia; however, blood counts in the exposed group showed no association between exposure and mutations linked to cytopenias.
A further analysis on mice, investigating how WTC particulate matter uniquely affects DNA, surprisingly showed that just one exposure to the material was associated with clonal hematopoietic changes.
“Exposure to particulates, even at a single time point, can yield clonal mutations that may be risk for multisystem end-organ changes,” Dr. Nolan said.
While the serious health effects of WTC exposure on humans, have been extensively documented, including a study published in February showing increases in skin, prostate and thyroid cancers, clonal hematopoiesis suggests further heightened risks as the exposed population grows older, Dr. Nolan noted.
“[Clonal hematopoiesis] is a concerning acquired risk not only for diseases that are already associated with WTC exposure, but also, as the population ages, this may exacerbate their risk profile,” she said.
Due to the risk, “clinicians should be aware that WTC-exposed first responders have had a significant exposure and that they are at risk for developing several conditions.”
Commenting on this study, William K. Oh, MD, whose team at the Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, has reported in a previous study on the increased risk of prostate cancer among WTC first responders, noted that more time may be necessary to better understand the full effects of the increases in clonal hematopoiesis.
“Though these findings are of concern, there were still no differences in the cohorts in actual hematologic cancers or even cytopenias, suggesting that more time and additional DNA damaging events were needed to transform the clonal hematopoiesis findings to clinically relevant diseases,” Dr. Oh, clinical professor of medicine, said in an interview.
Nevertheless, “if a patient is found on testing to have clonal hematopoiesis, they should be screened more closely for blood disorders and cardiovascular issues than they might otherwise be, though this remains an area of active investigation,” Dr. Oh said.
Dr. Nolan had no disclosures to report. Dr. Oh is the chief medical science officer at Sema4, a genomic testing and data company.
. These results add to concerns about the long-term health effects of that exposure and further underscore a need for screening of those exposed.
“These data demonstrate that environmental exposure to the WTC disaster site is associated with a higher burden of clonal hematopoiesis, exceeding that expected in normal aging, and establish a rationale for mutational testing of the larger WTC-exposed population,” report the authors in the study, published March 7 in Nature Medicine.
The findings come from a study of blood samples from WTC first responders, including 429 firefighters and 52 emergency medical service workers, collected between December 2013 and October 2015.
For comparisons, the authors collected blood samples from 255 firefighters from in and around Nashville, Tenn., none of whom had been exposed to the 9/11 disaster.
Genetic analysis of the samples showed that 10% of those in the WTC-exposed cohort (n = 48) had unique somatic mutations considered to likely be pathogenic, and six of those individuals carried one or more of the mutations.
After a multivariate adjustment controlling for age, sex and race/ethnicity, those among the WTC-exposed first responders had a significantly increased odds of clonal hematopoiesis versus nonexposed workers (odds ratio [OR] = 3.14; P = .0006).
The higher risk was further observed in a comparison limited only to the WTC-exposed firefighters versus nonexposed firefighters (OR = 2.93; P = .0014) after the multivariate adjustment. The greater association between WTC exposure and clonal hematopoiesis remained after the researchers controlled for smoking as well as other risk factors among the WTC-exposed group overall (OR = 3.05; P = .0015) and the firefighters-only comparison (OR = 2.78; P = .004).
A history of smoking was not significantly associated with an increased risk of clonal hematopoiesis in either model.
As a risk factor for hematologic malignancy, cardiovascular events, and mortality, “clonal hematopoiesis is a concerning acquired risk not only for diseases that are already associated with WTC exposure but also as the population ages, this may exacerbate their risk profile,” Dr. Anna Nolan, coauthor of the study, and professor of medicine and environmental medicine in the division of pulmonary and critical care, New York University, said in an interview.
The most common gene mutations observed in the WTC-exposed group were those associated with myeloid malignancies, such as chronic myeloid leukemia; however, blood counts in the exposed group showed no association between exposure and mutations linked to cytopenias.
A further analysis on mice, investigating how WTC particulate matter uniquely affects DNA, surprisingly showed that just one exposure to the material was associated with clonal hematopoietic changes.
“Exposure to particulates, even at a single time point, can yield clonal mutations that may be risk for multisystem end-organ changes,” Dr. Nolan said.
While the serious health effects of WTC exposure on humans, have been extensively documented, including a study published in February showing increases in skin, prostate and thyroid cancers, clonal hematopoiesis suggests further heightened risks as the exposed population grows older, Dr. Nolan noted.
“[Clonal hematopoiesis] is a concerning acquired risk not only for diseases that are already associated with WTC exposure, but also, as the population ages, this may exacerbate their risk profile,” she said.
Due to the risk, “clinicians should be aware that WTC-exposed first responders have had a significant exposure and that they are at risk for developing several conditions.”
Commenting on this study, William K. Oh, MD, whose team at the Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, has reported in a previous study on the increased risk of prostate cancer among WTC first responders, noted that more time may be necessary to better understand the full effects of the increases in clonal hematopoiesis.
“Though these findings are of concern, there were still no differences in the cohorts in actual hematologic cancers or even cytopenias, suggesting that more time and additional DNA damaging events were needed to transform the clonal hematopoiesis findings to clinically relevant diseases,” Dr. Oh, clinical professor of medicine, said in an interview.
Nevertheless, “if a patient is found on testing to have clonal hematopoiesis, they should be screened more closely for blood disorders and cardiovascular issues than they might otherwise be, though this remains an area of active investigation,” Dr. Oh said.
Dr. Nolan had no disclosures to report. Dr. Oh is the chief medical science officer at Sema4, a genomic testing and data company.
FROM NATURE MEDICINE
Tremors and memory loss precede Parkinson’s in diverse population
Tremors and memory symptoms were identified among individuals in a primary care setting as early as 10 years before a Parkinson’s disease diagnosis in a new study.
Most research on the causes and early signs of Parkinson’s disease (PD) have involved patients of Northern European ancestry, Cristina Simonet, MD, of Queen Mary University of London, and colleagues wrote in their paper, published in JAMA Neurology.
Additionally, data on how PD might manifest in different ethnic groups are limited, they said.
In their nested case-control, the researchers examined data from electronic health records of an ethnically diverse population of 1,016,277 adults seen in primary care practices between 1990 and Feb. 6, 2018. They compared individuals with PD with those without PD or other neurologic conditions.
The researchers identified 10 age and sex-matched controls for each PD case, and also conducted an unmatched analysis after adjusting for age and sex. The final study population included 1,055 patients with PD and 1,009,523 controls. The population of PD cases was 15.7% Black, 19.7% South Asian, 50.9% White, and 8.3% other; the population of controls was 13.3% Black, 21.5% South Asian, 43.7% White, and 11.3% other.
“We observed a constellation of symptoms noted by general practitioners up to a decade before diagnosis of PD,” the researchers said. Symptoms were identified across three time intervals (less than 2 years, 2-5 years, and 5-10 years before diagnosis) to better evaluate exposure outcome associations.
In the matched analysis of midlife risk factors, epilepsy showed the strongest association with PD diagnosis across all time periods, and type 2 diabetes or hypertension 5-10 years before diagnosis was associated with later PD.
Prediagnostic signs of PD included both motor and nonmotor manifestations.
The matched analysis revealed a significant increased association between tremor and memory symptoms less than 2 years before diagnosis (adjusted odds ratios of 151.24 and 8.73, respectively) as well as up to 10 years before diagnosis for tremors and up to 5 years for memory symptoms (aOR, 11.4 and 3.09, respectively) in PD patients, compared with controls.
Other strong associations between PD and early nonmotor features in cases, compared with controls, included hypotension (aOR, 6.81), constipation (aOR, 3.29), and depression (aOR, 4.61).
In addition, the researchers found associations for epilepsy that had not been identified in previous studies, and these associations persisted in a replication analysis.
The study findings were limited by several factors, mainly the use of routine primary care data with underascertained factors of interest, and potential mislabeling of PD, the researchers noted. Other limitations included the lack of data on prescription medication for PD, and the recording of memory problems in primary care without supportive testing to confirm cognitive impairment.
The results support a range of comorbidities and symptoms that may present in primary care, and clinicians should consider PD as a possible cause, the researchers wrote.
Make early referral a priority
The study is important because of the lack of diversity in Parkinson’s disease research, lead author Dr. Simonet said in an interview.
“Over the last decade, the global population suffering from Parkinson’s disease has more than doubled,” she said. Causes may include the increasing numbers of older people with longer life expectancy. “However, it seems there are other factors, including environmental, genetic, and lifestyle, that might play a role in increasing the prevalence of Parkinson’s disease.”
“More representative studies, including minority ethnic groups and those living in areas of high social and economic deprivation, are needed,” Dr. Simonet emphasized.
She said that there is little research on the association with epilepsy and hearing loss in early PD, and “for that reason, our results should encourage further studies to confirm a possible link between these manifestations and Parkinson’s disease.”
Early detection may drive better diagnoses
The current study is important for understanding the prediagnostic features and risk factors that may allow for earlier detection of Parkinson’s disease, William Hung, MD, a geriatrics and palliative care specialist of the Icahn School of Medicine at Mount Sinai, New York, said in an interview. “Prior to this study, there was limited understanding of these features.
“One surprise [in the findings] was that ethnicity and socioeconomic deprivation do not appear to be associated with the risk of PD, in contrast to other illnesses such as dementia,” said Dr. Hung. “The array of prediagnostic features associated with PD is not surprising, but nonetheless important for clinicians to know to consider whether PD could be the underlying cause.”
The take-home message for primary care is that “there are features, such as hearing loss, history of epilepsy, autonomic symptoms, motor symptoms, among others, for which clinicians should consider PD as part of the differential diagnosis as underlying cause and consider referral to specialists for diagnostic clarification,” said Dr. Hung.
“Additional research is needed to translate these findings to care, perhaps developing decision aids, interventions that may help with diagnosis and evaluation,” as is work on understanding the link between PD and symptoms such as hearing loss and epilepsy, he said.
Primary care offers opportunity to identify risk factors
The current study represents an important step in early recognition of PD, with implications for helping patients access treatments promptly and improve their quality of life, Bhavana Patel, DO, Shannon Chiu, MD, and Melissa J. Armstrong, MD, of the University of Florida, Gainesville, wrote in an accompanying editorial.
“The primary care setting is commonly where symptoms heralding the onset of PD are first discussed. However, little is known regarding the prediagnostic manifestations of PD that are seen in primary care clinics, particularly in underserved populations,” they wrote.
The study included many risk factors and prodromal markers associated with research criteria for prodromal PD, but did not include several risk and prodromal markers in the Movement Disorders Society research criteria, “such as symptoms suggestive of REM sleep behavior disorder, excessive daytime sleepiness (which overlaps with, but is distinct from, fatigue), urinary dysfunction, pesticide and solvent exposure, caffeine use, level of physical activity, and family history,” they said.
Even in individuals with diagnosed PD, certain symptoms, particularly nonmotor symptoms, are commonly underreported,” and primary care clinicians may not recognize these symptoms as PD risk factors, the authors noted.
However, “in addition to contributing to possible models of modifiable risk factors for PD, study results may also further inform algorithms designed to predict PD diagnoses in primary care,” they said. The study also highlights the need for more multivariable models to better identify PD risk factors and strategies for early identification of PD in primary care.
Several study coauthors received funding related to the study from Barts Charity, Health Data Research UK, the Department of Health and Social Care (England) and the devolved administrations, and leading medical research charities, as well as the National Institute for Health Research UCLH Biomedical Research Centre. Lead author Dr. Simonet and Dr. Hung had no financial conflicts to disclose. Dr. Patel disclosed support from the National Institute on Aging, the Mangurian-Fixel-McKnight Collaboration for Pilot Studies in Lewy Body Dementia, and the American Brain Foundation and the Mary E. Groff Charitable Trust. Dr. Chiu reported receiving grants from Mangurian-Fixel-McKnight Collaboration for Pilot Studies in Lewy Body Dementia and the Smallwood Foundation. Dr. Armstrong disclosed funding from the National Institute on Aging, the Florida Department of Health, the Lewy Body Dementia Association, the Alzheimer’s Therapeutic Research Institute/Alzheimer’s Clinical Trial Consortium, the Alzheimer’s Disease Cooperative Study as Data Safety Monitoring Board the Parkinson’s Foundation, and the American Academy of Neurology.
Tremors and memory symptoms were identified among individuals in a primary care setting as early as 10 years before a Parkinson’s disease diagnosis in a new study.
Most research on the causes and early signs of Parkinson’s disease (PD) have involved patients of Northern European ancestry, Cristina Simonet, MD, of Queen Mary University of London, and colleagues wrote in their paper, published in JAMA Neurology.
