Low Socioeconomic Status Associated With Higher Risk of Second Heart Attack or Stroke
Low socioeconomic status is associated with a higher risk of a second heart attack or stroke, according to Joel Ohm, MD, a physician at the Karolinska University Hospital and Karolinska Institute in Stockholm. The study of nearly 30,000 patients with a prior heart attack revealed that the risk of a second event was 36% lower for those in the highest income quintile, compared with the lowest, and increased by 14% in divorced patients, compared with married patients.

"Are you rich or poor? Married or divorced? That might affect your risk of a second heart attack or stroke," said Dr. Ohm. "Advances in prevention and acute treatment have increased survival after heart attack and stroke over the past several decades. The result is that more people live with cardiovascular disease in Sweden. Almost one-fifth of the total population is in this group."

Most research on cardiovascular prevention is based on healthy people, and it is unclear whether the findings apply to patients with established disease. An association between socioeconomic status in healthy individuals and future cardiovascular disease was found in the 1950s. This study investigated the link between socioeconomic status in patients who had survived a first heart attack and the risk of a second heart attack or a stroke.

The study included 29,953 patients from the Swedish nationwide registry, Secondary Prevention after Heart Intensive Care Admission (SEPHIA), who had been discharged approximately one year previously from a cardiac intensive care unit after treatment for a first myocardial infarction. Data on outcome over time and socioeconomic status (defined as disposable income, marital status, and level of education) was obtained from Statistics Sweden and the National Board of Health and Welfare.

During an average follow-up of four years, 2,405 patients (8%) had a heart attack or stroke. After adjustments for age, gender, smoking status, and the defined measures of socioeconomic status, being divorced was independently associated with a 14% greater risk of a second event, compared with being married. There was an independent and linear relationship between disposable income and the risk of a second event, with those in the highest quintile of income having a 36% lower risk than those in the lowest quintile. A higher level of education was associated with a lower risk of events, but the association was not significant after adjustment for income.

"Our study shows that in the years following a first myocardial infarction, men and women with low socioeconomic status have a higher risk of suffering another heart attack or stroke. This is a new finding and suggests that socioeconomic status should be included in risk assessment for secondary prevention after a heart attack," said Dr Ohm. "Even though health care providers are unlikely to keep track of their patients' yearly salary, simple questions about other socioeconomic variables such as marital status and educational level could make a difference."

According to the widely used assessment tools for cardiovascular risk, survivors of heart attacks are at the highest possible risk for subsequent events, regardless of other risk factors. There is, for example, no difference in the estimated risk level between a previously healthy 40-year old female from Spain and a heavily smoking, obese, elderly man with diabetes and high blood pressure from Finland.

"Risk assessment tools are designed for individuals without previous cardiovascular disease, and the calculations may not apply to patients with established cardiovascular disease. Socioeconomic status is perhaps a better marker to assess risk of future events in heart attack patients, and more research is needed to determine other factors that could be included, such as occupation or residential area," said Dr Ohm.

Alcohol-Related Hospitalization Associated With Doubled Stroke Risk in Atrial Fibrillation
Alcohol-related hospitalization is associated with a doubled risk of ischemic stroke in patients with nonvalvular atrial fibrillation (AF), according to research presented by Faris Al-Khalili, MD, PhD, a cardiologist at the Karolinska Institute Danderyd Hospital in Stockholm. The observational study was conducted in more than 25,000 patients with nonvalvular AF at low risk of stroke.

"AF is the most common heart rhythm disturbance and is associated with a fivefold ncreased risk of ischemic stroke," said Dr. Al-Khalili. "AF is also associated with increased mortality, reduced quality of life, and a higher risk of heart failure."

Treatment with oral anticoagulants reduces the risk of stroke and is recommended according to the patient's number of stroke risk factors. Risk is estimated using the CHA2DS2-VASc score, which gives points for clinical risk factors. Patients with nonvalvular AF under age 65 who have a score of zero (in men) or one (in women) are considered to be at low risk for ischemic stroke, and oral anticoagulation therapy is not indicated for them.

"Even if the risk for stroke is low, it is not negligible, and a number of such low-risk patients do present with ischemic stroke in clinical practice and in patient registers," said Dr. Al-Khalili.  

The objective of this study was to assess the incidence and predictors of ischemic stroke among low-risk patients with nonvalvular AF. This retrospective study included 25,252 patients (ages 18 to 64) of a total of 34,523 patients with AF identified from the Swedish nationwide patient register for the period between January 1, 2006 and December 31, 2012. The median age was 55, and 72% of participants were men.

Information was available regarding  all hospitalizations and visits to hospital-affiliated open clinics in Sweden. Socioeconomic variables were obtained from a database for health insurance and labor market studies. Information about current medication was obtained from the National Drug Register, which has information about all dispensed prescription in Sweden and is 100% complete.

During a median follow-up of five years, ischemic stroke occurred at an annual rate of 3.4 per 1,000 patient-years. The overall mortality was 7.5 per 1,000 patient-years in patients without ischemic stroke and 29.6 per 1,000 patient-years in patients who had had an ischemic stroke during follow-up.

In the multivariable analysis, the only variables that remained significantly associated with an increased risk of ischemic stroke were age (hazard ratio [HR], 1.06) and alcohol-related hospitalization (HR, 2.01). Use of oral anticoagulants was associated with a lower risk of ischemic stroke (HR, 0.78).

"Even though these patients are classified as low-risk, the incidence of ischemic stroke in our study population is neither negligible nor ignorable, and it carries a relatively high mortality," said Dr. Al-Khalili.

"Previous studies have shown a causal and dose-response relation between alcohol and AF. Our study found that alcohol is an independent risk factor for stroke in patients with AF. Alcohol might induce AF, leading to embolic stroke, or there could be a specific alcohol effect that causes systemic or cerebral thromboembolism. Using alcohol-related hospitalization as a proxy for alcohol abuse likely underestimates the extent of the problem and does not allow grading of the amount of alcohol consumed.

"Doctors should ask their AF patients about alcohol use and advise patients to cut down if they are drinking more than is recommended. The beneficial link between oral anticoagulant use and ischemic stroke in this low-risk population without a recognized indication for these drugs needs further investigation, including the benefit to harm (bleeding) ratio," Dr. Al-Khalili concluded.

New Oral Anticoagulants Provide Same Stroke Prevention as Warfarin But Cause Less Bleeding
The new oral anticoagulants provide the same stroke prevention as warfarin, but cause less intracranial bleeding, according to research presented by Laila Staerk, PhD, a research fellow at Herlev and Gentofte University Hospital in Hellerup, Denmark.

"Atrial fibrillation is the most common cardiac rhythm disorder and currently affects more than 10 million Europeans," said Dr. Staerk. "Atrial fibrillation is associated with a fivefold risk of stroke, potentially leading to disability and death. In the next four decades, the number of patients with atrial fibrillation is expected to triple, so the number of Europeans diagnosed could rise to a staggering 25 to 30 million."

Patients with atrial fibrillation are treated life-long with oral anticoagulation to reduce their risk of stroke. But treatment with non-vitamin K antagonist oral anticoagulants (NOACs) and vitamin K antagonists (eg, warfarin) lowers the risk of stroke at the cost of increased bleeding risk.  

Several treatment options are available, and physicians may be unsure about which one to use. "There has been a need to investigate the safety and effectiveness of NOACs versus warfarin in a real-world population, and our Danish registries provide this opportunity," said Dr. Staerk.

The current study compared the risk of stroke and intracranial bleeding associated with NOACs (ie, dabigatran, rivaroxaban, and apixaban) versus that associated with warfarin in a real-world setting. The study was conducted at the Cardiovascular Research Centre at Herlev and Gentofte University Hospital. It included 43,299 patients with atrial fibrillation who were recruited from Danish nationwide administrative registries.

Approximately 42% of patients were taking warfarin, while 29%, 16%, and 13% were taking dabigatran, apixaban, and rivaroxaban, respectively. During follow-up, stroke occurred in 1,054 patients, and there were 261 intracranial bleedings.

The risk of having a stroke within one year was similar between the NOAC and warfarin groups and ranged from 2.0% to 2.5%. At one year, the risk of intracranial bleeding was significantly lower in patients treated with dabigatran and apixaban (0.3% to 0.4%), compared with that in those treated with warfarin (0.6%).

"The inclusion and exclusion criteria in our study were broadly similar for patients initiating NOACs or warfarin, and this gave a straightforward opportunity to directly compare the treatment regimens, which is in contrast to the randomized trials. The results suggest that although they have similar effects in preventing stroke, dabigatran and apixaban were associated with a safer use regarding the absolute one-year risk of intracranial bleeding," said Dr Staerk. "Our results complement the large randomized phase III trials by providing real-world data on stroke and intracranial bleeding with NOACs versus warfarin, since fragile patients were not excluded from our nationwide cohort. For example, patients with increased risk of bleeding, liver disease, and chronic kidney disease are less represented in trials."

"Registry studies have some limitations such as the observational design, residual confounding, and confounding by drug indication. In the future, it would be exciting to see a head-to-head randomized trial performed to compare the different NOAC treatments in patients with atrial fibrillation," said Dr Staerk.

Moderate Physical Activity Reduces Risk of Cardiovascular Death
Moderate physical activity is associated with a greater than 50% reduction in cardiovascular death in people older than 65, according to Riitta Antikainen, MD, Professor of Geriatrics at the University of Oulu in Finland. "These results prompt us to investigate the mechanisms through which the Mediterranean diet may protect against death," she said.

The 12-year study in nearly 2,500 adults between ages 65 and 74 found that moderate physical activity reduced the risk of an acute cardiovascular event by more than 30%. High levels of physical activity led to greater risk reductions.

"The role of physical activity in preventing cardiovascular disease [CVD] in people of working age is well established," said Dr. Antikainen. "But relatively little is known about the effect of regular physical activity on CVD risk in older people."

The present study assessed the association between leisure time physical activity and CVD risk and mortality in 2,456 men and women who were enrolled into the National FINRISK Study between 1997 and 2007.

Baseline data collection included self-administered questionnaires on physical activity and other health related behavior, clinical measurements (eg, blood pressure, weight, and height), and laboratory measurements, including serum cholesterol. Participants were followed up until the end of 2013. Deaths were recorded from the National Causes of Death Register, and incident CVD events (ie, coronary heart disease and stroke) were collected from the National Hospital Discharge register.

The researchers classified self-reported physical activity as low, moderate, or high. Low physical activity included reading, watching TV, and working in the household without much physical activity. Moderate physical activity encompassed walking, cycling, or practicing other forms of light exercise (eg, fishing, gardening, hunting) for at least four hours per week. High physical activity included recreational sports (eg, running, jogging, skiing, gymnastics, swimming, or ball games) or intense training or sports competitions for at least three hours per week.  

During a median follow-up of 11.8 years, 197 participants died from CVD, and 416 had a first CVD event.

When the researchers assessed the link between physical activity and outcome, they adjusted for other cardiovascular risk factors (ie, blood pressure, smoking, and cholesterol) and social factors (ie, marital status and education). To minimize reverse causality, where worse health leads to less physical activity, patients with coronary heart disease, heart failure, cancer, or prior stroke at baseline were excluded from the analysis.

The investigators found that moderate and high leisure-time physical activity were associated with a 31% and 45% reduced risk of an acute CVD event, respectively. Moderate and high leisure-time physical activity were associated with a 54% and 66% reduction in CVD mortality, respectively.

"Our study provides further evidence that older adults who are physically active have a lower risk of coronary heart disease, stroke, and death from cardiovascular disease. The protective effect of leisure time physical activity is dose dependent. In other words, the more you do, the better. Activity is protective even if you have other risk factors for cardiovascular disease such as high cholesterol," said Dr. Antikainen.  

"Physical exercise may become more challenging with aging. However, it is important for older people to still get enough safe physical activity to stay healthy after their transition to retirement."         

Low Socioeconomic Status Associated With Higher Risk of Second Heart Attack or Stroke
Low socioeconomic status is associated with a higher risk of a second heart attack or stroke, according to Joel Ohm, MD, a physician at the Karolinska University Hospital and Karolinska Institute in Stockholm. The study of nearly 30,000 patients with a prior heart attack revealed that the risk of a second event was 36% lower for those in the highest income quintile, compared with the lowest, and increased by 14% in divorced patients, compared with married patients.

"Are you rich or poor? Married or divorced? That might affect your risk of a second heart attack or stroke," said Dr. Ohm. "Advances in prevention and acute treatment have increased survival after heart attack and stroke over the past several decades. The result is that more people live with cardiovascular disease in Sweden. Almost one-fifth of the total population is in this group."

Most research on cardiovascular prevention is based on healthy people, and it is unclear whether the findings apply to patients with established disease. An association between socioeconomic status in healthy individuals and future cardiovascular disease was found in the 1950s. This study investigated the link between socioeconomic status in patients who had survived a first heart attack and the risk of a second heart attack or a stroke.

The study included 29,953 patients from the Swedish nationwide registry, Secondary Prevention after Heart Intensive Care Admission (SEPHIA), who had been discharged approximately one year previously from a cardiac intensive care unit after treatment for a first myocardial infarction. Data on outcome over time and socioeconomic status (defined as disposable income, marital status, and level of education) was obtained from Statistics Sweden and the National Board of Health and Welfare.

During an average follow-up of four years, 2,405 patients (8%) had a heart attack or stroke. After adjustments for age, gender, smoking status, and the defined measures of socioeconomic status, being divorced was independently associated with a 14% greater risk of a second event, compared with being married. There was an independent and linear relationship between disposable income and the risk of a second event, with those in the highest quintile of income having a 36% lower risk than those in the lowest quintile. A higher level of education was associated with a lower risk of events, but the association was not significant after adjustment for income.

"Our study shows that in the years following a first myocardial infarction, men and women with low socioeconomic status have a higher risk of suffering another heart attack or stroke. This is a new finding and suggests that socioeconomic status should be included in risk assessment for secondary prevention after a heart attack," said Dr Ohm. "Even though health care providers are unlikely to keep track of their patients' yearly salary, simple questions about other socioeconomic variables such as marital status and educational level could make a difference."

According to the widely used assessment tools for cardiovascular risk, survivors of heart attacks are at the highest possible risk for subsequent events, regardless of other risk factors. There is, for example, no difference in the estimated risk level between a previously healthy 40-year old female from Spain and a heavily smoking, obese, elderly man with diabetes and high blood pressure from Finland.

