Discuss this article at www.facebook.com/CurrentPsychiatry

Patients today often are overfed but undernourished. A growing body of literature links dietary choices to brain health and the risk of psychiatric illness. Vitamin deficiencies can affect psychiatric patients in several ways:

• deficiencies may play a causative role in mental illness and exacerbate symptoms
• psychiatric symptoms can result in poor nutrition
• vitamin insufficiency—defined as subclinical deficiency—may compromise patient recovery.

Additionally, genetic differences may compromise vitamin and essential nutrient pathways.

Vitamins are dietary components other than carbohydrates, fats, minerals, and proteins that are necessary for life. B vitamins are required for proper functioning of the methylation cycle, monoamine production, DNA synthesis, and maintenance of phospholipids such as myelin (Figure). Fat-soluble vitamins A, D, and E play important roles in genetic transcription, antioxidant recycling, and inflammatory regulation in the brain.

Figure: The methylation cycle
Vitamins B2, B6, B9, and B12 directly impact the functioning of the methylation cycle. Deficiencies pertain to brain function, as neurotransmitters, myelin, and active glutathione are dependent on one-carbon metabolism
Illustration: Mala Nimalasuriya with permission from DrewRamseyMD.com

To help clinicians recognize and treat vitamin deficiencies among psychiatric patients, this article reviews the role of the 6 essential water-soluble vitamins (B1, B2, B6, B9, B12, and C; Table 1,¹) and 3 fat-soluble vitamins (A, D, and E; Table 2,¹) in brain metabolism and psychiatric pathology. Because numerous sources address using supplements to treat vitamin deficiencies, this article emphasizes food sources, which for many patients are adequate to sustain nutrient status.

Table 1

Water-soluble vitamins: Deficiency, insufficiency, symptoms, and dietary sources

Table 2

Fat-soluble vitamins: Deficiency, insufficiency, symptoms, and dietary sources

Water-soluble vitamins

Vitamin B1 (thiamine) is essential for glucose metabolism. Pregnancy, lactation, and fever increase the need for thiamine, and tea, coffee, and shellfish can impair its absorption. Although rare, severe B1 deficiency can lead to beriberi, Wernicke’s encephalopathy (confusion, ataxia, nystagmus), and Korsakoff’s psychosis (confabulation, lack of insight, retrograde and anterograde amnesia, and apathy). Confusion and disorientation stem from the brain’s inability to oxidize glucose for energy because B1 is a critical cofactor in glycolysis and the tricarboxylic acid cycle. Deficiency leads to an increase in reactive oxygen species, proinflammatory cytokines, and blood-brain barrier dysfunction.² Wernicke’s encephalopathy is most frequently encountered in patients with chronic alcoholism, diabetes, or eating disorders, and after bariatric surgery.³ Iatrogenic Wernicke’s encephalopathy may occur when depleted patients receive IV saline with dextrose without receiving thiamine. Top dietary sources of B1 include pork, fish, beans, lentils, nuts, rice, and wheat germ.

Vitamin B2 (riboflavin) is essential for oxidative pathways, monoamine synthesis, and the methylation cycle. B2 is needed to create the essential flavoprotein coenzymes for synthesis of L-methylfolate—the active form of folate—and for proper utilization of B6. Deficiency can occur after 4 months of inadequate intake.

Although generally B2 deficiency is rare, surveys in the United States have found that 10% to 27% of older adults (age ≥65) are deficient.⁴ Low intake of dairy products and meat and chronic, excessive alcohol intake are associated with deficiency. Marginal B2 levels are more prevalent in depressed patients, possibly because of B2’s role in the function of glutathione, an endogenous antioxidant.⁵ Top dietary sources of B2 are dairy products, meat and fish, eggs, mushrooms, almonds, leafy greens, and legumes.

Vitamin B6 refers to 3 distinct compounds: pyridoxine, pyridoxal, and pyridoxamine. B6 is essential to glycolysis, the methylation cycle, and recharging glutathione, an innate antioxidant in the brain. Higher levels of vitamin B6 are associated with a lower prevalence of depression in adolescents,⁶ and low dietary and plasma B6 increases the risk and severity of depression in geriatric patients⁷ and predicts depression in prospective trials.⁸ Deficiency is common (24% to 56%) among patients receiving hemodialysis.⁹ Women who take oral contraceptives are at increased risk of vitamin B6 deficiency.¹⁰ Top dietary sources are fish, beef, poultry, potatoes, legumes, and spinach.