Additionally, data on how PD might manifest in different ethnic groups are limited, they said.
In their nested case-control, the researchers examined data from electronic health records of an ethnically diverse population of 1,016,277 adults seen in primary care practices between 1990 and Feb. 6, 2018. They compared individuals with PD with those without PD or other neurologic conditions.
The researchers identified 10 age and sex-matched controls for each PD case, and also conducted an unmatched analysis after adjusting for age and sex. The final study population included 1,055 patients with PD and 1,009,523 controls. The population of PD cases was 15.7% Black, 19.7% South Asian, 50.9% White, and 8.3% other; the population of controls was 13.3% Black, 21.5% South Asian, 43.7% White, and 11.3% other.
“We observed a constellation of symptoms noted by general practitioners up to a decade before diagnosis of PD,” the researchers said. Symptoms were identified across three time intervals (less than 2 years, 2-5 years, and 5-10 years before diagnosis) to better evaluate exposure outcome associations.
In the matched analysis of midlife risk factors, epilepsy showed the strongest association with PD diagnosis across all time periods, and type 2 diabetes or hypertension 5-10 years before diagnosis was associated with later PD.
Prediagnostic signs of PD included both motor and nonmotor manifestations.
The matched analysis revealed a significant increased association between tremor and memory symptoms less than 2 years before diagnosis (adjusted odds ratios of 151.24 and 8.73, respectively) as well as up to 10 years before diagnosis for tremors and up to 5 years for memory symptoms (aOR, 11.4 and 3.09, respectively) in PD patients, compared with controls.
Other strong associations between PD and early nonmotor features in cases, compared with controls, included hypotension (aOR, 6.81), constipation (aOR, 3.29), and depression (aOR, 4.61).
In addition, the researchers found associations for epilepsy that had not been identified in previous studies, and these associations persisted in a replication analysis.
The study findings were limited by several factors, mainly the use of routine primary care data with underascertained factors of interest, and potential mislabeling of PD, the researchers noted. Other limitations included the lack of data on prescription medication for PD, and the recording of memory problems in primary care without supportive testing to confirm cognitive impairment.
The results support a range of comorbidities and symptoms that may present in primary care, and clinicians should consider PD as a possible cause, the researchers wrote.
Make early referral a priority
The study is important because of the lack of diversity in Parkinson’s disease research, lead author Dr. Simonet said in an interview.
“Over the last decade, the global population suffering from Parkinson’s disease has more than doubled,” she said. Causes may include the increasing numbers of older people with longer life expectancy. “However, it seems there are other factors, including environmental, genetic, and lifestyle, that might play a role in increasing the prevalence of Parkinson’s disease.”
“More representative studies, including minority ethnic groups and those living in areas of high social and economic deprivation, are needed,” Dr. Simonet emphasized.
She said that there is little research on the association with epilepsy and hearing loss in early PD, and “for that reason, our results should encourage further studies to confirm a possible link between these manifestations and Parkinson’s disease.”
Early detection may drive better diagnoses
The current study is important for understanding the prediagnostic features and risk factors that may allow for earlier detection of Parkinson’s disease, William Hung, MD, a geriatrics and palliative care specialist of the Icahn School of Medicine at Mount Sinai, New York, said in an interview. “Prior to this study, there was limited understanding of these features.
“One surprise [in the findings] was that ethnicity and socioeconomic deprivation do not appear to be associated with the risk of PD, in contrast to other illnesses such as dementia,” said Dr. Hung. “The array of prediagnostic features associated with PD is not surprising, but nonetheless important for clinicians to know to consider whether PD could be the underlying cause.”
The take-home message for primary care is that “there are features, such as hearing loss, history of epilepsy, autonomic symptoms, motor symptoms, among others, for which clinicians should consider PD as part of the differential diagnosis as underlying cause and consider referral to specialists for diagnostic clarification,” said Dr. Hung.
“Additional research is needed to translate these findings to care, perhaps developing decision aids, interventions that may help with diagnosis and evaluation,” as is work on understanding the link between PD and symptoms such as hearing loss and epilepsy, he said.
Primary care offers opportunity to identify risk factors
The current study represents an important step in early recognition of PD, with implications for helping patients access treatments promptly and improve their quality of life, Bhavana Patel, DO, Shannon Chiu, MD, and Melissa J. Armstrong, MD, of the University of Florida, Gainesville, wrote in an accompanying editorial.
“The primary care setting is commonly where symptoms heralding the onset of PD are first discussed. However, little is known regarding the prediagnostic manifestations of PD that are seen in primary care clinics, particularly in underserved populations,” they wrote.
The study included many risk factors and prodromal markers associated with research criteria for prodromal PD, but did not include several risk and prodromal markers in the Movement Disorders Society research criteria, “such as symptoms suggestive of REM sleep behavior disorder, excessive daytime sleepiness (which overlaps with, but is distinct from, fatigue), urinary dysfunction, pesticide and solvent exposure, caffeine use, level of physical activity, and family history,” they said.
Even in individuals with diagnosed PD, certain symptoms, particularly nonmotor symptoms, are commonly underreported,” and primary care clinicians may not recognize these symptoms as PD risk factors, the authors noted.
However, “in addition to contributing to possible models of modifiable risk factors for PD, study results may also further inform algorithms designed to predict PD diagnoses in primary care,” they said. The study also highlights the need for more multivariable models to better identify PD risk factors and strategies for early identification of PD in primary care.
Several study coauthors received funding related to the study from Barts Charity, Health Data Research UK, the Department of Health and Social Care (England) and the devolved administrations, and leading medical research charities, as well as the National Institute for Health Research UCLH Biomedical Research Centre. Lead author Dr. Simonet and Dr. Hung had no financial conflicts to disclose. Dr. Patel disclosed support from the National Institute on Aging, the Mangurian-Fixel-McKnight Collaboration for Pilot Studies in Lewy Body Dementia, and the American Brain Foundation and the Mary E. Groff Charitable Trust. Dr. Chiu reported receiving grants from Mangurian-Fixel-McKnight Collaboration for Pilot Studies in Lewy Body Dementia and the Smallwood Foundation. Dr. Armstrong disclosed funding from the National Institute on Aging, the Florida Department of Health, the Lewy Body Dementia Association, the Alzheimer’s Therapeutic Research Institute/Alzheimer’s Clinical Trial Consortium, the Alzheimer’s Disease Cooperative Study as Data Safety Monitoring Board the Parkinson’s Foundation, and the American Academy of Neurology.
Tremors and memory symptoms were identified among individuals in a primary care setting as early as 10 years before a Parkinson’s disease diagnosis in a new study.
Most research on the causes and early signs of Parkinson’s disease (PD) have involved patients of Northern European ancestry, Cristina Simonet, MD, of Queen Mary University of London, and colleagues wrote in their paper, published in JAMA Neurology.
Additionally, data on how PD might manifest in different ethnic groups are limited, they said.
In their nested case-control, the researchers examined data from electronic health records of an ethnically diverse population of 1,016,277 adults seen in primary care practices between 1990 and Feb. 6, 2018. They compared individuals with PD with those without PD or other neurologic conditions.
The researchers identified 10 age and sex-matched controls for each PD case, and also conducted an unmatched analysis after adjusting for age and sex. The final study population included 1,055 patients with PD and 1,009,523 controls. The population of PD cases was 15.7% Black, 19.7% South Asian, 50.9% White, and 8.3% other; the population of controls was 13.3% Black, 21.5% South Asian, 43.7% White, and 11.3% other.
“We observed a constellation of symptoms noted by general practitioners up to a decade before diagnosis of PD,” the researchers said. Symptoms were identified across three time intervals (less than 2 years, 2-5 years, and 5-10 years before diagnosis) to better evaluate exposure outcome associations.
In the matched analysis of midlife risk factors, epilepsy showed the strongest association with PD diagnosis across all time periods, and type 2 diabetes or hypertension 5-10 years before diagnosis was associated with later PD.
Prediagnostic signs of PD included both motor and nonmotor manifestations.
The matched analysis revealed a significant increased association between tremor and memory symptoms less than 2 years before diagnosis (adjusted odds ratios of 151.24 and 8.73, respectively) as well as up to 10 years before diagnosis for tremors and up to 5 years for memory symptoms (aOR, 11.4 and 3.09, respectively) in PD patients, compared with controls.
Other strong associations between PD and early nonmotor features in cases, compared with controls, included hypotension (aOR, 6.81), constipation (aOR, 3.29), and depression (aOR, 4.61).
In addition, the researchers found associations for epilepsy that had not been identified in previous studies, and these associations persisted in a replication analysis.
The study findings were limited by several factors, mainly the use of routine primary care data with underascertained factors of interest, and potential mislabeling of PD, the researchers noted. Other limitations included the lack of data on prescription medication for PD, and the recording of memory problems in primary care without supportive testing to confirm cognitive impairment.
The results support a range of comorbidities and symptoms that may present in primary care, and clinicians should consider PD as a possible cause, the researchers wrote.
Make early referral a priority
The study is important because of the lack of diversity in Parkinson’s disease research, lead author Dr. Simonet said in an interview.
“Over the last decade, the global population suffering from Parkinson’s disease has more than doubled,” she said. Causes may include the increasing numbers of older people with longer life expectancy. “However, it seems there are other factors, including environmental, genetic, and lifestyle, that might play a role in increasing the prevalence of Parkinson’s disease.”
“More representative studies, including minority ethnic groups and those living in areas of high social and economic deprivation, are needed,” Dr. Simonet emphasized.
She said that there is little research on the association with epilepsy and hearing loss in early PD, and “for that reason, our results should encourage further studies to confirm a possible link between these manifestations and Parkinson’s disease.”
Early detection may drive better diagnoses
The current study is important for understanding the prediagnostic features and risk factors that may allow for earlier detection of Parkinson’s disease, William Hung, MD, a geriatrics and palliative care specialist of the Icahn School of Medicine at Mount Sinai, New York, said in an interview. “Prior to this study, there was limited understanding of these features.
“One surprise [in the findings] was that ethnicity and socioeconomic deprivation do not appear to be associated with the risk of PD, in contrast to other illnesses such as dementia,” said Dr. Hung. “The array of prediagnostic features associated with PD is not surprising, but nonetheless important for clinicians to know to consider whether PD could be the underlying cause.”
The take-home message for primary care is that “there are features, such as hearing loss, history of epilepsy, autonomic symptoms, motor symptoms, among others, for which clinicians should consider PD as part of the differential diagnosis as underlying cause and consider referral to specialists for diagnostic clarification,” said Dr. Hung.
“Additional research is needed to translate these findings to care, perhaps developing decision aids, interventions that may help with diagnosis and evaluation,” as is work on understanding the link between PD and symptoms such as hearing loss and epilepsy, he said.
Primary care offers opportunity to identify risk factors
The current study represents an important step in early recognition of PD, with implications for helping patients access treatments promptly and improve their quality of life, Bhavana Patel, DO, Shannon Chiu, MD, and Melissa J. Armstrong, MD, of the University of Florida, Gainesville, wrote in an accompanying editorial.
“The primary care setting is commonly where symptoms heralding the onset of PD are first discussed. However, little is known regarding the prediagnostic manifestations of PD that are seen in primary care clinics, particularly in underserved populations,” they wrote.
The study included many risk factors and prodromal markers associated with research criteria for prodromal PD, but did not include several risk and prodromal markers in the Movement Disorders Society research criteria, “such as symptoms suggestive of REM sleep behavior disorder, excessive daytime sleepiness (which overlaps with, but is distinct from, fatigue), urinary dysfunction, pesticide and solvent exposure, caffeine use, level of physical activity, and family history,” they said.
Even in individuals with diagnosed PD, certain symptoms, particularly nonmotor symptoms, are commonly underreported,” and primary care clinicians may not recognize these symptoms as PD risk factors, the authors noted.
However, “in addition to contributing to possible models of modifiable risk factors for PD, study results may also further inform algorithms designed to predict PD diagnoses in primary care,” they said. The study also highlights the need for more multivariable models to better identify PD risk factors and strategies for early identification of PD in primary care.
Several study coauthors received funding related to the study from Barts Charity, Health Data Research UK, the Department of Health and Social Care (England) and the devolved administrations, and leading medical research charities, as well as the National Institute for Health Research UCLH Biomedical Research Centre. Lead author Dr. Simonet and Dr. Hung had no financial conflicts to disclose. Dr. Patel disclosed support from the National Institute on Aging, the Mangurian-Fixel-McKnight Collaboration for Pilot Studies in Lewy Body Dementia, and the American Brain Foundation and the Mary E. Groff Charitable Trust. Dr. Chiu reported receiving grants from Mangurian-Fixel-McKnight Collaboration for Pilot Studies in Lewy Body Dementia and the Smallwood Foundation. Dr. Armstrong disclosed funding from the National Institute on Aging, the Florida Department of Health, the Lewy Body Dementia Association, the Alzheimer’s Therapeutic Research Institute/Alzheimer’s Clinical Trial Consortium, the Alzheimer’s Disease Cooperative Study as Data Safety Monitoring Board the Parkinson’s Foundation, and the American Academy of Neurology.