"Risk assessment tools are designed for individuals without previous cardiovascular disease, and the calculations may not apply to patients with established cardiovascular disease. Socioeconomic status is perhaps a better marker to assess risk of future events in heart attack patients, and more research is needed to determine other factors that could be included, such as occupation or residential area," said Dr Ohm.

Alcohol-Related Hospitalization Associated With Doubled Stroke Risk in Atrial Fibrillation
Alcohol-related hospitalization is associated with a doubled risk of ischemic stroke in patients with nonvalvular atrial fibrillation (AF), according to research presented by Faris Al-Khalili, MD, PhD, a cardiologist at the Karolinska Institute Danderyd Hospital in Stockholm. The observational study was conducted in more than 25,000 patients with nonvalvular AF at low risk of stroke.

"AF is the most common heart rhythm disturbance and is associated with a fivefold ncreased risk of ischemic stroke," said Dr. Al-Khalili. "AF is also associated with increased mortality, reduced quality of life, and a higher risk of heart failure."

Treatment with oral anticoagulants reduces the risk of stroke and is recommended according to the patient's number of stroke risk factors. Risk is estimated using the CHA2DS2-VASc score, which gives points for clinical risk factors. Patients with nonvalvular AF under age 65 who have a score of zero (in men) or one (in women) are considered to be at low risk for ischemic stroke, and oral anticoagulation therapy is not indicated for them.

"Even if the risk for stroke is low, it is not negligible, and a number of such low-risk patients do present with ischemic stroke in clinical practice and in patient registers," said Dr. Al-Khalili.  

The objective of this study was to assess the incidence and predictors of ischemic stroke among low-risk patients with nonvalvular AF. This retrospective study included 25,252 patients (ages 18 to 64) of a total of 34,523 patients with AF identified from the Swedish nationwide patient register for the period between January 1, 2006 and December 31, 2012. The median age was 55, and 72% of participants were men.

Information was available regarding  all hospitalizations and visits to hospital-affiliated open clinics in Sweden. Socioeconomic variables were obtained from a database for health insurance and labor market studies. Information about current medication was obtained from the National Drug Register, which has information about all dispensed prescription in Sweden and is 100% complete.

During a median follow-up of five years, ischemic stroke occurred at an annual rate of 3.4 per 1,000 patient-years. The overall mortality was 7.5 per 1,000 patient-years in patients without ischemic stroke and 29.6 per 1,000 patient-years in patients who had had an ischemic stroke during follow-up.

In the multivariable analysis, the only variables that remained significantly associated with an increased risk of ischemic stroke were age (hazard ratio [HR], 1.06) and alcohol-related hospitalization (HR, 2.01). Use of oral anticoagulants was associated with a lower risk of ischemic stroke (HR, 0.78).

"Even though these patients are classified as low-risk, the incidence of ischemic stroke in our study population is neither negligible nor ignorable, and it carries a relatively high mortality," said Dr. Al-Khalili.

"Previous studies have shown a causal and dose-response relation between alcohol and AF. Our study found that alcohol is an independent risk factor for stroke in patients with AF. Alcohol might induce AF, leading to embolic stroke, or there could be a specific alcohol effect that causes systemic or cerebral thromboembolism. Using alcohol-related hospitalization as a proxy for alcohol abuse likely underestimates the extent of the problem and does not allow grading of the amount of alcohol consumed.

"Doctors should ask their AF patients about alcohol use and advise patients to cut down if they are drinking more than is recommended. The beneficial link between oral anticoagulant use and ischemic stroke in this low-risk population without a recognized indication for these drugs needs further investigation, including the benefit to harm (bleeding) ratio," Dr. Al-Khalili concluded.

New Oral Anticoagulants Provide Same Stroke Prevention as Warfarin But Cause Less Bleeding
The new oral anticoagulants provide the same stroke prevention as warfarin, but cause less intracranial bleeding, according to research presented by Laila Staerk, PhD, a research fellow at Herlev and Gentofte University Hospital in Hellerup, Denmark.

"Atrial fibrillation is the most common cardiac rhythm disorder and currently affects more than 10 million Europeans," said Dr. Staerk. "Atrial fibrillation is associated with a fivefold risk of stroke, potentially leading to disability and death. In the next four decades, the number of patients with atrial fibrillation is expected to triple, so the number of Europeans diagnosed could rise to a staggering 25 to 30 million."

Patients with atrial fibrillation are treated life-long with oral anticoagulation to reduce their risk of stroke. But treatment with non-vitamin K antagonist oral anticoagulants (NOACs) and vitamin K antagonists (eg, warfarin) lowers the risk of stroke at the cost of increased bleeding risk.  

Several treatment options are available, and physicians may be unsure about which one to use. "There has been a need to investigate the safety and effectiveness of NOACs versus warfarin in a real-world population, and our Danish registries provide this opportunity," said Dr. Staerk.

The current study compared the risk of stroke and intracranial bleeding associated with NOACs (ie, dabigatran, rivaroxaban, and apixaban) versus that associated with warfarin in a real-world setting. The study was conducted at the Cardiovascular Research Centre at Herlev and Gentofte University Hospital. It included 43,299 patients with atrial fibrillation who were recruited from Danish nationwide administrative registries.

Approximately 42% of patients were taking warfarin, while 29%, 16%, and 13% were taking dabigatran, apixaban, and rivaroxaban, respectively. During follow-up, stroke occurred in 1,054 patients, and there were 261 intracranial bleedings.

The risk of having a stroke within one year was similar between the NOAC and warfarin groups and ranged from 2.0% to 2.5%. At one year, the risk of intracranial bleeding was significantly lower in patients treated with dabigatran and apixaban (0.3% to 0.4%), compared with that in those treated with warfarin (0.6%).

"The inclusion and exclusion criteria in our study were broadly similar for patients initiating NOACs or warfarin, and this gave a straightforward opportunity to directly compare the treatment regimens, which is in contrast to the randomized trials. The results suggest that although they have similar effects in preventing stroke, dabigatran and apixaban were associated with a safer use regarding the absolute one-year risk of intracranial bleeding," said Dr Staerk. "Our results complement the large randomized phase III trials by providing real-world data on stroke and intracranial bleeding with NOACs versus warfarin, since fragile patients were not excluded from our nationwide cohort. For example, patients with increased risk of bleeding, liver disease, and chronic kidney disease are less represented in trials."

"Registry studies have some limitations such as the observational design, residual confounding, and confounding by drug indication. In the future, it would be exciting to see a head-to-head randomized trial performed to compare the different NOAC treatments in patients with atrial fibrillation," said Dr Staerk.

Moderate Physical Activity Reduces Risk of Cardiovascular Death
Moderate physical activity is associated with a greater than 50% reduction in cardiovascular death in people older than 65, according to Riitta Antikainen, MD, Professor of Geriatrics at the University of Oulu in Finland. "These results prompt us to investigate the mechanisms through which the Mediterranean diet may protect against death," she said.

The 12-year study in nearly 2,500 adults between ages 65 and 74 found that moderate physical activity reduced the risk of an acute cardiovascular event by more than 30%. High levels of physical activity led to greater risk reductions.

"The role of physical activity in preventing cardiovascular disease [CVD] in people of working age is well established," said Dr. Antikainen. "But relatively little is known about the effect of regular physical activity on CVD risk in older people."

The present study assessed the association between leisure time physical activity and CVD risk and mortality in 2,456 men and women who were enrolled into the National FINRISK Study between 1997 and 2007.

Baseline data collection included self-administered questionnaires on physical activity and other health related behavior, clinical measurements (eg, blood pressure, weight, and height), and laboratory measurements, including serum cholesterol. Participants were followed up until the end of 2013. Deaths were recorded from the National Causes of Death Register, and incident CVD events (ie, coronary heart disease and stroke) were collected from the National Hospital Discharge register.

The researchers classified self-reported physical activity as low, moderate, or high. Low physical activity included reading, watching TV, and working in the household without much physical activity. Moderate physical activity encompassed walking, cycling, or practicing other forms of light exercise (eg, fishing, gardening, hunting) for at least four hours per week. High physical activity included recreational sports (eg, running, jogging, skiing, gymnastics, swimming, or ball games) or intense training or sports competitions for at least three hours per week.  

During a median follow-up of 11.8 years, 197 participants died from CVD, and 416 had a first CVD event.

When the researchers assessed the link between physical activity and outcome, they adjusted for other cardiovascular risk factors (ie, blood pressure, smoking, and cholesterol) and social factors (ie, marital status and education). To minimize reverse causality, where worse health leads to less physical activity, patients with coronary heart disease, heart failure, cancer, or prior stroke at baseline were excluded from the analysis.

The investigators found that moderate and high leisure-time physical activity were associated with a 31% and 45% reduced risk of an acute CVD event, respectively. Moderate and high leisure-time physical activity were associated with a 54% and 66% reduction in CVD mortality, respectively.

"Our study provides further evidence that older adults who are physically active have a lower risk of coronary heart disease, stroke, and death from cardiovascular disease. The protective effect of leisure time physical activity is dose dependent. In other words, the more you do, the better. Activity is protective even if you have other risk factors for cardiovascular disease such as high cholesterol," said Dr. Antikainen.  

"Physical exercise may become more challenging with aging. However, it is important for older people to still get enough safe physical activity to stay healthy after their transition to retirement."         

Low Socioeconomic Status Associated With Higher Risk of Second Heart Attack or Stroke
Low socioeconomic status is associated with a higher risk of a second heart attack or stroke, according to Joel Ohm, MD, a physician at the Karolinska University Hospital and Karolinska Institute in Stockholm. The study of nearly 30,000 patients with a prior heart attack revealed that the risk of a second event was 36% lower for those in the highest income quintile, compared with the lowest, and increased by 14% in divorced patients, compared with married patients.

"Are you rich or poor? Married or divorced? That might affect your risk of a second heart attack or stroke," said Dr. Ohm. "Advances in prevention and acute treatment have increased survival after heart attack and stroke over the past several decades. The result is that more people live with cardiovascular disease in Sweden. Almost one-fifth of the total population is in this group."

Most research on cardiovascular prevention is based on healthy people, and it is unclear whether the findings apply to patients with established disease. An association between socioeconomic status in healthy individuals and future cardiovascular disease was found in the 1950s. This study investigated the link between socioeconomic status in patients who had survived a first heart attack and the risk of a second heart attack or a stroke.

The study included 29,953 patients from the Swedish nationwide registry, Secondary Prevention after Heart Intensive Care Admission (SEPHIA), who had been discharged approximately one year previously from a cardiac intensive care unit after treatment for a first myocardial infarction. Data on outcome over time and socioeconomic status (defined as disposable income, marital status, and level of education) was obtained from Statistics Sweden and the National Board of Health and Welfare.

During an average follow-up of four years, 2,405 patients (8%) had a heart attack or stroke. After adjustments for age, gender, smoking status, and the defined measures of socioeconomic status, being divorced was independently associated with a 14% greater risk of a second event, compared with being married. There was an independent and linear relationship between disposable income and the risk of a second event, with those in the highest quintile of income having a 36% lower risk than those in the lowest quintile. A higher level of education was associated with a lower risk of events, but the association was not significant after adjustment for income.

"Our study shows that in the years following a first myocardial infarction, men and women with low socioeconomic status have a higher risk of suffering another heart attack or stroke. This is a new finding and suggests that socioeconomic status should be included in risk assessment for secondary prevention after a heart attack," said Dr Ohm. "Even though health care providers are unlikely to keep track of their patients' yearly salary, simple questions about other socioeconomic variables such as marital status and educational level could make a difference."

According to the widely used assessment tools for cardiovascular risk, survivors of heart attacks are at the highest possible risk for subsequent events, regardless of other risk factors. There is, for example, no difference in the estimated risk level between a previously healthy 40-year old female from Spain and a heavily smoking, obese, elderly man with diabetes and high blood pressure from Finland.

"Risk assessment tools are designed for individuals without previous cardiovascular disease, and the calculations may not apply to patients with established cardiovascular disease. Socioeconomic status is perhaps a better marker to assess risk of future events in heart attack patients, and more research is needed to determine other factors that could be included, such as occupation or residential area," said Dr Ohm.

Alcohol-Related Hospitalization Associated With Doubled Stroke Risk in Atrial Fibrillation
Alcohol-related hospitalization is associated with a doubled risk of ischemic stroke in patients with nonvalvular atrial fibrillation (AF), according to research presented by Faris Al-Khalili, MD, PhD, a cardiologist at the Karolinska Institute Danderyd Hospital in Stockholm. The observational study was conducted in more than 25,000 patients with nonvalvular AF at low risk of stroke.

"AF is the most common heart rhythm disturbance and is associated with a fivefold ncreased risk of ischemic stroke," said Dr. Al-Khalili. "AF is also associated with increased mortality, reduced quality of life, and a higher risk of heart failure."

Treatment with oral anticoagulants reduces the risk of stroke and is recommended according to the patient's number of stroke risk factors. Risk is estimated using the CHA2DS2-VASc score, which gives points for clinical risk factors. Patients with nonvalvular AF under age 65 who have a score of zero (in men) or one (in women) are considered to be at low risk for ischemic stroke, and oral anticoagulation therapy is not indicated for them.

"Even if the risk for stroke is low, it is not negligible, and a number of such low-risk patients do present with ischemic stroke in clinical practice and in patient registers," said Dr. Al-Khalili.  

The objective of this study was to assess the incidence and predictors of ischemic stroke among low-risk patients with nonvalvular AF. This retrospective study included 25,252 patients (ages 18 to 64) of a total of 34,523 patients with AF identified from the Swedish nationwide patient register for the period between January 1, 2006 and December 31, 2012. The median age was 55, and 72% of participants were men.

Information was available regarding  all hospitalizations and visits to hospital-affiliated open clinics in Sweden. Socioeconomic variables were obtained from a database for health insurance and labor market studies. Information about current medication was obtained from the National Drug Register, which has information about all dispensed prescription in Sweden and is 100% complete.

During a median follow-up of five years, ischemic stroke occurred at an annual rate of 3.4 per 1,000 patient-years. The overall mortality was 7.5 per 1,000 patient-years in patients without ischemic stroke and 29.6 per 1,000 patient-years in patients who had had an ischemic stroke during follow-up.

