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Insomnia symptoms increase likelihood of stroke and heart disease
, according to a large cohort study of adults in China. A greater number of insomnia symptoms is associated with increased risk, and this relationship is more evident in younger adults and in adults without hypertension at baseline, researchers reported Nov. 6 in Neurology.
“These results suggest that, if we can target people who are having trouble sleeping with behavioral therapies, it’s possible that we could reduce the number of cases of stroke, heart attack, and other diseases later down the line,” study author Liming Li, MD, professor of epidemiology at Peking University, Beijing, said in a news release.
To clarify the relationships between individual insomnia symptoms, cardiocerebral vascular diseases, and potential effect modifiers, Dr. Li and colleagues analyzed data from the China Kadoorie Biobank Study. For this study, more than 500,000 adults in China aged 30-79 years completed a baseline survey during 2004-2008. The present analysis included data from 487,200 participants who did not have a history of stroke, coronary heart disease, or cancer at baseline.
For the baseline survey, participants answered questions about whether specific insomnia symptoms occurred at least 3 days per week during the past month. The symptoms included difficulty initiating or maintaining sleep (that is, sleep onset latency of 30 minutes or more after going to bed or waking up in the middle of the night); waking too early and being unable to fall back asleep; and trouble functioning during the day because of bad sleep.
The researchers assessed the incidence of cardiocerebral vascular diseases through 2016 by examining disease registries, national health insurance claims databases, and local records. Investigators identified participants with any cardiocerebral vascular disease and assessed the incidence of ischemic heart disease, acute myocardial infarction, hemorrhagic stroke, and ischemic stroke. The researchers followed each participant until the diagnosis of a cardiocerebral vascular disease outcome, death from any cause, loss to follow-up, or Dec. 31, 2016. The researchers used Cox proportional hazard models to estimate hazard ratios for the association between each insomnia symptom and cardiocerebral vascular disease outcomes. They adjusted the models for established and potential confounding factors, including age, income, smoking status, diet, and physical activity.
More than 16% had any insomnia symptom
Of the 487,200 participants, 11.3% had difficulty initiating or maintaining sleep, 10.4% had early morning awakening, and 2.2% had daytime dysfunction attributed to poor sleep. Compared with participants without insomnia symptoms, participants with insomnia symptoms tended to be older and were more likely to be female, not married, and from a rural area. In addition, those with insomnia symptoms were more likely have depression or anxiety symptoms, lower education level, lower household income, and lower body mass index. They also were more likely to have a history of diabetes mellitus. During a median follow-up of 9.6 years, 130,032 cases of cardiocerebral vascular disease occurred, including 40,348 cases of ischemic heart disease and 45,316 cases of stroke.
After adjustment for potential confounders, each insomnia symptom was associated with greater risk of cardiocerebral vascular disease. For difficulty initiating or maintaining sleep, the hazard ratio was 1.09. For early-morning awakening, the HR was 1.07. For daytime dysfunction, the HR was 1.13. Each insomnia symptom was associated with increased risk of ischemic heart disease and ischemic stroke, whereas only difficulty initiating or maintaining sleep was associated with increased risk of acute MI.
In all, 16.4% of participants reported any insomnia symptom; 10% had one symptom, 5.2% had two symptoms, and 1.2% had three symptoms. “Compared with those without any insomnia symptoms, participants with one, two, or three symptoms had a 7%, 10%, or 18% higher risk of total [cardiocerebral vascular disease] incidence, respectively,” the authors wrote. “Our study is the first large-scale cohort study that identified positive dose-response relationships between the number of insomnia symptoms and risks of [cardiocerebral vascular diseases, ischemic heart disease] and stroke incidence.”
Opportunity for intervention
Compared with clinical diagnostic criteria for insomnia, “individual insomnia symptoms are better defined and more feasible to assess with questionnaires in large-scale population studies and clinical practice,” Dr. Li and colleagues wrote. “Moreover, it is reasonable that insomnia symptoms are more modifiable and precisely targetable through behavioral therapies before developing into clinically significant insomnia disorder. Therefore, future clinical trials or community-based intervention studies should be conducted to test whether lifestyle or sleep hygiene interventions for insomnia symptoms can reduce subsequent [cardiocerebral vascular disease] risks.”
The results suggest that efforts aimed at early detection and intervention should include a focus on younger adults and people who do not have high blood pressure, Dr. Li said.
The self-reported insomnia symptoms used in this study have not been fully validated, the investigators noted. The researchers also lacked information about potential confounders, such as shift work and obstructive sleep apnea, that are risk factors for coronary heart disease or stroke and may interfere with insomnia symptoms. In addition, the study did not capture changes in insomnia symptoms over time.
This study was supported by the National Key Research and Development Program of China, the Chinese Ministry of Science and Technology, and the National Natural Science Foundation of China. The China Kadoorie Biobank surveys were supported by grants from the Kadoorie Charitable Foundation and the U.K. Wellcome Trust. The authors had no relevant disclosures.
SOURCE: Zheng B et al. Neurology. 2019 Nov 6. doi: 10.1212/WNL.0000000000008581.
, according to a large cohort study of adults in China. A greater number of insomnia symptoms is associated with increased risk, and this relationship is more evident in younger adults and in adults without hypertension at baseline, researchers reported Nov. 6 in Neurology.
“These results suggest that, if we can target people who are having trouble sleeping with behavioral therapies, it’s possible that we could reduce the number of cases of stroke, heart attack, and other diseases later down the line,” study author Liming Li, MD, professor of epidemiology at Peking University, Beijing, said in a news release.
To clarify the relationships between individual insomnia symptoms, cardiocerebral vascular diseases, and potential effect modifiers, Dr. Li and colleagues analyzed data from the China Kadoorie Biobank Study. For this study, more than 500,000 adults in China aged 30-79 years completed a baseline survey during 2004-2008. The present analysis included data from 487,200 participants who did not have a history of stroke, coronary heart disease, or cancer at baseline.
For the baseline survey, participants answered questions about whether specific insomnia symptoms occurred at least 3 days per week during the past month. The symptoms included difficulty initiating or maintaining sleep (that is, sleep onset latency of 30 minutes or more after going to bed or waking up in the middle of the night); waking too early and being unable to fall back asleep; and trouble functioning during the day because of bad sleep.
The researchers assessed the incidence of cardiocerebral vascular diseases through 2016 by examining disease registries, national health insurance claims databases, and local records. Investigators identified participants with any cardiocerebral vascular disease and assessed the incidence of ischemic heart disease, acute myocardial infarction, hemorrhagic stroke, and ischemic stroke. The researchers followed each participant until the diagnosis of a cardiocerebral vascular disease outcome, death from any cause, loss to follow-up, or Dec. 31, 2016. The researchers used Cox proportional hazard models to estimate hazard ratios for the association between each insomnia symptom and cardiocerebral vascular disease outcomes. They adjusted the models for established and potential confounding factors, including age, income, smoking status, diet, and physical activity.
More than 16% had any insomnia symptom
Of the 487,200 participants, 11.3% had difficulty initiating or maintaining sleep, 10.4% had early morning awakening, and 2.2% had daytime dysfunction attributed to poor sleep. Compared with participants without insomnia symptoms, participants with insomnia symptoms tended to be older and were more likely to be female, not married, and from a rural area. In addition, those with insomnia symptoms were more likely have depression or anxiety symptoms, lower education level, lower household income, and lower body mass index. They also were more likely to have a history of diabetes mellitus. During a median follow-up of 9.6 years, 130,032 cases of cardiocerebral vascular disease occurred, including 40,348 cases of ischemic heart disease and 45,316 cases of stroke.
After adjustment for potential confounders, each insomnia symptom was associated with greater risk of cardiocerebral vascular disease. For difficulty initiating or maintaining sleep, the hazard ratio was 1.09. For early-morning awakening, the HR was 1.07. For daytime dysfunction, the HR was 1.13. Each insomnia symptom was associated with increased risk of ischemic heart disease and ischemic stroke, whereas only difficulty initiating or maintaining sleep was associated with increased risk of acute MI.
In all, 16.4% of participants reported any insomnia symptom; 10% had one symptom, 5.2% had two symptoms, and 1.2% had three symptoms. “Compared with those without any insomnia symptoms, participants with one, two, or three symptoms had a 7%, 10%, or 18% higher risk of total [cardiocerebral vascular disease] incidence, respectively,” the authors wrote. “Our study is the first large-scale cohort study that identified positive dose-response relationships between the number of insomnia symptoms and risks of [cardiocerebral vascular diseases, ischemic heart disease] and stroke incidence.”
Opportunity for intervention
Compared with clinical diagnostic criteria for insomnia, “individual insomnia symptoms are better defined and more feasible to assess with questionnaires in large-scale population studies and clinical practice,” Dr. Li and colleagues wrote. “Moreover, it is reasonable that insomnia symptoms are more modifiable and precisely targetable through behavioral therapies before developing into clinically significant insomnia disorder. Therefore, future clinical trials or community-based intervention studies should be conducted to test whether lifestyle or sleep hygiene interventions for insomnia symptoms can reduce subsequent [cardiocerebral vascular disease] risks.”
The results suggest that efforts aimed at early detection and intervention should include a focus on younger adults and people who do not have high blood pressure, Dr. Li said.
The self-reported insomnia symptoms used in this study have not been fully validated, the investigators noted. The researchers also lacked information about potential confounders, such as shift work and obstructive sleep apnea, that are risk factors for coronary heart disease or stroke and may interfere with insomnia symptoms. In addition, the study did not capture changes in insomnia symptoms over time.
This study was supported by the National Key Research and Development Program of China, the Chinese Ministry of Science and Technology, and the National Natural Science Foundation of China. The China Kadoorie Biobank surveys were supported by grants from the Kadoorie Charitable Foundation and the U.K. Wellcome Trust. The authors had no relevant disclosures.
SOURCE: Zheng B et al. Neurology. 2019 Nov 6. doi: 10.1212/WNL.0000000000008581.
, according to a large cohort study of adults in China. A greater number of insomnia symptoms is associated with increased risk, and this relationship is more evident in younger adults and in adults without hypertension at baseline, researchers reported Nov. 6 in Neurology.
“These results suggest that, if we can target people who are having trouble sleeping with behavioral therapies, it’s possible that we could reduce the number of cases of stroke, heart attack, and other diseases later down the line,” study author Liming Li, MD, professor of epidemiology at Peking University, Beijing, said in a news release.
To clarify the relationships between individual insomnia symptoms, cardiocerebral vascular diseases, and potential effect modifiers, Dr. Li and colleagues analyzed data from the China Kadoorie Biobank Study. For this study, more than 500,000 adults in China aged 30-79 years completed a baseline survey during 2004-2008. The present analysis included data from 487,200 participants who did not have a history of stroke, coronary heart disease, or cancer at baseline.
For the baseline survey, participants answered questions about whether specific insomnia symptoms occurred at least 3 days per week during the past month. The symptoms included difficulty initiating or maintaining sleep (that is, sleep onset latency of 30 minutes or more after going to bed or waking up in the middle of the night); waking too early and being unable to fall back asleep; and trouble functioning during the day because of bad sleep.
The researchers assessed the incidence of cardiocerebral vascular diseases through 2016 by examining disease registries, national health insurance claims databases, and local records. Investigators identified participants with any cardiocerebral vascular disease and assessed the incidence of ischemic heart disease, acute myocardial infarction, hemorrhagic stroke, and ischemic stroke. The researchers followed each participant until the diagnosis of a cardiocerebral vascular disease outcome, death from any cause, loss to follow-up, or Dec. 31, 2016. The researchers used Cox proportional hazard models to estimate hazard ratios for the association between each insomnia symptom and cardiocerebral vascular disease outcomes. They adjusted the models for established and potential confounding factors, including age, income, smoking status, diet, and physical activity.
More than 16% had any insomnia symptom
Of the 487,200 participants, 11.3% had difficulty initiating or maintaining sleep, 10.4% had early morning awakening, and 2.2% had daytime dysfunction attributed to poor sleep. Compared with participants without insomnia symptoms, participants with insomnia symptoms tended to be older and were more likely to be female, not married, and from a rural area. In addition, those with insomnia symptoms were more likely have depression or anxiety symptoms, lower education level, lower household income, and lower body mass index. They also were more likely to have a history of diabetes mellitus. During a median follow-up of 9.6 years, 130,032 cases of cardiocerebral vascular disease occurred, including 40,348 cases of ischemic heart disease and 45,316 cases of stroke.
After adjustment for potential confounders, each insomnia symptom was associated with greater risk of cardiocerebral vascular disease. For difficulty initiating or maintaining sleep, the hazard ratio was 1.09. For early-morning awakening, the HR was 1.07. For daytime dysfunction, the HR was 1.13. Each insomnia symptom was associated with increased risk of ischemic heart disease and ischemic stroke, whereas only difficulty initiating or maintaining sleep was associated with increased risk of acute MI.
In all, 16.4% of participants reported any insomnia symptom; 10% had one symptom, 5.2% had two symptoms, and 1.2% had three symptoms. “Compared with those without any insomnia symptoms, participants with one, two, or three symptoms had a 7%, 10%, or 18% higher risk of total [cardiocerebral vascular disease] incidence, respectively,” the authors wrote. “Our study is the first large-scale cohort study that identified positive dose-response relationships between the number of insomnia symptoms and risks of [cardiocerebral vascular diseases, ischemic heart disease] and stroke incidence.”
Opportunity for intervention
Compared with clinical diagnostic criteria for insomnia, “individual insomnia symptoms are better defined and more feasible to assess with questionnaires in large-scale population studies and clinical practice,” Dr. Li and colleagues wrote. “Moreover, it is reasonable that insomnia symptoms are more modifiable and precisely targetable through behavioral therapies before developing into clinically significant insomnia disorder. Therefore, future clinical trials or community-based intervention studies should be conducted to test whether lifestyle or sleep hygiene interventions for insomnia symptoms can reduce subsequent [cardiocerebral vascular disease] risks.”
The results suggest that efforts aimed at early detection and intervention should include a focus on younger adults and people who do not have high blood pressure, Dr. Li said.
The self-reported insomnia symptoms used in this study have not been fully validated, the investigators noted. The researchers also lacked information about potential confounders, such as shift work and obstructive sleep apnea, that are risk factors for coronary heart disease or stroke and may interfere with insomnia symptoms. In addition, the study did not capture changes in insomnia symptoms over time.
This study was supported by the National Key Research and Development Program of China, the Chinese Ministry of Science and Technology, and the National Natural Science Foundation of China. The China Kadoorie Biobank surveys were supported by grants from the Kadoorie Charitable Foundation and the U.K. Wellcome Trust. The authors had no relevant disclosures.
SOURCE: Zheng B et al. Neurology. 2019 Nov 6. doi: 10.1212/WNL.0000000000008581.
FROM NEUROLOGY
Key clinical point: The presence of insomnia symptoms increases the likelihood of cardiovascular or cerebrovascular disease during approximately 10 years of follow-up.
Major finding: After adjustment for potential confounders, each insomnia symptom was associated with greater risk of cardiocerebral vascular disease. For difficulty initiating or maintaining sleep, the hazard ratio was 1.09. For early-morning awakening, the HR was 1.07. For daytime dysfunction, the HR was 1.13.
Study details: An analysis of data from 487,200 adults in China aged 30-79 years who completed a baseline survey during 2004-2008 and were followed through 2016.
Disclosures: This study was supported by the National Key Research and Development Program of China, the Chinese Ministry of Science and Technology, and the National Natural Science Foundation of China. The China Kadoorie Biobank surveys were supported by grants from the Kadoorie Charitable Foundation and the U.K. Wellcome Trust. The authors had no relevant disclosures.
Source: Zheng B et al. Neurology. 2019 Nov 6. doi: 10.1212/WNL.0000000000008581.
Cardiometabolic risk burden is high in under-50s with type 2 diabetes
BARCELONA – People diagnosed with type 2 diabetes when they are 18-39 years old have significantly higher cardiometabolic risk burden, compared with older people, according to the results of a large study from the United Kingdom presented at the annual meeting of the European Association for the Study of Diabetes.
Patients in that younger age group were found to have higher glycated hemoglobin (HbA1c) levels, along with higher levels of low-density lipoprotein cholesterol and higher body weight.
“We wanted to evaluate the population-level trend in the incidence of young-onset type 2 diabetes in the United Kingdom, compared with later-onset diabetes,” said senior study author Sanjoy Paul, PhD, the director of the Melbourne EpiCentre at the University of Melbourne at a press briefing during the meeting.