FROM JAMA NEUROLOGY
Concussion increases risk of mental health issues in children
Among children and adolescents aged 5-18 years, concussion was associated with a higher risk of mental health problems, compared with age- and sex-matched children and adolescents with an orthopedic injury, according to a cohort study published in JAMA Network Open.
While concussions are one of the most common head injuries in the pediatric population, the extent to which they increase the risk of new onset psychiatric disorders or subsequent psychopathology is unclear, lead author Andrée-Anne Ledoux, PhD, of the Children’s Hospital of Eastern Ontario Research Institute, Ottawa, and colleagues explained.
The researchers conducted a population-based retrospective cohort study to evaluate associations between concussion and risk of subsequent mental health issues, psychiatric hospitalizations, self-harm, or suicides in children and adolescents, with follow-up ranging from 1 month to 10 years.
The data were obtained from province-wide health administrative databases. Participants with concussion were included in an exposed group, while those with an orthopedic injury were included in a 1:2 age- and sex-matched comparison group.
Results
The study cohort comprised 448,803 participants, including 152,321 and 296,482 children and adolescents with concussion and orthopedic injury, respectively.
The incidence rates of any mental health problem were 11,141 per 100,000 person-years in the exposed group and 7,960 per 100,000 person-years in the unexposed group (difference, 3,181; 95% confidence interval, 3,073-3,291 per 100,000 person-years).
After concussion, the exposed group had a greater risk of developing a mental health issue (adjusted hazard ratio, 1.39; 95% CI, 1.37-1.40), psychiatric hospitalization (aHR, 1.47; 95% CI, 1.41-1.53), and self-harm (aHR, 1.49; 95% CI, 1.42-1.56). In addition, there was no significant difference in death by suicide between the exposed and unexposed groups (HR, 1.54; 95% CI, 0.90-2.61).
“Our results suggest that clinicians should assess for preexisting and new mental health symptoms throughout concussion recovery and treat mental health conditions or symptoms or refer the patient to a specialist in pediatric mental health,” wrote Dr. Ledoux and colleagues. “[Clinicians should also] assess suicidal ideation and self-harm behaviors during evaluation and follow-up visits for concussion.”
The researchers acknowledged that a key limitation of the study was the retrospective observational design. In addition, the identification of exposures using diagnostic billing codes could have introduced exposure or outcome misclassification.
Expert-recommended resources
“For more information, I’d recommend ‘Pedsconcussion,’ which are evidence-based living guidelines for pediatric concussion care,” Dr. Ledoux said in an interview. “Within domain 8, there are specific guidelines related to the management of mental health issues post concussion.”
Neuropsychology expert Talin Babikian, PhD, of the University of California, Los Angeles, commented: “Studies have shown that even a single psychoeducational session early after a concussion can minimize prolonged recoveries. Ensuring all stakeholders (family, clinicians, school, coach, peers) are on the same page and providing the same information is important to build trust and a sense of safety and agency.
“We want to provide psychoeducation early in the process to avoid unnecessary fear and avoidance. We also want to curtail misattribution of everyday symptoms or symptoms related to an unrelated condition to a brain injury, which are easier to do when caught early,” Dr. Babikian added.
This study was supported by the Institute for Clinical Evaluative Sciences, which is funded by an annual grant from the Ontario Ministry of Health and the Ministry of Long-term Care. One author reported financial relationships with the University of Ottawa, the National Football League, Parachute Canada, and 360 Concussion Care, an interdisciplinary concussion clinic; no other conflicts of interest were reported.
Among children and adolescents aged 5-18 years, concussion was associated with a higher risk of mental health problems, compared with age- and sex-matched children and adolescents with an orthopedic injury, according to a cohort study published in JAMA Network Open.
While concussions are one of the most common head injuries in the pediatric population, the extent to which they increase the risk of new onset psychiatric disorders or subsequent psychopathology is unclear, lead author Andrée-Anne Ledoux, PhD, of the Children’s Hospital of Eastern Ontario Research Institute, Ottawa, and colleagues explained.
The researchers conducted a population-based retrospective cohort study to evaluate associations between concussion and risk of subsequent mental health issues, psychiatric hospitalizations, self-harm, or suicides in children and adolescents, with follow-up ranging from 1 month to 10 years.
The data were obtained from province-wide health administrative databases. Participants with concussion were included in an exposed group, while those with an orthopedic injury were included in a 1:2 age- and sex-matched comparison group.
Results
The study cohort comprised 448,803 participants, including 152,321 and 296,482 children and adolescents with concussion and orthopedic injury, respectively.
The incidence rates of any mental health problem were 11,141 per 100,000 person-years in the exposed group and 7,960 per 100,000 person-years in the unexposed group (difference, 3,181; 95% confidence interval, 3,073-3,291 per 100,000 person-years).
After concussion, the exposed group had a greater risk of developing a mental health issue (adjusted hazard ratio, 1.39; 95% CI, 1.37-1.40), psychiatric hospitalization (aHR, 1.47; 95% CI, 1.41-1.53), and self-harm (aHR, 1.49; 95% CI, 1.42-1.56). In addition, there was no significant difference in death by suicide between the exposed and unexposed groups (HR, 1.54; 95% CI, 0.90-2.61).
“Our results suggest that clinicians should assess for preexisting and new mental health symptoms throughout concussion recovery and treat mental health conditions or symptoms or refer the patient to a specialist in pediatric mental health,” wrote Dr. Ledoux and colleagues. “[Clinicians should also] assess suicidal ideation and self-harm behaviors during evaluation and follow-up visits for concussion.”
The researchers acknowledged that a key limitation of the study was the retrospective observational design. In addition, the identification of exposures using diagnostic billing codes could have introduced exposure or outcome misclassification.
Expert-recommended resources
“For more information, I’d recommend ‘Pedsconcussion,’ which are evidence-based living guidelines for pediatric concussion care,” Dr. Ledoux said in an interview. “Within domain 8, there are specific guidelines related to the management of mental health issues post concussion.”
Neuropsychology expert Talin Babikian, PhD, of the University of California, Los Angeles, commented: “Studies have shown that even a single psychoeducational session early after a concussion can minimize prolonged recoveries. Ensuring all stakeholders (family, clinicians, school, coach, peers) are on the same page and providing the same information is important to build trust and a sense of safety and agency.
“We want to provide psychoeducation early in the process to avoid unnecessary fear and avoidance. We also want to curtail misattribution of everyday symptoms or symptoms related to an unrelated condition to a brain injury, which are easier to do when caught early,” Dr. Babikian added.
This study was supported by the Institute for Clinical Evaluative Sciences, which is funded by an annual grant from the Ontario Ministry of Health and the Ministry of Long-term Care. One author reported financial relationships with the University of Ottawa, the National Football League, Parachute Canada, and 360 Concussion Care, an interdisciplinary concussion clinic; no other conflicts of interest were reported.
Among children and adolescents aged 5-18 years, concussion was associated with a higher risk of mental health problems, compared with age- and sex-matched children and adolescents with an orthopedic injury, according to a cohort study published in JAMA Network Open.
While concussions are one of the most common head injuries in the pediatric population, the extent to which they increase the risk of new onset psychiatric disorders or subsequent psychopathology is unclear, lead author Andrée-Anne Ledoux, PhD, of the Children’s Hospital of Eastern Ontario Research Institute, Ottawa, and colleagues explained.
The researchers conducted a population-based retrospective cohort study to evaluate associations between concussion and risk of subsequent mental health issues, psychiatric hospitalizations, self-harm, or suicides in children and adolescents, with follow-up ranging from 1 month to 10 years.
The data were obtained from province-wide health administrative databases. Participants with concussion were included in an exposed group, while those with an orthopedic injury were included in a 1:2 age- and sex-matched comparison group.
Results
The study cohort comprised 448,803 participants, including 152,321 and 296,482 children and adolescents with concussion and orthopedic injury, respectively.
The incidence rates of any mental health problem were 11,141 per 100,000 person-years in the exposed group and 7,960 per 100,000 person-years in the unexposed group (difference, 3,181; 95% confidence interval, 3,073-3,291 per 100,000 person-years).
After concussion, the exposed group had a greater risk of developing a mental health issue (adjusted hazard ratio, 1.39; 95% CI, 1.37-1.40), psychiatric hospitalization (aHR, 1.47; 95% CI, 1.41-1.53), and self-harm (aHR, 1.49; 95% CI, 1.42-1.56). In addition, there was no significant difference in death by suicide between the exposed and unexposed groups (HR, 1.54; 95% CI, 0.90-2.61).
“Our results suggest that clinicians should assess for preexisting and new mental health symptoms throughout concussion recovery and treat mental health conditions or symptoms or refer the patient to a specialist in pediatric mental health,” wrote Dr. Ledoux and colleagues. “[Clinicians should also] assess suicidal ideation and self-harm behaviors during evaluation and follow-up visits for concussion.”
The researchers acknowledged that a key limitation of the study was the retrospective observational design. In addition, the identification of exposures using diagnostic billing codes could have introduced exposure or outcome misclassification.
Expert-recommended resources
“For more information, I’d recommend ‘Pedsconcussion,’ which are evidence-based living guidelines for pediatric concussion care,” Dr. Ledoux said in an interview. “Within domain 8, there are specific guidelines related to the management of mental health issues post concussion.”
Neuropsychology expert Talin Babikian, PhD, of the University of California, Los Angeles, commented: “Studies have shown that even a single psychoeducational session early after a concussion can minimize prolonged recoveries. Ensuring all stakeholders (family, clinicians, school, coach, peers) are on the same page and providing the same information is important to build trust and a sense of safety and agency.
“We want to provide psychoeducation early in the process to avoid unnecessary fear and avoidance. We also want to curtail misattribution of everyday symptoms or symptoms related to an unrelated condition to a brain injury, which are easier to do when caught early,” Dr. Babikian added.
This study was supported by the Institute for Clinical Evaluative Sciences, which is funded by an annual grant from the Ontario Ministry of Health and the Ministry of Long-term Care. One author reported financial relationships with the University of Ottawa, the National Football League, Parachute Canada, and 360 Concussion Care, an interdisciplinary concussion clinic; no other conflicts of interest were reported.
FROM JAMA NETWORK OPEN
Past spontaneous abortion raises risk for gestational diabetes
Pregnant women with a history of spontaneous abortion had a significantly increased risk of gestational diabetes in subsequent pregnancies, based on data from more than 100,000 women.
Gestational diabetes is associated not only with adverse perinatal outcomes, but also with an increased risk of long-term cardiovascular and metabolic health issues in mothers and children, wrote Yan Zhao, PhD, of Tongji University, Shanghai, and colleagues.
Previous studies also have shown that spontaneous abortion (SAB) is associated with later maternal risk of cardiovascular disease and venous thromboembolism, the researchers said. The same mechanisms might contribute to the development of gestational diabetes, but the association between abortion history and gestational diabetes risk in subsequent pregnancies remains unclear, they added.
In a study published in JAMA Network Open, the researchers identified 102,259 pregnant women seen for routine prenatal care at a single hospital in Shanghai between January 2014 and December 2019. The mean age of the women was 29.8 years.
During the study period, 14,579 women experienced SAB (14.3%), 17,935 experienced induced abortion (17.5%), and 4,017 experienced both (11.9%).
In all, 12,153 cases of gestational diabetes were identified, for a prevalence of 11.9%. The relative risk of gestational diabetes was 1.25 for women who experienced SAB and 1.15 for those who experienced both SAB and induced abortion, and the association between SAB and gestational diabetes increased in a number-dependent manner, the researchers said. The increase in relative risk for gestational diabetes in pregnant women with one SAB, two SABs, and three or more SABs was 18%, 41%, and 43%, compared to pregnant women with no SAB history.
However, no association appeared between a history of induced abortion and gestational diabetes, the researchers said. “To date, no study has reported the association of prior induced abortion with gestational diabetes,” they wrote.
The study findings were limited by several factors including the reliance on self-reports for history of SAB and therefore possible underreporting, the researchers noted. Other limitations included the lack of data on the timing of SABs; therefore, the time between SAB and gestational diabetes diagnosis could not be included in the analysis, they said. Unknown variables and the inclusion only of women from a single city in China might limit the generalizability of the results, they added.