In the multivariable analysis, the only variables that remained significantly associated with an increased risk of ischemic stroke were age (hazard ratio [HR], 1.06) and alcohol-related hospitalization (HR, 2.01). Use of oral anticoagulants was associated with a lower risk of ischemic stroke (HR, 0.78).

"Even though these patients are classified as low-risk, the incidence of ischemic stroke in our study population is neither negligible nor ignorable, and it carries a relatively high mortality," said Dr. Al-Khalili.

"Previous studies have shown a causal and dose-response relation between alcohol and AF. Our study found that alcohol is an independent risk factor for stroke in patients with AF. Alcohol might induce AF, leading to embolic stroke, or there could be a specific alcohol effect that causes systemic or cerebral thromboembolism. Using alcohol-related hospitalization as a proxy for alcohol abuse likely underestimates the extent of the problem and does not allow grading of the amount of alcohol consumed.

"Doctors should ask their AF patients about alcohol use and advise patients to cut down if they are drinking more than is recommended. The beneficial link between oral anticoagulant use and ischemic stroke in this low-risk population without a recognized indication for these drugs needs further investigation, including the benefit to harm (bleeding) ratio," Dr. Al-Khalili concluded.

New Oral Anticoagulants Provide Same Stroke Prevention as Warfarin But Cause Less Bleeding
The new oral anticoagulants provide the same stroke prevention as warfarin, but cause less intracranial bleeding, according to research presented by Laila Staerk, PhD, a research fellow at Herlev and Gentofte University Hospital in Hellerup, Denmark.

"Atrial fibrillation is the most common cardiac rhythm disorder and currently affects more than 10 million Europeans," said Dr. Staerk. "Atrial fibrillation is associated with a fivefold risk of stroke, potentially leading to disability and death. In the next four decades, the number of patients with atrial fibrillation is expected to triple, so the number of Europeans diagnosed could rise to a staggering 25 to 30 million."

Patients with atrial fibrillation are treated life-long with oral anticoagulation to reduce their risk of stroke. But treatment with non-vitamin K antagonist oral anticoagulants (NOACs) and vitamin K antagonists (eg, warfarin) lowers the risk of stroke at the cost of increased bleeding risk.  

Several treatment options are available, and physicians may be unsure about which one to use. "There has been a need to investigate the safety and effectiveness of NOACs versus warfarin in a real-world population, and our Danish registries provide this opportunity," said Dr. Staerk.

The current study compared the risk of stroke and intracranial bleeding associated with NOACs (ie, dabigatran, rivaroxaban, and apixaban) versus that associated with warfarin in a real-world setting. The study was conducted at the Cardiovascular Research Centre at Herlev and Gentofte University Hospital. It included 43,299 patients with atrial fibrillation who were recruited from Danish nationwide administrative registries.

Approximately 42% of patients were taking warfarin, while 29%, 16%, and 13% were taking dabigatran, apixaban, and rivaroxaban, respectively. During follow-up, stroke occurred in 1,054 patients, and there were 261 intracranial bleedings.

The risk of having a stroke within one year was similar between the NOAC and warfarin groups and ranged from 2.0% to 2.5%. At one year, the risk of intracranial bleeding was significantly lower in patients treated with dabigatran and apixaban (0.3% to 0.4%), compared with that in those treated with warfarin (0.6%).

"The inclusion and exclusion criteria in our study were broadly similar for patients initiating NOACs or warfarin, and this gave a straightforward opportunity to directly compare the treatment regimens, which is in contrast to the randomized trials. The results suggest that although they have similar effects in preventing stroke, dabigatran and apixaban were associated with a safer use regarding the absolute one-year risk of intracranial bleeding," said Dr Staerk. "Our results complement the large randomized phase III trials by providing real-world data on stroke and intracranial bleeding with NOACs versus warfarin, since fragile patients were not excluded from our nationwide cohort. For example, patients with increased risk of bleeding, liver disease, and chronic kidney disease are less represented in trials."

"Registry studies have some limitations such as the observational design, residual confounding, and confounding by drug indication. In the future, it would be exciting to see a head-to-head randomized trial performed to compare the different NOAC treatments in patients with atrial fibrillation," said Dr Staerk.

Moderate Physical Activity Reduces Risk of Cardiovascular Death
Moderate physical activity is associated with a greater than 50% reduction in cardiovascular death in people older than 65, according to Riitta Antikainen, MD, Professor of Geriatrics at the University of Oulu in Finland. "These results prompt us to investigate the mechanisms through which the Mediterranean diet may protect against death," she said.

The 12-year study in nearly 2,500 adults between ages 65 and 74 found that moderate physical activity reduced the risk of an acute cardiovascular event by more than 30%. High levels of physical activity led to greater risk reductions.

"The role of physical activity in preventing cardiovascular disease [CVD] in people of working age is well established," said Dr. Antikainen. "But relatively little is known about the effect of regular physical activity on CVD risk in older people."

The present study assessed the association between leisure time physical activity and CVD risk and mortality in 2,456 men and women who were enrolled into the National FINRISK Study between 1997 and 2007.

Baseline data collection included self-administered questionnaires on physical activity and other health related behavior, clinical measurements (eg, blood pressure, weight, and height), and laboratory measurements, including serum cholesterol. Participants were followed up until the end of 2013. Deaths were recorded from the National Causes of Death Register, and incident CVD events (ie, coronary heart disease and stroke) were collected from the National Hospital Discharge register.

The researchers classified self-reported physical activity as low, moderate, or high. Low physical activity included reading, watching TV, and working in the household without much physical activity. Moderate physical activity encompassed walking, cycling, or practicing other forms of light exercise (eg, fishing, gardening, hunting) for at least four hours per week. High physical activity included recreational sports (eg, running, jogging, skiing, gymnastics, swimming, or ball games) or intense training or sports competitions for at least three hours per week.  

During a median follow-up of 11.8 years, 197 participants died from CVD, and 416 had a first CVD event.

When the researchers assessed the link between physical activity and outcome, they adjusted for other cardiovascular risk factors (ie, blood pressure, smoking, and cholesterol) and social factors (ie, marital status and education). To minimize reverse causality, where worse health leads to less physical activity, patients with coronary heart disease, heart failure, cancer, or prior stroke at baseline were excluded from the analysis.

The investigators found that moderate and high leisure-time physical activity were associated with a 31% and 45% reduced risk of an acute CVD event, respectively. Moderate and high leisure-time physical activity were associated with a 54% and 66% reduction in CVD mortality, respectively.

"Our study provides further evidence that older adults who are physically active have a lower risk of coronary heart disease, stroke, and death from cardiovascular disease. The protective effect of leisure time physical activity is dose dependent. In other words, the more you do, the better. Activity is protective even if you have other risk factors for cardiovascular disease such as high cholesterol," said Dr. Antikainen.  

"Physical exercise may become more challenging with aging. However, it is important for older people to still get enough safe physical activity to stay healthy after their transition to retirement."         

The National Institutes of Health has released a 10-year road map for optimizing youth suicide prevention efforts.

The abridged version of the final report from a March 2016 NIH Pathways to Prevention Workshop entitled “Advancing Research to Prevent Youth Suicide,” highlights strategies for guiding the next decade of research on youth suicide prevention, Todd D. Little, PhD, from Texas Tech University, Lubbock, and his colleagues reported online Oct. 3.

The article outlines 29 recommendations aimed at improving data systems, enhancing data collection and analysis, and strengthening the research and practice community, and calls on researchers and practitioners to “unite to stop youth suicide in order to circumvent its associated economic cost and devastating pain and suffering” (Ann Intern Med. 2016 Oct 4. doi: 10.7326/M16-1568).

“Adherence to the recommendations summarized herein provides us with a road map to our ultimate goal – eliminating suicide,” the authors concluded.

In an accompanying evidence review, Holly C. Wilcox, PhD, and her colleagues from Johns Hopkins University, Baltimore, identified studies and potentially linkable external data systems with suicide outcomes and concluded that community data systems should be linked to suicide prevention data for the purpose of evaluating and enhancing prevention efforts.

“By integrating data from health care delivery systems, health insurance systems, and other populationwide data sources ... a national health research data infrastructure could be developed,” they wrote, adding that such a “national resource” could facilitate linkage with suicide prevention data (Ann Intern Med. 2016 Oct 4. doi: 10.7326/M16-1281).

During a press telebriefing on the panel’s findings, Dr. Little, who served as panel and workshop chair, stressed that suicide is the second-leading cause of death among youth aged 10 to 24 years, and in young adults aged 25 to 34 years.

“Although these numbers are disheartening, we feel that suicide prevention is possible. New research strategies that embrace the complex factors involved in suicide can be coordinated and are necessary,” he said, adding that “the complexity of suicide prevention must be embraced in order to forge new research strategies,” and that researchers and practitioners must work together and with the larger “policy, practice, and research communities” to promote data sharing and stop youth suicide.

Dr. Little also noted the importance of destigmatizing suicide attempts and suicidal behavior to remove one of the roadblocks to reporting, which in turn will increase the available data for linkage.

The linkage of data from various sources, such as emergency departments, electronic health records, Medicaid, and Medicare, is particularly important for informing future prevention efforts, said panelist Leslie-Ann Byam, project director for the Families First Project at Evidence-Based Associates in Washington.

Continuing to work in the field and to work with young people without having information that encompasses that kind of data leaves practitioners at a disadvantage in terms of planning, she said.

Panelist Kathleen M. Roche, PhD, of George Washington University in Washington, stressed the importance of obtaining data on subpopulations of youth at very elevated risk of suicide, including transgender youth, Latinas, and Native Americans.

The NIH workshop was cosponsored by the NIH Office of Disease Prevention, the National Institute of Mental Health, the National Institute on Drug Abuse, and the National Center for Complementary and Integrative Health. Individual authors were supported by grants from the National Science Foundation; the NIH; the Penn State Quantitative Social Sciences Initiative; the Institute for Measurement, Methodology, Analysis, and Policy at Texas Tech University; and the National Center for Advancing Translational Sciences. Dr. Little reported receiving fees from Yhat Enterprises outside the submitted work. The evidence review was funded by the Agency for Healthcare Research and Quality. The review authors reported having no disclosures.

[email protected]

The National Institutes of Health has released a 10-year road map for optimizing youth suicide prevention efforts.

The abridged version of the final report from a March 2016 NIH Pathways to Prevention Workshop entitled “Advancing Research to Prevent Youth Suicide,” highlights strategies for guiding the next decade of research on youth suicide prevention, Todd D. Little, PhD, from Texas Tech University, Lubbock, and his colleagues reported online Oct. 3.

The article outlines 29 recommendations aimed at improving data systems, enhancing data collection and analysis, and strengthening the research and practice community, and calls on researchers and practitioners to “unite to stop youth suicide in order to circumvent its associated economic cost and devastating pain and suffering” (Ann Intern Med. 2016 Oct 4. doi: 10.7326/M16-1568).

“Adherence to the recommendations summarized herein provides us with a road map to our ultimate goal – eliminating suicide,” the authors concluded.

In an accompanying evidence review, Holly C. Wilcox, PhD, and her colleagues from Johns Hopkins University, Baltimore, identified studies and potentially linkable external data systems with suicide outcomes and concluded that community data systems should be linked to suicide prevention data for the purpose of evaluating and enhancing prevention efforts.

“By integrating data from health care delivery systems, health insurance systems, and other populationwide data sources ... a national health research data infrastructure could be developed,” they wrote, adding that such a “national resource” could facilitate linkage with suicide prevention data (Ann Intern Med. 2016 Oct 4. doi: 10.7326/M16-1281).

During a press telebriefing on the panel’s findings, Dr. Little, who served as panel and workshop chair, stressed that suicide is the second-leading cause of death among youth aged 10 to 24 years, and in young adults aged 25 to 34 years.

“Although these numbers are disheartening, we feel that suicide prevention is possible. New research strategies that embrace the complex factors involved in suicide can be coordinated and are necessary,” he said, adding that “the complexity of suicide prevention must be embraced in order to forge new research strategies,” and that researchers and practitioners must work together and with the larger “policy, practice, and research communities” to promote data sharing and stop youth suicide.

Dr. Little also noted the importance of destigmatizing suicide attempts and suicidal behavior to remove one of the roadblocks to reporting, which in turn will increase the available data for linkage.

The linkage of data from various sources, such as emergency departments, electronic health records, Medicaid, and Medicare, is particularly important for informing future prevention efforts, said panelist Leslie-Ann Byam, project director for the Families First Project at Evidence-Based Associates in Washington.

Continuing to work in the field and to work with young people without having information that encompasses that kind of data leaves practitioners at a disadvantage in terms of planning, she said.

Panelist Kathleen M. Roche, PhD, of George Washington University in Washington, stressed the importance of obtaining data on subpopulations of youth at very elevated risk of suicide, including transgender youth, Latinas, and Native Americans.

The NIH workshop was cosponsored by the NIH Office of Disease Prevention, the National Institute of Mental Health, the National Institute on Drug Abuse, and the National Center for Complementary and Integrative Health. Individual authors were supported by grants from the National Science Foundation; the NIH; the Penn State Quantitative Social Sciences Initiative; the Institute for Measurement, Methodology, Analysis, and Policy at Texas Tech University; and the National Center for Advancing Translational Sciences. Dr. Little reported receiving fees from Yhat Enterprises outside the submitted work. The evidence review was funded by the Agency for Healthcare Research and Quality. The review authors reported having no disclosures.

[email protected]

The National Institutes of Health has released a 10-year road map for optimizing youth suicide prevention efforts.

The abridged version of the final report from a March 2016 NIH Pathways to Prevention Workshop entitled “Advancing Research to Prevent Youth Suicide,” highlights strategies for guiding the next decade of research on youth suicide prevention, Todd D. Little, PhD, from Texas Tech University, Lubbock, and his colleagues reported online Oct. 3.

The article outlines 29 recommendations aimed at improving data systems, enhancing data collection and analysis, and strengthening the research and practice community, and calls on researchers and practitioners to “unite to stop youth suicide in order to circumvent its associated economic cost and devastating pain and suffering” (Ann Intern Med. 2016 Oct 4. doi: 10.7326/M16-1568).

“Adherence to the recommendations summarized herein provides us with a road map to our ultimate goal – eliminating suicide,” the authors concluded.