Other aims of the study were to compare temporal trends in the incidence of atherosclerotic cardiovascular disease in younger and older patients with type 2 diabetes, and to see how being “high risk” at diagnosis affected patients’ risk of ASCVD and subsequent risk of death.
High-risk status was defined as having at least two of the risk factors for ASCVD – smoking, high systolic blood pressure, high low-density lipoprotein cholesterol, or chronic kidney disease.
The investigators searched a nationally representative sample of primary care electronic medical records from The Health Improvement Network (THIN) database to find incident cases of type 2 diabetes that occurred between 2000 and 2017, with a total of 370,854 cases identified.
At diagnosis of type 2 diabetes, 8% of the sample (n = 29,678) was aged 18-39 years; 15% (n = 56,798), 40-49 years; 25% (n = 93,698), 50-59 years; 29% (n = 107,261), 60-69 years; and 23% (n = 83,419), 70-79 years. Follow-up was just more than 6 years.
Baseline HbA1c in the respective age groups was 8.6%, 8.4%, 8.1%, 7.8%, and 7.6%, with more than 55% of patients in the two youngest age groups having an HbA1c of 7.5% or higher, compared with 34%-47% in the three oldest age groups.
The percentage of patients with a high LDL cholesterol value (2.6 mmol/L or higher in those without ASCVD, and 1.8 or higher in those with ASCVD) was 71%, 75%, 74%, 69%, and 65%, from the youngest to oldest age groups. A respective 71%, 70%, 66%, 57%, and 44% of the patients had a body mass index of 35 kg/m2 or higher.
Few younger patients had ASCVD at diagnosis (2% of the 18-39 age group; 6% of the 40-49 group), with higher rates in the older age groups (13% of the 50-59 group; 23% of the 60-69 group; and 33% of the 70-79 group).
The percentage of patients considered to be at high risk of ASCVD at diagnosis was 23%, 37%, 45%, 50%, and 53%, respectively, across the five age groups.
Although high systolic blood pressure (SBP; 130 mmHg in those with ASCVD, 140 mmHg in those without) was more common in the older age groups (52% at 50-59 years; 60% at 60-69 years, and 64% at 70-79 years,) a substantial proportion of the younger patients also had a high SBP (27% at 18-39 years and 41% at 40-49 years).
Digsu Koye, PhD, also of the Melbourne EpiCentre, presented the main findings of the study during the meeting, noting that the proportion of people diagnosed when they were younger than 50 years remained stable between 2000 and 2017, with a marginal increase in those diagnosed when they were aged 50-59 years, and a decline in those diagnosed when they were older than 70 years.
In the youngest and oldest age groups, equal numbers of men and women were diagnosed with type 2 diabetes, and more women than men were diagnosed in the 60-69 age group, Dr. Koye said. However, for the 40-49 and 50-59 age groups, there were more men than women diagnosed with type 2 diabetes.
Patients were followed for an average of just more than 6 years. “The rate of atherosclerotic cardiovascular disease was declining in all age categories during 2000-2006, but after that, we saw a stable and consistent pattern for all age categories after 2007,” Dr. Koye observed.
In regard to all-cause mortality, there was a 30% decline in the oldest age group (70-79 years), and a 20% decline in the 60-69 age group, but there was no significant decline in the younger age groups, he added.
The investigators determined the average time to event (ASCVD or all-cause mortality) by high-risk status at type 2 diabetes diagnosis for each age group. These analyses showed that there was little difference between the high- and low-risk groups for the average time to ASCVD or all-cause mortality in the youngest age group, with wider differences in the older patients of 1-2 years for ASCVD and 0.5-2 years for all-cause mortality.
Dr. Koye noted that people with young-onset type 2 diabetes had a risk of ASCVD or all-cause mortality that was similar to that of older people, irrespective of whether or not they were considered to be at high or low risk of events. “So we need a more focused treatment strategy for the youngest age group, irrespective of the cardiometabolic risk level at diagnosis,” he said.
Dr. Paul and Dr. Koye reported having no conflicts of interest.
SOURCE: Koye D et al. EASD 2019, Abstract 82.
BARCELONA – People diagnosed with type 2 diabetes when they are 18-39 years old have significantly higher cardiometabolic risk burden, compared with older people, according to the results of a large study from the United Kingdom presented at the annual meeting of the European Association for the Study of Diabetes.
Patients in that younger age group were found to have higher glycated hemoglobin (HbA1c) levels, along with higher levels of low-density lipoprotein cholesterol and higher body weight.
“We wanted to evaluate the population-level trend in the incidence of young-onset type 2 diabetes in the United Kingdom, compared with later-onset diabetes,” said senior study author Sanjoy Paul, PhD, the director of the Melbourne EpiCentre at the University of Melbourne at a press briefing during the meeting.
Other aims of the study were to compare temporal trends in the incidence of atherosclerotic cardiovascular disease in younger and older patients with type 2 diabetes, and to see how being “high risk” at diagnosis affected patients’ risk of ASCVD and subsequent risk of death.
High-risk status was defined as having at least two of the risk factors for ASCVD – smoking, high systolic blood pressure, high low-density lipoprotein cholesterol, or chronic kidney disease.
The investigators searched a nationally representative sample of primary care electronic medical records from The Health Improvement Network (THIN) database to find incident cases of type 2 diabetes that occurred between 2000 and 2017, with a total of 370,854 cases identified.
At diagnosis of type 2 diabetes, 8% of the sample (n = 29,678) was aged 18-39 years; 15% (n = 56,798), 40-49 years; 25% (n = 93,698), 50-59 years; 29% (n = 107,261), 60-69 years; and 23% (n = 83,419), 70-79 years. Follow-up was just more than 6 years.
Baseline HbA1c in the respective age groups was 8.6%, 8.4%, 8.1%, 7.8%, and 7.6%, with more than 55% of patients in the two youngest age groups having an HbA1c of 7.5% or higher, compared with 34%-47% in the three oldest age groups.
The percentage of patients with a high LDL cholesterol value (2.6 mmol/L or higher in those without ASCVD, and 1.8 or higher in those with ASCVD) was 71%, 75%, 74%, 69%, and 65%, from the youngest to oldest age groups. A respective 71%, 70%, 66%, 57%, and 44% of the patients had a body mass index of 35 kg/m2 or higher.
Few younger patients had ASCVD at diagnosis (2% of the 18-39 age group; 6% of the 40-49 group), with higher rates in the older age groups (13% of the 50-59 group; 23% of the 60-69 group; and 33% of the 70-79 group).
The percentage of patients considered to be at high risk of ASCVD at diagnosis was 23%, 37%, 45%, 50%, and 53%, respectively, across the five age groups.
Although high systolic blood pressure (SBP; 130 mmHg in those with ASCVD, 140 mmHg in those without) was more common in the older age groups (52% at 50-59 years; 60% at 60-69 years, and 64% at 70-79 years,) a substantial proportion of the younger patients also had a high SBP (27% at 18-39 years and 41% at 40-49 years).
Digsu Koye, PhD, also of the Melbourne EpiCentre, presented the main findings of the study during the meeting, noting that the proportion of people diagnosed when they were younger than 50 years remained stable between 2000 and 2017, with a marginal increase in those diagnosed when they were aged 50-59 years, and a decline in those diagnosed when they were older than 70 years.
In the youngest and oldest age groups, equal numbers of men and women were diagnosed with type 2 diabetes, and more women than men were diagnosed in the 60-69 age group, Dr. Koye said. However, for the 40-49 and 50-59 age groups, there were more men than women diagnosed with type 2 diabetes.
Patients were followed for an average of just more than 6 years. “The rate of atherosclerotic cardiovascular disease was declining in all age categories during 2000-2006, but after that, we saw a stable and consistent pattern for all age categories after 2007,” Dr. Koye observed.
In regard to all-cause mortality, there was a 30% decline in the oldest age group (70-79 years), and a 20% decline in the 60-69 age group, but there was no significant decline in the younger age groups, he added.
The investigators determined the average time to event (ASCVD or all-cause mortality) by high-risk status at type 2 diabetes diagnosis for each age group. These analyses showed that there was little difference between the high- and low-risk groups for the average time to ASCVD or all-cause mortality in the youngest age group, with wider differences in the older patients of 1-2 years for ASCVD and 0.5-2 years for all-cause mortality.
Dr. Koye noted that people with young-onset type 2 diabetes had a risk of ASCVD or all-cause mortality that was similar to that of older people, irrespective of whether or not they were considered to be at high or low risk of events. “So we need a more focused treatment strategy for the youngest age group, irrespective of the cardiometabolic risk level at diagnosis,” he said.
Dr. Paul and Dr. Koye reported having no conflicts of interest.
SOURCE: Koye D et al. EASD 2019, Abstract 82.
BARCELONA – People diagnosed with type 2 diabetes when they are 18-39 years old have significantly higher cardiometabolic risk burden, compared with older people, according to the results of a large study from the United Kingdom presented at the annual meeting of the European Association for the Study of Diabetes.
Patients in that younger age group were found to have higher glycated hemoglobin (HbA1c) levels, along with higher levels of low-density lipoprotein cholesterol and higher body weight.
“We wanted to evaluate the population-level trend in the incidence of young-onset type 2 diabetes in the United Kingdom, compared with later-onset diabetes,” said senior study author Sanjoy Paul, PhD, the director of the Melbourne EpiCentre at the University of Melbourne at a press briefing during the meeting.
Other aims of the study were to compare temporal trends in the incidence of atherosclerotic cardiovascular disease in younger and older patients with type 2 diabetes, and to see how being “high risk” at diagnosis affected patients’ risk of ASCVD and subsequent risk of death.
High-risk status was defined as having at least two of the risk factors for ASCVD – smoking, high systolic blood pressure, high low-density lipoprotein cholesterol, or chronic kidney disease.
The investigators searched a nationally representative sample of primary care electronic medical records from The Health Improvement Network (THIN) database to find incident cases of type 2 diabetes that occurred between 2000 and 2017, with a total of 370,854 cases identified.
At diagnosis of type 2 diabetes, 8% of the sample (n = 29,678) was aged 18-39 years; 15% (n = 56,798), 40-49 years; 25% (n = 93,698), 50-59 years; 29% (n = 107,261), 60-69 years; and 23% (n = 83,419), 70-79 years. Follow-up was just more than 6 years.
Baseline HbA1c in the respective age groups was 8.6%, 8.4%, 8.1%, 7.8%, and 7.6%, with more than 55% of patients in the two youngest age groups having an HbA1c of 7.5% or higher, compared with 34%-47% in the three oldest age groups.
The percentage of patients with a high LDL cholesterol value (2.6 mmol/L or higher in those without ASCVD, and 1.8 or higher in those with ASCVD) was 71%, 75%, 74%, 69%, and 65%, from the youngest to oldest age groups. A respective 71%, 70%, 66%, 57%, and 44% of the patients had a body mass index of 35 kg/m2 or higher.
Few younger patients had ASCVD at diagnosis (2% of the 18-39 age group; 6% of the 40-49 group), with higher rates in the older age groups (13% of the 50-59 group; 23% of the 60-69 group; and 33% of the 70-79 group).
The percentage of patients considered to be at high risk of ASCVD at diagnosis was 23%, 37%, 45%, 50%, and 53%, respectively, across the five age groups.
Although high systolic blood pressure (SBP; 130 mmHg in those with ASCVD, 140 mmHg in those without) was more common in the older age groups (52% at 50-59 years; 60% at 60-69 years, and 64% at 70-79 years,) a substantial proportion of the younger patients also had a high SBP (27% at 18-39 years and 41% at 40-49 years).
Digsu Koye, PhD, also of the Melbourne EpiCentre, presented the main findings of the study during the meeting, noting that the proportion of people diagnosed when they were younger than 50 years remained stable between 2000 and 2017, with a marginal increase in those diagnosed when they were aged 50-59 years, and a decline in those diagnosed when they were older than 70 years.
In the youngest and oldest age groups, equal numbers of men and women were diagnosed with type 2 diabetes, and more women than men were diagnosed in the 60-69 age group, Dr. Koye said. However, for the 40-49 and 50-59 age groups, there were more men than women diagnosed with type 2 diabetes.
Patients were followed for an average of just more than 6 years. “The rate of atherosclerotic cardiovascular disease was declining in all age categories during 2000-2006, but after that, we saw a stable and consistent pattern for all age categories after 2007,” Dr. Koye observed.
In regard to all-cause mortality, there was a 30% decline in the oldest age group (70-79 years), and a 20% decline in the 60-69 age group, but there was no significant decline in the younger age groups, he added.
The investigators determined the average time to event (ASCVD or all-cause mortality) by high-risk status at type 2 diabetes diagnosis for each age group. These analyses showed that there was little difference between the high- and low-risk groups for the average time to ASCVD or all-cause mortality in the youngest age group, with wider differences in the older patients of 1-2 years for ASCVD and 0.5-2 years for all-cause mortality.
Dr. Koye noted that people with young-onset type 2 diabetes had a risk of ASCVD or all-cause mortality that was similar to that of older people, irrespective of whether or not they were considered to be at high or low risk of events. “So we need a more focused treatment strategy for the youngest age group, irrespective of the cardiometabolic risk level at diagnosis,” he said.
Dr. Paul and Dr. Koye reported having no conflicts of interest.
SOURCE: Koye D et al. EASD 2019, Abstract 82.
REPORTING FROM EASD 2019
Measles infection linked to impaired ‘immune memory’
Infection with the measles virus appears to reduce immunity to other pathogens, according to a paper published in Science.
The hypothesis that the measles virus could cause “immunological amnesia” by impairing immune memory is supported by early research showing children with measles had negative cutaneous tuberculin reactions after having previously tested positive.
“Subsequent studies have shown decreased interferon signaling, skewed cytokine responses, lymphopenia, and suppression of lymphocyte proliferation shortly after infection,” wrote Michael Mina, MD, from Brigham and Women’s Hospital in Boston, and coauthors.
“Given the variation in the degree of immune repertoire modulation we observed, we anticipate that future risk of morbidity and mortality after measles would not be homogeneous but would be skewed toward individuals with the most severe elimination of immunological memory,” they wrote. “These findings underscore the crucial need for continued widespread vaccination.”
In this study, researchers compared the levels of around 400 pathogen-specific antibodies in blood samples from 77 unvaccinated children, taken before and 2 months after natural measles infection, with 5 unvaccinated children who did not contract measles. A total of 34 the children experienced mild measles, and 43 had severe measles.
They found that the samples taken after measles infection showed “substantial” reductions in the number of pathogen epitopes, compared with the samples from children who did not get infected with measles.
This amounted to approximately a 20% mean reduction in overall diversity or size of the antibody repertoire. However, in children who experienced severe measles, there was a median loss of 40% (range, 11%-62%) of antibody repertoire, compared with a median of 33% (range, 12%-73%) range in children who experienced mild infection. Meanwhile, the control subjects retained approximately 90% of their antibody repertoire over a similar or longer time period. Some children lost up to 70% of antibodies for specific pathogens.
The study did find increases in measles virus–specific antigens in children both after measles infection and MMR vaccination. However the authors did not detect any changes in total IgG, IgA, or IgM levels.
Dr. Mina and associates wrote.
They also noted that controls who received the MMR vaccine showed a marked increase in overall antibody repertoire.
In a separate investigation reported in Science Immunology, Velislava N. Petrova, PhD, of the Wellcome Sanger Institute in Cambridge, England, and coauthors investigated genetic changes in 26 unvaccinated children from the Netherlands who previously had measles to determine if B-cell impairment can lead to measles-associated immunosuppression. Their antibody genes were sequenced before any symptoms of measles developed and roughly 40 days after rash. Two control groups also were sequenced accordingly: vaccinated adults and three unvaccinated children from the same community who were not infected with measles.
Naive B cells from individuals in the vaccinated and uninfected control groups showed high correlation of immunoglobulin heavy chain (IgVH-J) gene frequencies across time periods (R2 = 0.96 and 0.92, respectively) but no significant differences in gene expression (P greater than .05). At the same time, although B-cell frequencies in measles patients recovered to levels before infection, they had significant changes in IgVH-J gene frequencies (P = .01) and decreased correlation in gene expression (R2 = 0.78).
In addition, individuals in the control groups had “a stable genetic composition of B memory cells” but no significant changes in the third complementarity-determining region (CDR3) lengths or mutational frequency of IgVH-J genes (P greater than .05). B memory cells in measles patients, however, showed increases in mutational frequency (P = .0008) and a reduction in CDR3 length (P = .017) of IgVH genes, Dr. Petrova and associates reported.