More research is needed to understand the biological mechanisms behind the association between SAB and gestational diabetes, an association that has potential public health implications, they noted. However, the results suggest that “pregnant women with a history of SAB, especially those with a history of recurrent SAB, should attend more antenatal visits to monitor their blood glucose and implement early prevention and intervention,” such as healthful eating and regular exercise, they wrote.
Findings confirm, not surprise
The diagnosis of gestational diabetes in the current study “was made with a slightly different test than we typically use in the United States – a 1-hour nonfasting glucola followed by a confirmatory 3-hour fasting glucola,” Sarah W. Prager, MD, of the University of Washington, Seattle, said in an interview. The current study of both SAB and gestational diabetes is important because both conditions are very common and have been the focus of increased attention in the popular media and in scientific study, she said.
Dr. Prager said she was not surprised by the findings of a link between a history of gestational diabetes and a history of SAB, “but the association is likely that people at risk for gestational diabetes or who have undiagnosed diabetes/glucose intolerance are more likely to experience SAB,” she noted. “I would be surprised if the direction of the association is that SAB puts people at risk for gestational diabetes; more likely undiagnosed diabetes is a risk factor for SAB,” she added. “Perhaps we should be screening for glucose intolerance and other metabolic disorders more frequently in people who have especially recurrent SAB, as the more miscarriages someone had, the more likely they were in this study to be diagnosed with gestational diabetes;” or perhaps those with a history of SAB/recurrent SAB should be screened closer to 24 weeks’ than 28 weeks’ gestation to enable earlier intervention in those more likely to have gestational diabetes, Dr. Prager said.
The study was supported by the Key Program of the National Natural Science Foundation of China, the National Natural Science Foundation of China, the National Key Research and Development Program of China, the Shanghai Municipal Medical and Health Discipline Construction Projects, and the Shanghai Rising-Star Program. The researchers and Dr. Prager had no financial conflicts to disclose. Dr. Prager serves on the editorial advisory board of Ob.Gyn. News.
Pregnant women with a history of spontaneous abortion had a significantly increased risk of gestational diabetes in subsequent pregnancies, based on data from more than 100,000 women.
Gestational diabetes is associated not only with adverse perinatal outcomes, but also with an increased risk of long-term cardiovascular and metabolic health issues in mothers and children, wrote Yan Zhao, PhD, of Tongji University, Shanghai, and colleagues.
Previous studies also have shown that spontaneous abortion (SAB) is associated with later maternal risk of cardiovascular disease and venous thromboembolism, the researchers said. The same mechanisms might contribute to the development of gestational diabetes, but the association between abortion history and gestational diabetes risk in subsequent pregnancies remains unclear, they added.
In a study published in JAMA Network Open, the researchers identified 102,259 pregnant women seen for routine prenatal care at a single hospital in Shanghai between January 2014 and December 2019. The mean age of the women was 29.8 years.
During the study period, 14,579 women experienced SAB (14.3%), 17,935 experienced induced abortion (17.5%), and 4,017 experienced both (11.9%).
In all, 12,153 cases of gestational diabetes were identified, for a prevalence of 11.9%. The relative risk of gestational diabetes was 1.25 for women who experienced SAB and 1.15 for those who experienced both SAB and induced abortion, and the association between SAB and gestational diabetes increased in a number-dependent manner, the researchers said. The increase in relative risk for gestational diabetes in pregnant women with one SAB, two SABs, and three or more SABs was 18%, 41%, and 43%, compared to pregnant women with no SAB history.
However, no association appeared between a history of induced abortion and gestational diabetes, the researchers said. “To date, no study has reported the association of prior induced abortion with gestational diabetes,” they wrote.
The study findings were limited by several factors including the reliance on self-reports for history of SAB and therefore possible underreporting, the researchers noted. Other limitations included the lack of data on the timing of SABs; therefore, the time between SAB and gestational diabetes diagnosis could not be included in the analysis, they said. Unknown variables and the inclusion only of women from a single city in China might limit the generalizability of the results, they added.
More research is needed to understand the biological mechanisms behind the association between SAB and gestational diabetes, an association that has potential public health implications, they noted. However, the results suggest that “pregnant women with a history of SAB, especially those with a history of recurrent SAB, should attend more antenatal visits to monitor their blood glucose and implement early prevention and intervention,” such as healthful eating and regular exercise, they wrote.
Findings confirm, not surprise
The diagnosis of gestational diabetes in the current study “was made with a slightly different test than we typically use in the United States – a 1-hour nonfasting glucola followed by a confirmatory 3-hour fasting glucola,” Sarah W. Prager, MD, of the University of Washington, Seattle, said in an interview. The current study of both SAB and gestational diabetes is important because both conditions are very common and have been the focus of increased attention in the popular media and in scientific study, she said.
Dr. Prager said she was not surprised by the findings of a link between a history of gestational diabetes and a history of SAB, “but the association is likely that people at risk for gestational diabetes or who have undiagnosed diabetes/glucose intolerance are more likely to experience SAB,” she noted. “I would be surprised if the direction of the association is that SAB puts people at risk for gestational diabetes; more likely undiagnosed diabetes is a risk factor for SAB,” she added. “Perhaps we should be screening for glucose intolerance and other metabolic disorders more frequently in people who have especially recurrent SAB, as the more miscarriages someone had, the more likely they were in this study to be diagnosed with gestational diabetes;” or perhaps those with a history of SAB/recurrent SAB should be screened closer to 24 weeks’ than 28 weeks’ gestation to enable earlier intervention in those more likely to have gestational diabetes, Dr. Prager said.
The study was supported by the Key Program of the National Natural Science Foundation of China, the National Natural Science Foundation of China, the National Key Research and Development Program of China, the Shanghai Municipal Medical and Health Discipline Construction Projects, and the Shanghai Rising-Star Program. The researchers and Dr. Prager had no financial conflicts to disclose. Dr. Prager serves on the editorial advisory board of Ob.Gyn. News.
Pregnant women with a history of spontaneous abortion had a significantly increased risk of gestational diabetes in subsequent pregnancies, based on data from more than 100,000 women.
Gestational diabetes is associated not only with adverse perinatal outcomes, but also with an increased risk of long-term cardiovascular and metabolic health issues in mothers and children, wrote Yan Zhao, PhD, of Tongji University, Shanghai, and colleagues.
Previous studies also have shown that spontaneous abortion (SAB) is associated with later maternal risk of cardiovascular disease and venous thromboembolism, the researchers said. The same mechanisms might contribute to the development of gestational diabetes, but the association between abortion history and gestational diabetes risk in subsequent pregnancies remains unclear, they added.
In a study published in JAMA Network Open, the researchers identified 102,259 pregnant women seen for routine prenatal care at a single hospital in Shanghai between January 2014 and December 2019. The mean age of the women was 29.8 years.
During the study period, 14,579 women experienced SAB (14.3%), 17,935 experienced induced abortion (17.5%), and 4,017 experienced both (11.9%).
In all, 12,153 cases of gestational diabetes were identified, for a prevalence of 11.9%. The relative risk of gestational diabetes was 1.25 for women who experienced SAB and 1.15 for those who experienced both SAB and induced abortion, and the association between SAB and gestational diabetes increased in a number-dependent manner, the researchers said. The increase in relative risk for gestational diabetes in pregnant women with one SAB, two SABs, and three or more SABs was 18%, 41%, and 43%, compared to pregnant women with no SAB history.
However, no association appeared between a history of induced abortion and gestational diabetes, the researchers said. “To date, no study has reported the association of prior induced abortion with gestational diabetes,” they wrote.
The study findings were limited by several factors including the reliance on self-reports for history of SAB and therefore possible underreporting, the researchers noted. Other limitations included the lack of data on the timing of SABs; therefore, the time between SAB and gestational diabetes diagnosis could not be included in the analysis, they said. Unknown variables and the inclusion only of women from a single city in China might limit the generalizability of the results, they added.
More research is needed to understand the biological mechanisms behind the association between SAB and gestational diabetes, an association that has potential public health implications, they noted. However, the results suggest that “pregnant women with a history of SAB, especially those with a history of recurrent SAB, should attend more antenatal visits to monitor their blood glucose and implement early prevention and intervention,” such as healthful eating and regular exercise, they wrote.
Findings confirm, not surprise
The diagnosis of gestational diabetes in the current study “was made with a slightly different test than we typically use in the United States – a 1-hour nonfasting glucola followed by a confirmatory 3-hour fasting glucola,” Sarah W. Prager, MD, of the University of Washington, Seattle, said in an interview. The current study of both SAB and gestational diabetes is important because both conditions are very common and have been the focus of increased attention in the popular media and in scientific study, she said.
Dr. Prager said she was not surprised by the findings of a link between a history of gestational diabetes and a history of SAB, “but the association is likely that people at risk for gestational diabetes or who have undiagnosed diabetes/glucose intolerance are more likely to experience SAB,” she noted. “I would be surprised if the direction of the association is that SAB puts people at risk for gestational diabetes; more likely undiagnosed diabetes is a risk factor for SAB,” she added. “Perhaps we should be screening for glucose intolerance and other metabolic disorders more frequently in people who have especially recurrent SAB, as the more miscarriages someone had, the more likely they were in this study to be diagnosed with gestational diabetes;” or perhaps those with a history of SAB/recurrent SAB should be screened closer to 24 weeks’ than 28 weeks’ gestation to enable earlier intervention in those more likely to have gestational diabetes, Dr. Prager said.
The study was supported by the Key Program of the National Natural Science Foundation of China, the National Natural Science Foundation of China, the National Key Research and Development Program of China, the Shanghai Municipal Medical and Health Discipline Construction Projects, and the Shanghai Rising-Star Program. The researchers and Dr. Prager had no financial conflicts to disclose. Dr. Prager serves on the editorial advisory board of Ob.Gyn. News.
FROM JAMA NETWORK OPEN
15th Report on Carcinogens Adds to Its List
From environmental tobacco smoke to ultraviolet (UV) radiation, diesel exhaust particulates, lead, and now, chronic infection with Helicobacter pylori (H pylori)—the Report on Carcinogens has regularly updated the list of substances known or “reasonably anticipated” to cause cancer.
The 15th report, which is prepared by the National Toxicology Program (NTP) for the Department of Health and Human Services, has 8 new entries, bringing the number of human carcinogens (eg, metals, pesticides, and drugs) on the list to 256. (The first report, released in 1980, listed 26.) In addition to H pylori infection, this edition adds the flame-retardant chemical antimony trioxide, and 6 haloacetic acids found as water disinfection byproducts.
In 1971, then President Nixon declared “war on cancer” (the second leading cause of death in the US) and signed the National Cancer Act. In 1978, Congress ordered the Report on Carcinogens, to educate the public and health professionals on potential environmental carcinogenic hazards.
Perhaps disheartening to know that even with 256 entries, the list probably understates the number of carcinogens humans and other creatures are exposed to. But things can change with time. Each list goes through a rigorous round of reviews. Sometimes substances are “delisted” after, for instance, litigation or new research. Saccharin, for example, was removed from the ninth edition. It was listed as “reasonably anticipated” in 1981, based on “sufficient evidence of carcinogenicity in experimental animals.” It was removed, however, after extensive review of decades of saccharin use determined that the data were not sufficient to meet current criteria. Further research had revealed, also, that the observed bladder tumors in rats arose from a mechanism not relevant to humans.
Other entries, such as the controversial listing of the cancer drug tamoxifen, walk a fine line between risk and benefit. Tamoxifen, first listed in the ninth report (and still in the 15th report), was included because studies revealed that it could increase the risk of uterine cancer in women. But there also was conclusive evidence that it may prevent or delay breast cancer in women who are at high risk.
Ultimately, the report’s authors make it clear that it is for informative value and guidance, not necessarily a dictate. As one report put it: “Personal decisions concerning voluntary exposures to carcinogenic agents need to be based on additional information that is beyond the scope” of the report.
“As the identification of carcinogens is a key step in cancer prevention,” said Rick Woychik, PhD, director of the National Institute of Environmental Health Sciences and NTP, “publication of the report represents an important government activity towards improving public health.”
From environmental tobacco smoke to ultraviolet (UV) radiation, diesel exhaust particulates, lead, and now, chronic infection with Helicobacter pylori (H pylori)—the Report on Carcinogens has regularly updated the list of substances known or “reasonably anticipated” to cause cancer.
The 15th report, which is prepared by the National Toxicology Program (NTP) for the Department of Health and Human Services, has 8 new entries, bringing the number of human carcinogens (eg, metals, pesticides, and drugs) on the list to 256. (The first report, released in 1980, listed 26.) In addition to H pylori infection, this edition adds the flame-retardant chemical antimony trioxide, and 6 haloacetic acids found as water disinfection byproducts.