Vitamin B9 (folate) is needed for proper one-carbon metabolism and thus requisite in synthesis of serotonin, norepinephrine, dopamine, and DNA and in phospholipid production. Low maternal folate status increases the risk of neural tube defects in newborns. Folate deficiency and insufficiency are common among patients with mood disorders and correlate with illness severity.¹¹ In a study of 2,682 Finnish men, those in the lowest one-third of folate consumption had a 67% increased relative risk of depression.¹² A meta-analysis of 11 studies of 15,315 persons found those who had low folate levels had a significant risk of depression.¹³ Patients without deficiency but with folate levels near the low end of the normal range also report low mood.¹⁴ Compared with controls, patients experiencing a first episode of psychosis have lower levels of folate, B12, and docosahexaenoic acid.¹⁵

Dietary folate must be converted to L-methylfolate for use in the brain. Patients with a methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism produce a less active form of the enzyme. The TT genotype is associated with major depression and bipolar disorder.¹⁶ Clinical trials have shown that several forms of folate can enhance antidepressant treatment.¹⁷ Augmentation with L-methylfolate, which bypasses the MTHFR enzyme, can be an effective strategy for treating depression in these patients.¹⁸

Leafy greens and legumes such as lentils are top dietary sources of folate; supplemental folic acid has been linked to an increased risk of cancer and overall mortality.^19,20

Vitamin B12 (cobalamin). An essential cofactor in one-carbon metabolism, B12 is needed to produce monoamine neurotransmitters and maintain myelin. Deficiency is found in up to one-third of depressed patients¹¹ and compromises antidepressant response,²¹ whereas higher vitamin B12 levels are associated with better treatment outcomes.²² B12 deficiency can cause depression, irritability, agitation, psychosis, and obsessive symptoms.^23,24 Low B12 levels and elevated homocysteine increase the risk of cognitive decline and Alzheimer’s disease and are linked to a 5-fold increase in the rate of brain atrophy.²⁶

B12 deficiencies may be seen in patients with gastrointestinal illness, older adults with achlorhydria, and vegans and vegetarians, in whom B12 intake can be low. Proton pump inhibitors such as omeprazole interfere with B12 absorption from food.

Psychiatric symptoms of B12 deficiency may present before hematologic findings.²³ Folic acid supplementation may mask a B12 deficiency by delaying anemia but will not delay psychiatric symptoms. Ten percent of patients with an insufficiency (low normal levels of 200 to 400 pg/mL) have elevated homocysteine, which increases the risk of psychiatric disorders as well as comorbid illnesses such as cardiovascular disease. Top dietary sources include fish, mollusks (oysters, mussels, and clams), meat, and dairy products.

Vitamin C is vital for the synthesis of monoamines such as serotonin and norepinephrine. Vitamin C’s primary role in the brain is as an antioxidant. As a necessary cofactor, it keeps the copper and iron in metalloenzymes reduced, and also recycles vitamin E. Proper function of the methylation cycle depends on vitamin C, as does collagen synthesis and metabolism of xenobiotics by the liver. It is concentrated in cerebrospinal fluid.

Humans cannot manufacture vitamin C. Although the need for vitamin C (90 mg/d) is thought to be met by diet, studies have found that up to 13.7% of healthy, middle class patients in the United States are depleted.²⁷ Older adults and patients with a poor diet due to drug or alcohol abuse, eating disorders, or affective symptoms are at risk.

Scurvy is caused by vitamin C deficiency and leads to bleeding gums and petechiae. Patients with insufficiency report irritability, loss of appetite, weight loss, and hypochondriasis. Vitamin C intake is significantly lower in older adults (age ≥60) with depression.²⁸ Some research indicates patients with schizophrenia have decreased vitamin C levels and dysfunction of antioxidant defenses.²⁹ Citrus, potatoes, and tomatoes are top dietary sources of vitamin C.

Fat-soluble vitamins

Vitamin A. Although vitamin A activity in the brain is poorly understood, retinol—the active form of vitamin A—is crucial for formation of opsins, which are the basis for vision. Childhood vitamin A deficiency may lead to blindness. Vitamin A also plays an important role in maintaining bone growth, reproduction, cell division, and immune system integrity.³⁰ Animal sources such as beef liver, dairy products, and eggs provide retinol, and plant sources such as carrots, sweet potatoes, and leafy greens provide provitamin A carotenoids that humans convert into retinol.