The study by Mina et al. was supported by grants from various U.S., European, and Finnish foundations and national organizations. Some of the coauthors had relationships with biotechnology and pharmaceutical companies, and three reported a patent holding related to technology used in the study. The study by Petrova et al. was funded by grants to the investigators from various Indonesian and German organizations and the Wellcome Trust. The authors reported no conflicts of interest.
SOURCES: Mina M et al. Science. 2019 Nov 1;366:599-606; Petrova VN et al. Sci Immunol. 2019 Nov 1. doi: 10.1126/sciimmunol.aay6125.
As a result of reduced vaccination, after decades of decline, the number of worldwide cases of measles has increased by nearly 300% since 2018. Epidemiologic evidence has associated measles infections with increases in morbidity and mortality for as long as 5 years after the infection and suggests that, in the prevaccine era, measles virus may have been associated with up to 50% of all childhood deaths, mostly because of nonmeasles infections. Measles replication in immune cells has been hypothesized to impair immune memory, potentially causing what some scientists call “immunological amnesia.”A measles virus receptor, called CD150/ SLAMF1, is highly expressed on memory T, B, and plasma cells. Measles virus gains entry to these immune memory cells using that receptor and kills the cells.
The scientists stated that it could take months or years to return the immune repertoire back to baseline. During the rebuilding process, children would be at increased risk for infectious diseases they had previously experienced.
In a second outstanding paper, Petrova et al. in Science Immunology studied B cells before and after measles infection, and identified two immunologic consequences: The naive B-cell pool was depleted, leading to a return to immunologic immaturity, and the memory B-cell pool was depleted, resulting in compromised immune memory to previously encountered pathogens.
Thus, the link between measles infections and increased susceptibility to other infections and increased deaths from nonmeasles infectious diseases in the aftermath of measles has been revealed. This information adds new data to share with parents who consider refusing measles vaccination. The risks are far greater than getting measles.
Michael E. Pichichero, MD, is a specialist in pediatric infectious diseases and director of the Research Institute at Rochester (N.Y.) General Hospital. He was asked to comment on the articles. Dr. Pichichero has no conflicts to declare.
As a result of reduced vaccination, after decades of decline, the number of worldwide cases of measles has increased by nearly 300% since 2018. Epidemiologic evidence has associated measles infections with increases in morbidity and mortality for as long as 5 years after the infection and suggests that, in the prevaccine era, measles virus may have been associated with up to 50% of all childhood deaths, mostly because of nonmeasles infections. Measles replication in immune cells has been hypothesized to impair immune memory, potentially causing what some scientists call “immunological amnesia.”A measles virus receptor, called CD150/ SLAMF1, is highly expressed on memory T, B, and plasma cells. Measles virus gains entry to these immune memory cells using that receptor and kills the cells.
The scientists stated that it could take months or years to return the immune repertoire back to baseline. During the rebuilding process, children would be at increased risk for infectious diseases they had previously experienced.
In a second outstanding paper, Petrova et al. in Science Immunology studied B cells before and after measles infection, and identified two immunologic consequences: The naive B-cell pool was depleted, leading to a return to immunologic immaturity, and the memory B-cell pool was depleted, resulting in compromised immune memory to previously encountered pathogens.
Thus, the link between measles infections and increased susceptibility to other infections and increased deaths from nonmeasles infectious diseases in the aftermath of measles has been revealed. This information adds new data to share with parents who consider refusing measles vaccination. The risks are far greater than getting measles.
Michael E. Pichichero, MD, is a specialist in pediatric infectious diseases and director of the Research Institute at Rochester (N.Y.) General Hospital. He was asked to comment on the articles. Dr. Pichichero has no conflicts to declare.
As a result of reduced vaccination, after decades of decline, the number of worldwide cases of measles has increased by nearly 300% since 2018. Epidemiologic evidence has associated measles infections with increases in morbidity and mortality for as long as 5 years after the infection and suggests that, in the prevaccine era, measles virus may have been associated with up to 50% of all childhood deaths, mostly because of nonmeasles infections. Measles replication in immune cells has been hypothesized to impair immune memory, potentially causing what some scientists call “immunological amnesia.”A measles virus receptor, called CD150/ SLAMF1, is highly expressed on memory T, B, and plasma cells. Measles virus gains entry to these immune memory cells using that receptor and kills the cells.
The scientists stated that it could take months or years to return the immune repertoire back to baseline. During the rebuilding process, children would be at increased risk for infectious diseases they had previously experienced.
In a second outstanding paper, Petrova et al. in Science Immunology studied B cells before and after measles infection, and identified two immunologic consequences: The naive B-cell pool was depleted, leading to a return to immunologic immaturity, and the memory B-cell pool was depleted, resulting in compromised immune memory to previously encountered pathogens.
Thus, the link between measles infections and increased susceptibility to other infections and increased deaths from nonmeasles infectious diseases in the aftermath of measles has been revealed. This information adds new data to share with parents who consider refusing measles vaccination. The risks are far greater than getting measles.
Michael E. Pichichero, MD, is a specialist in pediatric infectious diseases and director of the Research Institute at Rochester (N.Y.) General Hospital. He was asked to comment on the articles. Dr. Pichichero has no conflicts to declare.
Infection with the measles virus appears to reduce immunity to other pathogens, according to a paper published in Science.
The hypothesis that the measles virus could cause “immunological amnesia” by impairing immune memory is supported by early research showing children with measles had negative cutaneous tuberculin reactions after having previously tested positive.
“Subsequent studies have shown decreased interferon signaling, skewed cytokine responses, lymphopenia, and suppression of lymphocyte proliferation shortly after infection,” wrote Michael Mina, MD, from Brigham and Women’s Hospital in Boston, and coauthors.
“Given the variation in the degree of immune repertoire modulation we observed, we anticipate that future risk of morbidity and mortality after measles would not be homogeneous but would be skewed toward individuals with the most severe elimination of immunological memory,” they wrote. “These findings underscore the crucial need for continued widespread vaccination.”
In this study, researchers compared the levels of around 400 pathogen-specific antibodies in blood samples from 77 unvaccinated children, taken before and 2 months after natural measles infection, with 5 unvaccinated children who did not contract measles. A total of 34 the children experienced mild measles, and 43 had severe measles.
They found that the samples taken after measles infection showed “substantial” reductions in the number of pathogen epitopes, compared with the samples from children who did not get infected with measles.
This amounted to approximately a 20% mean reduction in overall diversity or size of the antibody repertoire. However, in children who experienced severe measles, there was a median loss of 40% (range, 11%-62%) of antibody repertoire, compared with a median of 33% (range, 12%-73%) range in children who experienced mild infection. Meanwhile, the control subjects retained approximately 90% of their antibody repertoire over a similar or longer time period. Some children lost up to 70% of antibodies for specific pathogens.
The study did find increases in measles virus–specific antigens in children both after measles infection and MMR vaccination. However the authors did not detect any changes in total IgG, IgA, or IgM levels.
Dr. Mina and associates wrote.
They also noted that controls who received the MMR vaccine showed a marked increase in overall antibody repertoire.
In a separate investigation reported in Science Immunology, Velislava N. Petrova, PhD, of the Wellcome Sanger Institute in Cambridge, England, and coauthors investigated genetic changes in 26 unvaccinated children from the Netherlands who previously had measles to determine if B-cell impairment can lead to measles-associated immunosuppression. Their antibody genes were sequenced before any symptoms of measles developed and roughly 40 days after rash. Two control groups also were sequenced accordingly: vaccinated adults and three unvaccinated children from the same community who were not infected with measles.
Naive B cells from individuals in the vaccinated and uninfected control groups showed high correlation of immunoglobulin heavy chain (IgVH-J) gene frequencies across time periods (R2 = 0.96 and 0.92, respectively) but no significant differences in gene expression (P greater than .05). At the same time, although B-cell frequencies in measles patients recovered to levels before infection, they had significant changes in IgVH-J gene frequencies (P = .01) and decreased correlation in gene expression (R2 = 0.78).
In addition, individuals in the control groups had “a stable genetic composition of B memory cells” but no significant changes in the third complementarity-determining region (CDR3) lengths or mutational frequency of IgVH-J genes (P greater than .05). B memory cells in measles patients, however, showed increases in mutational frequency (P = .0008) and a reduction in CDR3 length (P = .017) of IgVH genes, Dr. Petrova and associates reported.
The study by Mina et al. was supported by grants from various U.S., European, and Finnish foundations and national organizations. Some of the coauthors had relationships with biotechnology and pharmaceutical companies, and three reported a patent holding related to technology used in the study. The study by Petrova et al. was funded by grants to the investigators from various Indonesian and German organizations and the Wellcome Trust. The authors reported no conflicts of interest.
SOURCES: Mina M et al. Science. 2019 Nov 1;366:599-606; Petrova VN et al. Sci Immunol. 2019 Nov 1. doi: 10.1126/sciimmunol.aay6125.
Infection with the measles virus appears to reduce immunity to other pathogens, according to a paper published in Science.
The hypothesis that the measles virus could cause “immunological amnesia” by impairing immune memory is supported by early research showing children with measles had negative cutaneous tuberculin reactions after having previously tested positive.
“Subsequent studies have shown decreased interferon signaling, skewed cytokine responses, lymphopenia, and suppression of lymphocyte proliferation shortly after infection,” wrote Michael Mina, MD, from Brigham and Women’s Hospital in Boston, and coauthors.
“Given the variation in the degree of immune repertoire modulation we observed, we anticipate that future risk of morbidity and mortality after measles would not be homogeneous but would be skewed toward individuals with the most severe elimination of immunological memory,” they wrote. “These findings underscore the crucial need for continued widespread vaccination.”
In this study, researchers compared the levels of around 400 pathogen-specific antibodies in blood samples from 77 unvaccinated children, taken before and 2 months after natural measles infection, with 5 unvaccinated children who did not contract measles. A total of 34 the children experienced mild measles, and 43 had severe measles.
They found that the samples taken after measles infection showed “substantial” reductions in the number of pathogen epitopes, compared with the samples from children who did not get infected with measles.
This amounted to approximately a 20% mean reduction in overall diversity or size of the antibody repertoire. However, in children who experienced severe measles, there was a median loss of 40% (range, 11%-62%) of antibody repertoire, compared with a median of 33% (range, 12%-73%) range in children who experienced mild infection. Meanwhile, the control subjects retained approximately 90% of their antibody repertoire over a similar or longer time period. Some children lost up to 70% of antibodies for specific pathogens.
The study did find increases in measles virus–specific antigens in children both after measles infection and MMR vaccination. However the authors did not detect any changes in total IgG, IgA, or IgM levels.
Dr. Mina and associates wrote.
They also noted that controls who received the MMR vaccine showed a marked increase in overall antibody repertoire.
In a separate investigation reported in Science Immunology, Velislava N. Petrova, PhD, of the Wellcome Sanger Institute in Cambridge, England, and coauthors investigated genetic changes in 26 unvaccinated children from the Netherlands who previously had measles to determine if B-cell impairment can lead to measles-associated immunosuppression. Their antibody genes were sequenced before any symptoms of measles developed and roughly 40 days after rash. Two control groups also were sequenced accordingly: vaccinated adults and three unvaccinated children from the same community who were not infected with measles.
Naive B cells from individuals in the vaccinated and uninfected control groups showed high correlation of immunoglobulin heavy chain (IgVH-J) gene frequencies across time periods (R2 = 0.96 and 0.92, respectively) but no significant differences in gene expression (P greater than .05). At the same time, although B-cell frequencies in measles patients recovered to levels before infection, they had significant changes in IgVH-J gene frequencies (P = .01) and decreased correlation in gene expression (R2 = 0.78).
In addition, individuals in the control groups had “a stable genetic composition of B memory cells” but no significant changes in the third complementarity-determining region (CDR3) lengths or mutational frequency of IgVH-J genes (P greater than .05). B memory cells in measles patients, however, showed increases in mutational frequency (P = .0008) and a reduction in CDR3 length (P = .017) of IgVH genes, Dr. Petrova and associates reported.
The study by Mina et al. was supported by grants from various U.S., European, and Finnish foundations and national organizations. Some of the coauthors had relationships with biotechnology and pharmaceutical companies, and three reported a patent holding related to technology used in the study. The study by Petrova et al. was funded by grants to the investigators from various Indonesian and German organizations and the Wellcome Trust. The authors reported no conflicts of interest.
SOURCES: Mina M et al. Science. 2019 Nov 1;366:599-606; Petrova VN et al. Sci Immunol. 2019 Nov 1. doi: 10.1126/sciimmunol.aay6125.
FROM SCIENCE
The fundamental things apply
Dear Colleagues,
or questions about cosmetic procedures or skin care advice.
Needle nippers were around, but no elaborate, molded-plastic contraptions like the sharps containers now in wide use. You sent pathology specimens in plastic cylinders by U.S. mail; then you called the lab 2 weeks later to ask, “Where’s the report on Jane Smith, with the rule out melanoma,” and the lab said, “Jane who?”
Of course, some things about practice have not changed. Patients with atopic dermatitis still ask why eczema comes back and why we can’t give them something to make it go away once and for all. Some referring physicians still treat scaly rashes with ketoconazole cream (and when that fails, oral fluconazole, which doesn’t work either).
Of course the biggest change between then and now, coincident with the rise of computers and technology, is the advent and ubiquity of that great swindle foisted upon the profession and the public – electronic health records – with their unfulfilled promises of cost-savings and efficiency and unconceded consequences: turning healers into harried data-entry drudges too busy clicking mice to make eye contact with humans. Yes, the Emperor has clothes. The Emperor is wearing Depends.
I wrote my first column for this periodical 22 years ago; this will be my last. My wonderful editor, Elizabeth Mechcatie, has agreed to take under advisement a proposal that I go on sending occasional dispatches under the heading “Pruritus Emeritus.” My family used to refer to those in the anomalous state of being emeritus – it means, roughly, “Forgotten, but not gone” – by rhyming emeritus with sinusitis.
There is no way to remember 40 years of patients. Many came just once, others several times. Some moved away, some passed away, changed primary doctors, changed insurances. Some grew too old to visit, sent regretful notes apologizing for finding the drive too long, the parking too hard. Some returned after an absence of a decade or 3, having forgotten that they had once come for the same problem, or come at all.
But there have been other patients who formed a real bond, whose names and faces still come readily to mind, who visited over long periods, sent their spouses, family members, even children and grandchildren. The stories of their lives became part of mine, and sometimes mine part of theirs.
Though hardly an old-movie buff, I know the famous scene in Casablanca in which a radiant Ingrid Bergman (that skin!) asks Dooley Wilson – the piano player, Sam – to play the song Humphrey Bogart does not want to hear:
“You must remember this
A kiss is just a kiss
A sigh is just a sigh
The fundamental things apply
As time goes by.”
Over the last 40 years there have been substantial advances in the way we treat patients, though perhaps not enough to justify the endless noisy hype about imminent breakthroughs and looming disruptions, therapies, and apps that are sure to change practice and civilization as we know them. Altogether too much noise, at least for my taste. But not inside the examining room.
Outside the room rages the din of demographic updates, of online checks of insurance eligibility, referral status, prior authorizations, the blare of marketing and promotion, the cacophony of metrics and algorithms.
Inside the room, however, quiet reigns. A patient presents with a symptom or a sign, or the fear of a symptom or anxiety over the meaning of a sign, filtered through a jumble of ideas – misremembered, half understood, at times mutually contradictory – that amplify fears common to anyone who visits a practitioner, however minor the presenting complaint: pain, debility, decline, isolation, solitude, death.
And the practitioner attends, considers, contextualizes, counsels, consoles, and conveys a response to the patient’s questions, whether in so many words or by body language or tone of voice, offers answers not just to what the patient has asked but the ones the patient meant to ask but did not know how.
“Yes, sir, death waits for all of us in the end, but for you, perhaps, not today.”
“Yes, madam, illness can be a frightening affair, but your case is not as bad as you think it is and won’t move as fast as you imagine. And as to your being limited and alone – well, not yet. There are those you can rely on, people with a bit of knowledge and a little experience, who are committed to doing what can be done to bend the arc of illness in your favor.”
That fundamental role will, it seems to me, always apply as long people practice medicine.
With all good wishes for personal happiness and professional success,
Alan Rockoff
Dear Colleagues,
or questions about cosmetic procedures or skin care advice.
Needle nippers were around, but no elaborate, molded-plastic contraptions like the sharps containers now in wide use. You sent pathology specimens in plastic cylinders by U.S. mail; then you called the lab 2 weeks later to ask, “Where’s the report on Jane Smith, with the rule out melanoma,” and the lab said, “Jane who?”