In 1971, then President Nixon declared “war on cancer” (the second leading cause of death in the US) and signed the National Cancer Act. In 1978, Congress ordered the Report on Carcinogens, to educate the public and health professionals on potential environmental carcinogenic hazards.
Perhaps disheartening to know that even with 256 entries, the list probably understates the number of carcinogens humans and other creatures are exposed to. But things can change with time. Each list goes through a rigorous round of reviews. Sometimes substances are “delisted” after, for instance, litigation or new research. Saccharin, for example, was removed from the ninth edition. It was listed as “reasonably anticipated” in 1981, based on “sufficient evidence of carcinogenicity in experimental animals.” It was removed, however, after extensive review of decades of saccharin use determined that the data were not sufficient to meet current criteria. Further research had revealed, also, that the observed bladder tumors in rats arose from a mechanism not relevant to humans.
Other entries, such as the controversial listing of the cancer drug tamoxifen, walk a fine line between risk and benefit. Tamoxifen, first listed in the ninth report (and still in the 15th report), was included because studies revealed that it could increase the risk of uterine cancer in women. But there also was conclusive evidence that it may prevent or delay breast cancer in women who are at high risk.
Ultimately, the report’s authors make it clear that it is for informative value and guidance, not necessarily a dictate. As one report put it: “Personal decisions concerning voluntary exposures to carcinogenic agents need to be based on additional information that is beyond the scope” of the report.
“As the identification of carcinogens is a key step in cancer prevention,” said Rick Woychik, PhD, director of the National Institute of Environmental Health Sciences and NTP, “publication of the report represents an important government activity towards improving public health.”
From environmental tobacco smoke to ultraviolet (UV) radiation, diesel exhaust particulates, lead, and now, chronic infection with Helicobacter pylori (H pylori)—the Report on Carcinogens has regularly updated the list of substances known or “reasonably anticipated” to cause cancer.
The 15th report, which is prepared by the National Toxicology Program (NTP) for the Department of Health and Human Services, has 8 new entries, bringing the number of human carcinogens (eg, metals, pesticides, and drugs) on the list to 256. (The first report, released in 1980, listed 26.) In addition to H pylori infection, this edition adds the flame-retardant chemical antimony trioxide, and 6 haloacetic acids found as water disinfection byproducts.
In 1971, then President Nixon declared “war on cancer” (the second leading cause of death in the US) and signed the National Cancer Act. In 1978, Congress ordered the Report on Carcinogens, to educate the public and health professionals on potential environmental carcinogenic hazards.
Perhaps disheartening to know that even with 256 entries, the list probably understates the number of carcinogens humans and other creatures are exposed to. But things can change with time. Each list goes through a rigorous round of reviews. Sometimes substances are “delisted” after, for instance, litigation or new research. Saccharin, for example, was removed from the ninth edition. It was listed as “reasonably anticipated” in 1981, based on “sufficient evidence of carcinogenicity in experimental animals.” It was removed, however, after extensive review of decades of saccharin use determined that the data were not sufficient to meet current criteria. Further research had revealed, also, that the observed bladder tumors in rats arose from a mechanism not relevant to humans.
Other entries, such as the controversial listing of the cancer drug tamoxifen, walk a fine line between risk and benefit. Tamoxifen, first listed in the ninth report (and still in the 15th report), was included because studies revealed that it could increase the risk of uterine cancer in women. But there also was conclusive evidence that it may prevent or delay breast cancer in women who are at high risk.
Ultimately, the report’s authors make it clear that it is for informative value and guidance, not necessarily a dictate. As one report put it: “Personal decisions concerning voluntary exposures to carcinogenic agents need to be based on additional information that is beyond the scope” of the report.
“As the identification of carcinogens is a key step in cancer prevention,” said Rick Woychik, PhD, director of the National Institute of Environmental Health Sciences and NTP, “publication of the report represents an important government activity towards improving public health.”
Fewer than half with severe aortic stenosis get new valves
The chance that patients with severe aortic stenosis (AS) will receive aortic valve replacement (AVR) is worse than the flip of a coin, even a decade after the gamechanging transcatheter option became available, a new study suggests.
Of the study’s 6,150 patients with an indication or potential indication for AVR, 48% received the procedure at Massachusetts General Hospital and its partner institution Brigham and Women’s Hospital, both in Boston – both of which have active, high-volume transcatheter and surgical AVR (TAVR/SAVR) programs.
“Essentially, this is a best-case scenario. So, unfortunately, I think on the national level we are likely to see rates that are far worse than what we observed here,” senior author Sammy Elmariah, MD, PhD, Massachusetts General Hospital, told this news organization.
The volume of AVR increased more than 10-fold over the 18-year study period (2000 to 2017), driven by the exponential growth of TAVR, he noted. However, the graying of America led to an even greater increase in the number of patients with severe AS and an indication for AVR.
The study, led by Shawn X. Li, MD, MBA, of Mass General, was published in the March 8 issue of the Journal of the American College of Cardiology.
Previous research has provided equally compelling data on the undertreatment of AS, including a 2021 study using natural language processing (NLP) that found AVR use was just 35.6% within 1 year of diagnosis and varied wildly among managing cardiologists.
The present study used NLP tools to identify symptoms consistent with severe AS in the medical record coupled with echocardiographic data from 10,795 patients with severe AS (valve area <1 cm2). Patients were divided into four AS subtypes and then classified as having a class 1 indication (high-gradient AS with symptoms or reduced ejection fraction [EF]) or a potential class 2a indication (low-gradient AS with symptoms) for AVR.
Among patients with high-gradient AS and class 1 indication for AVR, 1 in 3 did not receive AVR over the study period, including 30% with a normal EF and 47% with a low EF.
In those with low-gradient AS, 67% with a normal EF and 62% with a low EF did not receive AVR. The low-gradient groups were significantly less likely to receive AVR both in the entire study period and in the more contemporary period from 2014 to 2017, despite the valvular heart disease guideline 2014 update indicating AVR was “reasonable” in patients with low-gradient AS – a 2a recommendation upgraded to class 1 in the most recent 2020 update.
Better survival
In patients with a class 1 or potential class 2a indication, AVR was associated with a significantly lower risk of mortality in all four AS subgroups:
- High gradient/normal EF: 3% vs. 15%; adjusted hazard ratio, 0.42
- High-gradient/low EF: 16% vs. 72%; aHR, 0.28
- Low-gradient/normal EF: 5% vs. 14%; aHR, 0.73
- Low-gradient/low EF: 11% vs. 34%; aHR, 0.48; P < .001 for all
“I think what we need to do is change the paradigm, such that patients with a valve area that is less than or equal to 1 [cm2] is severe aortic stenosis until proven otherwise, and that essentially establishes a premise by which we default to treat these patients unless we can prove that it is in fact moderate,” Dr. Elmariah said.
Unfortunately, the opposite is currently true today, he said, and the default is not to treat and put patients through surgery or an invasive TAVR procedure unless physicians can definitively prove that it is severe AS. But they’re not always correct and don’t always have the ability to truly differentiate moderate from severe disease.
“The question, therefore, is ‘What do we do with those patients?’” Dr. Elmariah asked. “I think if a patient has symptoms, then we are obligated to intervene, given the stark difference in mortality that one sees when these patients go undertreated.”
Sounding the alarm
Robert Bonow, MD, a professor of cardiology at Northwestern University in Chicago and a writing committee member for the 2014 guideline update, said the study is a “big wake-up call” and “the take-home message is that we are missing some patients who have treatable aortic stenosis.”
The sheer magnitude of the problem, however, can be difficult to fully ascertain from administrative data like this, he said. Notably, patients who did not receive AVR were significantly older, with 37% aged 81-90 years and 12% over age 90, and had a lower hematocrit and lower estimated glomerular filtration rate. But it’s not clear how many had cancer, end-stage renal disease, or severe lung disease, which could have factored into the decision to undergo AVR.
“What’s also an issue is that over 50% of patients had low gradient disease, which is very problematic and takes careful assessment in an individual patient,” said Dr. Bonow, who is also editor-in-chief of JAMA Cardiology. “That’s all being generated by a low valve area of less than 1 cm2 from echo reports, so that’s not necessarily a careful prospective echo assessment ... so some of the patients with low-gradient disease may not have true severe aortic stenosis.”
Dr. Elmariah agreed that echocardiogram reports are not always clear cut and pointed out that referral to a valve specialist was highly predictive of whether or not a patient underwent AVR, supporting the class 1 guideline recommendation.
He also noted that Mass General is launching the DETECT-AS trial to determine whether electronic physician notifications highlighting clinical practice guideline recommendations will improve AVR utilization over standard care in 940 patients with severe AS on echocardiogram, defined by a valve area less than 1 cm2.
Reached for comment, Catherine Otto, MD, director of the Heart Valve Clinic at the University of Washington, Seattle, and a fellow member of the 2014 guideline writing committee, said “this adds to the data [that] we’re undertreating severe aortic stenosis, and it continues to be surprising given the availability of transcatheter options.”
The biggest challenge is trying to find out why it persists, which is difficult to determine from these data, she said. Whether that’s because the diagnosis is being missed or whether there are barriers to access because cardiologists aren’t understanding the indications or patients aren’t understanding what’s being offered, isn’t clear.
“The other [issue], of course, is are there inappropriate inequities in care? Is it fewer women, age-related, ethnic/racial-related; is it financial? Do people have coverage to get the treatment they need in our country?” Dr. Otto said. “All of those issues are areas that need to be addressed, and I think that is a concern we all have.”
An accompanying editorial points out that the “key lever” in combating undertreatment of AS is getting patients seen by a multidisciplinary heart team and details other possible solutions, such as adding process metrics regarding evaluation and treatment of AS to hospital performance.
“We track quality when AVR is performed (desirable), but how a hospital system performs in getting individuals treated who would benefit from AVR remains a complete blind spot,” write Brian Lindman, MD, MSc, and Angela Lowenstern, MD, MHS, both of Vanderbilt University Medical Center, Nashville, Tenn.
“Is it appropriate to consider the hospital ‘high performing’ when data from Li et al. show a 2-year absolute mortality difference from 9% to 56% based on treatment versus nontreatment with AVR for various AS patient subgroups?” they add.
Dr. Lindman and Dr. Lowenstern observe that having a 50% utilization rate for an effective therapy for a deadly cancer or stenting of ST-segment elevation myocardial infarction (STEMI) would generate negative headlines and a collective commitment to swift action by multiple stakeholders to address what would be “incontrovertibly unacceptable.”
“In one of America’s leading health care systems, there was evidence of an overwhelming reduction in the risk of death with AVR in all AS subgroups examined, but <50% of patients with AS with an indication or potential indication for AVR were treated with an AVR. Let that set in; hear and internalize the alarm. The status quo is unacceptable. What will you do? What will we do?” they conclude.
The study was funded by Edwards Lifesciences. Dr. Elmariah has received research grants from the American Heart Association, National Institutes of Health, Edwards Lifesciences, Svelte Medical, Abbott Vascular, and Medtronic, and has received consulting fees from Edwards Lifesciences. Dr. Bonow and Dr. Otto have disclosed no relevant financial relationships. Dr. Lindman has received investigator-initiated research grants from Edwards. Dr. Lowenstern has received consulting fees from Edwards.
A version of this article first appeared on Medscape.com.
The chance that patients with severe aortic stenosis (AS) will receive aortic valve replacement (AVR) is worse than the flip of a coin, even a decade after the gamechanging transcatheter option became available, a new study suggests.
Of the study’s 6,150 patients with an indication or potential indication for AVR, 48% received the procedure at Massachusetts General Hospital and its partner institution Brigham and Women’s Hospital, both in Boston – both of which have active, high-volume transcatheter and surgical AVR (TAVR/SAVR) programs.
“Essentially, this is a best-case scenario. So, unfortunately, I think on the national level we are likely to see rates that are far worse than what we observed here,” senior author Sammy Elmariah, MD, PhD, Massachusetts General Hospital, told this news organization.
The volume of AVR increased more than 10-fold over the 18-year study period (2000 to 2017), driven by the exponential growth of TAVR, he noted. However, the graying of America led to an even greater increase in the number of patients with severe AS and an indication for AVR.
The study, led by Shawn X. Li, MD, MBA, of Mass General, was published in the March 8 issue of the Journal of the American College of Cardiology.
Previous research has provided equally compelling data on the undertreatment of AS, including a 2021 study using natural language processing (NLP) that found AVR use was just 35.6% within 1 year of diagnosis and varied wildly among managing cardiologists.