In an accompanying evidence review, Holly C. Wilcox, PhD, and her colleagues from Johns Hopkins University, Baltimore, identified studies and potentially linkable external data systems with suicide outcomes and concluded that community data systems should be linked to suicide prevention data for the purpose of evaluating and enhancing prevention efforts.

“By integrating data from health care delivery systems, health insurance systems, and other populationwide data sources ... a national health research data infrastructure could be developed,” they wrote, adding that such a “national resource” could facilitate linkage with suicide prevention data (Ann Intern Med. 2016 Oct 4. doi: 10.7326/M16-1281).

During a press telebriefing on the panel’s findings, Dr. Little, who served as panel and workshop chair, stressed that suicide is the second-leading cause of death among youth aged 10 to 24 years, and in young adults aged 25 to 34 years.

“Although these numbers are disheartening, we feel that suicide prevention is possible. New research strategies that embrace the complex factors involved in suicide can be coordinated and are necessary,” he said, adding that “the complexity of suicide prevention must be embraced in order to forge new research strategies,” and that researchers and practitioners must work together and with the larger “policy, practice, and research communities” to promote data sharing and stop youth suicide.

Dr. Little also noted the importance of destigmatizing suicide attempts and suicidal behavior to remove one of the roadblocks to reporting, which in turn will increase the available data for linkage.

The linkage of data from various sources, such as emergency departments, electronic health records, Medicaid, and Medicare, is particularly important for informing future prevention efforts, said panelist Leslie-Ann Byam, project director for the Families First Project at Evidence-Based Associates in Washington.

Continuing to work in the field and to work with young people without having information that encompasses that kind of data leaves practitioners at a disadvantage in terms of planning, she said.

Panelist Kathleen M. Roche, PhD, of George Washington University in Washington, stressed the importance of obtaining data on subpopulations of youth at very elevated risk of suicide, including transgender youth, Latinas, and Native Americans.

The NIH workshop was cosponsored by the NIH Office of Disease Prevention, the National Institute of Mental Health, the National Institute on Drug Abuse, and the National Center for Complementary and Integrative Health. Individual authors were supported by grants from the National Science Foundation; the NIH; the Penn State Quantitative Social Sciences Initiative; the Institute for Measurement, Methodology, Analysis, and Policy at Texas Tech University; and the National Center for Advancing Translational Sciences. Dr. Little reported receiving fees from Yhat Enterprises outside the submitted work. The evidence review was funded by the Agency for Healthcare Research and Quality. The review authors reported having no disclosures.

[email protected]

Individuals with type 2 diabetes should receive the seasonal influenza vaccines annually, as doing so significantly mitigates their chances of being hospitalized for – or dying from – cardiovascular complications such as stroke, heart failure, and myocardial infarction.

“Studies assessing influenza vaccine effectiveness in people with diabetes are scarce and have shown inconclusive results,” wrote Eszter P. Vamos, MD, PhD, of Imperial College London and her coauthors in a study published in the Canadian Medical Association Journal. “None of the previous studies adjusted for residual confounding, and most of them reported composite endpoints such as admission to hospital for any cause.”

lisafx/istockphoto.com

[email protected]

Individuals with type 2 diabetes should receive the seasonal influenza vaccines annually, as doing so significantly mitigates their chances of being hospitalized for – or dying from – cardiovascular complications such as stroke, heart failure, and myocardial infarction.

“Studies assessing influenza vaccine effectiveness in people with diabetes are scarce and have shown inconclusive results,” wrote Eszter P. Vamos, MD, PhD, of Imperial College London and her coauthors in a study published in the Canadian Medical Association Journal. “None of the previous studies adjusted for residual confounding, and most of them reported composite endpoints such as admission to hospital for any cause.”

lisafx/istockphoto.com

[email protected]

Individuals with type 2 diabetes should receive the seasonal influenza vaccines annually, as doing so significantly mitigates their chances of being hospitalized for – or dying from – cardiovascular complications such as stroke, heart failure, and myocardial infarction.

“Studies assessing influenza vaccine effectiveness in people with diabetes are scarce and have shown inconclusive results,” wrote Eszter P. Vamos, MD, PhD, of Imperial College London and her coauthors in a study published in the Canadian Medical Association Journal. “None of the previous studies adjusted for residual confounding, and most of them reported composite endpoints such as admission to hospital for any cause.”

lisafx/istockphoto.com

[email protected]

At the end of my junior surgical residency years, I was in a pretty bad physical and mental space. With resident coverage shortages, long hours, chronic fatigue, and personal pressures to perform and shine, I wound up digging myself into a hole, heading straight to resident burnout. Although there were others around me experiencing similar environmental stressors, I certainly felt alone – not knowing how to climb out of the hole I created for myself.

This was probably the lowest I have been in my life, but I finally got myself back on track. Coming from a fairly physically active background, I returned to a life of proper nutrition and physical activity. I began swimming, biking, and running, with the hopes of maybe one day doing a triathlon. There were a few health care professionals at my institution who competed in yearly triathlons, which certainly inspired me to take up the sport. So, last August, I signed up for my first Half-IRONMAN in Mont-Tremblant, Quebec, and had roughly 10 months to train. Looking back, I am not sure what possessed me to think I could achieve such a feat, but it was certainly a goal to work toward.

Courtesy Laura Drudi

At the end of my junior surgical residency years, I was in a pretty bad physical and mental space. With resident coverage shortages, long hours, chronic fatigue, and personal pressures to perform and shine, I wound up digging myself into a hole, heading straight to resident burnout. Although there were others around me experiencing similar environmental stressors, I certainly felt alone – not knowing how to climb out of the hole I created for myself.

This was probably the lowest I have been in my life, but I finally got myself back on track. Coming from a fairly physically active background, I returned to a life of proper nutrition and physical activity. I began swimming, biking, and running, with the hopes of maybe one day doing a triathlon. There were a few health care professionals at my institution who competed in yearly triathlons, which certainly inspired me to take up the sport. So, last August, I signed up for my first Half-IRONMAN in Mont-Tremblant, Quebec, and had roughly 10 months to train. Looking back, I am not sure what possessed me to think I could achieve such a feat, but it was certainly a goal to work toward.

Courtesy Laura Drudi

At the end of my junior surgical residency years, I was in a pretty bad physical and mental space. With resident coverage shortages, long hours, chronic fatigue, and personal pressures to perform and shine, I wound up digging myself into a hole, heading straight to resident burnout. Although there were others around me experiencing similar environmental stressors, I certainly felt alone – not knowing how to climb out of the hole I created for myself.

This was probably the lowest I have been in my life, but I finally got myself back on track. Coming from a fairly physically active background, I returned to a life of proper nutrition and physical activity. I began swimming, biking, and running, with the hopes of maybe one day doing a triathlon. There were a few health care professionals at my institution who competed in yearly triathlons, which certainly inspired me to take up the sport. So, last August, I signed up for my first Half-IRONMAN in Mont-Tremblant, Quebec, and had roughly 10 months to train. Looking back, I am not sure what possessed me to think I could achieve such a feat, but it was certainly a goal to work toward.

Courtesy Laura Drudi

The Nuremberg Code in 1947,¹ the Declaration of Helsinki in 1964,² and the Belmont Report in 1979³ were cornerstones in the establishment of ethical principles in the medical field. These documents specifically highlight the concept of informed consent, which maintains that to practice ethical medicine, physicians must fully inform patients of all therapeutic benefits and especially risks as well as treatment alternatives before they consent to therapeutic intervention. Educating patients about risks of treatment is obligatory. Risk communication involves a mutual exchange of information between physicians and patients; the physician presents risk information in an understandable manner that adequately conveys pertinent data that is critical for the patient to make an informed therapeutic decision.⁴

An inherent problem with risk education is that patients may be terrified about risks associated with treatment. Some patients will refuse needed treatment because of fear.⁵ When patients have concerns about the safety profile of a treatment regimen and potential adverse effects, they may be less compliant with treatment.⁶ The intelligent noncompliance phenomenon occurs when a patient knowingly makes the choice to not adhere to treatment, and concern regarding treatment risks relative to benefits is a common reason underlying this phenomenon.^7,8

Behavioral economists have studied how individuals weigh risks. Kahneman and Tversky’s⁹ prospect theory asserts that individuals tend to overweigh unlikely risks and underweigh more certain risks, which they call the certainty effect; it is the basis of the human tendency to avoid risks in situations of likely gain and to pursue risks in situations of likely loss. The tendency to overweigh rare risks is even more pronounced for affect-rich events such as serious side effects.¹⁰ The way data are presented can affect how patients interpret the information. Context and framing of data affect patients’ perceptions.¹¹ We describe several ways to present safety data using graphical presentation of psoriasis treatment safety data as an example and explain how each one can affect patients’ perception of treatment risks.

Approaches to Presenting Safety Data

There are numerous ways to present safety data to patients, including verbal, numeric, and visual strategies.¹² Many methods of presentation are a combination of these strategies. Graphs are visual strategies to further categorize and present numeric data, and physicians may choose to incorporate these aids when presenting safety information to patients. Graphical presentations give the patient a mental picture of the data. Numerous types of graphs can be constructed. Kalb et al¹³ determined the effect of psoriasis treatment on the risk of serious infection from the Psoriasis Longitudinal Assessment and Registry (PSOLAR). We used the results from this study to demonstrate multiple ways of presenting safety data (Figures 1–3).

A graphical presentation with a truncated y-axis is a common approach (Figure 1). Graphs with truncated axes are sometimes used to conserve space or to accentuate certain differences in the graph that would otherwise be less obvious without the zoomed in y-axis.¹⁴ These graphs present quantitatively accurate information that can be visually misleading at the same time. Truncated axes accentuate differences, creating mental impressions that are not reflective of the magnitude of the numeric differences. Alternatively, a graph with a full y-axis includes both the maximum and minimum data values on the y-axis (Figure 2). The y-axis also extends maximally to the total number of patients or patient-years studied. This type of graph presents all of the numeric data without distortion.

Focus on the Patients Who Do Not Have Adverse Effects of Treatments

Fear of adverse effects is one of the most commonly reported causes of poor treatment adherence.¹⁵ New therapies for psoriasis are highly effective and safe, but as with all treatments, they also are associated with some risks. Patients may latch onto those risks too tightly or perhaps, in other circumstances, not tightly enough. The method used by a physician to present safety data to a patient may determine the patient’s perception about treatments.

When trying to give patients an accurate impression of treatment risks, it may be helpful to avoid approaches that focus on presenting the (few) cases of severe adverse drug effects since patients (and physicians) are likely to overweigh the unlikely risk of having an adverse effect if presented with this information. It may be more reassuring to focus on presenting information about the chance of not having an adverse drug effect, assuming the physician’s goal is to be reassuring.

Poor communication with patients when presenting safety data can foster exaggerated fears of an unlikely consequence to the point that patients can be left undertreated and sustaining disease symptoms.¹⁶ Physicians may strive to do no harm to their patients, but without careful presentation of safety data in the process of helping the patient make an informed decision, it is possible to do mental harm to patients in the form of fear or even, in the case of nonadherence or treatment refusal, physical harm in the form of continued disease symptoms.

One limitation of this review is that we only used graphical presentation of data as an example. Similar concerns apply to numerical data presentation. Telling a patient the risk of a severe adverse reaction is doubled by a certain treatment may be terrifying, though if the baseline risk is rare, doubling the baseline risk may represent only a minimal increase in the absolute risk. Telling a patient the risk is only 1 in 1000 may still be alarming because many patients tend to focus on the 1, but telling a patient that 999 of 1000 patients do not have a problem can be much more reassuring.

The physician’s goal—to help patients make informed decisions about their treatment—calls for him/her to assimilate safety data into useful information that the patient can use to make an informed decision.¹⁷ Overly comforting or alarming, confusing, and inaccurate information can misguide the patient, violating the ethical principle of nonmaleficence. Although there is an obligation to educate patients about risks, there may not be a purely objective way to do it. When physicians present objective data to patients, whether in numerical or graphical form, there will be an unavoidable subjective interpretation of the data. The form of presentation will have a critical effect on patients’ subjective perceptions. Physicians can present objective data in such a way as to be reassuring or frightening.

Conclusion

Despite physicians’ best-intentioned efforts, it may be impossible to avoid presenting safety data in a way that will be subjectively interpreted by patients. Physicians have a choice in how they present data to patients; their best judgment should be used in how they present data to inform patients, guide them, and offer them the best treatment outcomes.

Acknowledgment

We thank Scott Jaros, BA (Winston-Salem, North Carolina), for his assistance in the revision of the manuscript.

The Nuremberg Code in 1947,¹ the Declaration of Helsinki in 1964,² and the Belmont Report in 1979³ were cornerstones in the establishment of ethical principles in the medical field. These documents specifically highlight the concept of informed consent, which maintains that to practice ethical medicine, physicians must fully inform patients of all therapeutic benefits and especially risks as well as treatment alternatives before they consent to therapeutic intervention. Educating patients about risks of treatment is obligatory. Risk communication involves a mutual exchange of information between physicians and patients; the physician presents risk information in an understandable manner that adequately conveys pertinent data that is critical for the patient to make an informed therapeutic decision.⁴

An inherent problem with risk education is that patients may be terrified about risks associated with treatment. Some patients will refuse needed treatment because of fear.⁵ When patients have concerns about the safety profile of a treatment regimen and potential adverse effects, they may be less compliant with treatment.⁶ The intelligent noncompliance phenomenon occurs when a patient knowingly makes the choice to not adhere to treatment, and concern regarding treatment risks relative to benefits is a common reason underlying this phenomenon.^7,8

Behavioral economists have studied how individuals weigh risks. Kahneman and Tversky’s⁹ prospect theory asserts that individuals tend to overweigh unlikely risks and underweigh more certain risks, which they call the certainty effect; it is the basis of the human tendency to avoid risks in situations of likely gain and to pursue risks in situations of likely loss. The tendency to overweigh rare risks is even more pronounced for affect-rich events such as serious side effects.¹⁰ The way data are presented can affect how patients interpret the information. Context and framing of data affect patients’ perceptions.¹¹ We describe several ways to present safety data using graphical presentation of psoriasis treatment safety data as an example and explain how each one can affect patients’ perception of treatment risks.