Of course, some things about practice have not changed. Patients with atopic dermatitis still ask why eczema comes back and why we can’t give them something to make it go away once and for all. Some referring physicians still treat scaly rashes with ketoconazole cream (and when that fails, oral fluconazole, which doesn’t work either).
Of course the biggest change between then and now, coincident with the rise of computers and technology, is the advent and ubiquity of that great swindle foisted upon the profession and the public – electronic health records – with their unfulfilled promises of cost-savings and efficiency and unconceded consequences: turning healers into harried data-entry drudges too busy clicking mice to make eye contact with humans. Yes, the Emperor has clothes. The Emperor is wearing Depends.
I wrote my first column for this periodical 22 years ago; this will be my last. My wonderful editor, Elizabeth Mechcatie, has agreed to take under advisement a proposal that I go on sending occasional dispatches under the heading “Pruritus Emeritus.” My family used to refer to those in the anomalous state of being emeritus – it means, roughly, “Forgotten, but not gone” – by rhyming emeritus with sinusitis.
There is no way to remember 40 years of patients. Many came just once, others several times. Some moved away, some passed away, changed primary doctors, changed insurances. Some grew too old to visit, sent regretful notes apologizing for finding the drive too long, the parking too hard. Some returned after an absence of a decade or 3, having forgotten that they had once come for the same problem, or come at all.
But there have been other patients who formed a real bond, whose names and faces still come readily to mind, who visited over long periods, sent their spouses, family members, even children and grandchildren. The stories of their lives became part of mine, and sometimes mine part of theirs.
Though hardly an old-movie buff, I know the famous scene in Casablanca in which a radiant Ingrid Bergman (that skin!) asks Dooley Wilson – the piano player, Sam – to play the song Humphrey Bogart does not want to hear:
“You must remember this
A kiss is just a kiss
A sigh is just a sigh
The fundamental things apply
As time goes by.”
Over the last 40 years there have been substantial advances in the way we treat patients, though perhaps not enough to justify the endless noisy hype about imminent breakthroughs and looming disruptions, therapies, and apps that are sure to change practice and civilization as we know them. Altogether too much noise, at least for my taste. But not inside the examining room.
Outside the room rages the din of demographic updates, of online checks of insurance eligibility, referral status, prior authorizations, the blare of marketing and promotion, the cacophony of metrics and algorithms.
Inside the room, however, quiet reigns. A patient presents with a symptom or a sign, or the fear of a symptom or anxiety over the meaning of a sign, filtered through a jumble of ideas – misremembered, half understood, at times mutually contradictory – that amplify fears common to anyone who visits a practitioner, however minor the presenting complaint: pain, debility, decline, isolation, solitude, death.
And the practitioner attends, considers, contextualizes, counsels, consoles, and conveys a response to the patient’s questions, whether in so many words or by body language or tone of voice, offers answers not just to what the patient has asked but the ones the patient meant to ask but did not know how.
“Yes, sir, death waits for all of us in the end, but for you, perhaps, not today.”
“Yes, madam, illness can be a frightening affair, but your case is not as bad as you think it is and won’t move as fast as you imagine. And as to your being limited and alone – well, not yet. There are those you can rely on, people with a bit of knowledge and a little experience, who are committed to doing what can be done to bend the arc of illness in your favor.”
That fundamental role will, it seems to me, always apply as long people practice medicine.
With all good wishes for personal happiness and professional success,
Alan Rockoff
Dear Colleagues,
or questions about cosmetic procedures or skin care advice.
Needle nippers were around, but no elaborate, molded-plastic contraptions like the sharps containers now in wide use. You sent pathology specimens in plastic cylinders by U.S. mail; then you called the lab 2 weeks later to ask, “Where’s the report on Jane Smith, with the rule out melanoma,” and the lab said, “Jane who?”
Of course, some things about practice have not changed. Patients with atopic dermatitis still ask why eczema comes back and why we can’t give them something to make it go away once and for all. Some referring physicians still treat scaly rashes with ketoconazole cream (and when that fails, oral fluconazole, which doesn’t work either).
Of course the biggest change between then and now, coincident with the rise of computers and technology, is the advent and ubiquity of that great swindle foisted upon the profession and the public – electronic health records – with their unfulfilled promises of cost-savings and efficiency and unconceded consequences: turning healers into harried data-entry drudges too busy clicking mice to make eye contact with humans. Yes, the Emperor has clothes. The Emperor is wearing Depends.
I wrote my first column for this periodical 22 years ago; this will be my last. My wonderful editor, Elizabeth Mechcatie, has agreed to take under advisement a proposal that I go on sending occasional dispatches under the heading “Pruritus Emeritus.” My family used to refer to those in the anomalous state of being emeritus – it means, roughly, “Forgotten, but not gone” – by rhyming emeritus with sinusitis.
There is no way to remember 40 years of patients. Many came just once, others several times. Some moved away, some passed away, changed primary doctors, changed insurances. Some grew too old to visit, sent regretful notes apologizing for finding the drive too long, the parking too hard. Some returned after an absence of a decade or 3, having forgotten that they had once come for the same problem, or come at all.
But there have been other patients who formed a real bond, whose names and faces still come readily to mind, who visited over long periods, sent their spouses, family members, even children and grandchildren. The stories of their lives became part of mine, and sometimes mine part of theirs.
Though hardly an old-movie buff, I know the famous scene in Casablanca in which a radiant Ingrid Bergman (that skin!) asks Dooley Wilson – the piano player, Sam – to play the song Humphrey Bogart does not want to hear:
“You must remember this
A kiss is just a kiss
A sigh is just a sigh
The fundamental things apply
As time goes by.”
Over the last 40 years there have been substantial advances in the way we treat patients, though perhaps not enough to justify the endless noisy hype about imminent breakthroughs and looming disruptions, therapies, and apps that are sure to change practice and civilization as we know them. Altogether too much noise, at least for my taste. But not inside the examining room.
Outside the room rages the din of demographic updates, of online checks of insurance eligibility, referral status, prior authorizations, the blare of marketing and promotion, the cacophony of metrics and algorithms.
Inside the room, however, quiet reigns. A patient presents with a symptom or a sign, or the fear of a symptom or anxiety over the meaning of a sign, filtered through a jumble of ideas – misremembered, half understood, at times mutually contradictory – that amplify fears common to anyone who visits a practitioner, however minor the presenting complaint: pain, debility, decline, isolation, solitude, death.
And the practitioner attends, considers, contextualizes, counsels, consoles, and conveys a response to the patient’s questions, whether in so many words or by body language or tone of voice, offers answers not just to what the patient has asked but the ones the patient meant to ask but did not know how.
“Yes, sir, death waits for all of us in the end, but for you, perhaps, not today.”
“Yes, madam, illness can be a frightening affair, but your case is not as bad as you think it is and won’t move as fast as you imagine. And as to your being limited and alone – well, not yet. There are those you can rely on, people with a bit of knowledge and a little experience, who are committed to doing what can be done to bend the arc of illness in your favor.”
That fundamental role will, it seems to me, always apply as long people practice medicine.
With all good wishes for personal happiness and professional success,
Alan Rockoff
Two regenerative techniques prove comparable for repairing knee cartilage
When it comes to repairing knee cartilage, a new study found no significant differences between autologous matrix-induced chondrogenesis (AMIC) and autologous chondrocyte implantation with a collagen membrane (ACI-C) as treatment options.
“If the conclusion of the present study stands and is confirmed by further clinical trials, AMIC could be considered an equal alternative to techniques based on chondrocyte transplantation for treatment of cartilage defects of the knee,” wrote Vegard Fossum, MD, of University Hospital of North Norway, Tromsø, and coauthors, adding that cost and comparative ease might actually make AMIC the preferred choice. The study was published in the Orthopaedic Journal of Sports Medicine.
To evaluate outcomes of the two procedures, the researchers initiated a clinical trial of 41 patients with at least one chondral or osteochondral defect of the distal femur or patella. They were split into two groups: those treated with ACI-C (n = 21) and those treated with AMIC (n = 20). At 1- and 2-year follow-up, patients were assessed via improvements in Knee Injury and Osteoarthritis Outcome Score (KOOS), compared with baseline, along with Lysholm and visual analog scale (VAS) pain scores.
After 1 and 2 years, both groups saw improvements from baseline. At 2 years, the AMIC group had an 18.1 change in KOOS, compared with 10.3 in the ACI-C group (P = .17). Two-year improvements on the Lysholm score (19.7 in AMIC, compared with 17.0 in ACI-C, P = .66) and VAS pain score (30.6 in AMIC versus 19.6 in ACI-C, P = .19) were not significantly different. Two patients in the AMIC group had undergone total knee replacement after 2 years, compared with zero in the ACI-C group.
The authors noted their study’s potential limitations, including the small number of patients in each group – the initial plan was to include 80 total – and its broad inclusion criteria. However, since the aim was to compare treatment results and not evaluate effectiveness, they did not consider the broad criteria “a major limitation.”
The authors reported no conflicts of interest.
SOURCE: Fossum V et al. Orthop J Sports Med. 2019 Sept 17. doi: 10.1177/2325967119868212.
When it comes to repairing knee cartilage, a new study found no significant differences between autologous matrix-induced chondrogenesis (AMIC) and autologous chondrocyte implantation with a collagen membrane (ACI-C) as treatment options.
“If the conclusion of the present study stands and is confirmed by further clinical trials, AMIC could be considered an equal alternative to techniques based on chondrocyte transplantation for treatment of cartilage defects of the knee,” wrote Vegard Fossum, MD, of University Hospital of North Norway, Tromsø, and coauthors, adding that cost and comparative ease might actually make AMIC the preferred choice. The study was published in the Orthopaedic Journal of Sports Medicine.
To evaluate outcomes of the two procedures, the researchers initiated a clinical trial of 41 patients with at least one chondral or osteochondral defect of the distal femur or patella. They were split into two groups: those treated with ACI-C (n = 21) and those treated with AMIC (n = 20). At 1- and 2-year follow-up, patients were assessed via improvements in Knee Injury and Osteoarthritis Outcome Score (KOOS), compared with baseline, along with Lysholm and visual analog scale (VAS) pain scores.
After 1 and 2 years, both groups saw improvements from baseline. At 2 years, the AMIC group had an 18.1 change in KOOS, compared with 10.3 in the ACI-C group (P = .17). Two-year improvements on the Lysholm score (19.7 in AMIC, compared with 17.0 in ACI-C, P = .66) and VAS pain score (30.6 in AMIC versus 19.6 in ACI-C, P = .19) were not significantly different. Two patients in the AMIC group had undergone total knee replacement after 2 years, compared with zero in the ACI-C group.
The authors noted their study’s potential limitations, including the small number of patients in each group – the initial plan was to include 80 total – and its broad inclusion criteria. However, since the aim was to compare treatment results and not evaluate effectiveness, they did not consider the broad criteria “a major limitation.”
The authors reported no conflicts of interest.
SOURCE: Fossum V et al. Orthop J Sports Med. 2019 Sept 17. doi: 10.1177/2325967119868212.
When it comes to repairing knee cartilage, a new study found no significant differences between autologous matrix-induced chondrogenesis (AMIC) and autologous chondrocyte implantation with a collagen membrane (ACI-C) as treatment options.
“If the conclusion of the present study stands and is confirmed by further clinical trials, AMIC could be considered an equal alternative to techniques based on chondrocyte transplantation for treatment of cartilage defects of the knee,” wrote Vegard Fossum, MD, of University Hospital of North Norway, Tromsø, and coauthors, adding that cost and comparative ease might actually make AMIC the preferred choice. The study was published in the Orthopaedic Journal of Sports Medicine.
To evaluate outcomes of the two procedures, the researchers initiated a clinical trial of 41 patients with at least one chondral or osteochondral defect of the distal femur or patella. They were split into two groups: those treated with ACI-C (n = 21) and those treated with AMIC (n = 20). At 1- and 2-year follow-up, patients were assessed via improvements in Knee Injury and Osteoarthritis Outcome Score (KOOS), compared with baseline, along with Lysholm and visual analog scale (VAS) pain scores.
After 1 and 2 years, both groups saw improvements from baseline. At 2 years, the AMIC group had an 18.1 change in KOOS, compared with 10.3 in the ACI-C group (P = .17). Two-year improvements on the Lysholm score (19.7 in AMIC, compared with 17.0 in ACI-C, P = .66) and VAS pain score (30.6 in AMIC versus 19.6 in ACI-C, P = .19) were not significantly different. Two patients in the AMIC group had undergone total knee replacement after 2 years, compared with zero in the ACI-C group.
The authors noted their study’s potential limitations, including the small number of patients in each group – the initial plan was to include 80 total – and its broad inclusion criteria. However, since the aim was to compare treatment results and not evaluate effectiveness, they did not consider the broad criteria “a major limitation.”
The authors reported no conflicts of interest.
SOURCE: Fossum V et al. Orthop J Sports Med. 2019 Sept 17. doi: 10.1177/2325967119868212.
FROM THE ORTHOPAEDIC JOURNAL OF SPORTS MEDICINE
Survival ‘excellent’ after rituximab-bendamustine induction in transplant-eligible MCL
The combination of rituximab and bendamustine (RB) provided “excellent” survival with less toxicity, compared with a cytarabine-based induction regimen, in transplant-eligible patients with mantle cell lymphoma, according to a long-term follow-up report from randomized phase 2 trial.
The 5-year survival rates for RB were “provocatively similar” to what was achieved with the standard, intensive R-hyperCVAD regimen, investigators said in this update on the Southwest Oncology Group (SWOG) S1106 study.
By contrast, the R-hyperCVAD regimen was associated with more toxicity and higher failure rates for stem cell mobilization, according to the report’s lead author, Manali Kamdar, MD, of the University of Colorado, Denver, and coauthors.
“Overall, S1106 demonstrated that an outpatient-based, less intensive induction therapy of bendamustine plus rituximab is highly effective, safe, and durable in untreated transplant-eligible MCL patients,” Dr. Kamdar and her colleagues reported in Blood Advances.
The results have guided the design of an upcoming study, EA4181, in which patients with mantle cell lymphoma will be treated with an RB backbone plus cytarabine, the BTK inhibitor acalabrutinib, or both, according to the authors.
In the present study, S1106, patients with mantle cell lymphoma were randomized to receive RB or the R-hyperCVAD regimen, which consisted of rituximab with hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone, alternating with high-dose cytarabine and methotrexate. Both regimens were followed by autologous hematopoietic stem cell transplant.
The stem cell mobilization failure rate was 29% in the R-hyperCVAD arm in an interim analysis conducted after 53 of a planned 160 patients had been enrolled, including 35 in the RB arm and 17 in the R-hyperCVAD arm, according to a report published in the British Journal of Haematology (2016 Dec 19. doi: 10.1111/bjh.14480). That analysis triggered a shutdown of the study, based on a rule stating that either arm would be deemed “unacceptably toxic” if the mobilization rate exceeded 10%.
Accordingly, R-hyperCVAD is “not an ideal platform” for future trials, the investigators said. At that time, the estimated 2-year progression-free survival (PFS) was 81% versus 82% for RB and R-hyperCVAD, respectively, while overall survival (OS) was 87% versus 88%.
With additional follow-up, the 5-year PFS is 66% and 62% in the RB and R-hyperCVAD arms, respectively, while 5-year OS is 80% and 74%, according to the investigators.
The RB regimen also results in “excellent” minimal residual disease (MRD) negativity, they added.
MRD status was evaluated in 12 paired pre- and postinduction therapy specimens, of which 2 pairs were from patients in the R-hyperCVAD arm, and 10 pairs were from patients in the RB arm.
In the R-hyperCVAD arm, both patients were MRD positive at baseline, and MRD negative after induction, according to the investigators. Similarly, 9 of 10 patients in the RB arm were MRD positive at baseline, and of those, 7 converted to MRD negative following induction.
The research was supported by the National Cancer Institute, and in part by Sequenta (Adaptive Biotechnologies). Dr. Kamdar reported being on the speakers bureau of Seattle Genetics and receiving consultancy fees from AstraZeneca, Celgene, and Genentech. Co-authors of the study provided disclosures related to Millennium Pharmaceuticals, Affimed, Seattle Genetics, Pharmacyclics, and Merck, among others.
SOURCE: Kamdar M et al. Blood Adv. 2019 Oct 22;3(20):3132-5.
The combination of rituximab and bendamustine (RB) provided “excellent” survival with less toxicity, compared with a cytarabine-based induction regimen, in transplant-eligible patients with mantle cell lymphoma, according to a long-term follow-up report from randomized phase 2 trial.