The present study used NLP tools to identify symptoms consistent with severe AS in the medical record coupled with echocardiographic data from 10,795 patients with severe AS (valve area <1 cm2). Patients were divided into four AS subtypes and then classified as having a class 1 indication (high-gradient AS with symptoms or reduced ejection fraction [EF]) or a potential class 2a indication (low-gradient AS with symptoms) for AVR.
Among patients with high-gradient AS and class 1 indication for AVR, 1 in 3 did not receive AVR over the study period, including 30% with a normal EF and 47% with a low EF.
In those with low-gradient AS, 67% with a normal EF and 62% with a low EF did not receive AVR. The low-gradient groups were significantly less likely to receive AVR both in the entire study period and in the more contemporary period from 2014 to 2017, despite the valvular heart disease guideline 2014 update indicating AVR was “reasonable” in patients with low-gradient AS – a 2a recommendation upgraded to class 1 in the most recent 2020 update.
Better survival
In patients with a class 1 or potential class 2a indication, AVR was associated with a significantly lower risk of mortality in all four AS subgroups:
- High gradient/normal EF: 3% vs. 15%; adjusted hazard ratio, 0.42
- High-gradient/low EF: 16% vs. 72%; aHR, 0.28
- Low-gradient/normal EF: 5% vs. 14%; aHR, 0.73
- Low-gradient/low EF: 11% vs. 34%; aHR, 0.48; P < .001 for all
“I think what we need to do is change the paradigm, such that patients with a valve area that is less than or equal to 1 [cm2] is severe aortic stenosis until proven otherwise, and that essentially establishes a premise by which we default to treat these patients unless we can prove that it is in fact moderate,” Dr. Elmariah said.
Unfortunately, the opposite is currently true today, he said, and the default is not to treat and put patients through surgery or an invasive TAVR procedure unless physicians can definitively prove that it is severe AS. But they’re not always correct and don’t always have the ability to truly differentiate moderate from severe disease.
“The question, therefore, is ‘What do we do with those patients?’” Dr. Elmariah asked. “I think if a patient has symptoms, then we are obligated to intervene, given the stark difference in mortality that one sees when these patients go undertreated.”
Sounding the alarm
Robert Bonow, MD, a professor of cardiology at Northwestern University in Chicago and a writing committee member for the 2014 guideline update, said the study is a “big wake-up call” and “the take-home message is that we are missing some patients who have treatable aortic stenosis.”
The sheer magnitude of the problem, however, can be difficult to fully ascertain from administrative data like this, he said. Notably, patients who did not receive AVR were significantly older, with 37% aged 81-90 years and 12% over age 90, and had a lower hematocrit and lower estimated glomerular filtration rate. But it’s not clear how many had cancer, end-stage renal disease, or severe lung disease, which could have factored into the decision to undergo AVR.
“What’s also an issue is that over 50% of patients had low gradient disease, which is very problematic and takes careful assessment in an individual patient,” said Dr. Bonow, who is also editor-in-chief of JAMA Cardiology. “That’s all being generated by a low valve area of less than 1 cm2 from echo reports, so that’s not necessarily a careful prospective echo assessment ... so some of the patients with low-gradient disease may not have true severe aortic stenosis.”
Dr. Elmariah agreed that echocardiogram reports are not always clear cut and pointed out that referral to a valve specialist was highly predictive of whether or not a patient underwent AVR, supporting the class 1 guideline recommendation.
He also noted that Mass General is launching the DETECT-AS trial to determine whether electronic physician notifications highlighting clinical practice guideline recommendations will improve AVR utilization over standard care in 940 patients with severe AS on echocardiogram, defined by a valve area less than 1 cm2.
Reached for comment, Catherine Otto, MD, director of the Heart Valve Clinic at the University of Washington, Seattle, and a fellow member of the 2014 guideline writing committee, said “this adds to the data [that] we’re undertreating severe aortic stenosis, and it continues to be surprising given the availability of transcatheter options.”
The biggest challenge is trying to find out why it persists, which is difficult to determine from these data, she said. Whether that’s because the diagnosis is being missed or whether there are barriers to access because cardiologists aren’t understanding the indications or patients aren’t understanding what’s being offered, isn’t clear.
“The other [issue], of course, is are there inappropriate inequities in care? Is it fewer women, age-related, ethnic/racial-related; is it financial? Do people have coverage to get the treatment they need in our country?” Dr. Otto said. “All of those issues are areas that need to be addressed, and I think that is a concern we all have.”
An accompanying editorial points out that the “key lever” in combating undertreatment of AS is getting patients seen by a multidisciplinary heart team and details other possible solutions, such as adding process metrics regarding evaluation and treatment of AS to hospital performance.
“We track quality when AVR is performed (desirable), but how a hospital system performs in getting individuals treated who would benefit from AVR remains a complete blind spot,” write Brian Lindman, MD, MSc, and Angela Lowenstern, MD, MHS, both of Vanderbilt University Medical Center, Nashville, Tenn.
“Is it appropriate to consider the hospital ‘high performing’ when data from Li et al. show a 2-year absolute mortality difference from 9% to 56% based on treatment versus nontreatment with AVR for various AS patient subgroups?” they add.
Dr. Lindman and Dr. Lowenstern observe that having a 50% utilization rate for an effective therapy for a deadly cancer or stenting of ST-segment elevation myocardial infarction (STEMI) would generate negative headlines and a collective commitment to swift action by multiple stakeholders to address what would be “incontrovertibly unacceptable.”
“In one of America’s leading health care systems, there was evidence of an overwhelming reduction in the risk of death with AVR in all AS subgroups examined, but <50% of patients with AS with an indication or potential indication for AVR were treated with an AVR. Let that set in; hear and internalize the alarm. The status quo is unacceptable. What will you do? What will we do?” they conclude.
The study was funded by Edwards Lifesciences. Dr. Elmariah has received research grants from the American Heart Association, National Institutes of Health, Edwards Lifesciences, Svelte Medical, Abbott Vascular, and Medtronic, and has received consulting fees from Edwards Lifesciences. Dr. Bonow and Dr. Otto have disclosed no relevant financial relationships. Dr. Lindman has received investigator-initiated research grants from Edwards. Dr. Lowenstern has received consulting fees from Edwards.
A version of this article first appeared on Medscape.com.
The chance that patients with severe aortic stenosis (AS) will receive aortic valve replacement (AVR) is worse than the flip of a coin, even a decade after the gamechanging transcatheter option became available, a new study suggests.
Of the study’s 6,150 patients with an indication or potential indication for AVR, 48% received the procedure at Massachusetts General Hospital and its partner institution Brigham and Women’s Hospital, both in Boston – both of which have active, high-volume transcatheter and surgical AVR (TAVR/SAVR) programs.
“Essentially, this is a best-case scenario. So, unfortunately, I think on the national level we are likely to see rates that are far worse than what we observed here,” senior author Sammy Elmariah, MD, PhD, Massachusetts General Hospital, told this news organization.
The volume of AVR increased more than 10-fold over the 18-year study period (2000 to 2017), driven by the exponential growth of TAVR, he noted. However, the graying of America led to an even greater increase in the number of patients with severe AS and an indication for AVR.
The study, led by Shawn X. Li, MD, MBA, of Mass General, was published in the March 8 issue of the Journal of the American College of Cardiology.
Previous research has provided equally compelling data on the undertreatment of AS, including a 2021 study using natural language processing (NLP) that found AVR use was just 35.6% within 1 year of diagnosis and varied wildly among managing cardiologists.
The present study used NLP tools to identify symptoms consistent with severe AS in the medical record coupled with echocardiographic data from 10,795 patients with severe AS (valve area <1 cm2). Patients were divided into four AS subtypes and then classified as having a class 1 indication (high-gradient AS with symptoms or reduced ejection fraction [EF]) or a potential class 2a indication (low-gradient AS with symptoms) for AVR.
Among patients with high-gradient AS and class 1 indication for AVR, 1 in 3 did not receive AVR over the study period, including 30% with a normal EF and 47% with a low EF.
In those with low-gradient AS, 67% with a normal EF and 62% with a low EF did not receive AVR. The low-gradient groups were significantly less likely to receive AVR both in the entire study period and in the more contemporary period from 2014 to 2017, despite the valvular heart disease guideline 2014 update indicating AVR was “reasonable” in patients with low-gradient AS – a 2a recommendation upgraded to class 1 in the most recent 2020 update.
Better survival
In patients with a class 1 or potential class 2a indication, AVR was associated with a significantly lower risk of mortality in all four AS subgroups:
- High gradient/normal EF: 3% vs. 15%; adjusted hazard ratio, 0.42
- High-gradient/low EF: 16% vs. 72%; aHR, 0.28
- Low-gradient/normal EF: 5% vs. 14%; aHR, 0.73
- Low-gradient/low EF: 11% vs. 34%; aHR, 0.48; P < .001 for all
“I think what we need to do is change the paradigm, such that patients with a valve area that is less than or equal to 1 [cm2] is severe aortic stenosis until proven otherwise, and that essentially establishes a premise by which we default to treat these patients unless we can prove that it is in fact moderate,” Dr. Elmariah said.
Unfortunately, the opposite is currently true today, he said, and the default is not to treat and put patients through surgery or an invasive TAVR procedure unless physicians can definitively prove that it is severe AS. But they’re not always correct and don’t always have the ability to truly differentiate moderate from severe disease.
“The question, therefore, is ‘What do we do with those patients?’” Dr. Elmariah asked. “I think if a patient has symptoms, then we are obligated to intervene, given the stark difference in mortality that one sees when these patients go undertreated.”
Sounding the alarm
Robert Bonow, MD, a professor of cardiology at Northwestern University in Chicago and a writing committee member for the 2014 guideline update, said the study is a “big wake-up call” and “the take-home message is that we are missing some patients who have treatable aortic stenosis.”
The sheer magnitude of the problem, however, can be difficult to fully ascertain from administrative data like this, he said. Notably, patients who did not receive AVR were significantly older, with 37% aged 81-90 years and 12% over age 90, and had a lower hematocrit and lower estimated glomerular filtration rate. But it’s not clear how many had cancer, end-stage renal disease, or severe lung disease, which could have factored into the decision to undergo AVR.
“What’s also an issue is that over 50% of patients had low gradient disease, which is very problematic and takes careful assessment in an individual patient,” said Dr. Bonow, who is also editor-in-chief of JAMA Cardiology. “That’s all being generated by a low valve area of less than 1 cm2 from echo reports, so that’s not necessarily a careful prospective echo assessment ... so some of the patients with low-gradient disease may not have true severe aortic stenosis.”
Dr. Elmariah agreed that echocardiogram reports are not always clear cut and pointed out that referral to a valve specialist was highly predictive of whether or not a patient underwent AVR, supporting the class 1 guideline recommendation.
He also noted that Mass General is launching the DETECT-AS trial to determine whether electronic physician notifications highlighting clinical practice guideline recommendations will improve AVR utilization over standard care in 940 patients with severe AS on echocardiogram, defined by a valve area less than 1 cm2.
Reached for comment, Catherine Otto, MD, director of the Heart Valve Clinic at the University of Washington, Seattle, and a fellow member of the 2014 guideline writing committee, said “this adds to the data [that] we’re undertreating severe aortic stenosis, and it continues to be surprising given the availability of transcatheter options.”
The biggest challenge is trying to find out why it persists, which is difficult to determine from these data, she said. Whether that’s because the diagnosis is being missed or whether there are barriers to access because cardiologists aren’t understanding the indications or patients aren’t understanding what’s being offered, isn’t clear.
“The other [issue], of course, is are there inappropriate inequities in care? Is it fewer women, age-related, ethnic/racial-related; is it financial? Do people have coverage to get the treatment they need in our country?” Dr. Otto said. “All of those issues are areas that need to be addressed, and I think that is a concern we all have.”
An accompanying editorial points out that the “key lever” in combating undertreatment of AS is getting patients seen by a multidisciplinary heart team and details other possible solutions, such as adding process metrics regarding evaluation and treatment of AS to hospital performance.
“We track quality when AVR is performed (desirable), but how a hospital system performs in getting individuals treated who would benefit from AVR remains a complete blind spot,” write Brian Lindman, MD, MSc, and Angela Lowenstern, MD, MHS, both of Vanderbilt University Medical Center, Nashville, Tenn.
“Is it appropriate to consider the hospital ‘high performing’ when data from Li et al. show a 2-year absolute mortality difference from 9% to 56% based on treatment versus nontreatment with AVR for various AS patient subgroups?” they add.
Dr. Lindman and Dr. Lowenstern observe that having a 50% utilization rate for an effective therapy for a deadly cancer or stenting of ST-segment elevation myocardial infarction (STEMI) would generate negative headlines and a collective commitment to swift action by multiple stakeholders to address what would be “incontrovertibly unacceptable.”