Approaches to Presenting Safety Data

There are numerous ways to present safety data to patients, including verbal, numeric, and visual strategies.¹² Many methods of presentation are a combination of these strategies. Graphs are visual strategies to further categorize and present numeric data, and physicians may choose to incorporate these aids when presenting safety information to patients. Graphical presentations give the patient a mental picture of the data. Numerous types of graphs can be constructed. Kalb et al¹³ determined the effect of psoriasis treatment on the risk of serious infection from the Psoriasis Longitudinal Assessment and Registry (PSOLAR). We used the results from this study to demonstrate multiple ways of presenting safety data (Figures 1–3).

A graphical presentation with a truncated y-axis is a common approach (Figure 1). Graphs with truncated axes are sometimes used to conserve space or to accentuate certain differences in the graph that would otherwise be less obvious without the zoomed in y-axis.¹⁴ These graphs present quantitatively accurate information that can be visually misleading at the same time. Truncated axes accentuate differences, creating mental impressions that are not reflective of the magnitude of the numeric differences. Alternatively, a graph with a full y-axis includes both the maximum and minimum data values on the y-axis (Figure 2). The y-axis also extends maximally to the total number of patients or patient-years studied. This type of graph presents all of the numeric data without distortion.

Focus on the Patients Who Do Not Have Adverse Effects of Treatments

Fear of adverse effects is one of the most commonly reported causes of poor treatment adherence.¹⁵ New therapies for psoriasis are highly effective and safe, but as with all treatments, they also are associated with some risks. Patients may latch onto those risks too tightly or perhaps, in other circumstances, not tightly enough. The method used by a physician to present safety data to a patient may determine the patient’s perception about treatments.

When trying to give patients an accurate impression of treatment risks, it may be helpful to avoid approaches that focus on presenting the (few) cases of severe adverse drug effects since patients (and physicians) are likely to overweigh the unlikely risk of having an adverse effect if presented with this information. It may be more reassuring to focus on presenting information about the chance of not having an adverse drug effect, assuming the physician’s goal is to be reassuring.

Poor communication with patients when presenting safety data can foster exaggerated fears of an unlikely consequence to the point that patients can be left undertreated and sustaining disease symptoms.¹⁶ Physicians may strive to do no harm to their patients, but without careful presentation of safety data in the process of helping the patient make an informed decision, it is possible to do mental harm to patients in the form of fear or even, in the case of nonadherence or treatment refusal, physical harm in the form of continued disease symptoms.

One limitation of this review is that we only used graphical presentation of data as an example. Similar concerns apply to numerical data presentation. Telling a patient the risk of a severe adverse reaction is doubled by a certain treatment may be terrifying, though if the baseline risk is rare, doubling the baseline risk may represent only a minimal increase in the absolute risk. Telling a patient the risk is only 1 in 1000 may still be alarming because many patients tend to focus on the 1, but telling a patient that 999 of 1000 patients do not have a problem can be much more reassuring.

The physician’s goal—to help patients make informed decisions about their treatment—calls for him/her to assimilate safety data into useful information that the patient can use to make an informed decision.¹⁷ Overly comforting or alarming, confusing, and inaccurate information can misguide the patient, violating the ethical principle of nonmaleficence. Although there is an obligation to educate patients about risks, there may not be a purely objective way to do it. When physicians present objective data to patients, whether in numerical or graphical form, there will be an unavoidable subjective interpretation of the data. The form of presentation will have a critical effect on patients’ subjective perceptions. Physicians can present objective data in such a way as to be reassuring or frightening.

Conclusion

Despite physicians’ best-intentioned efforts, it may be impossible to avoid presenting safety data in a way that will be subjectively interpreted by patients. Physicians have a choice in how they present data to patients; their best judgment should be used in how they present data to inform patients, guide them, and offer them the best treatment outcomes.

Acknowledgment

We thank Scott Jaros, BA (Winston-Salem, North Carolina), for his assistance in the revision of the manuscript.

The Nuremberg Code in 1947,¹ the Declaration of Helsinki in 1964,² and the Belmont Report in 1979³ were cornerstones in the establishment of ethical principles in the medical field. These documents specifically highlight the concept of informed consent, which maintains that to practice ethical medicine, physicians must fully inform patients of all therapeutic benefits and especially risks as well as treatment alternatives before they consent to therapeutic intervention. Educating patients about risks of treatment is obligatory. Risk communication involves a mutual exchange of information between physicians and patients; the physician presents risk information in an understandable manner that adequately conveys pertinent data that is critical for the patient to make an informed therapeutic decision.⁴

An inherent problem with risk education is that patients may be terrified about risks associated with treatment. Some patients will refuse needed treatment because of fear.⁵ When patients have concerns about the safety profile of a treatment regimen and potential adverse effects, they may be less compliant with treatment.⁶ The intelligent noncompliance phenomenon occurs when a patient knowingly makes the choice to not adhere to treatment, and concern regarding treatment risks relative to benefits is a common reason underlying this phenomenon.^7,8

Behavioral economists have studied how individuals weigh risks. Kahneman and Tversky’s⁹ prospect theory asserts that individuals tend to overweigh unlikely risks and underweigh more certain risks, which they call the certainty effect; it is the basis of the human tendency to avoid risks in situations of likely gain and to pursue risks in situations of likely loss. The tendency to overweigh rare risks is even more pronounced for affect-rich events such as serious side effects.¹⁰ The way data are presented can affect how patients interpret the information. Context and framing of data affect patients’ perceptions.¹¹ We describe several ways to present safety data using graphical presentation of psoriasis treatment safety data as an example and explain how each one can affect patients’ perception of treatment risks.

Approaches to Presenting Safety Data

There are numerous ways to present safety data to patients, including verbal, numeric, and visual strategies.¹² Many methods of presentation are a combination of these strategies. Graphs are visual strategies to further categorize and present numeric data, and physicians may choose to incorporate these aids when presenting safety information to patients. Graphical presentations give the patient a mental picture of the data. Numerous types of graphs can be constructed. Kalb et al¹³ determined the effect of psoriasis treatment on the risk of serious infection from the Psoriasis Longitudinal Assessment and Registry (PSOLAR). We used the results from this study to demonstrate multiple ways of presenting safety data (Figures 1–3).

A graphical presentation with a truncated y-axis is a common approach (Figure 1). Graphs with truncated axes are sometimes used to conserve space or to accentuate certain differences in the graph that would otherwise be less obvious without the zoomed in y-axis.¹⁴ These graphs present quantitatively accurate information that can be visually misleading at the same time. Truncated axes accentuate differences, creating mental impressions that are not reflective of the magnitude of the numeric differences. Alternatively, a graph with a full y-axis includes both the maximum and minimum data values on the y-axis (Figure 2). The y-axis also extends maximally to the total number of patients or patient-years studied. This type of graph presents all of the numeric data without distortion.

Focus on the Patients Who Do Not Have Adverse Effects of Treatments

Fear of adverse effects is one of the most commonly reported causes of poor treatment adherence.¹⁵ New therapies for psoriasis are highly effective and safe, but as with all treatments, they also are associated with some risks. Patients may latch onto those risks too tightly or perhaps, in other circumstances, not tightly enough. The method used by a physician to present safety data to a patient may determine the patient’s perception about treatments.

When trying to give patients an accurate impression of treatment risks, it may be helpful to avoid approaches that focus on presenting the (few) cases of severe adverse drug effects since patients (and physicians) are likely to overweigh the unlikely risk of having an adverse effect if presented with this information. It may be more reassuring to focus on presenting information about the chance of not having an adverse drug effect, assuming the physician’s goal is to be reassuring.

Poor communication with patients when presenting safety data can foster exaggerated fears of an unlikely consequence to the point that patients can be left undertreated and sustaining disease symptoms.¹⁶ Physicians may strive to do no harm to their patients, but without careful presentation of safety data in the process of helping the patient make an informed decision, it is possible to do mental harm to patients in the form of fear or even, in the case of nonadherence or treatment refusal, physical harm in the form of continued disease symptoms.

One limitation of this review is that we only used graphical presentation of data as an example. Similar concerns apply to numerical data presentation. Telling a patient the risk of a severe adverse reaction is doubled by a certain treatment may be terrifying, though if the baseline risk is rare, doubling the baseline risk may represent only a minimal increase in the absolute risk. Telling a patient the risk is only 1 in 1000 may still be alarming because many patients tend to focus on the 1, but telling a patient that 999 of 1000 patients do not have a problem can be much more reassuring.

The physician’s goal—to help patients make informed decisions about their treatment—calls for him/her to assimilate safety data into useful information that the patient can use to make an informed decision.¹⁷ Overly comforting or alarming, confusing, and inaccurate information can misguide the patient, violating the ethical principle of nonmaleficence. Although there is an obligation to educate patients about risks, there may not be a purely objective way to do it. When physicians present objective data to patients, whether in numerical or graphical form, there will be an unavoidable subjective interpretation of the data. The form of presentation will have a critical effect on patients’ subjective perceptions. Physicians can present objective data in such a way as to be reassuring or frightening.

Conclusion

Despite physicians’ best-intentioned efforts, it may be impossible to avoid presenting safety data in a way that will be subjectively interpreted by patients. Physicians have a choice in how they present data to patients; their best judgment should be used in how they present data to inform patients, guide them, and offer them the best treatment outcomes.

Acknowledgment

We thank Scott Jaros, BA (Winston-Salem, North Carolina), for his assistance in the revision of the manuscript.

Psoriasis was not consistently associated with adverse pregnancy outcomes across nine studies in a systematic review of the literature, but four of the studies reported significant increases in at least one adverse outcome among women with psoriasis, according to a report in the British Journal of Dermatology.

Many women with psoriasis develop the disorder during their reproductive years, and more than 100,000 births to such patients are estimated to occur in the United States each year. Other autoimmune diseases are known to adversely affect pregnancy outcomes, but the issue has not been well studied among women with psoriasis, said Robert Bobotsis, a medical student at Western University, London (Ont.), and his associates.

They performed a systematic review of the literature to examine a possible link, but were only able to find nine fair- or good-quality studies involving a total of 4,756 pregnancies from which to extract data concerning a possible association. This small sample size may have been underpowered to detect the uncommon adverse pregnancy outcomes being assessed. Moreover, the investigators were unable to conduct a meta-analysis pooling the data because the effect measures were inconsistent across the nine studies, Mr. Bobotsis and his associates noted.

The review included a retrospective case series, a retrospective case control study, three retrospective cohort studies, two prospective cohort studies, one cross-sectional study, and one study combining prospective and retrospective cohorts. It “did not demonstrate an increased risk of poor outcomes in pregnant women with psoriasis” (Br J Dermatol. 2016 Jul 24;175:464-72).

However, four studies showed that compared with women who didn’t have psoriasis, those who did were at significantly increased risk for spontaneous abortion, cesarean delivery, low birth weight, macrosomia, large for gestational age, and prematurity, with odds ratios as high as 5.6. “Our results should be viewed as an opportunity to further research pregnancy outcomes in psoriasis,” the investigators said.

[email protected]

Psoriasis was not consistently associated with adverse pregnancy outcomes across nine studies in a systematic review of the literature, but four of the studies reported significant increases in at least one adverse outcome among women with psoriasis, according to a report in the British Journal of Dermatology.

Many women with psoriasis develop the disorder during their reproductive years, and more than 100,000 births to such patients are estimated to occur in the United States each year. Other autoimmune diseases are known to adversely affect pregnancy outcomes, but the issue has not been well studied among women with psoriasis, said Robert Bobotsis, a medical student at Western University, London (Ont.), and his associates.

They performed a systematic review of the literature to examine a possible link, but were only able to find nine fair- or good-quality studies involving a total of 4,756 pregnancies from which to extract data concerning a possible association. This small sample size may have been underpowered to detect the uncommon adverse pregnancy outcomes being assessed. Moreover, the investigators were unable to conduct a meta-analysis pooling the data because the effect measures were inconsistent across the nine studies, Mr. Bobotsis and his associates noted.

The review included a retrospective case series, a retrospective case control study, three retrospective cohort studies, two prospective cohort studies, one cross-sectional study, and one study combining prospective and retrospective cohorts. It “did not demonstrate an increased risk of poor outcomes in pregnant women with psoriasis” (Br J Dermatol. 2016 Jul 24;175:464-72).

However, four studies showed that compared with women who didn’t have psoriasis, those who did were at significantly increased risk for spontaneous abortion, cesarean delivery, low birth weight, macrosomia, large for gestational age, and prematurity, with odds ratios as high as 5.6. “Our results should be viewed as an opportunity to further research pregnancy outcomes in psoriasis,” the investigators said.

[email protected]

Psoriasis was not consistently associated with adverse pregnancy outcomes across nine studies in a systematic review of the literature, but four of the studies reported significant increases in at least one adverse outcome among women with psoriasis, according to a report in the British Journal of Dermatology.

Many women with psoriasis develop the disorder during their reproductive years, and more than 100,000 births to such patients are estimated to occur in the United States each year. Other autoimmune diseases are known to adversely affect pregnancy outcomes, but the issue has not been well studied among women with psoriasis, said Robert Bobotsis, a medical student at Western University, London (Ont.), and his associates.

They performed a systematic review of the literature to examine a possible link, but were only able to find nine fair- or good-quality studies involving a total of 4,756 pregnancies from which to extract data concerning a possible association. This small sample size may have been underpowered to detect the uncommon adverse pregnancy outcomes being assessed. Moreover, the investigators were unable to conduct a meta-analysis pooling the data because the effect measures were inconsistent across the nine studies, Mr. Bobotsis and his associates noted.

The review included a retrospective case series, a retrospective case control study, three retrospective cohort studies, two prospective cohort studies, one cross-sectional study, and one study combining prospective and retrospective cohorts. It “did not demonstrate an increased risk of poor outcomes in pregnant women with psoriasis” (Br J Dermatol. 2016 Jul 24;175:464-72).

However, four studies showed that compared with women who didn’t have psoriasis, those who did were at significantly increased risk for spontaneous abortion, cesarean delivery, low birth weight, macrosomia, large for gestational age, and prematurity, with odds ratios as high as 5.6. “Our results should be viewed as an opportunity to further research pregnancy outcomes in psoriasis,” the investigators said.

[email protected]

When Jason Vargas, MD, first moved to the Phoenix area 13 years ago, he found an atmosphere of distant relationships between general pediatricians like him, subspecialists, and hospitals. Getting patients a referral to a subspecialist could take months, and communication among providers was often weak, Dr. Vargas said.