The 5-year survival rates for RB were “provocatively similar” to what was achieved with the standard, intensive R-hyperCVAD regimen, investigators said in this update on the Southwest Oncology Group (SWOG) S1106 study.
By contrast, the R-hyperCVAD regimen was associated with more toxicity and higher failure rates for stem cell mobilization, according to the report’s lead author, Manali Kamdar, MD, of the University of Colorado, Denver, and coauthors.
“Overall, S1106 demonstrated that an outpatient-based, less intensive induction therapy of bendamustine plus rituximab is highly effective, safe, and durable in untreated transplant-eligible MCL patients,” Dr. Kamdar and her colleagues reported in Blood Advances.
The results have guided the design of an upcoming study, EA4181, in which patients with mantle cell lymphoma will be treated with an RB backbone plus cytarabine, the BTK inhibitor acalabrutinib, or both, according to the authors.
In the present study, S1106, patients with mantle cell lymphoma were randomized to receive RB or the R-hyperCVAD regimen, which consisted of rituximab with hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone, alternating with high-dose cytarabine and methotrexate. Both regimens were followed by autologous hematopoietic stem cell transplant.
The stem cell mobilization failure rate was 29% in the R-hyperCVAD arm in an interim analysis conducted after 53 of a planned 160 patients had been enrolled, including 35 in the RB arm and 17 in the R-hyperCVAD arm, according to a report published in the British Journal of Haematology (2016 Dec 19. doi: 10.1111/bjh.14480). That analysis triggered a shutdown of the study, based on a rule stating that either arm would be deemed “unacceptably toxic” if the mobilization rate exceeded 10%.
Accordingly, R-hyperCVAD is “not an ideal platform” for future trials, the investigators said. At that time, the estimated 2-year progression-free survival (PFS) was 81% versus 82% for RB and R-hyperCVAD, respectively, while overall survival (OS) was 87% versus 88%.
With additional follow-up, the 5-year PFS is 66% and 62% in the RB and R-hyperCVAD arms, respectively, while 5-year OS is 80% and 74%, according to the investigators.
The RB regimen also results in “excellent” minimal residual disease (MRD) negativity, they added.
MRD status was evaluated in 12 paired pre- and postinduction therapy specimens, of which 2 pairs were from patients in the R-hyperCVAD arm, and 10 pairs were from patients in the RB arm.
In the R-hyperCVAD arm, both patients were MRD positive at baseline, and MRD negative after induction, according to the investigators. Similarly, 9 of 10 patients in the RB arm were MRD positive at baseline, and of those, 7 converted to MRD negative following induction.
The research was supported by the National Cancer Institute, and in part by Sequenta (Adaptive Biotechnologies). Dr. Kamdar reported being on the speakers bureau of Seattle Genetics and receiving consultancy fees from AstraZeneca, Celgene, and Genentech. Co-authors of the study provided disclosures related to Millennium Pharmaceuticals, Affimed, Seattle Genetics, Pharmacyclics, and Merck, among others.
SOURCE: Kamdar M et al. Blood Adv. 2019 Oct 22;3(20):3132-5.
The combination of rituximab and bendamustine (RB) provided “excellent” survival with less toxicity, compared with a cytarabine-based induction regimen, in transplant-eligible patients with mantle cell lymphoma, according to a long-term follow-up report from randomized phase 2 trial.
The 5-year survival rates for RB were “provocatively similar” to what was achieved with the standard, intensive R-hyperCVAD regimen, investigators said in this update on the Southwest Oncology Group (SWOG) S1106 study.
By contrast, the R-hyperCVAD regimen was associated with more toxicity and higher failure rates for stem cell mobilization, according to the report’s lead author, Manali Kamdar, MD, of the University of Colorado, Denver, and coauthors.
“Overall, S1106 demonstrated that an outpatient-based, less intensive induction therapy of bendamustine plus rituximab is highly effective, safe, and durable in untreated transplant-eligible MCL patients,” Dr. Kamdar and her colleagues reported in Blood Advances.
The results have guided the design of an upcoming study, EA4181, in which patients with mantle cell lymphoma will be treated with an RB backbone plus cytarabine, the BTK inhibitor acalabrutinib, or both, according to the authors.
In the present study, S1106, patients with mantle cell lymphoma were randomized to receive RB or the R-hyperCVAD regimen, which consisted of rituximab with hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone, alternating with high-dose cytarabine and methotrexate. Both regimens were followed by autologous hematopoietic stem cell transplant.
The stem cell mobilization failure rate was 29% in the R-hyperCVAD arm in an interim analysis conducted after 53 of a planned 160 patients had been enrolled, including 35 in the RB arm and 17 in the R-hyperCVAD arm, according to a report published in the British Journal of Haematology (2016 Dec 19. doi: 10.1111/bjh.14480). That analysis triggered a shutdown of the study, based on a rule stating that either arm would be deemed “unacceptably toxic” if the mobilization rate exceeded 10%.
Accordingly, R-hyperCVAD is “not an ideal platform” for future trials, the investigators said. At that time, the estimated 2-year progression-free survival (PFS) was 81% versus 82% for RB and R-hyperCVAD, respectively, while overall survival (OS) was 87% versus 88%.
With additional follow-up, the 5-year PFS is 66% and 62% in the RB and R-hyperCVAD arms, respectively, while 5-year OS is 80% and 74%, according to the investigators.
The RB regimen also results in “excellent” minimal residual disease (MRD) negativity, they added.
MRD status was evaluated in 12 paired pre- and postinduction therapy specimens, of which 2 pairs were from patients in the R-hyperCVAD arm, and 10 pairs were from patients in the RB arm.
In the R-hyperCVAD arm, both patients were MRD positive at baseline, and MRD negative after induction, according to the investigators. Similarly, 9 of 10 patients in the RB arm were MRD positive at baseline, and of those, 7 converted to MRD negative following induction.
The research was supported by the National Cancer Institute, and in part by Sequenta (Adaptive Biotechnologies). Dr. Kamdar reported being on the speakers bureau of Seattle Genetics and receiving consultancy fees from AstraZeneca, Celgene, and Genentech. Co-authors of the study provided disclosures related to Millennium Pharmaceuticals, Affimed, Seattle Genetics, Pharmacyclics, and Merck, among others.
SOURCE: Kamdar M et al. Blood Adv. 2019 Oct 22;3(20):3132-5.
FROM BLOOD ADVANCES
Rapid improvement seen with nemolizumab for prurigo nodularis in phase 2b study
MADRID – Nemolizumab, an investigational humanized monoclonal antibody targeting the interleukin-31 receptor alpha subunit, achieved rapid and clinically meaningful improvement in both itch and skin lesions of severe prurigo nodularis in a phase 2b, randomized trial, Sonja Stander, MD, said at the annual congress of the European Academy of Dermatology and Venereology.
“We saw onset of pruritus improvement in week 1 and onset of lesion healing at week 4,” reported Dr. Stander, professor of dermatology and neurodermatology and head of the Center for Chronic Pruritus at the University of Münster (Germany).
The study results confirm IL-31 signaling as an important therapeutic target in prurigo nodularis and herald the arrival of nemolizumab as a promising potential therapy for severely affected patients, she added.
Prurigo nodularis is a chronic, highly pruritic disease that is difficult to treat and carries a high disease burden. While the disease’s pathogenesis is not completely understood, IL-31 is up-regulated in affected patients. And IL-31, a proinflammatory and immunomodulatory cytokine, is known to have a broad range of actions, including serving as a link between the immune and neural systems, as well as induction of itch and skin lesions.
Dr. Stander presented the results of a 20-center, double-blind, at weeks 0, 4, and 8, then followed off therapy out to week 18. These were severely affected patients: their mean weekly peak pruritus score on a 0-10 numeric rating scale was 8.4, with 7 being the accepted threshold for severe itch. The group had a mean Dermatologic Life Quality Index score of 16.4; 40% of patients had more than 100 nodules on their body, and the rest had 20-100.
The primary endpoint was the percentage decrease in the peak pruritus score from baseline to week 4, at which point they had only received one dose. The nemolizumab group averaged a 53.4% reduction, compared with 15.3% in placebo-treated controls. At week 12, a full month after the final injection, the split was 63.2% versus 20.2%. And at week 18, the nemolizumab group maintained a mean 58.2% reduction from baseline versus 20.9% in controls.
“The effect starts at week 1, with a 26% reduction in itch intensity in the nemolizumab group, compared to 6.7% with placebo,” the dermatologist observed.
The absolute decrease in weekly peak pruritus score at week 12 was 5.2 points with nemolizumab and 1.7 points with placebo.
Among the secondary endpoints was achievement of an Investigator Global Assessment score of 0-1, meaning clear or almost clear of skin lesions. The rate in the nemolizumab group climbed steadily from week 4 on, reaching 38.2% and still rising without a plateau at week 18, versus 5.6% in controls.
Another secondary endpoint was 75% or greater healing on the 7-item Prurigo Activity Scale. By week 4 there was already a statistically significant between-group difference: 23.5% versus 11.2%. Once again, in the nemolizumab group, this rate climbed without a plateau through the study’s end at week 18, by which point it was 44.1%, compared with 8.4% among those on placebo.
Scores on the Dermatologic Life Quality Index improved by an average of 10.2 points at week 4 in patients on nemolizumab, compared with 6 points among controls.
Self-reported sleep disturbance scores improved by 56% at week 4 in the nemolizumab group and 22.9% with placebo.
The safety profile of nemolizumab was similar to that of placebo, with roughly 5.7% of patients in each study arm withdrawing because of treatment-emergent adverse events. Unlike in the positive studies of the IL-31 inhibitor in patients with atopic dermatitis – another potential indication under active investigation – there was no signal of an increased risk of staphylococcal skin infections, conjunctivitis, or head and neck dermatitis in patients on nemolizumab for prurigo nodularis. Patients with comorbid atopic dermatitis were excluded from the prurigo nodularis trial in order to get a clearer picture of the biologic’s efficacy and safety specifically for that condition.
Dr. Stander reported serving as a consultant to Galderma, the study sponsor, as well as numerous other pharmaceutical companies.
MADRID – Nemolizumab, an investigational humanized monoclonal antibody targeting the interleukin-31 receptor alpha subunit, achieved rapid and clinically meaningful improvement in both itch and skin lesions of severe prurigo nodularis in a phase 2b, randomized trial, Sonja Stander, MD, said at the annual congress of the European Academy of Dermatology and Venereology.
“We saw onset of pruritus improvement in week 1 and onset of lesion healing at week 4,” reported Dr. Stander, professor of dermatology and neurodermatology and head of the Center for Chronic Pruritus at the University of Münster (Germany).
The study results confirm IL-31 signaling as an important therapeutic target in prurigo nodularis and herald the arrival of nemolizumab as a promising potential therapy for severely affected patients, she added.
Prurigo nodularis is a chronic, highly pruritic disease that is difficult to treat and carries a high disease burden. While the disease’s pathogenesis is not completely understood, IL-31 is up-regulated in affected patients. And IL-31, a proinflammatory and immunomodulatory cytokine, is known to have a broad range of actions, including serving as a link between the immune and neural systems, as well as induction of itch and skin lesions.
Dr. Stander presented the results of a 20-center, double-blind, at weeks 0, 4, and 8, then followed off therapy out to week 18. These were severely affected patients: their mean weekly peak pruritus score on a 0-10 numeric rating scale was 8.4, with 7 being the accepted threshold for severe itch. The group had a mean Dermatologic Life Quality Index score of 16.4; 40% of patients had more than 100 nodules on their body, and the rest had 20-100.
The primary endpoint was the percentage decrease in the peak pruritus score from baseline to week 4, at which point they had only received one dose. The nemolizumab group averaged a 53.4% reduction, compared with 15.3% in placebo-treated controls. At week 12, a full month after the final injection, the split was 63.2% versus 20.2%. And at week 18, the nemolizumab group maintained a mean 58.2% reduction from baseline versus 20.9% in controls.
“The effect starts at week 1, with a 26% reduction in itch intensity in the nemolizumab group, compared to 6.7% with placebo,” the dermatologist observed.
The absolute decrease in weekly peak pruritus score at week 12 was 5.2 points with nemolizumab and 1.7 points with placebo.
Among the secondary endpoints was achievement of an Investigator Global Assessment score of 0-1, meaning clear or almost clear of skin lesions. The rate in the nemolizumab group climbed steadily from week 4 on, reaching 38.2% and still rising without a plateau at week 18, versus 5.6% in controls.
Another secondary endpoint was 75% or greater healing on the 7-item Prurigo Activity Scale. By week 4 there was already a statistically significant between-group difference: 23.5% versus 11.2%. Once again, in the nemolizumab group, this rate climbed without a plateau through the study’s end at week 18, by which point it was 44.1%, compared with 8.4% among those on placebo.
Scores on the Dermatologic Life Quality Index improved by an average of 10.2 points at week 4 in patients on nemolizumab, compared with 6 points among controls.
Self-reported sleep disturbance scores improved by 56% at week 4 in the nemolizumab group and 22.9% with placebo.
The safety profile of nemolizumab was similar to that of placebo, with roughly 5.7% of patients in each study arm withdrawing because of treatment-emergent adverse events. Unlike in the positive studies of the IL-31 inhibitor in patients with atopic dermatitis – another potential indication under active investigation – there was no signal of an increased risk of staphylococcal skin infections, conjunctivitis, or head and neck dermatitis in patients on nemolizumab for prurigo nodularis. Patients with comorbid atopic dermatitis were excluded from the prurigo nodularis trial in order to get a clearer picture of the biologic’s efficacy and safety specifically for that condition.
Dr. Stander reported serving as a consultant to Galderma, the study sponsor, as well as numerous other pharmaceutical companies.
MADRID – Nemolizumab, an investigational humanized monoclonal antibody targeting the interleukin-31 receptor alpha subunit, achieved rapid and clinically meaningful improvement in both itch and skin lesions of severe prurigo nodularis in a phase 2b, randomized trial, Sonja Stander, MD, said at the annual congress of the European Academy of Dermatology and Venereology.
“We saw onset of pruritus improvement in week 1 and onset of lesion healing at week 4,” reported Dr. Stander, professor of dermatology and neurodermatology and head of the Center for Chronic Pruritus at the University of Münster (Germany).
The study results confirm IL-31 signaling as an important therapeutic target in prurigo nodularis and herald the arrival of nemolizumab as a promising potential therapy for severely affected patients, she added.
Prurigo nodularis is a chronic, highly pruritic disease that is difficult to treat and carries a high disease burden. While the disease’s pathogenesis is not completely understood, IL-31 is up-regulated in affected patients. And IL-31, a proinflammatory and immunomodulatory cytokine, is known to have a broad range of actions, including serving as a link between the immune and neural systems, as well as induction of itch and skin lesions.
Dr. Stander presented the results of a 20-center, double-blind, at weeks 0, 4, and 8, then followed off therapy out to week 18. These were severely affected patients: their mean weekly peak pruritus score on a 0-10 numeric rating scale was 8.4, with 7 being the accepted threshold for severe itch. The group had a mean Dermatologic Life Quality Index score of 16.4; 40% of patients had more than 100 nodules on their body, and the rest had 20-100.
The primary endpoint was the percentage decrease in the peak pruritus score from baseline to week 4, at which point they had only received one dose. The nemolizumab group averaged a 53.4% reduction, compared with 15.3% in placebo-treated controls. At week 12, a full month after the final injection, the split was 63.2% versus 20.2%. And at week 18, the nemolizumab group maintained a mean 58.2% reduction from baseline versus 20.9% in controls.
“The effect starts at week 1, with a 26% reduction in itch intensity in the nemolizumab group, compared to 6.7% with placebo,” the dermatologist observed.
The absolute decrease in weekly peak pruritus score at week 12 was 5.2 points with nemolizumab and 1.7 points with placebo.
Among the secondary endpoints was achievement of an Investigator Global Assessment score of 0-1, meaning clear or almost clear of skin lesions. The rate in the nemolizumab group climbed steadily from week 4 on, reaching 38.2% and still rising without a plateau at week 18, versus 5.6% in controls.
Another secondary endpoint was 75% or greater healing on the 7-item Prurigo Activity Scale. By week 4 there was already a statistically significant between-group difference: 23.5% versus 11.2%. Once again, in the nemolizumab group, this rate climbed without a plateau through the study’s end at week 18, by which point it was 44.1%, compared with 8.4% among those on placebo.
Scores on the Dermatologic Life Quality Index improved by an average of 10.2 points at week 4 in patients on nemolizumab, compared with 6 points among controls.
Self-reported sleep disturbance scores improved by 56% at week 4 in the nemolizumab group and 22.9% with placebo.