“In one of America’s leading health care systems, there was evidence of an overwhelming reduction in the risk of death with AVR in all AS subgroups examined, but <50% of patients with AS with an indication or potential indication for AVR were treated with an AVR. Let that set in; hear and internalize the alarm. The status quo is unacceptable. What will you do? What will we do?” they conclude.
The study was funded by Edwards Lifesciences. Dr. Elmariah has received research grants from the American Heart Association, National Institutes of Health, Edwards Lifesciences, Svelte Medical, Abbott Vascular, and Medtronic, and has received consulting fees from Edwards Lifesciences. Dr. Bonow and Dr. Otto have disclosed no relevant financial relationships. Dr. Lindman has received investigator-initiated research grants from Edwards. Dr. Lowenstern has received consulting fees from Edwards.
A version of this article first appeared on Medscape.com.
Clozapine interrupted: APA, others seek FDA forum on REMS
In a Feb. 14 letter, the groups asked the FDA to reconsider its new risk evaluation and mitigation strategy (REMS) for clozapine because of concerns it had the potential to cause abrupt discontinuation of the medication.
The groups cite an Institute for Safe Medication Practices (ISMP) report of a 40-year-old woman who was a long-time clozapine user, had a cardiac arrest, and died after she stopped taking the drug because her psychiatrist was unable to register for the updated version of the REMS.
“It is unacceptable for a REMS with unproven effectiveness at meeting its goal to carry risks of interruptions that can result in rehospitalization, acute exacerbation of psychosis, increased risk of suicide, and potentially fatal orthostatic hypotension/bradycardic syndromes associated with incorrect restarts,” the groups said in the letter.
“We feel certain that this case reported in the literature is not the only serious adverse outcome from the REMS and the transition,” they added.
The letter was signed by the American Psychiatric Association, the American Association for Community Psychiatry, the American Psychiatric Nurses Association, the College of Psychiatric and Neurologic Pharmacists, the National Alliance on Mental Illness, the National Association of State Mental Health Program Directors, and the National Council for Mental Wellbeing.
Clozapine can decrease the neutrophil count, which can lead to severe neutropenia, serious infection, and death. Consequently, the FDA put additional safety measures in place governing clozapine prescribing.
In 2015, a centralized clozapine REMS replaced separate prescribing registries that the drug manufacturers maintained. There were technical issues with the 2015 start-up of that website, including data migration problems and long call wait times, the FDA said.
Subsequently, the drug’s manufacturers then decided to change the REMS platform, which created new issues that led to high call volume and long wait times for clinicians and pharmacists who were trying to enroll.
Maintaining access
In November 2021, the FDA announced it would put some aspects of a planned switch on hold. A month later, the agency made further modifications to its plan.
The FDA said it would exercise “enforcement discretion” to try to maintain access to clozapine amid hitches with the REMS transition efforts. The agency also said at the time that it would not object if pharmacists dispensed clozapine without the usual authorization. In addition, wholesalers could ship the drug to pharmacies and health care settings without confirming REMS enrollment.
The FDA also held two December meetings to allow various stakeholders to air concerns.
In their letter, the APA and other groups asked if the FDA intends to continue with accommodations, such as allowing pharmacies to order clozapine from wholesalers without restriction.
“We do not feel the issues are resolved,” the groups said.
A version of this article first appeared on Medscape.com.
In a Feb. 14 letter, the groups asked the FDA to reconsider its new risk evaluation and mitigation strategy (REMS) for clozapine because of concerns it had the potential to cause abrupt discontinuation of the medication.
The groups cite an Institute for Safe Medication Practices (ISMP) report of a 40-year-old woman who was a long-time clozapine user, had a cardiac arrest, and died after she stopped taking the drug because her psychiatrist was unable to register for the updated version of the REMS.
“It is unacceptable for a REMS with unproven effectiveness at meeting its goal to carry risks of interruptions that can result in rehospitalization, acute exacerbation of psychosis, increased risk of suicide, and potentially fatal orthostatic hypotension/bradycardic syndromes associated with incorrect restarts,” the groups said in the letter.
“We feel certain that this case reported in the literature is not the only serious adverse outcome from the REMS and the transition,” they added.
The letter was signed by the American Psychiatric Association, the American Association for Community Psychiatry, the American Psychiatric Nurses Association, the College of Psychiatric and Neurologic Pharmacists, the National Alliance on Mental Illness, the National Association of State Mental Health Program Directors, and the National Council for Mental Wellbeing.
Clozapine can decrease the neutrophil count, which can lead to severe neutropenia, serious infection, and death. Consequently, the FDA put additional safety measures in place governing clozapine prescribing.
In 2015, a centralized clozapine REMS replaced separate prescribing registries that the drug manufacturers maintained. There were technical issues with the 2015 start-up of that website, including data migration problems and long call wait times, the FDA said.
Subsequently, the drug’s manufacturers then decided to change the REMS platform, which created new issues that led to high call volume and long wait times for clinicians and pharmacists who were trying to enroll.
Maintaining access
In November 2021, the FDA announced it would put some aspects of a planned switch on hold. A month later, the agency made further modifications to its plan.
The FDA said it would exercise “enforcement discretion” to try to maintain access to clozapine amid hitches with the REMS transition efforts. The agency also said at the time that it would not object if pharmacists dispensed clozapine without the usual authorization. In addition, wholesalers could ship the drug to pharmacies and health care settings without confirming REMS enrollment.
The FDA also held two December meetings to allow various stakeholders to air concerns.
In their letter, the APA and other groups asked if the FDA intends to continue with accommodations, such as allowing pharmacies to order clozapine from wholesalers without restriction.
“We do not feel the issues are resolved,” the groups said.
A version of this article first appeared on Medscape.com.
In a Feb. 14 letter, the groups asked the FDA to reconsider its new risk evaluation and mitigation strategy (REMS) for clozapine because of concerns it had the potential to cause abrupt discontinuation of the medication.
The groups cite an Institute for Safe Medication Practices (ISMP) report of a 40-year-old woman who was a long-time clozapine user, had a cardiac arrest, and died after she stopped taking the drug because her psychiatrist was unable to register for the updated version of the REMS.
“It is unacceptable for a REMS with unproven effectiveness at meeting its goal to carry risks of interruptions that can result in rehospitalization, acute exacerbation of psychosis, increased risk of suicide, and potentially fatal orthostatic hypotension/bradycardic syndromes associated with incorrect restarts,” the groups said in the letter.
“We feel certain that this case reported in the literature is not the only serious adverse outcome from the REMS and the transition,” they added.
The letter was signed by the American Psychiatric Association, the American Association for Community Psychiatry, the American Psychiatric Nurses Association, the College of Psychiatric and Neurologic Pharmacists, the National Alliance on Mental Illness, the National Association of State Mental Health Program Directors, and the National Council for Mental Wellbeing.
Clozapine can decrease the neutrophil count, which can lead to severe neutropenia, serious infection, and death. Consequently, the FDA put additional safety measures in place governing clozapine prescribing.
In 2015, a centralized clozapine REMS replaced separate prescribing registries that the drug manufacturers maintained. There were technical issues with the 2015 start-up of that website, including data migration problems and long call wait times, the FDA said.
Subsequently, the drug’s manufacturers then decided to change the REMS platform, which created new issues that led to high call volume and long wait times for clinicians and pharmacists who were trying to enroll.
Maintaining access
In November 2021, the FDA announced it would put some aspects of a planned switch on hold. A month later, the agency made further modifications to its plan.
The FDA said it would exercise “enforcement discretion” to try to maintain access to clozapine amid hitches with the REMS transition efforts. The agency also said at the time that it would not object if pharmacists dispensed clozapine without the usual authorization. In addition, wholesalers could ship the drug to pharmacies and health care settings without confirming REMS enrollment.
The FDA also held two December meetings to allow various stakeholders to air concerns.
In their letter, the APA and other groups asked if the FDA intends to continue with accommodations, such as allowing pharmacies to order clozapine from wholesalers without restriction.
“We do not feel the issues are resolved,” the groups said.
A version of this article first appeared on Medscape.com.
Managing overuse of food IgE panels: Multiple approaches needed
PHOENIX – For at least a decade, professional allergy and pediatrics societies have urged against using food IgE tests unless the patient has a history consistent with potential IgE-mediated food allergies. Yet virtually every health system offers these blood tests, and their inappropriate use – especially of panels that measure many allergens at once – remains a huge problem.
Beyond wasteful spending, excessive food IgE testing can lead patients to worry needlessly and to avoid foods they aren’t allergic to. For babies and toddlers, avoidance can drive up the risk of developing allergies to those foods later in life – a consequence that was convincingly proven by the LEAP study but has still not translated to a widespread change in practice.
“I think we all know that there’s just a lot of system-wide resistance to making these changes, and we don’t completely understand why,” Nicholas Hartog, MD, an allergist with Spectrum Health in Grand Rapids, Mich., told this news organization.
At the American Academy of Allergy, Asthma & Immunology annual meeting, one of Dr. Hartog’s residents, Courtney Cotter, DO, presented a poster detailing their team’s retrospective review of food panel ordering practices across Spectrum Health, a large, multispecialty physician group in west Michigan.
The team combed Epic health records to evaluate food IgE ordering from January 2016 to December 2021. They tracked monthly figures for the number of patients who underwent food IgE tests, the percentage of tested patients for whom food panels were available, and the number of food panels and total number of food IgE tests ordered. They compared average rates from the final 3 months with rates from the first 3 months, which predated the August 2016 establishment of an academic pediatric allergy/immunology department.
Initially, Dr. Hartog and his colleagues focused on educating doctors on appropriate use of food IgE tests through informal conversations and lectures, but, he said, “It’s really difficult to change physician behavior, so sometimes we have to go about it by making it hard to do the wrong thing.”
To that end, the team tried to eliminate the food panels. However, some lab staff feared the possibility of losing revenue if physicians decided to order these tests elsewhere. After more negotiations, the laboratory agreed in December 2019 to restrict and rework food IgE testing by dropping the number of panels from nine to two and by restricting the number of foods in those panels. For example, in the basic panel, “we limited it to just four allergens, so even if you order a panel, you’re not getting 20 results,” Dr. Hartog told this news organization. “I finally found a friendly pathologist who was very on board with this positive change.”
In December 2020, the team implemented yet another strategy: Epic alerts. Each time doctors request a food panel, they receive a pop-up message stating that panel tests are not recommended and asking if they wish to proceed.
The multipronged effort had a modest impact on the number of food panels ordered per month, which dipped from 112.7 to 84.7 for the first and last 3 months of the study. Monthly totals of individual food IgE tests showed a steeper drop, decreasing from 2,379 to 1,180 in the initial and final 3-month periods – a change Dr. Hartog attributes to the revamped food panels. They estimated the cost savings at around $40 per patient, “and we were getting on average about 200 patients a month, so it adds up,” he said.
But the Epic alerts seemed to have little effect. Over the duration of the study, the monthly number of IgE tests ordered per clinician did not change. Neither did the percentage of patients evaluated with a food panel. “The alerts pop up, but people are still ordering,” Dr. Hartog said.
On the whole, the analysis shows that, “despite major efforts to educate providers and the public about these things, it is rampantly disregarded and is a huge problem for our specialty and is likely causing harm to patients,” said allergist-immunologist Gerald Lee, MD, of Emory University in Atlanta.
Dr. Lee said that a common scenario for inappropriate food IgE testing is severe eczema. Many parents request blood tests because they assume their child’s skin condition is driven by food allergies. When the child turns up positive to various foods on panel tests, which have high false-positive rates, the physician may recommend eliminating those foods to improve the skin rash – which “actually delays introduction of the food and potentially increases the risk for food allergy,” Dr. Lee said. “That was a common practice when I was in fellowship (2011) and is widely prevalent today.”
Edwin Kim, MD, director of the UNC Food Allergy Initiative at the University of North Carolina at Chapel Hill, agrees that food IgE panels are wasteful and harmful. However, he thinks the solution is not to tell primary care physicians and pediatricians to stop using the tests. “We’re insinuating that they’re being used inappropriately, but the problem is that these are people that are patient facing, the patients are asking a question, and the appropriate tests aren’t there,” Dr. Kim said. “A big part of that problem is that the tests we have available to us are not good enough.”
The Spectrum Health analysis did not examine ICD codes associated with the food IgE tests or track which physicians ordered the tests. A 2016 retrospective review published in Pediatrics did evaluate ordering practices by specialty and found that primary care providers ordered “significantly more food allergen panels, tests for uncommon causes of food allergy, and generate higher cost per patient compared with allergists.”