Today, things are vastly different thanks in large part to the clinically integrated network of which Dr. Vargas and 950 area providers are a part.

Courtesy Dr. Vargas

Going from splintered to unified

Like most communities, care delivery in the Phoenix area was relatively fractured prior to 2014. To bring everyone together, Phoenix Children’s started with community outreach and education.

A changing payer relationship

As a network, PCCN works with payers to assume the risk that insurers have historically taken. Payers continue to handle the administrative and billing side of the equation, while the network controls the medical management and care coordination of the patient population, Mr. Johnson said.

“We feel we can do it much more efficiently, much more effectively, and we feel it’s better care for the patient when we’re the one controlling that,” he said. “The insurance companies don’t disagree.”

The network partners with Medicaid and commercial payers and has a direct-to-employer agreement with a major employer in conjunction with an adult partner system/network. Early performance efforts by the PCCN have been rewarded by shared savings disbursements from two payers, according to PCCN officials. The network has also met or exceeded state Medicaid pediatric quality targets and consistently contained medical expenses below expected medical cost trends for its managed pediatric populations.

Building a population health model

For more than 2 decades, PFK in Ohio has taken a novel care delivery approach that has focused on value and community partnerships.

Back in 1994, Nationwide Children’s Hospital partnered with community pediatricians to create PFK, a physician/hospital organization with governance shared equally. Today, PFK has assumed full financial and clinical risk for pediatric managed Medicaid enrollees, and is the largest and oldest known pediatric ACO.

Guidance for other practices

Dr. Gleeson encouraged other pediatricians interested in transitioning to value-based care to start by evaluating their data. Take a hard look at the quality of care you provide and begin to measure it, he said. For smaller practices, consider joining a larger group or network that will allow pediatricians to engage in collaborative work, he added.

Dr. Vargas stressed that change is coming whether pediatricians are prepared or not. Aligning with the right partners will be the difference between sinking or staying afloat in the value-based landscape.

“Payers are moving toward value-based models and it is not practical for the general pediatrician to be able to provide the infrastructure and professional resources necessary,” he said. “To maintain our professional livelihood as independent pediatricians, and to continue to provide the individually crafted, quality care our families are accustomed to, we will have to align ourselves with organizations that value the experience and insight of the independent pediatrician to deliver that care.”

[email protected]

On Twitter @legal_med

When Jason Vargas, MD, first moved to the Phoenix area 13 years ago, he found an atmosphere of distant relationships between general pediatricians like him, subspecialists, and hospitals. Getting patients a referral to a subspecialist could take months, and communication among providers was often weak, Dr. Vargas said.

Today, things are vastly different thanks in large part to the clinically integrated network of which Dr. Vargas and 950 area providers are a part.

Courtesy Dr. Vargas

Going from splintered to unified

Like most communities, care delivery in the Phoenix area was relatively fractured prior to 2014. To bring everyone together, Phoenix Children’s started with community outreach and education.

A changing payer relationship

As a network, PCCN works with payers to assume the risk that insurers have historically taken. Payers continue to handle the administrative and billing side of the equation, while the network controls the medical management and care coordination of the patient population, Mr. Johnson said.

“We feel we can do it much more efficiently, much more effectively, and we feel it’s better care for the patient when we’re the one controlling that,” he said. “The insurance companies don’t disagree.”

The network partners with Medicaid and commercial payers and has a direct-to-employer agreement with a major employer in conjunction with an adult partner system/network. Early performance efforts by the PCCN have been rewarded by shared savings disbursements from two payers, according to PCCN officials. The network has also met or exceeded state Medicaid pediatric quality targets and consistently contained medical expenses below expected medical cost trends for its managed pediatric populations.

Building a population health model

For more than 2 decades, PFK in Ohio has taken a novel care delivery approach that has focused on value and community partnerships.

Back in 1994, Nationwide Children’s Hospital partnered with community pediatricians to create PFK, a physician/hospital organization with governance shared equally. Today, PFK has assumed full financial and clinical risk for pediatric managed Medicaid enrollees, and is the largest and oldest known pediatric ACO.

Guidance for other practices

Dr. Gleeson encouraged other pediatricians interested in transitioning to value-based care to start by evaluating their data. Take a hard look at the quality of care you provide and begin to measure it, he said. For smaller practices, consider joining a larger group or network that will allow pediatricians to engage in collaborative work, he added.

Dr. Vargas stressed that change is coming whether pediatricians are prepared or not. Aligning with the right partners will be the difference between sinking or staying afloat in the value-based landscape.

“Payers are moving toward value-based models and it is not practical for the general pediatrician to be able to provide the infrastructure and professional resources necessary,” he said. “To maintain our professional livelihood as independent pediatricians, and to continue to provide the individually crafted, quality care our families are accustomed to, we will have to align ourselves with organizations that value the experience and insight of the independent pediatrician to deliver that care.”

[email protected]

On Twitter @legal_med

When Jason Vargas, MD, first moved to the Phoenix area 13 years ago, he found an atmosphere of distant relationships between general pediatricians like him, subspecialists, and hospitals. Getting patients a referral to a subspecialist could take months, and communication among providers was often weak, Dr. Vargas said.

Today, things are vastly different thanks in large part to the clinically integrated network of which Dr. Vargas and 950 area providers are a part.

Courtesy Dr. Vargas

Going from splintered to unified

Like most communities, care delivery in the Phoenix area was relatively fractured prior to 2014. To bring everyone together, Phoenix Children’s started with community outreach and education.

A changing payer relationship

As a network, PCCN works with payers to assume the risk that insurers have historically taken. Payers continue to handle the administrative and billing side of the equation, while the network controls the medical management and care coordination of the patient population, Mr. Johnson said.

“We feel we can do it much more efficiently, much more effectively, and we feel it’s better care for the patient when we’re the one controlling that,” he said. “The insurance companies don’t disagree.”

The network partners with Medicaid and commercial payers and has a direct-to-employer agreement with a major employer in conjunction with an adult partner system/network. Early performance efforts by the PCCN have been rewarded by shared savings disbursements from two payers, according to PCCN officials. The network has also met or exceeded state Medicaid pediatric quality targets and consistently contained medical expenses below expected medical cost trends for its managed pediatric populations.

Building a population health model

For more than 2 decades, PFK in Ohio has taken a novel care delivery approach that has focused on value and community partnerships.

Back in 1994, Nationwide Children’s Hospital partnered with community pediatricians to create PFK, a physician/hospital organization with governance shared equally. Today, PFK has assumed full financial and clinical risk for pediatric managed Medicaid enrollees, and is the largest and oldest known pediatric ACO.

Guidance for other practices

Dr. Gleeson encouraged other pediatricians interested in transitioning to value-based care to start by evaluating their data. Take a hard look at the quality of care you provide and begin to measure it, he said. For smaller practices, consider joining a larger group or network that will allow pediatricians to engage in collaborative work, he added.

Dr. Vargas stressed that change is coming whether pediatricians are prepared or not. Aligning with the right partners will be the difference between sinking or staying afloat in the value-based landscape.

“Payers are moving toward value-based models and it is not practical for the general pediatrician to be able to provide the infrastructure and professional resources necessary,” he said. “To maintain our professional livelihood as independent pediatricians, and to continue to provide the individually crafted, quality care our families are accustomed to, we will have to align ourselves with organizations that value the experience and insight of the independent pediatrician to deliver that care.”

[email protected]

On Twitter @legal_med

TORONTO—High levels of occupational complexity, specifically related to work with people, enable individuals to maintain normal cognition despite white matter pathology in the brain, according to research described at the Alzheimer’s Association International Conference. The results “could have potential implications for preventing or maybe delaying Alzheimer’s disease onset in the future,” said Elizabeth Boots, research specialist at Wisconsin Alzheimer’s Disease Research Center in Madison.

According to one estimate, about 30% of cognitively healthy elderly adults may have widespread Alzheimer’s disease pathology. Cognitive reserve may allow these individuals to perform at a normal level of cognition despite this pathology. Because many people spend the majority of their lives at work, Ms. Boots and colleagues chose to examine occupational complexity as a measure of cognitive reserve. The investigators also focused on white matter hyperintensities, which increase the risk for cognitive decline and are common in Alzheimer’s disease. “The objective of our study was to determine whether occupational complexity is associated with more white matter hyperintensities when participants are matched for cognitive function, which would support the cognitive reserve hypothesis,” said Ms. Boots.

Examining Cognitive Testing and Imaging

She and her colleagues, led by senior author Ozioma Okonkwo, PhD, Assistant Professor of Geriatrics at the University of Wisconsin School of Medicine in Madison, selected 284 participants in the Wisconsin Registry for Alzheimer’s Prevention, a group of approximately 1,500 cognitively healthy people with increased risk for Alzheimer’s disease because of parental family history. Participants underwent extensive cognitive testing, and the researchers looked at the average of four cognitive domains—verbal learning and memory, immediate memory, working memory, and speed and flexibility—to match individuals on cognitive function. Participants also underwent a brain scan for white matter hyperintensities.

In addition, study participants described as many as three occupations that they had performed, including the number of years spent on each occupation. Ms. Boots and her colleagues rated each job for three categories of occupational complexity (ie, complexity of work with data, people, and things). In the domain of work with people, for example, the researchers considered taking instructions as the least complex occupation, and mentoring the most complex. They weighted the scores by the number of years on the job and summed the scores to create a total occupational complexity measure.

Social Interaction May Be Crucial

Average age in the study cohort was 60, and 67% of participants were female. Study participants had an average of 16.67 years of education. When the investigators controlled the data for cognitive function, they found that higher levels of occupational complexity were associated with increased white matter hyperintensities in the brain. “Those with higher levels of occupational complexity are able to tolerate more white matter pathology in the brain and still perform at the same cognitive level as their peers,” said Ms. Boots. The association did not change when the researchers controlled for potential confounders such as education, socioeconomic status, and vascular risk. Furthermore, Ms. Boots and colleagues found that complexity of work with people, but not complexity of work with data or things, had the greatest effect on preserving cognitive performance.

The results support the cognitive reserve hypothesis and suggest that social interaction plays a unique role in cognitive reserve, according to Dr. Okonkwo. “These analyses underscore the importance of social engagement in the work setting for building resilience to Alzheimer’s disease,” he added. The Alzheimer’s Association, the NIH, and the Extendicare Foundation funded the study.

Suggested Reading

Boots EA, Schultz SA, Almeida RP, et al. Occupational complexity and cognitive reserve in a middle-aged cohort at risk for Alzheimer’s disease. Arch Clin Neuropsychol. 2015;30(7):634-642.

Lo RY, Jagust WJ; Alzheimer’s Disease Neuroimaging Initiative. Effect of cognitive reserve markers on Alzheimer pathologic progression. Alzheimer Dis Assoc Disord. 2013;27(4):343-350.

Pool LR, Weuve J, Wilson RS, et al. Occupational cognitive requirements and late-life cognitive aging. Neurology. 2016;86(15):1386-1392.

Stern Y. Cognitive reserve in ageing and Alzheimer’s disease. Lancet Neurol. 2012; 11(11):1006-1012.

TORONTO—High levels of occupational complexity, specifically related to work with people, enable individuals to maintain normal cognition despite white matter pathology in the brain, according to research described at the Alzheimer’s Association International Conference. The results “could have potential implications for preventing or maybe delaying Alzheimer’s disease onset in the future,” said Elizabeth Boots, research specialist at Wisconsin Alzheimer’s Disease Research Center in Madison.

According to one estimate, about 30% of cognitively healthy elderly adults may have widespread Alzheimer’s disease pathology. Cognitive reserve may allow these individuals to perform at a normal level of cognition despite this pathology. Because many people spend the majority of their lives at work, Ms. Boots and colleagues chose to examine occupational complexity as a measure of cognitive reserve. The investigators also focused on white matter hyperintensities, which increase the risk for cognitive decline and are common in Alzheimer’s disease. “The objective of our study was to determine whether occupational complexity is associated with more white matter hyperintensities when participants are matched for cognitive function, which would support the cognitive reserve hypothesis,” said Ms. Boots.

Examining Cognitive Testing and Imaging

She and her colleagues, led by senior author Ozioma Okonkwo, PhD, Assistant Professor of Geriatrics at the University of Wisconsin School of Medicine in Madison, selected 284 participants in the Wisconsin Registry for Alzheimer’s Prevention, a group of approximately 1,500 cognitively healthy people with increased risk for Alzheimer’s disease because of parental family history. Participants underwent extensive cognitive testing, and the researchers looked at the average of four cognitive domains—verbal learning and memory, immediate memory, working memory, and speed and flexibility—to match individuals on cognitive function. Participants also underwent a brain scan for white matter hyperintensities.

In addition, study participants described as many as three occupations that they had performed, including the number of years spent on each occupation. Ms. Boots and her colleagues rated each job for three categories of occupational complexity (ie, complexity of work with data, people, and things). In the domain of work with people, for example, the researchers considered taking instructions as the least complex occupation, and mentoring the most complex. They weighted the scores by the number of years on the job and summed the scores to create a total occupational complexity measure.

Social Interaction May Be Crucial

Average age in the study cohort was 60, and 67% of participants were female. Study participants had an average of 16.67 years of education. When the investigators controlled the data for cognitive function, they found that higher levels of occupational complexity were associated with increased white matter hyperintensities in the brain. “Those with higher levels of occupational complexity are able to tolerate more white matter pathology in the brain and still perform at the same cognitive level as their peers,” said Ms. Boots. The association did not change when the researchers controlled for potential confounders such as education, socioeconomic status, and vascular risk. Furthermore, Ms. Boots and colleagues found that complexity of work with people, but not complexity of work with data or things, had the greatest effect on preserving cognitive performance.

The results support the cognitive reserve hypothesis and suggest that social interaction plays a unique role in cognitive reserve, according to Dr. Okonkwo. “These analyses underscore the importance of social engagement in the work setting for building resilience to Alzheimer’s disease,” he added. The Alzheimer’s Association, the NIH, and the Extendicare Foundation funded the study.

Suggested Reading

Boots EA, Schultz SA, Almeida RP, et al. Occupational complexity and cognitive reserve in a middle-aged cohort at risk for Alzheimer’s disease. Arch Clin Neuropsychol. 2015;30(7):634-642.