The safety profile of nemolizumab was similar to that of placebo, with roughly 5.7% of patients in each study arm withdrawing because of treatment-emergent adverse events. Unlike in the positive studies of the IL-31 inhibitor in patients with atopic dermatitis – another potential indication under active investigation – there was no signal of an increased risk of staphylococcal skin infections, conjunctivitis, or head and neck dermatitis in patients on nemolizumab for prurigo nodularis. Patients with comorbid atopic dermatitis were excluded from the prurigo nodularis trial in order to get a clearer picture of the biologic’s efficacy and safety specifically for that condition.
Dr. Stander reported serving as a consultant to Galderma, the study sponsor, as well as numerous other pharmaceutical companies.
REPORTING FROM THE EADV CONGRESS
New psoriatic patients may have lower serious infection risk with IL-12/23 inhibition
, according to data from a retrospective study of nearly 10,000 adults.
Biologics, though effective, can increase the risk for serious infection in psoriatic arthritis and psoriasis patients, and comparison data on the safety of various biologics are limited, wrote Xintong Li of Johns Hopkins University, Baltimore, and colleagues.
In a study published in Annals of the Rheumatic Diseases, the researchers identified 11,560 treatment episodes for 9,305 adults during January 1, 2015, through May 1, 2018, which included 6,043 episodes of psoriasis only, 1,869 episodes of psoriatic arthritis only, and 3,648 episodes of both conditions. The average age of the patients was 46 years, and 53% were men. The investigators studied the IL-12/23 inhibitor ustekinumab (Stelara), the IL-17A inhibitors secukinumab (Cosentyx) and ixekizumab (Taltz), and TNF inhibitors adalimumab (Humira), certolizumab pegol (Cimzia), etanercept (Enbrel), golimumab (Simponi), and infliximab (Remicade). They did not study the interleukin-17 (IL-17) inhibitor brodalumab (Siliq) or IL-23 inhibitors guselkumab (Tremfya), risankizumab (Skyrizi), or tildrakizumab (Ilumya) since they were FDA approved after or toward the end of the study period.
The primary outcome of serious infection, defined as hospitalization with infection as part of the diagnostic codes, occurred in 190 cases (2% of all treatment episodes); the most common serious infections were sepsis and pneumonia.
Overall, new biologics users had similar infection risks with IL-17 and TNF inhibitors, with incidence rates per 100 person-years of 3.4 and 2.2, respectively. By contrast, the incidence rate per 100 person-years was 0.9 with IL-12/23 inhibitors. Incidence rates were similar across all three biologic types for experienced biologics users.
The researchers also grouped patients by condition, including both treatment-naive and -experienced patients. Of the 156 serious infections in psoriasis patients, 26 occurred with IL-17 inhibitors, 29 with IL-12/23 inhibitors, and 101 with TNF inhibitors. Of 105 serious infections in the psoriatic arthritis group, 14 occurred with IL-17, 13 with IL-12/23, and 78 with TNF.
After adjusting for propensity scores, researchers found no evidence of increased serious infection risk for treatment with IL-17 inhibitors, compared with IL-12/23 (hazard ratio, 1.12; 95% confidence interval, 0.62-2.03) or TNF inhibitors (HR, 0.89; 95% CI, 0.48-1.66).
The study findings were limited by several factors, including the use of ICD diagnostic codes that were not fully validated in the patient population, a short follow-up period, and inclusion of only insured patients in the United States, the researchers noted.
However, the results suggest that serious infection risk may vary between patients with psoriasis and psoriatic arthritis, and between biologic-naive and -experienced patients, and that, despite the relatively small difference in absolute effect, “this potentially clinically relevant signal for reduced infections among the IL-12/23 inhibitors warrants further investigation and surveillance efforts,” they concluded. In addition, they said, the findings might guide clinicians and patients in choosing appropriate biologics for a particular condition.
The study was supported by the Center for Drug Safety and Effectiveness at the Johns Hopkins Bloomberg School of Public Health. The researchers had no financial conflicts to disclose. Ms. Li conducted the research while she was at Johns Hopkins, but is now with the University of North Carolina, Chapel Hill.
SOURCE: Li X et al. Ann Rheum Dis. 2019 Oct 31. doi: 10.1136/annrheumdis-2019-216102.
, according to data from a retrospective study of nearly 10,000 adults.
Biologics, though effective, can increase the risk for serious infection in psoriatic arthritis and psoriasis patients, and comparison data on the safety of various biologics are limited, wrote Xintong Li of Johns Hopkins University, Baltimore, and colleagues.
In a study published in Annals of the Rheumatic Diseases, the researchers identified 11,560 treatment episodes for 9,305 adults during January 1, 2015, through May 1, 2018, which included 6,043 episodes of psoriasis only, 1,869 episodes of psoriatic arthritis only, and 3,648 episodes of both conditions. The average age of the patients was 46 years, and 53% were men. The investigators studied the IL-12/23 inhibitor ustekinumab (Stelara), the IL-17A inhibitors secukinumab (Cosentyx) and ixekizumab (Taltz), and TNF inhibitors adalimumab (Humira), certolizumab pegol (Cimzia), etanercept (Enbrel), golimumab (Simponi), and infliximab (Remicade). They did not study the interleukin-17 (IL-17) inhibitor brodalumab (Siliq) or IL-23 inhibitors guselkumab (Tremfya), risankizumab (Skyrizi), or tildrakizumab (Ilumya) since they were FDA approved after or toward the end of the study period.
The primary outcome of serious infection, defined as hospitalization with infection as part of the diagnostic codes, occurred in 190 cases (2% of all treatment episodes); the most common serious infections were sepsis and pneumonia.
Overall, new biologics users had similar infection risks with IL-17 and TNF inhibitors, with incidence rates per 100 person-years of 3.4 and 2.2, respectively. By contrast, the incidence rate per 100 person-years was 0.9 with IL-12/23 inhibitors. Incidence rates were similar across all three biologic types for experienced biologics users.
The researchers also grouped patients by condition, including both treatment-naive and -experienced patients. Of the 156 serious infections in psoriasis patients, 26 occurred with IL-17 inhibitors, 29 with IL-12/23 inhibitors, and 101 with TNF inhibitors. Of 105 serious infections in the psoriatic arthritis group, 14 occurred with IL-17, 13 with IL-12/23, and 78 with TNF.
After adjusting for propensity scores, researchers found no evidence of increased serious infection risk for treatment with IL-17 inhibitors, compared with IL-12/23 (hazard ratio, 1.12; 95% confidence interval, 0.62-2.03) or TNF inhibitors (HR, 0.89; 95% CI, 0.48-1.66).
The study findings were limited by several factors, including the use of ICD diagnostic codes that were not fully validated in the patient population, a short follow-up period, and inclusion of only insured patients in the United States, the researchers noted.
However, the results suggest that serious infection risk may vary between patients with psoriasis and psoriatic arthritis, and between biologic-naive and -experienced patients, and that, despite the relatively small difference in absolute effect, “this potentially clinically relevant signal for reduced infections among the IL-12/23 inhibitors warrants further investigation and surveillance efforts,” they concluded. In addition, they said, the findings might guide clinicians and patients in choosing appropriate biologics for a particular condition.
The study was supported by the Center for Drug Safety and Effectiveness at the Johns Hopkins Bloomberg School of Public Health. The researchers had no financial conflicts to disclose. Ms. Li conducted the research while she was at Johns Hopkins, but is now with the University of North Carolina, Chapel Hill.
SOURCE: Li X et al. Ann Rheum Dis. 2019 Oct 31. doi: 10.1136/annrheumdis-2019-216102.
, according to data from a retrospective study of nearly 10,000 adults.
Biologics, though effective, can increase the risk for serious infection in psoriatic arthritis and psoriasis patients, and comparison data on the safety of various biologics are limited, wrote Xintong Li of Johns Hopkins University, Baltimore, and colleagues.
In a study published in Annals of the Rheumatic Diseases, the researchers identified 11,560 treatment episodes for 9,305 adults during January 1, 2015, through May 1, 2018, which included 6,043 episodes of psoriasis only, 1,869 episodes of psoriatic arthritis only, and 3,648 episodes of both conditions. The average age of the patients was 46 years, and 53% were men. The investigators studied the IL-12/23 inhibitor ustekinumab (Stelara), the IL-17A inhibitors secukinumab (Cosentyx) and ixekizumab (Taltz), and TNF inhibitors adalimumab (Humira), certolizumab pegol (Cimzia), etanercept (Enbrel), golimumab (Simponi), and infliximab (Remicade). They did not study the interleukin-17 (IL-17) inhibitor brodalumab (Siliq) or IL-23 inhibitors guselkumab (Tremfya), risankizumab (Skyrizi), or tildrakizumab (Ilumya) since they were FDA approved after or toward the end of the study period.
The primary outcome of serious infection, defined as hospitalization with infection as part of the diagnostic codes, occurred in 190 cases (2% of all treatment episodes); the most common serious infections were sepsis and pneumonia.
Overall, new biologics users had similar infection risks with IL-17 and TNF inhibitors, with incidence rates per 100 person-years of 3.4 and 2.2, respectively. By contrast, the incidence rate per 100 person-years was 0.9 with IL-12/23 inhibitors. Incidence rates were similar across all three biologic types for experienced biologics users.
The researchers also grouped patients by condition, including both treatment-naive and -experienced patients. Of the 156 serious infections in psoriasis patients, 26 occurred with IL-17 inhibitors, 29 with IL-12/23 inhibitors, and 101 with TNF inhibitors. Of 105 serious infections in the psoriatic arthritis group, 14 occurred with IL-17, 13 with IL-12/23, and 78 with TNF.
After adjusting for propensity scores, researchers found no evidence of increased serious infection risk for treatment with IL-17 inhibitors, compared with IL-12/23 (hazard ratio, 1.12; 95% confidence interval, 0.62-2.03) or TNF inhibitors (HR, 0.89; 95% CI, 0.48-1.66).
The study findings were limited by several factors, including the use of ICD diagnostic codes that were not fully validated in the patient population, a short follow-up period, and inclusion of only insured patients in the United States, the researchers noted.
However, the results suggest that serious infection risk may vary between patients with psoriasis and psoriatic arthritis, and between biologic-naive and -experienced patients, and that, despite the relatively small difference in absolute effect, “this potentially clinically relevant signal for reduced infections among the IL-12/23 inhibitors warrants further investigation and surveillance efforts,” they concluded. In addition, they said, the findings might guide clinicians and patients in choosing appropriate biologics for a particular condition.
The study was supported by the Center for Drug Safety and Effectiveness at the Johns Hopkins Bloomberg School of Public Health. The researchers had no financial conflicts to disclose. Ms. Li conducted the research while she was at Johns Hopkins, but is now with the University of North Carolina, Chapel Hill.
SOURCE: Li X et al. Ann Rheum Dis. 2019 Oct 31. doi: 10.1136/annrheumdis-2019-216102.
FROM ANNALS OF THE RHEUMATIC DISEASES
Adverse childhood experiences increase the risk of poor long-term health
and societal outcomes, according to a new report by the Centers for Disease Control and Prevention.
“Our analysis suggests that preventing or reducing these adverse childhood experiences [ACEs] could potentially reduce the annual number of coronary heart disease cases by up to 13%,” said Ann Schuchat, MD, the CDC’s principal deputy director. “If we apply this analysis to other national disease estimates, preventing ACEs could prevent 1.9 million cases of heart disease, 2.5 million cases of overweight or obesity, 21 million cases of depression, and 1.5 million high-school incompletions.”
The analysis, conducted by Melissa T. Merrick, PhD, and colleagues at the National Center for Injury Prevention and Control at the CDC, Atlanta, is based on data acquired from more than 144,000 adults in 27 states.
It’s the first time the CDC has waded into this territory, Dr. Schuchat said during a press briefing. But a hard look into the data is long overdue. ACEs have been linked to at least 5 of the top 10 leading causes of death in the United States: heart disease, cancer, respiratory disease, diabetes, and suicide.
“It’s been proven that exposure to abuse, violence, and familial substance abuse and mental health problems can lead to health and social problems during the entire lifespan. Multiple exposures can produce toxic stress and chronic activation of the stress response system,” Dr. Schuchat continued. “Our report found that more than half of adults have experienced at least one type of ACE, and one in six adults has been exposed to four or more. The effects add up – the more types of ACE encountered, the higher the risk for negative outcomes that limit their entire lives.”
Dr. Merrick, a behavioral scientist with the CDC, and her team reviewed data collected from the Behavioral Risk Factor Surveillance System (BRFSS), a telephone survey of noninstitutionalized adults administered every year within each state. During the 2015-2017 data collection years, 27 states included questions about ACEs. The experiences included childhood exposure to three types of abuse (physical, emotional, and sexual) and five types of household challenges (household member substance misuse, incarceration, mental illness, parental divorce, or witnessing intimate partner violence) before age 18 years.
In all, 61% of respondents reported experiencing at least one of the events; 16% reported experiencing four or more. Women, Native Americans, Native Alaskans, and blacks were more likely to have these experiences than were men and whites.
A multivariate regression analysis found that adults with the highest level of ACE exposure had significantly elevated risks of several chronic health issues and social challenges, compared with nonexposed subjects. These included increased risk of overweight or obesity (adjusted odds ratio, 1.2), chronic obstructive pulmonary disease (aOR, 2.8), depression (aOR 5.3), smoking (aOR 3.1), heavy drinking (aOR 1.8), and underemployment (aOR 1.7), compared with adults reporting no ACEs.
Reducing ACE exposures could in turn reduce many of these challenges, especially among people with the highest number of exposures. Among this group, preventing all ACE exposure could cut overweight and obesity by up to 1.7%, chronic obstructive pulmonary disease by up to 27%, depression by up to 44%, smoking by up to 33%, and heavy drinking by 24%. Preventing ACE exposure also could reduce lack of health insurance by 4% and unemployment by 15%, the researchers said.
The good news, Dr. Merrick and associates said, is that ACE exposure can be at least partially offset by positive interactions with adults and in social and community settings.
“Prevention of adverse childhood experiences is possible with state and community efforts to build resilient families and communities, provide parental support to develop positive parenting and coping skills, and increase access to, and use of, comprehensive health services,” they said.
The CDC recommends a comprehensive approach to preventing ACEs and mitigating their impact. The data-driven suggestions include:
- Promoting family economic health, including tax credits and family-focused work policy.
- Endorsing programs to mitigate violence and adversity, including public education programs that support parents.
- Promoting early childhood development with high-quality child care and preschool programs.
- Recommending stress reduction skills for parents and young people, and programs that teach safe dating and healthy relationship skills.
- Supporting youth development by connecting youth to adult mentors and after-school programs.
- Encouraging clinicians to identify and address ACE exposure with screening, referral, and support.
“This is important for reducing the consequences of adverse childhood experiences and for helping to protect the next generation of children from exposure to violence and other adverse experiences, such as witnessing substance misuse in their household,” Dr. Merrick and associates said.
The researchers had no relevant financial disclosures.
SOURCE: Merrick M et al. MMWR. 2019 Nov 5. doi: 10.15585/mmwr.mm6844e1.
Adverse childhood experiences (ACEs) trigger pathophysiologic responses that exert real physical and psychological harm. Thus, clinicians can and should address them as part of good medical care, Christopher M. Jones, PharmD, Melissa T. Merrick, PhD, and Debra E. Houry, MD, MPH, said in a JAMA commentary.
“A large and growing body of research indicates that the underlying mechanism by which ACEs are associated with health outcomes is through the development of toxic stress, a chronic activation of the stress response system. Toxic stress results in dysregulation of the limbic-hypothalamic-pituitary-adrenal axis, elevating levels of catecholamines (“fight or flight” response), cortisol, and proinflammatory cytokines, leading to cascading effects on the nervous, endocrine, and immune systems. These changes can affect attention and other executive functioning, impulsive behavior, brain reward systems, decision-making, and response to stress throughout the life span,” they said.
While societies and communities at large must work together to reduce ACE exposure, clinicians also have a role. Research indicates that many don’t routinely ask questions about these issues, in a large part because they lack training in how and when to screen.
“Incorporating components of primary ACEs prevention into everyday clinical practice may be achievable through talking with parents and caregivers about creating safe, stable, nurturing environments and protective relationships, and reinforcing positive parenting techniques and coping skills at routine clinical visits,” the editorialists said. “In addition, clinicians can refer parents to parenting skills classes or refer higher-risk parents to home visitation programs such as Healthy Families America and Nurse-Family Partnership. Home visitation programs have demonstrated significant reductions in rates of child abuse and neglect and have improved substance use, violence, and parenting outcomes.”