Given the immense challenges with implementing system-wide changes, sometimes it can help to educate parents and families. “When you sit down and take 2 or 3 minutes to explain why this is a bad test and that I care about your kid but just don’t want inappropriate testing, they’re okay with it. They understand,” Dr. Hartog said. “When I teach residents, I make sure to emphasize that we have these conversations all the time.”
Dr. Hartog reports financial relationships with Binding Site (speaker), Regeneron (advisory board), Genentech (advisory board), Horizon Pharmaceuticals (advisory board, consulting, speaker), Takeda (speaker, advisory board) and Pharming Healthcare (advisory board, scientific steering committee, consulting), though none related to food allergy. Dr. Lee has disclosed no relevant financial relationships. Dr. Kim reports consultancy with Aimmune Therapeutics, Allako, AllerGenis, Belhaven Pharma, DBV Technologies, Duke Clinical Research Institute, and Nutricia; advisory board membership with ALK, DBV Technologies, Kenota Health, and Ukko; and grant support from the National Institute of Allergy and Infectious Diseases and the Immune Tolerance Network; the National Center for Complementary and Integrative Health; Food Allergy Research and Education; and the Wallace Research Foundation.
A version of this article first appeared on Medscape.com.
PHOENIX – For at least a decade, professional allergy and pediatrics societies have urged against using food IgE tests unless the patient has a history consistent with potential IgE-mediated food allergies. Yet virtually every health system offers these blood tests, and their inappropriate use – especially of panels that measure many allergens at once – remains a huge problem.
Beyond wasteful spending, excessive food IgE testing can lead patients to worry needlessly and to avoid foods they aren’t allergic to. For babies and toddlers, avoidance can drive up the risk of developing allergies to those foods later in life – a consequence that was convincingly proven by the LEAP study but has still not translated to a widespread change in practice.
“I think we all know that there’s just a lot of system-wide resistance to making these changes, and we don’t completely understand why,” Nicholas Hartog, MD, an allergist with Spectrum Health in Grand Rapids, Mich., told this news organization.
At the American Academy of Allergy, Asthma & Immunology annual meeting, one of Dr. Hartog’s residents, Courtney Cotter, DO, presented a poster detailing their team’s retrospective review of food panel ordering practices across Spectrum Health, a large, multispecialty physician group in west Michigan.
The team combed Epic health records to evaluate food IgE ordering from January 2016 to December 2021. They tracked monthly figures for the number of patients who underwent food IgE tests, the percentage of tested patients for whom food panels were available, and the number of food panels and total number of food IgE tests ordered. They compared average rates from the final 3 months with rates from the first 3 months, which predated the August 2016 establishment of an academic pediatric allergy/immunology department.
Initially, Dr. Hartog and his colleagues focused on educating doctors on appropriate use of food IgE tests through informal conversations and lectures, but, he said, “It’s really difficult to change physician behavior, so sometimes we have to go about it by making it hard to do the wrong thing.”
To that end, the team tried to eliminate the food panels. However, some lab staff feared the possibility of losing revenue if physicians decided to order these tests elsewhere. After more negotiations, the laboratory agreed in December 2019 to restrict and rework food IgE testing by dropping the number of panels from nine to two and by restricting the number of foods in those panels. For example, in the basic panel, “we limited it to just four allergens, so even if you order a panel, you’re not getting 20 results,” Dr. Hartog told this news organization. “I finally found a friendly pathologist who was very on board with this positive change.”
In December 2020, the team implemented yet another strategy: Epic alerts. Each time doctors request a food panel, they receive a pop-up message stating that panel tests are not recommended and asking if they wish to proceed.
The multipronged effort had a modest impact on the number of food panels ordered per month, which dipped from 112.7 to 84.7 for the first and last 3 months of the study. Monthly totals of individual food IgE tests showed a steeper drop, decreasing from 2,379 to 1,180 in the initial and final 3-month periods – a change Dr. Hartog attributes to the revamped food panels. They estimated the cost savings at around $40 per patient, “and we were getting on average about 200 patients a month, so it adds up,” he said.
But the Epic alerts seemed to have little effect. Over the duration of the study, the monthly number of IgE tests ordered per clinician did not change. Neither did the percentage of patients evaluated with a food panel. “The alerts pop up, but people are still ordering,” Dr. Hartog said.
On the whole, the analysis shows that, “despite major efforts to educate providers and the public about these things, it is rampantly disregarded and is a huge problem for our specialty and is likely causing harm to patients,” said allergist-immunologist Gerald Lee, MD, of Emory University in Atlanta.
Dr. Lee said that a common scenario for inappropriate food IgE testing is severe eczema. Many parents request blood tests because they assume their child’s skin condition is driven by food allergies. When the child turns up positive to various foods on panel tests, which have high false-positive rates, the physician may recommend eliminating those foods to improve the skin rash – which “actually delays introduction of the food and potentially increases the risk for food allergy,” Dr. Lee said. “That was a common practice when I was in fellowship (2011) and is widely prevalent today.”
Edwin Kim, MD, director of the UNC Food Allergy Initiative at the University of North Carolina at Chapel Hill, agrees that food IgE panels are wasteful and harmful. However, he thinks the solution is not to tell primary care physicians and pediatricians to stop using the tests. “We’re insinuating that they’re being used inappropriately, but the problem is that these are people that are patient facing, the patients are asking a question, and the appropriate tests aren’t there,” Dr. Kim said. “A big part of that problem is that the tests we have available to us are not good enough.”
The Spectrum Health analysis did not examine ICD codes associated with the food IgE tests or track which physicians ordered the tests. A 2016 retrospective review published in Pediatrics did evaluate ordering practices by specialty and found that primary care providers ordered “significantly more food allergen panels, tests for uncommon causes of food allergy, and generate higher cost per patient compared with allergists.”
Given the immense challenges with implementing system-wide changes, sometimes it can help to educate parents and families. “When you sit down and take 2 or 3 minutes to explain why this is a bad test and that I care about your kid but just don’t want inappropriate testing, they’re okay with it. They understand,” Dr. Hartog said. “When I teach residents, I make sure to emphasize that we have these conversations all the time.”
Dr. Hartog reports financial relationships with Binding Site (speaker), Regeneron (advisory board), Genentech (advisory board), Horizon Pharmaceuticals (advisory board, consulting, speaker), Takeda (speaker, advisory board) and Pharming Healthcare (advisory board, scientific steering committee, consulting), though none related to food allergy. Dr. Lee has disclosed no relevant financial relationships. Dr. Kim reports consultancy with Aimmune Therapeutics, Allako, AllerGenis, Belhaven Pharma, DBV Technologies, Duke Clinical Research Institute, and Nutricia; advisory board membership with ALK, DBV Technologies, Kenota Health, and Ukko; and grant support from the National Institute of Allergy and Infectious Diseases and the Immune Tolerance Network; the National Center for Complementary and Integrative Health; Food Allergy Research and Education; and the Wallace Research Foundation.
A version of this article first appeared on Medscape.com.
PHOENIX – For at least a decade, professional allergy and pediatrics societies have urged against using food IgE tests unless the patient has a history consistent with potential IgE-mediated food allergies. Yet virtually every health system offers these blood tests, and their inappropriate use – especially of panels that measure many allergens at once – remains a huge problem.
Beyond wasteful spending, excessive food IgE testing can lead patients to worry needlessly and to avoid foods they aren’t allergic to. For babies and toddlers, avoidance can drive up the risk of developing allergies to those foods later in life – a consequence that was convincingly proven by the LEAP study but has still not translated to a widespread change in practice.
“I think we all know that there’s just a lot of system-wide resistance to making these changes, and we don’t completely understand why,” Nicholas Hartog, MD, an allergist with Spectrum Health in Grand Rapids, Mich., told this news organization.
At the American Academy of Allergy, Asthma & Immunology annual meeting, one of Dr. Hartog’s residents, Courtney Cotter, DO, presented a poster detailing their team’s retrospective review of food panel ordering practices across Spectrum Health, a large, multispecialty physician group in west Michigan.
The team combed Epic health records to evaluate food IgE ordering from January 2016 to December 2021. They tracked monthly figures for the number of patients who underwent food IgE tests, the percentage of tested patients for whom food panels were available, and the number of food panels and total number of food IgE tests ordered. They compared average rates from the final 3 months with rates from the first 3 months, which predated the August 2016 establishment of an academic pediatric allergy/immunology department.
Initially, Dr. Hartog and his colleagues focused on educating doctors on appropriate use of food IgE tests through informal conversations and lectures, but, he said, “It’s really difficult to change physician behavior, so sometimes we have to go about it by making it hard to do the wrong thing.”
To that end, the team tried to eliminate the food panels. However, some lab staff feared the possibility of losing revenue if physicians decided to order these tests elsewhere. After more negotiations, the laboratory agreed in December 2019 to restrict and rework food IgE testing by dropping the number of panels from nine to two and by restricting the number of foods in those panels. For example, in the basic panel, “we limited it to just four allergens, so even if you order a panel, you’re not getting 20 results,” Dr. Hartog told this news organization. “I finally found a friendly pathologist who was very on board with this positive change.”
In December 2020, the team implemented yet another strategy: Epic alerts. Each time doctors request a food panel, they receive a pop-up message stating that panel tests are not recommended and asking if they wish to proceed.
The multipronged effort had a modest impact on the number of food panels ordered per month, which dipped from 112.7 to 84.7 for the first and last 3 months of the study. Monthly totals of individual food IgE tests showed a steeper drop, decreasing from 2,379 to 1,180 in the initial and final 3-month periods – a change Dr. Hartog attributes to the revamped food panels. They estimated the cost savings at around $40 per patient, “and we were getting on average about 200 patients a month, so it adds up,” he said.
But the Epic alerts seemed to have little effect. Over the duration of the study, the monthly number of IgE tests ordered per clinician did not change. Neither did the percentage of patients evaluated with a food panel. “The alerts pop up, but people are still ordering,” Dr. Hartog said.
On the whole, the analysis shows that, “despite major efforts to educate providers and the public about these things, it is rampantly disregarded and is a huge problem for our specialty and is likely causing harm to patients,” said allergist-immunologist Gerald Lee, MD, of Emory University in Atlanta.
Dr. Lee said that a common scenario for inappropriate food IgE testing is severe eczema. Many parents request blood tests because they assume their child’s skin condition is driven by food allergies. When the child turns up positive to various foods on panel tests, which have high false-positive rates, the physician may recommend eliminating those foods to improve the skin rash – which “actually delays introduction of the food and potentially increases the risk for food allergy,” Dr. Lee said. “That was a common practice when I was in fellowship (2011) and is widely prevalent today.”
Edwin Kim, MD, director of the UNC Food Allergy Initiative at the University of North Carolina at Chapel Hill, agrees that food IgE panels are wasteful and harmful. However, he thinks the solution is not to tell primary care physicians and pediatricians to stop using the tests. “We’re insinuating that they’re being used inappropriately, but the problem is that these are people that are patient facing, the patients are asking a question, and the appropriate tests aren’t there,” Dr. Kim said. “A big part of that problem is that the tests we have available to us are not good enough.”
The Spectrum Health analysis did not examine ICD codes associated with the food IgE tests or track which physicians ordered the tests. A 2016 retrospective review published in Pediatrics did evaluate ordering practices by specialty and found that primary care providers ordered “significantly more food allergen panels, tests for uncommon causes of food allergy, and generate higher cost per patient compared with allergists.”
Given the immense challenges with implementing system-wide changes, sometimes it can help to educate parents and families. “When you sit down and take 2 or 3 minutes to explain why this is a bad test and that I care about your kid but just don’t want inappropriate testing, they’re okay with it. They understand,” Dr. Hartog said. “When I teach residents, I make sure to emphasize that we have these conversations all the time.”
Dr. Hartog reports financial relationships with Binding Site (speaker), Regeneron (advisory board), Genentech (advisory board), Horizon Pharmaceuticals (advisory board, consulting, speaker), Takeda (speaker, advisory board) and Pharming Healthcare (advisory board, scientific steering committee, consulting), though none related to food allergy. Dr. Lee has disclosed no relevant financial relationships. Dr. Kim reports consultancy with Aimmune Therapeutics, Allako, AllerGenis, Belhaven Pharma, DBV Technologies, Duke Clinical Research Institute, and Nutricia; advisory board membership with ALK, DBV Technologies, Kenota Health, and Ukko; and grant support from the National Institute of Allergy and Infectious Diseases and the Immune Tolerance Network; the National Center for Complementary and Integrative Health; Food Allergy Research and Education; and the Wallace Research Foundation.
A version of this article first appeared on Medscape.com.