Lo RY, Jagust WJ; Alzheimer’s Disease Neuroimaging Initiative. Effect of cognitive reserve markers on Alzheimer pathologic progression. Alzheimer Dis Assoc Disord. 2013;27(4):343-350.

Pool LR, Weuve J, Wilson RS, et al. Occupational cognitive requirements and late-life cognitive aging. Neurology. 2016;86(15):1386-1392.

Stern Y. Cognitive reserve in ageing and Alzheimer’s disease. Lancet Neurol. 2012; 11(11):1006-1012.

TORONTO—High levels of occupational complexity, specifically related to work with people, enable individuals to maintain normal cognition despite white matter pathology in the brain, according to research described at the Alzheimer’s Association International Conference. The results “could have potential implications for preventing or maybe delaying Alzheimer’s disease onset in the future,” said Elizabeth Boots, research specialist at Wisconsin Alzheimer’s Disease Research Center in Madison.

According to one estimate, about 30% of cognitively healthy elderly adults may have widespread Alzheimer’s disease pathology. Cognitive reserve may allow these individuals to perform at a normal level of cognition despite this pathology. Because many people spend the majority of their lives at work, Ms. Boots and colleagues chose to examine occupational complexity as a measure of cognitive reserve. The investigators also focused on white matter hyperintensities, which increase the risk for cognitive decline and are common in Alzheimer’s disease. “The objective of our study was to determine whether occupational complexity is associated with more white matter hyperintensities when participants are matched for cognitive function, which would support the cognitive reserve hypothesis,” said Ms. Boots.

Examining Cognitive Testing and Imaging

She and her colleagues, led by senior author Ozioma Okonkwo, PhD, Assistant Professor of Geriatrics at the University of Wisconsin School of Medicine in Madison, selected 284 participants in the Wisconsin Registry for Alzheimer’s Prevention, a group of approximately 1,500 cognitively healthy people with increased risk for Alzheimer’s disease because of parental family history. Participants underwent extensive cognitive testing, and the researchers looked at the average of four cognitive domains—verbal learning and memory, immediate memory, working memory, and speed and flexibility—to match individuals on cognitive function. Participants also underwent a brain scan for white matter hyperintensities.

In addition, study participants described as many as three occupations that they had performed, including the number of years spent on each occupation. Ms. Boots and her colleagues rated each job for three categories of occupational complexity (ie, complexity of work with data, people, and things). In the domain of work with people, for example, the researchers considered taking instructions as the least complex occupation, and mentoring the most complex. They weighted the scores by the number of years on the job and summed the scores to create a total occupational complexity measure.

Social Interaction May Be Crucial

Average age in the study cohort was 60, and 67% of participants were female. Study participants had an average of 16.67 years of education. When the investigators controlled the data for cognitive function, they found that higher levels of occupational complexity were associated with increased white matter hyperintensities in the brain. “Those with higher levels of occupational complexity are able to tolerate more white matter pathology in the brain and still perform at the same cognitive level as their peers,” said Ms. Boots. The association did not change when the researchers controlled for potential confounders such as education, socioeconomic status, and vascular risk. Furthermore, Ms. Boots and colleagues found that complexity of work with people, but not complexity of work with data or things, had the greatest effect on preserving cognitive performance.

The results support the cognitive reserve hypothesis and suggest that social interaction plays a unique role in cognitive reserve, according to Dr. Okonkwo. “These analyses underscore the importance of social engagement in the work setting for building resilience to Alzheimer’s disease,” he added. The Alzheimer’s Association, the NIH, and the Extendicare Foundation funded the study.

Suggested Reading

Boots EA, Schultz SA, Almeida RP, et al. Occupational complexity and cognitive reserve in a middle-aged cohort at risk for Alzheimer’s disease. Arch Clin Neuropsychol. 2015;30(7):634-642.

Lo RY, Jagust WJ; Alzheimer’s Disease Neuroimaging Initiative. Effect of cognitive reserve markers on Alzheimer pathologic progression. Alzheimer Dis Assoc Disord. 2013;27(4):343-350.

Pool LR, Weuve J, Wilson RS, et al. Occupational cognitive requirements and late-life cognitive aging. Neurology. 2016;86(15):1386-1392.

Stern Y. Cognitive reserve in ageing and Alzheimer’s disease. Lancet Neurol. 2012; 11(11):1006-1012.

Bullous pemphigoid (BP) is an acquired, autoimmune, subepidermal blistering disease that is more common in elderly patients.¹ An association with internal neoplasms and BP has been established; however, there is debate regarding the precise nature of the relationship.² Several gastrointestinal tract tumors have been associated with BP, including adenocarcinoma of the colon, adenosquamous cell carcinoma and adenocarcinoma of the stomach, adenocarcinoma of the rectum, and liver and bile duct malignancies.^3-5 Association with pancreatic neoplasms (eg, carcinoma of the pancreas) rarely has been reported.^5-7 We present an unusual case of a lymphoepithelial cyst of the pancreas in a patient with BP.

Case Report

A 67-year-old man presented with erythematous crusted plaques and pink scars over the chest, back, arms, and legs (Figure 1). A 1.5-cm tense bullous lesion was observed on the right knee. The patient’s medical history was notable for biopsy-proven BP of 8 months’ duration as well as diabetes mellitus and hypothyroidism. The patient was being followed by his surgeon for a 1.9-cm soft-tissue lesion in the pancreatic tail and was awaiting surgical excision at the time of the current presentation. The pancreatic lesion was discovered incidentally on magnetic resonance imaging performed following urologic concerns. At the current presentation, the patient’s medications included nifedipine, hydralazine, metoprolol, torsemide, aspirin, levothyroxine, atorvastatin, insulin lispro, and insulin glargine. He had previously been treated for BP with prednisone at a maximum dosage of 60 mg daily, clobetasol propionate cream 0.05%, and mupirocin ointment 2% without improvement. Because of substantial weight gain and poorly controlled diabetes, prednisone was discontinued.

Bullous pemphigoid had been diagnosed histopathologically by a prior dermatologist. Hematoxylin and eosin staining demonstrated a subepidermal separation with eosinophils within the perivascular infiltrate (Figure 2). Direct immunofluorescence was noted in a linear pattern at the dermoepidermal junction with IgG and C3. Bullous pemphigoid antigen antibodies 1 and 2 were obtained via enzyme-linked immunosorbent assay with a positive BP-1 antigen antibody of 19 U/mL (positive, >15 U/mL) and a normal BP-2 antigen antibody of less than 9 U/mL (reference range, <9 U/mL). The glucagon level was elevated at 245 pg/mL (reference range, ≤134 pg/mL).

The patient was prescribed minocycline 100 mg twice daily and niacinamide 500 mg 3 times daily. Topical treatment with clobetasol and mupirocin was continued. One month later, the patient returned with an increase in disease activity. Changes to his therapeutic regimen were deferred until after excision of the pancreatic lesion based on the decision not to start immunosuppressive therapy until the precise nature of the pancreatic lesion was determined.

The patient underwent excision of the pancreatic lesion approximately 3 months later, which proved to be a benign lymphoepithelial cyst of the pancreas. Histology of the cyst consisted of dense fibrous tissue with a squamous epithelial lining focally infiltrated by lymphocytes (Figure 3A). Immunoperoxidase staining of the cyst revealed focal linear areas of C3d staining along the basement membrane of the stratified squamous epithelium (Figure 3B).

The patient stated that his skin started to improve virtually immediately following the excision without systemic treatment for BP. On follow-up examination 3 weeks postoperatively, no bullae were observed and there was a notable decrease in erythematous crusted plaques (Figure 4).

Comment

Paraneoplastic BP has been documented; however, lymphoepithelial cysts of the pancreas in association with BP are rare. We propose that the lymphoepithelial cyst of the pancreas provided the immunologic stimulus for the development of cutaneous BP based on the observation that our patient’s condition remarkably improved with resection of the tumor.

There are fewer than 100 cases of lymphoepithelial cysts of the pancreas reported in the literature.⁸ The histologic appearance is consistent with a true cyst exhibiting a well-differentiated stratified squamous epithelium, often with keratinization, surrounded by lymphoid tissue. These tumors are most commonly seen in middle-aged men and are frequently found incidentally,^8-10 as was the case with our patient. Although histologically similar, lymphoepithelial cysts of the pancreas are considered distinct from lymphoepithelial cysts of the parotid gland or head and neck region.¹⁰ Lymphoepithelial cysts of the pancreas are unrelated to elevated glucagon levels; it is likely that our patient’s glucagon levels were associated with his history of diabetes.¹¹

In theory, any process that involves deposition of C3 should be positive for C3d on immunoperoxidase staining. Other dermatologic inflammatory conditions stain positively with C3d, such as systemic lupus erythematosus, discoid lupus erythematosus, subacute cutaneous lupus erythematosus, and dermatomysositis.¹³ The staining for these diseases correlates with the site of the associated inflammatory component seen on hematoxylin and eosin staining. The staining of C3d along the basement membrane of stratified squamous epithelium in the lymphoepithelial cyst of the pancreas seen in our patient closely resembles the staining seen in cutaneous BP.

A proposed mechanism for BP in our patient would be exposure of BP-1 antigen in the pancreatic cyst leading to antibody recognition and C3 deposition along the basement membrane in the cyst, as evidenced by C3d immunoperoxidase staining. The IgG and C3 deposition along the cutaneous basement membrane would then represent a systemic response to the antigen exposure in the cyst. Thus, the lymphoepithelial cyst provided the immunologic stimulus for the development of the cutaneous BP. This theory is based on the observation of our patient’s rapid improvement without a change in his treatment regimen immediately after surgical excision of the cyst.

Despite the plausibility of our hypothesis, several questions remain regarding the validity of our assumptions. Although sensitive for C3 deposition, C3d immunoperoxidase staining is not specific for BP. If the proposed mechanism for causation is true, one might have expected that a subepithelial cleft along the basement membrane of the pancreatic cyst would be observed, which was not seen. A repeat BP antigen antibody was not obtained, which would have been helpful in determining if there was clearance of the antibody that would have correlated with the clinical resolution of the BP lesions.

Conclusion

Our case suggests that paraneoplastic BP is a genuine entity. Indeed, the primary tumor itself may be the immunologic stimulus in the development of BP. Recalcitrant BP should raise the question of a neoplastic process that is exposing the BP antigen. If a thorough review of systems accompanied by corroborating laboratory studies suggests a neoplastic process, the suspect lesion should be further evaluated and surgically excised if clinically indicated. Further evaluation of neoplasms with advanced staining methods may aid in establishing the causative nature of tumors in the development of BP.

Acknowledgments

We are grateful to John Stanley, MD, and Aimee Payne, MD (both from Philadelphia, Pennsylvania), for theirinsights into this case.

Bullous pemphigoid (BP) is an acquired, autoimmune, subepidermal blistering disease that is more common in elderly patients.¹ An association with internal neoplasms and BP has been established; however, there is debate regarding the precise nature of the relationship.² Several gastrointestinal tract tumors have been associated with BP, including adenocarcinoma of the colon, adenosquamous cell carcinoma and adenocarcinoma of the stomach, adenocarcinoma of the rectum, and liver and bile duct malignancies.^3-5 Association with pancreatic neoplasms (eg, carcinoma of the pancreas) rarely has been reported.^5-7 We present an unusual case of a lymphoepithelial cyst of the pancreas in a patient with BP.

Case Report

A 67-year-old man presented with erythematous crusted plaques and pink scars over the chest, back, arms, and legs (Figure 1). A 1.5-cm tense bullous lesion was observed on the right knee. The patient’s medical history was notable for biopsy-proven BP of 8 months’ duration as well as diabetes mellitus and hypothyroidism. The patient was being followed by his surgeon for a 1.9-cm soft-tissue lesion in the pancreatic tail and was awaiting surgical excision at the time of the current presentation. The pancreatic lesion was discovered incidentally on magnetic resonance imaging performed following urologic concerns. At the current presentation, the patient’s medications included nifedipine, hydralazine, metoprolol, torsemide, aspirin, levothyroxine, atorvastatin, insulin lispro, and insulin glargine. He had previously been treated for BP with prednisone at a maximum dosage of 60 mg daily, clobetasol propionate cream 0.05%, and mupirocin ointment 2% without improvement. Because of substantial weight gain and poorly controlled diabetes, prednisone was discontinued.

Bullous pemphigoid had been diagnosed histopathologically by a prior dermatologist. Hematoxylin and eosin staining demonstrated a subepidermal separation with eosinophils within the perivascular infiltrate (Figure 2). Direct immunofluorescence was noted in a linear pattern at the dermoepidermal junction with IgG and C3. Bullous pemphigoid antigen antibodies 1 and 2 were obtained via enzyme-linked immunosorbent assay with a positive BP-1 antigen antibody of 19 U/mL (positive, >15 U/mL) and a normal BP-2 antigen antibody of less than 9 U/mL (reference range, <9 U/mL). The glucagon level was elevated at 245 pg/mL (reference range, ≤134 pg/mL).

The patient was prescribed minocycline 100 mg twice daily and niacinamide 500 mg 3 times daily. Topical treatment with clobetasol and mupirocin was continued. One month later, the patient returned with an increase in disease activity. Changes to his therapeutic regimen were deferred until after excision of the pancreatic lesion based on the decision not to start immunosuppressive therapy until the precise nature of the pancreatic lesion was determined.

The patient underwent excision of the pancreatic lesion approximately 3 months later, which proved to be a benign lymphoepithelial cyst of the pancreas. Histology of the cyst consisted of dense fibrous tissue with a squamous epithelial lining focally infiltrated by lymphocytes (Figure 3A). Immunoperoxidase staining of the cyst revealed focal linear areas of C3d staining along the basement membrane of the stratified squamous epithelium (Figure 3B).

The patient stated that his skin started to improve virtually immediately following the excision without systemic treatment for BP. On follow-up examination 3 weeks postoperatively, no bullae were observed and there was a notable decrease in erythematous crusted plaques (Figure 4).

Comment

Paraneoplastic BP has been documented; however, lymphoepithelial cysts of the pancreas in association with BP are rare. We propose that the lymphoepithelial cyst of the pancreas provided the immunologic stimulus for the development of cutaneous BP based on the observation that our patient’s condition remarkably improved with resection of the tumor.