Clinicians also may have a role to play in mitigating the harms of ACEs, by incorporating trauma-informed care and services into their daily practice.
“Important elements of trauma-informed care include understanding how trauma affects health, routinely screening for ACEs and trauma, using culturally responsive assessments, promoting resilience and protective factors, addressing trauma-related somatic and mental health issues, and ensuring appropriate linkage to services and supports for identified issues,” the editorialists concluded.
Dr. Jones is associate director in the Office of Strategy and Innovation in the CDC Injury Center. Dr. Merrick is president and CEO of Prevent Childhood Abuse America, Chicago. Dr. Houry is director of the National Center for Injury Prevention and Control at the CDC, Atlanta. They discussed the MMWR analysis in a commentary (JAMA. 2019 Nov 5. doi: 10.1001/jama.2019.18499). They had no relevant financial disclosures.
Adverse childhood experiences (ACEs) trigger pathophysiologic responses that exert real physical and psychological harm. Thus, clinicians can and should address them as part of good medical care, Christopher M. Jones, PharmD, Melissa T. Merrick, PhD, and Debra E. Houry, MD, MPH, said in a JAMA commentary.
“A large and growing body of research indicates that the underlying mechanism by which ACEs are associated with health outcomes is through the development of toxic stress, a chronic activation of the stress response system. Toxic stress results in dysregulation of the limbic-hypothalamic-pituitary-adrenal axis, elevating levels of catecholamines (“fight or flight” response), cortisol, and proinflammatory cytokines, leading to cascading effects on the nervous, endocrine, and immune systems. These changes can affect attention and other executive functioning, impulsive behavior, brain reward systems, decision-making, and response to stress throughout the life span,” they said.
While societies and communities at large must work together to reduce ACE exposure, clinicians also have a role. Research indicates that many don’t routinely ask questions about these issues, in a large part because they lack training in how and when to screen.
“Incorporating components of primary ACEs prevention into everyday clinical practice may be achievable through talking with parents and caregivers about creating safe, stable, nurturing environments and protective relationships, and reinforcing positive parenting techniques and coping skills at routine clinical visits,” the editorialists said. “In addition, clinicians can refer parents to parenting skills classes or refer higher-risk parents to home visitation programs such as Healthy Families America and Nurse-Family Partnership. Home visitation programs have demonstrated significant reductions in rates of child abuse and neglect and have improved substance use, violence, and parenting outcomes.”
Clinicians also may have a role to play in mitigating the harms of ACEs, by incorporating trauma-informed care and services into their daily practice.
“Important elements of trauma-informed care include understanding how trauma affects health, routinely screening for ACEs and trauma, using culturally responsive assessments, promoting resilience and protective factors, addressing trauma-related somatic and mental health issues, and ensuring appropriate linkage to services and supports for identified issues,” the editorialists concluded.
Dr. Jones is associate director in the Office of Strategy and Innovation in the CDC Injury Center. Dr. Merrick is president and CEO of Prevent Childhood Abuse America, Chicago. Dr. Houry is director of the National Center for Injury Prevention and Control at the CDC, Atlanta. They discussed the MMWR analysis in a commentary (JAMA. 2019 Nov 5. doi: 10.1001/jama.2019.18499). They had no relevant financial disclosures.
Adverse childhood experiences (ACEs) trigger pathophysiologic responses that exert real physical and psychological harm. Thus, clinicians can and should address them as part of good medical care, Christopher M. Jones, PharmD, Melissa T. Merrick, PhD, and Debra E. Houry, MD, MPH, said in a JAMA commentary.
“A large and growing body of research indicates that the underlying mechanism by which ACEs are associated with health outcomes is through the development of toxic stress, a chronic activation of the stress response system. Toxic stress results in dysregulation of the limbic-hypothalamic-pituitary-adrenal axis, elevating levels of catecholamines (“fight or flight” response), cortisol, and proinflammatory cytokines, leading to cascading effects on the nervous, endocrine, and immune systems. These changes can affect attention and other executive functioning, impulsive behavior, brain reward systems, decision-making, and response to stress throughout the life span,” they said.
While societies and communities at large must work together to reduce ACE exposure, clinicians also have a role. Research indicates that many don’t routinely ask questions about these issues, in a large part because they lack training in how and when to screen.
“Incorporating components of primary ACEs prevention into everyday clinical practice may be achievable through talking with parents and caregivers about creating safe, stable, nurturing environments and protective relationships, and reinforcing positive parenting techniques and coping skills at routine clinical visits,” the editorialists said. “In addition, clinicians can refer parents to parenting skills classes or refer higher-risk parents to home visitation programs such as Healthy Families America and Nurse-Family Partnership. Home visitation programs have demonstrated significant reductions in rates of child abuse and neglect and have improved substance use, violence, and parenting outcomes.”
Clinicians also may have a role to play in mitigating the harms of ACEs, by incorporating trauma-informed care and services into their daily practice.
“Important elements of trauma-informed care include understanding how trauma affects health, routinely screening for ACEs and trauma, using culturally responsive assessments, promoting resilience and protective factors, addressing trauma-related somatic and mental health issues, and ensuring appropriate linkage to services and supports for identified issues,” the editorialists concluded.
Dr. Jones is associate director in the Office of Strategy and Innovation in the CDC Injury Center. Dr. Merrick is president and CEO of Prevent Childhood Abuse America, Chicago. Dr. Houry is director of the National Center for Injury Prevention and Control at the CDC, Atlanta. They discussed the MMWR analysis in a commentary (JAMA. 2019 Nov 5. doi: 10.1001/jama.2019.18499). They had no relevant financial disclosures.
and societal outcomes, according to a new report by the Centers for Disease Control and Prevention.
“Our analysis suggests that preventing or reducing these adverse childhood experiences [ACEs] could potentially reduce the annual number of coronary heart disease cases by up to 13%,” said Ann Schuchat, MD, the CDC’s principal deputy director. “If we apply this analysis to other national disease estimates, preventing ACEs could prevent 1.9 million cases of heart disease, 2.5 million cases of overweight or obesity, 21 million cases of depression, and 1.5 million high-school incompletions.”
The analysis, conducted by Melissa T. Merrick, PhD, and colleagues at the National Center for Injury Prevention and Control at the CDC, Atlanta, is based on data acquired from more than 144,000 adults in 27 states.
It’s the first time the CDC has waded into this territory, Dr. Schuchat said during a press briefing. But a hard look into the data is long overdue. ACEs have been linked to at least 5 of the top 10 leading causes of death in the United States: heart disease, cancer, respiratory disease, diabetes, and suicide.
“It’s been proven that exposure to abuse, violence, and familial substance abuse and mental health problems can lead to health and social problems during the entire lifespan. Multiple exposures can produce toxic stress and chronic activation of the stress response system,” Dr. Schuchat continued. “Our report found that more than half of adults have experienced at least one type of ACE, and one in six adults has been exposed to four or more. The effects add up – the more types of ACE encountered, the higher the risk for negative outcomes that limit their entire lives.”
Dr. Merrick, a behavioral scientist with the CDC, and her team reviewed data collected from the Behavioral Risk Factor Surveillance System (BRFSS), a telephone survey of noninstitutionalized adults administered every year within each state. During the 2015-2017 data collection years, 27 states included questions about ACEs. The experiences included childhood exposure to three types of abuse (physical, emotional, and sexual) and five types of household challenges (household member substance misuse, incarceration, mental illness, parental divorce, or witnessing intimate partner violence) before age 18 years.
In all, 61% of respondents reported experiencing at least one of the events; 16% reported experiencing four or more. Women, Native Americans, Native Alaskans, and blacks were more likely to have these experiences than were men and whites.
A multivariate regression analysis found that adults with the highest level of ACE exposure had significantly elevated risks of several chronic health issues and social challenges, compared with nonexposed subjects. These included increased risk of overweight or obesity (adjusted odds ratio, 1.2), chronic obstructive pulmonary disease (aOR, 2.8), depression (aOR 5.3), smoking (aOR 3.1), heavy drinking (aOR 1.8), and underemployment (aOR 1.7), compared with adults reporting no ACEs.
Reducing ACE exposures could in turn reduce many of these challenges, especially among people with the highest number of exposures. Among this group, preventing all ACE exposure could cut overweight and obesity by up to 1.7%, chronic obstructive pulmonary disease by up to 27%, depression by up to 44%, smoking by up to 33%, and heavy drinking by 24%. Preventing ACE exposure also could reduce lack of health insurance by 4% and unemployment by 15%, the researchers said.
The good news, Dr. Merrick and associates said, is that ACE exposure can be at least partially offset by positive interactions with adults and in social and community settings.
“Prevention of adverse childhood experiences is possible with state and community efforts to build resilient families and communities, provide parental support to develop positive parenting and coping skills, and increase access to, and use of, comprehensive health services,” they said.
The CDC recommends a comprehensive approach to preventing ACEs and mitigating their impact. The data-driven suggestions include:
- Promoting family economic health, including tax credits and family-focused work policy.
- Endorsing programs to mitigate violence and adversity, including public education programs that support parents.
- Promoting early childhood development with high-quality child care and preschool programs.
- Recommending stress reduction skills for parents and young people, and programs that teach safe dating and healthy relationship skills.
- Supporting youth development by connecting youth to adult mentors and after-school programs.
- Encouraging clinicians to identify and address ACE exposure with screening, referral, and support.
“This is important for reducing the consequences of adverse childhood experiences and for helping to protect the next generation of children from exposure to violence and other adverse experiences, such as witnessing substance misuse in their household,” Dr. Merrick and associates said.
The researchers had no relevant financial disclosures.
SOURCE: Merrick M et al. MMWR. 2019 Nov 5. doi: 10.15585/mmwr.mm6844e1.
and societal outcomes, according to a new report by the Centers for Disease Control and Prevention.
“Our analysis suggests that preventing or reducing these adverse childhood experiences [ACEs] could potentially reduce the annual number of coronary heart disease cases by up to 13%,” said Ann Schuchat, MD, the CDC’s principal deputy director. “If we apply this analysis to other national disease estimates, preventing ACEs could prevent 1.9 million cases of heart disease, 2.5 million cases of overweight or obesity, 21 million cases of depression, and 1.5 million high-school incompletions.”
The analysis, conducted by Melissa T. Merrick, PhD, and colleagues at the National Center for Injury Prevention and Control at the CDC, Atlanta, is based on data acquired from more than 144,000 adults in 27 states.
It’s the first time the CDC has waded into this territory, Dr. Schuchat said during a press briefing. But a hard look into the data is long overdue. ACEs have been linked to at least 5 of the top 10 leading causes of death in the United States: heart disease, cancer, respiratory disease, diabetes, and suicide.
“It’s been proven that exposure to abuse, violence, and familial substance abuse and mental health problems can lead to health and social problems during the entire lifespan. Multiple exposures can produce toxic stress and chronic activation of the stress response system,” Dr. Schuchat continued. “Our report found that more than half of adults have experienced at least one type of ACE, and one in six adults has been exposed to four or more. The effects add up – the more types of ACE encountered, the higher the risk for negative outcomes that limit their entire lives.”
Dr. Merrick, a behavioral scientist with the CDC, and her team reviewed data collected from the Behavioral Risk Factor Surveillance System (BRFSS), a telephone survey of noninstitutionalized adults administered every year within each state. During the 2015-2017 data collection years, 27 states included questions about ACEs. The experiences included childhood exposure to three types of abuse (physical, emotional, and sexual) and five types of household challenges (household member substance misuse, incarceration, mental illness, parental divorce, or witnessing intimate partner violence) before age 18 years.
In all, 61% of respondents reported experiencing at least one of the events; 16% reported experiencing four or more. Women, Native Americans, Native Alaskans, and blacks were more likely to have these experiences than were men and whites.
A multivariate regression analysis found that adults with the highest level of ACE exposure had significantly elevated risks of several chronic health issues and social challenges, compared with nonexposed subjects. These included increased risk of overweight or obesity (adjusted odds ratio, 1.2), chronic obstructive pulmonary disease (aOR, 2.8), depression (aOR 5.3), smoking (aOR 3.1), heavy drinking (aOR 1.8), and underemployment (aOR 1.7), compared with adults reporting no ACEs.
Reducing ACE exposures could in turn reduce many of these challenges, especially among people with the highest number of exposures. Among this group, preventing all ACE exposure could cut overweight and obesity by up to 1.7%, chronic obstructive pulmonary disease by up to 27%, depression by up to 44%, smoking by up to 33%, and heavy drinking by 24%. Preventing ACE exposure also could reduce lack of health insurance by 4% and unemployment by 15%, the researchers said.
The good news, Dr. Merrick and associates said, is that ACE exposure can be at least partially offset by positive interactions with adults and in social and community settings.
“Prevention of adverse childhood experiences is possible with state and community efforts to build resilient families and communities, provide parental support to develop positive parenting and coping skills, and increase access to, and use of, comprehensive health services,” they said.
The CDC recommends a comprehensive approach to preventing ACEs and mitigating their impact. The data-driven suggestions include:
- Promoting family economic health, including tax credits and family-focused work policy.
- Endorsing programs to mitigate violence and adversity, including public education programs that support parents.
- Promoting early childhood development with high-quality child care and preschool programs.
- Recommending stress reduction skills for parents and young people, and programs that teach safe dating and healthy relationship skills.
- Supporting youth development by connecting youth to adult mentors and after-school programs.
- Encouraging clinicians to identify and address ACE exposure with screening, referral, and support.
“This is important for reducing the consequences of adverse childhood experiences and for helping to protect the next generation of children from exposure to violence and other adverse experiences, such as witnessing substance misuse in their household,” Dr. Merrick and associates said.
The researchers had no relevant financial disclosures.
SOURCE: Merrick M et al. MMWR. 2019 Nov 5. doi: 10.15585/mmwr.mm6844e1.
FROM MMWR
ACP: Low-risk adults aged 50-75 should undergo regular screening for colorectal cancer
issued by the American College of Physicians.
Regular screening can be discontinued after age 75 years, Amir Qaseem, MD, president of clinical policy and the Center for Evidence Reviews at the American College of Physicians, and colleagues wrote in the Annals of Internal Medicine.
No one test is preferred over another, according to the guidance statement. Patients and physicians can select the test type together, based on individual needs and preferences, and each test carries its own screening interval. But regular testing has been proven time and again to reduce the risk of colorectal cancer mortality, and more people should have it, according to the guidance.
“Not enough people in the United States get screened for colorectal cancer,” ACP President Robert M. McLean, MD, said in a press statement. “Physicians should perform an individualized risk assessment for colorectal cancer in all adults. Doctors and patients should select the screening test based on a discussion of the benefits, harms, costs, availability, frequency, and patient preferences.”
The guidance is an attempt to balance existing guidelines authored by the U.S. Preventive Services Task Force and the Canadian Task Force on Preventive Health Care (CTFPHC), but it also was developed following critical review of those from the American Cancer Society and other organizations.
The ACP guidance is for adults at average risk for colorectal cancer who do not have symptoms; it does not apply to adults with a family history of colorectal cancer, a long-standing history of inflammatory bowel disease, genetic syndromes such as familial cancerous polyps, a personal history of previous colorectal cancer or benign polyps, or other risk factors.
The guidance was based on evaluations of stool-based tests, including the fecal immunochemical test (FIT), also called the immunochemical-based fecal occult blood test (FOBT), and direct visualization with endoscopic and radiologic tests, including flexible sigmoidoscopy, colonoscopy, and CT colonography. The guidance includes the following recommendations:
Clinicians should regularly screen for colorectal cancer in average-risk adults between the ages of 50 and 75 years.
This recommendation is in line with those made by the U.S. Preventive Services Task Force and the CTFPHC. Data suggest that regular screening reduces colorectal cancer–specific mortality in this age group, with those aged 65-75 years likely to garner the most benefit.
The absolute risk reduction increases with age and varies with test type. For every-other-year FOBT, it rises from 0.037% in those younger than 60 years to 0.20% in those aged 60 years or older. For flexible sigmoidoscopy, the risk reduction rises from 0.05% in the younger group to 0.29% in the older group.
Data from the CTFPHC show that the net benefit in those aged 50-59 years is small, however. This may influence the decision about when to start screening.
Clinicians should select the colorectal cancer screening test with the patient based on a discussion of benefits, harms, costs, availability, frequency, and patient preferences.
The FIT or FOBT should be performed every 2 years, colonoscopy every 10 years, and flexible sigmoidoscopy every 10 years, plus FIT every 2 years.
No data suggest a benefit of one test over another; however, “all screening tests are associated with potential benefits as well as harms,” the document states. “Clinical decisions need to be individualized using patient clinical characteristics, patient preferences, and screening test frequency and availability. Because many eligible patients have never been screened and some may not adhere to recommendations about subsequent screening or follow-up of positive findings on screening tests (such as colonoscopy after a positive result on a stool-based screening test), patient informed decision making and adherence are important factors in selection of a [colorectal cancer] screening test.”
Discussions with patients should include topics like the recommended frequency of each test, bowel preparation, anesthesia, transportation to and from testing site, time commitments, and the necessary steps if a test result is positive.
Clinicians should discontinue screening for colorectal cancer in average-risk adults older than 75 years or in adults with a life expectancy of 10 years or less.
While the benefit from screening increases with age, so do the risks for harm, especially serious harm. Data show the balance of harms and benefits reaching a tipping point at around 75 years of age. But again, this isn’t a universal recommendation, the statement says.
“Persons with no history of [colorectal cancer] screening may benefit from screening after age 75 years, whereas those who have received regular screening with negative results may not.”
Cessation of testing considers life expectancy after age 75 years. The average life expectancy for healthy 75-year-old men and women in the United States is 9.9 and 12 years, respectively. But among men and women with serious medical comorbidities, average life expectancy after age 70 years drops to 8.9 and 10.8 years, respectively.
“Therefore, most persons aged 75 years or older, as well as most adults who are younger than 75 years but have serious comorbid conditions [such as chronic renal failure], are unlikely to benefit from screening but would undergo unnecessary, burdensome, potentially harmful, and costly screening tests.”
As in any testing discussion, personal preferences are important, but not just to make patients feel comfortable about their choice. Mindset about colorectal cancer testing has a very big effect on compliance, the statement noted.
“For example, a biennial stool test is not a good screening strategy for patients who may be unwilling or unlikely to follow up every other year. In addition, given the tradeoffs between benefits and harms, some patients may want less intensive screening, such as screening that begins at a later age, stops at an earlier age, or recurs less frequently regardless of modality selected.”
SOURCE: Qassam A et al. Ann Intern Med. 2019;171:643-54.
Cost-effectiveness is one more factor in the colorectal screening discussion, Michael Pignone, MD, said in an accompanying editorial.
Two studies by Ladabaum et al. reported cost-effectiveness modeling for various CRC screening techniques: “Comparative effectiveness and cost effectiveness of a multitarget stool DNA test to screen for colorectal neoplasia” (Gastroenterology. 2019;151,:427-39.e6) and “Cost-effectiveness and national effects of initiating colorectal cancer screening for average-risk persons at age 45 years instead of 50 years” (Gastroenterology. 2019;157:137-48).
These reports concluded that annual stool testing is more effective – but also more costly – than biennial testing. However, the additional cost per unit of benefit (figured in quality-adjusted life-years) is about $33,000 per life-year gained – a reasonable cost. “Hence, annual testing is a viable screening option,” wrote Dr. Pignone.
Starting screening at age 45 years instead of 50 years also produced an additional cost per life-year, but again, it is reasonable at $33,900 for colonoscopy screening and $7,700 for stool testing.
“However, for the same amount of additional resources, increasing screening rates in 55- or 65-year-olds or improving the proportion of positive stool test results that are followed by colonoscopy from 60% to 90% would yield much more benefit in life-years gained than lowering the starting age to 45 years.”
Analyses such as these conditionally support earlier colorectal cancer screening only if the universal screening rate for 50- to 75-year-olds is more than 80%, he wrote. “They also reinforce the most important point in all of the major guidelines: Any recommended form of screening in the 50- to 75-year age range is likely to be very cost-effective (if not cost-saving) compared with no screening and should be strongly encouraged.”
Dr. Pignone is director of the program on cancer prevention and control at the LIVESTRONG Cancer Institutes at the University of Texas, Austin.
Cost-effectiveness is one more factor in the colorectal screening discussion, Michael Pignone, MD, said in an accompanying editorial.
Two studies by Ladabaum et al. reported cost-effectiveness modeling for various CRC screening techniques: “Comparative effectiveness and cost effectiveness of a multitarget stool DNA test to screen for colorectal neoplasia” (Gastroenterology. 2019;151,:427-39.e6) and “Cost-effectiveness and national effects of initiating colorectal cancer screening for average-risk persons at age 45 years instead of 50 years” (Gastroenterology. 2019;157:137-48).
These reports concluded that annual stool testing is more effective – but also more costly – than biennial testing. However, the additional cost per unit of benefit (figured in quality-adjusted life-years) is about $33,000 per life-year gained – a reasonable cost. “Hence, annual testing is a viable screening option,” wrote Dr. Pignone.
Starting screening at age 45 years instead of 50 years also produced an additional cost per life-year, but again, it is reasonable at $33,900 for colonoscopy screening and $7,700 for stool testing.
“However, for the same amount of additional resources, increasing screening rates in 55- or 65-year-olds or improving the proportion of positive stool test results that are followed by colonoscopy from 60% to 90% would yield much more benefit in life-years gained than lowering the starting age to 45 years.”
Analyses such as these conditionally support earlier colorectal cancer screening only if the universal screening rate for 50- to 75-year-olds is more than 80%, he wrote. “They also reinforce the most important point in all of the major guidelines: Any recommended form of screening in the 50- to 75-year age range is likely to be very cost-effective (if not cost-saving) compared with no screening and should be strongly encouraged.”
Dr. Pignone is director of the program on cancer prevention and control at the LIVESTRONG Cancer Institutes at the University of Texas, Austin.
Cost-effectiveness is one more factor in the colorectal screening discussion, Michael Pignone, MD, said in an accompanying editorial.
Two studies by Ladabaum et al. reported cost-effectiveness modeling for various CRC screening techniques: “Comparative effectiveness and cost effectiveness of a multitarget stool DNA test to screen for colorectal neoplasia” (Gastroenterology. 2019;151,:427-39.e6) and “Cost-effectiveness and national effects of initiating colorectal cancer screening for average-risk persons at age 45 years instead of 50 years” (Gastroenterology. 2019;157:137-48).
These reports concluded that annual stool testing is more effective – but also more costly – than biennial testing. However, the additional cost per unit of benefit (figured in quality-adjusted life-years) is about $33,000 per life-year gained – a reasonable cost. “Hence, annual testing is a viable screening option,” wrote Dr. Pignone.
Starting screening at age 45 years instead of 50 years also produced an additional cost per life-year, but again, it is reasonable at $33,900 for colonoscopy screening and $7,700 for stool testing.
“However, for the same amount of additional resources, increasing screening rates in 55- or 65-year-olds or improving the proportion of positive stool test results that are followed by colonoscopy from 60% to 90% would yield much more benefit in life-years gained than lowering the starting age to 45 years.”
Analyses such as these conditionally support earlier colorectal cancer screening only if the universal screening rate for 50- to 75-year-olds is more than 80%, he wrote. “They also reinforce the most important point in all of the major guidelines: Any recommended form of screening in the 50- to 75-year age range is likely to be very cost-effective (if not cost-saving) compared with no screening and should be strongly encouraged.”
Dr. Pignone is director of the program on cancer prevention and control at the LIVESTRONG Cancer Institutes at the University of Texas, Austin.
issued by the American College of Physicians.
Regular screening can be discontinued after age 75 years, Amir Qaseem, MD, president of clinical policy and the Center for Evidence Reviews at the American College of Physicians, and colleagues wrote in the Annals of Internal Medicine.
No one test is preferred over another, according to the guidance statement. Patients and physicians can select the test type together, based on individual needs and preferences, and each test carries its own screening interval. But regular testing has been proven time and again to reduce the risk of colorectal cancer mortality, and more people should have it, according to the guidance.
“Not enough people in the United States get screened for colorectal cancer,” ACP President Robert M. McLean, MD, said in a press statement. “Physicians should perform an individualized risk assessment for colorectal cancer in all adults. Doctors and patients should select the screening test based on a discussion of the benefits, harms, costs, availability, frequency, and patient preferences.”
The guidance is an attempt to balance existing guidelines authored by the U.S. Preventive Services Task Force and the Canadian Task Force on Preventive Health Care (CTFPHC), but it also was developed following critical review of those from the American Cancer Society and other organizations.
The ACP guidance is for adults at average risk for colorectal cancer who do not have symptoms; it does not apply to adults with a family history of colorectal cancer, a long-standing history of inflammatory bowel disease, genetic syndromes such as familial cancerous polyps, a personal history of previous colorectal cancer or benign polyps, or other risk factors.
The guidance was based on evaluations of stool-based tests, including the fecal immunochemical test (FIT), also called the immunochemical-based fecal occult blood test (FOBT), and direct visualization with endoscopic and radiologic tests, including flexible sigmoidoscopy, colonoscopy, and CT colonography. The guidance includes the following recommendations:
Clinicians should regularly screen for colorectal cancer in average-risk adults between the ages of 50 and 75 years.
This recommendation is in line with those made by the U.S. Preventive Services Task Force and the CTFPHC. Data suggest that regular screening reduces colorectal cancer–specific mortality in this age group, with those aged 65-75 years likely to garner the most benefit.
The absolute risk reduction increases with age and varies with test type. For every-other-year FOBT, it rises from 0.037% in those younger than 60 years to 0.20% in those aged 60 years or older. For flexible sigmoidoscopy, the risk reduction rises from 0.05% in the younger group to 0.29% in the older group.
Data from the CTFPHC show that the net benefit in those aged 50-59 years is small, however. This may influence the decision about when to start screening.
Clinicians should select the colorectal cancer screening test with the patient based on a discussion of benefits, harms, costs, availability, frequency, and patient preferences.
The FIT or FOBT should be performed every 2 years, colonoscopy every 10 years, and flexible sigmoidoscopy every 10 years, plus FIT every 2 years.
No data suggest a benefit of one test over another; however, “all screening tests are associated with potential benefits as well as harms,” the document states. “Clinical decisions need to be individualized using patient clinical characteristics, patient preferences, and screening test frequency and availability. Because many eligible patients have never been screened and some may not adhere to recommendations about subsequent screening or follow-up of positive findings on screening tests (such as colonoscopy after a positive result on a stool-based screening test), patient informed decision making and adherence are important factors in selection of a [colorectal cancer] screening test.”
Discussions with patients should include topics like the recommended frequency of each test, bowel preparation, anesthesia, transportation to and from testing site, time commitments, and the necessary steps if a test result is positive.
Clinicians should discontinue screening for colorectal cancer in average-risk adults older than 75 years or in adults with a life expectancy of 10 years or less.
While the benefit from screening increases with age, so do the risks for harm, especially serious harm. Data show the balance of harms and benefits reaching a tipping point at around 75 years of age. But again, this isn’t a universal recommendation, the statement says.
“Persons with no history of [colorectal cancer] screening may benefit from screening after age 75 years, whereas those who have received regular screening with negative results may not.”
Cessation of testing considers life expectancy after age 75 years. The average life expectancy for healthy 75-year-old men and women in the United States is 9.9 and 12 years, respectively. But among men and women with serious medical comorbidities, average life expectancy after age 70 years drops to 8.9 and 10.8 years, respectively.
“Therefore, most persons aged 75 years or older, as well as most adults who are younger than 75 years but have serious comorbid conditions [such as chronic renal failure], are unlikely to benefit from screening but would undergo unnecessary, burdensome, potentially harmful, and costly screening tests.”
As in any testing discussion, personal preferences are important, but not just to make patients feel comfortable about their choice. Mindset about colorectal cancer testing has a very big effect on compliance, the statement noted.
“For example, a biennial stool test is not a good screening strategy for patients who may be unwilling or unlikely to follow up every other year. In addition, given the tradeoffs between benefits and harms, some patients may want less intensive screening, such as screening that begins at a later age, stops at an earlier age, or recurs less frequently regardless of modality selected.”
SOURCE: Qassam A et al. Ann Intern Med. 2019;171:643-54.
issued by the American College of Physicians.
Regular screening can be discontinued after age 75 years, Amir Qaseem, MD, president of clinical policy and the Center for Evidence Reviews at the American College of Physicians, and colleagues wrote in the Annals of Internal Medicine.
No one test is preferred over another, according to the guidance statement. Patients and physicians can select the test type together, based on individual needs and preferences, and each test carries its own screening interval. But regular testing has been proven time and again to reduce the risk of colorectal cancer mortality, and more people should have it, according to the guidance.
“Not enough people in the United States get screened for colorectal cancer,” ACP President Robert M. McLean, MD, said in a press statement. “Physicians should perform an individualized risk assessment for colorectal cancer in all adults. Doctors and patients should select the screening test based on a discussion of the benefits, harms, costs, availability, frequency, and patient preferences.”
The guidance is an attempt to balance existing guidelines authored by the U.S. Preventive Services Task Force and the Canadian Task Force on Preventive Health Care (CTFPHC), but it also was developed following critical review of those from the American Cancer Society and other organizations.
The ACP guidance is for adults at average risk for colorectal cancer who do not have symptoms; it does not apply to adults with a family history of colorectal cancer, a long-standing history of inflammatory bowel disease, genetic syndromes such as familial cancerous polyps, a personal history of previous colorectal cancer or benign polyps, or other risk factors.
The guidance was based on evaluations of stool-based tests, including the fecal immunochemical test (FIT), also called the immunochemical-based fecal occult blood test (FOBT), and direct visualization with endoscopic and radiologic tests, including flexible sigmoidoscopy, colonoscopy, and CT colonography. The guidance includes the following recommendations:
Clinicians should regularly screen for colorectal cancer in average-risk adults between the ages of 50 and 75 years.
This recommendation is in line with those made by the U.S. Preventive Services Task Force and the CTFPHC. Data suggest that regular screening reduces colorectal cancer–specific mortality in this age group, with those aged 65-75 years likely to garner the most benefit.
The absolute risk reduction increases with age and varies with test type. For every-other-year FOBT, it rises from 0.037% in those younger than 60 years to 0.20% in those aged 60 years or older. For flexible sigmoidoscopy, the risk reduction rises from 0.05% in the younger group to 0.29% in the older group.
Data from the CTFPHC show that the net benefit in those aged 50-59 years is small, however. This may influence the decision about when to start screening.
Clinicians should select the colorectal cancer screening test with the patient based on a discussion of benefits, harms, costs, availability, frequency, and patient preferences.
The FIT or FOBT should be performed every 2 years, colonoscopy every 10 years, and flexible sigmoidoscopy every 10 years, plus FIT every 2 years.
No data suggest a benefit of one test over another; however, “all screening tests are associated with potential benefits as well as harms,” the document states. “Clinical decisions need to be individualized using patient clinical characteristics, patient preferences, and screening test frequency and availability. Because many eligible patients have never been screened and some may not adhere to recommendations about subsequent screening or follow-up of positive findings on screening tests (such as colonoscopy after a positive result on a stool-based screening test), patient informed decision making and adherence are important factors in selection of a [colorectal cancer] screening test.”
Discussions with patients should include topics like the recommended frequency of each test, bowel preparation, anesthesia, transportation to and from testing site, time commitments, and the necessary steps if a test result is positive.
Clinicians should discontinue screening for colorectal cancer in average-risk adults older than 75 years or in adults with a life expectancy of 10 years or less.
While the benefit from screening increases with age, so do the risks for harm, especially serious harm. Data show the balance of harms and benefits reaching a tipping point at around 75 years of age. But again, this isn’t a universal recommendation, the statement says.
“Persons with no history of [colorectal cancer] screening may benefit from screening after age 75 years, whereas those who have received regular screening with negative results may not.”
Cessation of testing considers life expectancy after age 75 years. The average life expectancy for healthy 75-year-old men and women in the United States is 9.9 and 12 years, respectively. But among men and women with serious medical comorbidities, average life expectancy after age 70 years drops to 8.9 and 10.8 years, respectively.
“Therefore, most persons aged 75 years or older, as well as most adults who are younger than 75 years but have serious comorbid conditions [such as chronic renal failure], are unlikely to benefit from screening but would undergo unnecessary, burdensome, potentially harmful, and costly screening tests.”
As in any testing discussion, personal preferences are important, but not just to make patients feel comfortable about their choice. Mindset about colorectal cancer testing has a very big effect on compliance, the statement noted.
“For example, a biennial stool test is not a good screening strategy for patients who may be unwilling or unlikely to follow up every other year. In addition, given the tradeoffs between benefits and harms, some patients may want less intensive screening, such as screening that begins at a later age, stops at an earlier age, or recurs less frequently regardless of modality selected.”
SOURCE: Qassam A et al. Ann Intern Med. 2019;171:643-54.
FROM THE ANNALS OF INTERNAL MEDICINE