There are fewer than 100 cases of lymphoepithelial cysts of the pancreas reported in the literature.⁸ The histologic appearance is consistent with a true cyst exhibiting a well-differentiated stratified squamous epithelium, often with keratinization, surrounded by lymphoid tissue. These tumors are most commonly seen in middle-aged men and are frequently found incidentally,^8-10 as was the case with our patient. Although histologically similar, lymphoepithelial cysts of the pancreas are considered distinct from lymphoepithelial cysts of the parotid gland or head and neck region.¹⁰ Lymphoepithelial cysts of the pancreas are unrelated to elevated glucagon levels; it is likely that our patient’s glucagon levels were associated with his history of diabetes.¹¹

In theory, any process that involves deposition of C3 should be positive for C3d on immunoperoxidase staining. Other dermatologic inflammatory conditions stain positively with C3d, such as systemic lupus erythematosus, discoid lupus erythematosus, subacute cutaneous lupus erythematosus, and dermatomysositis.¹³ The staining for these diseases correlates with the site of the associated inflammatory component seen on hematoxylin and eosin staining. The staining of C3d along the basement membrane of stratified squamous epithelium in the lymphoepithelial cyst of the pancreas seen in our patient closely resembles the staining seen in cutaneous BP.

A proposed mechanism for BP in our patient would be exposure of BP-1 antigen in the pancreatic cyst leading to antibody recognition and C3 deposition along the basement membrane in the cyst, as evidenced by C3d immunoperoxidase staining. The IgG and C3 deposition along the cutaneous basement membrane would then represent a systemic response to the antigen exposure in the cyst. Thus, the lymphoepithelial cyst provided the immunologic stimulus for the development of the cutaneous BP. This theory is based on the observation of our patient’s rapid improvement without a change in his treatment regimen immediately after surgical excision of the cyst.

Despite the plausibility of our hypothesis, several questions remain regarding the validity of our assumptions. Although sensitive for C3 deposition, C3d immunoperoxidase staining is not specific for BP. If the proposed mechanism for causation is true, one might have expected that a subepithelial cleft along the basement membrane of the pancreatic cyst would be observed, which was not seen. A repeat BP antigen antibody was not obtained, which would have been helpful in determining if there was clearance of the antibody that would have correlated with the clinical resolution of the BP lesions.

Conclusion

Our case suggests that paraneoplastic BP is a genuine entity. Indeed, the primary tumor itself may be the immunologic stimulus in the development of BP. Recalcitrant BP should raise the question of a neoplastic process that is exposing the BP antigen. If a thorough review of systems accompanied by corroborating laboratory studies suggests a neoplastic process, the suspect lesion should be further evaluated and surgically excised if clinically indicated. Further evaluation of neoplasms with advanced staining methods may aid in establishing the causative nature of tumors in the development of BP.

Acknowledgments

We are grateful to John Stanley, MD, and Aimee Payne, MD (both from Philadelphia, Pennsylvania), for theirinsights into this case.

Bullous pemphigoid (BP) is an acquired, autoimmune, subepidermal blistering disease that is more common in elderly patients.¹ An association with internal neoplasms and BP has been established; however, there is debate regarding the precise nature of the relationship.² Several gastrointestinal tract tumors have been associated with BP, including adenocarcinoma of the colon, adenosquamous cell carcinoma and adenocarcinoma of the stomach, adenocarcinoma of the rectum, and liver and bile duct malignancies.^3-5 Association with pancreatic neoplasms (eg, carcinoma of the pancreas) rarely has been reported.^5-7 We present an unusual case of a lymphoepithelial cyst of the pancreas in a patient with BP.

Case Report

A 67-year-old man presented with erythematous crusted plaques and pink scars over the chest, back, arms, and legs (Figure 1). A 1.5-cm tense bullous lesion was observed on the right knee. The patient’s medical history was notable for biopsy-proven BP of 8 months’ duration as well as diabetes mellitus and hypothyroidism. The patient was being followed by his surgeon for a 1.9-cm soft-tissue lesion in the pancreatic tail and was awaiting surgical excision at the time of the current presentation. The pancreatic lesion was discovered incidentally on magnetic resonance imaging performed following urologic concerns. At the current presentation, the patient’s medications included nifedipine, hydralazine, metoprolol, torsemide, aspirin, levothyroxine, atorvastatin, insulin lispro, and insulin glargine. He had previously been treated for BP with prednisone at a maximum dosage of 60 mg daily, clobetasol propionate cream 0.05%, and mupirocin ointment 2% without improvement. Because of substantial weight gain and poorly controlled diabetes, prednisone was discontinued.

Bullous pemphigoid had been diagnosed histopathologically by a prior dermatologist. Hematoxylin and eosin staining demonstrated a subepidermal separation with eosinophils within the perivascular infiltrate (Figure 2). Direct immunofluorescence was noted in a linear pattern at the dermoepidermal junction with IgG and C3. Bullous pemphigoid antigen antibodies 1 and 2 were obtained via enzyme-linked immunosorbent assay with a positive BP-1 antigen antibody of 19 U/mL (positive, >15 U/mL) and a normal BP-2 antigen antibody of less than 9 U/mL (reference range, <9 U/mL). The glucagon level was elevated at 245 pg/mL (reference range, ≤134 pg/mL).

The patient was prescribed minocycline 100 mg twice daily and niacinamide 500 mg 3 times daily. Topical treatment with clobetasol and mupirocin was continued. One month later, the patient returned with an increase in disease activity. Changes to his therapeutic regimen were deferred until after excision of the pancreatic lesion based on the decision not to start immunosuppressive therapy until the precise nature of the pancreatic lesion was determined.

The patient underwent excision of the pancreatic lesion approximately 3 months later, which proved to be a benign lymphoepithelial cyst of the pancreas. Histology of the cyst consisted of dense fibrous tissue with a squamous epithelial lining focally infiltrated by lymphocytes (Figure 3A). Immunoperoxidase staining of the cyst revealed focal linear areas of C3d staining along the basement membrane of the stratified squamous epithelium (Figure 3B).

The patient stated that his skin started to improve virtually immediately following the excision without systemic treatment for BP. On follow-up examination 3 weeks postoperatively, no bullae were observed and there was a notable decrease in erythematous crusted plaques (Figure 4).

Comment

Paraneoplastic BP has been documented; however, lymphoepithelial cysts of the pancreas in association with BP are rare. We propose that the lymphoepithelial cyst of the pancreas provided the immunologic stimulus for the development of cutaneous BP based on the observation that our patient’s condition remarkably improved with resection of the tumor.

There are fewer than 100 cases of lymphoepithelial cysts of the pancreas reported in the literature.⁸ The histologic appearance is consistent with a true cyst exhibiting a well-differentiated stratified squamous epithelium, often with keratinization, surrounded by lymphoid tissue. These tumors are most commonly seen in middle-aged men and are frequently found incidentally,^8-10 as was the case with our patient. Although histologically similar, lymphoepithelial cysts of the pancreas are considered distinct from lymphoepithelial cysts of the parotid gland or head and neck region.¹⁰ Lymphoepithelial cysts of the pancreas are unrelated to elevated glucagon levels; it is likely that our patient’s glucagon levels were associated with his history of diabetes.¹¹

In theory, any process that involves deposition of C3 should be positive for C3d on immunoperoxidase staining. Other dermatologic inflammatory conditions stain positively with C3d, such as systemic lupus erythematosus, discoid lupus erythematosus, subacute cutaneous lupus erythematosus, and dermatomysositis.¹³ The staining for these diseases correlates with the site of the associated inflammatory component seen on hematoxylin and eosin staining. The staining of C3d along the basement membrane of stratified squamous epithelium in the lymphoepithelial cyst of the pancreas seen in our patient closely resembles the staining seen in cutaneous BP.

A proposed mechanism for BP in our patient would be exposure of BP-1 antigen in the pancreatic cyst leading to antibody recognition and C3 deposition along the basement membrane in the cyst, as evidenced by C3d immunoperoxidase staining. The IgG and C3 deposition along the cutaneous basement membrane would then represent a systemic response to the antigen exposure in the cyst. Thus, the lymphoepithelial cyst provided the immunologic stimulus for the development of the cutaneous BP. This theory is based on the observation of our patient’s rapid improvement without a change in his treatment regimen immediately after surgical excision of the cyst.

Despite the plausibility of our hypothesis, several questions remain regarding the validity of our assumptions. Although sensitive for C3 deposition, C3d immunoperoxidase staining is not specific for BP. If the proposed mechanism for causation is true, one might have expected that a subepithelial cleft along the basement membrane of the pancreatic cyst would be observed, which was not seen. A repeat BP antigen antibody was not obtained, which would have been helpful in determining if there was clearance of the antibody that would have correlated with the clinical resolution of the BP lesions.

Conclusion

Our case suggests that paraneoplastic BP is a genuine entity. Indeed, the primary tumor itself may be the immunologic stimulus in the development of BP. Recalcitrant BP should raise the question of a neoplastic process that is exposing the BP antigen. If a thorough review of systems accompanied by corroborating laboratory studies suggests a neoplastic process, the suspect lesion should be further evaluated and surgically excised if clinically indicated. Further evaluation of neoplasms with advanced staining methods may aid in establishing the causative nature of tumors in the development of BP.

Acknowledgments

We are grateful to John Stanley, MD, and Aimee Payne, MD (both from Philadelphia, Pennsylvania), for theirinsights into this case.

We live inundated with promises that technology will solve our most challenging problems, yet we are regularly disappointed when it does not. New technological solutions seem to appear daily, and we feel like we are falling behind if we do not jump to join the people who are implementing, selling, or imposing new solutions. Often these solutions are offered before the problem is even fully understood, and no assessment has been made to determine if the solution actually helps to solve the challenge identified. With 80% of us now having transitioned to EHRs, we know full well their benefits as well as their pitfalls. While we have mostly accommodated to electronic documentation, we are now at the point where we are beginning to explore some of the most exciting potential benefits of our EHRs – population health, enhanced data on medication adherence, and improved patient communication. As we look at this next stage of growth, we are reminded of a lesson from an old joke:

A rabbi dies and goes to heaven. When he gets there he is given an old robe and a wooden walking stick and is told to get in line to the entrance to heaven. While the rabbi waits in the long line, a taxi driver walks up and is greeted by a group of angels blowing their horns announcing his arrival. One of the angels walks over to the driver and gives him a flowing white satin robe and a golden walking stick. Another angel then escorts him to the front of the line.

Reference

Jakicic JM, et al. Effect of Wearable Technology Combined With a Lifestyle Intervention on Long-term Weight Loss The IDEA Randomized Clinical Trial. JAMA. 2016;316[11]:1161-71. doi: 10.1001/jama.2016.12858

Dr. Skolnik is associate director of the family medicine residency program at Abington Memorial Hospital and professor of family and community medicine at Temple University in Philadelphia. Dr. Notte is a family physician and clinical informaticist for Abington (Pa.) Memorial Hospital. He is a partner in EHR Practice Consultants, a firm that aids physicians in adopting electronic health records.

We live inundated with promises that technology will solve our most challenging problems, yet we are regularly disappointed when it does not. New technological solutions seem to appear daily, and we feel like we are falling behind if we do not jump to join the people who are implementing, selling, or imposing new solutions. Often these solutions are offered before the problem is even fully understood, and no assessment has been made to determine if the solution actually helps to solve the challenge identified. With 80% of us now having transitioned to EHRs, we know full well their benefits as well as their pitfalls. While we have mostly accommodated to electronic documentation, we are now at the point where we are beginning to explore some of the most exciting potential benefits of our EHRs – population health, enhanced data on medication adherence, and improved patient communication. As we look at this next stage of growth, we are reminded of a lesson from an old joke:

A rabbi dies and goes to heaven. When he gets there he is given an old robe and a wooden walking stick and is told to get in line to the entrance to heaven. While the rabbi waits in the long line, a taxi driver walks up and is greeted by a group of angels blowing their horns announcing his arrival. One of the angels walks over to the driver and gives him a flowing white satin robe and a golden walking stick. Another angel then escorts him to the front of the line.

Reference

Jakicic JM, et al. Effect of Wearable Technology Combined With a Lifestyle Intervention on Long-term Weight Loss The IDEA Randomized Clinical Trial. JAMA. 2016;316[11]:1161-71. doi: 10.1001/jama.2016.12858

Dr. Skolnik is associate director of the family medicine residency program at Abington Memorial Hospital and professor of family and community medicine at Temple University in Philadelphia. Dr. Notte is a family physician and clinical informaticist for Abington (Pa.) Memorial Hospital. He is a partner in EHR Practice Consultants, a firm that aids physicians in adopting electronic health records.

We live inundated with promises that technology will solve our most challenging problems, yet we are regularly disappointed when it does not. New technological solutions seem to appear daily, and we feel like we are falling behind if we do not jump to join the people who are implementing, selling, or imposing new solutions. Often these solutions are offered before the problem is even fully understood, and no assessment has been made to determine if the solution actually helps to solve the challenge identified. With 80% of us now having transitioned to EHRs, we know full well their benefits as well as their pitfalls. While we have mostly accommodated to electronic documentation, we are now at the point where we are beginning to explore some of the most exciting potential benefits of our EHRs – population health, enhanced data on medication adherence, and improved patient communication. As we look at this next stage of growth, we are reminded of a lesson from an old joke:

A rabbi dies and goes to heaven. When he gets there he is given an old robe and a wooden walking stick and is told to get in line to the entrance to heaven. While the rabbi waits in the long line, a taxi driver walks up and is greeted by a group of angels blowing their horns announcing his arrival. One of the angels walks over to the driver and gives him a flowing white satin robe and a golden walking stick. Another angel then escorts him to the front of the line.

Reference

Jakicic JM, et al. Effect of Wearable Technology Combined With a Lifestyle Intervention on Long-term Weight Loss The IDEA Randomized Clinical Trial. JAMA. 2016;316[11]:1161-71. doi: 10.1001/jama.2016.12858

Dr. Skolnik is associate director of the family medicine residency program at Abington Memorial Hospital and professor of family and community medicine at Temple University in Philadelphia. Dr. Notte is a family physician and clinical informaticist for Abington (Pa.) Memorial Hospital. He is a partner in EHR Practice Consultants, a firm that aids physicians in adopting electronic health records.