Deficiency rarely is observed in the United States but remains a common problem for developing nations. In the United States, vitamin A deficiency is most often seen with excessive alcohol use, rigorous dietary restrictions, and gastrointestinal diseases accompanied by poor fat absorption.

Excess vitamin A ingestion may result in bone abnormalities, liver damage, birth defects, and depression. Isotretinoin—a form of vitamin A used to treat severe acne—carries an FDA “black-box” warning for psychiatric adverse effects, including aggression, depression, psychosis, and suicide.

Vitamin D is produced from cholesterol in the epidermis through exposure to sunlight, namely ultraviolet B radiation. After dermal synthesis or ingestion, vitamin D is converted through a series of steps into the active form of vitamin D, calcitriol, which also is known as 25(OH)D3.

Although vitamin D is known for its role in bone growth and mineralization,³¹ increasing evidence reveals vitamin D’s role in brain function and development.³² Both glial and neuronal cells possess vitamin D receptors in the hippocampus, prefrontal cortex, hypothalamus, thalamus, and substantia nigra—all regions theorized to be linked to depression pathophysiology.³³ A review of the association of vitamin D deficiency and psychiatric illnesses will be published in a future issue of Current Psychiatry.

Vitamin D exists in food as either D2 or D3, from plant and animal sources, respectively. Concentrated sources include oily fish, sun-dried or “UVB-irradiated” mushrooms, and milk.

Vitamin E. There are 8 isoforms of vitamin E—4 tocopherols and 4 tocotrienols—that function as fat-soluble antioxidants and also promote innate antioxidant enzymes. Because vitamin E protects neuronal membranes from oxidation, low levels may affect the brain via increased inflammation. Alpha-tocopherol is the most common form of vitamin E in humans, but emerging evidence suggests tocotrienols mediate disease by modifying transcription factors in the brain, such as glutathione reductase, superoxide dismutase, and nuclear factor-kappaB.³⁴ Low plasma vitamin E levels are found in depressed patients, although some data suggest this may be caused by factors other than dietary intake.³⁵ Low vitamin status has been found in up to 70% of older adults.³⁶ Although deficiency is rare, most of the U.S. population (93%) has inadequate dietary intake of vitamin E.¹ The reasons for this discrepancy are unclear. Foods rich in vitamin E include almonds, sunflower seeds, leafy greens, and wheat germ.

Recommendations

Patients with depression, alcohol abuse, eating disorders, obsessive-compulsive disorder, or schizophrenia may neglect to care for themselves or adopt particular eating patterns. Deficiencies are more common among geriatric patients and those who are medically ill. Because dietary patterns are linked to the risk of psychiatric disorders, nutritional inquiry often identifies multiple modifiable risk factors, such as folate, vitamin B12, and vitamin D intake.^37,38 Nutritional counseling offers clinicians an intervention with minimal side effect risks and the opportunity to modify a behavior that patients engage in 3 times a day.

Psychiatrists should assess patients’ dietary patterns and vitamin status, particularly older adults and those with:

• lower socioeconomic status or food insecurity
• a history of treatment resistance
• restrictive dietary patterns such as veganism
• alcohol abuse.

On initial assessment, test or obtain from other health care providers your patient’s blood levels of folate and vitamins D and B12. In some patients, assessing B2 and B6 levels may provide etiological guidance regarding onset of psychiatric symptoms or failure to respond to pharmacologic treatment. Because treating vitamin deficiencies often includes using supplements, evaluate recent reviews of specific deficiencies and consider consulting with the patient’s primary care provider.

Conduct a simple assessment of dietary patterns by asking patients about a typical breakfast, lunch, and dinner, their favorite snacks and foods, and specific dietary habits or restrictions (eg, not consuming seafood, dairy, meat, etc.). Rudimentary nutritional recommendations can be effective in changing a patient’s eating habits, particularly when provided by a physician. Encourage patients to eat nutrient-dense foods such as leafy greens, beans and legumes, seafood, whole grains, and a variety of vegetables and fruits. For more complex patients, consult with a clinical nutritionist.

Related Resources

• Institute of Medicine. Dietary Reference Intakes: Recommended intakes for individuals. SummaryDRIs/~/media/Files
  /Activity%20Files/Nutrition
  /DRIs/5_Summary%20Table%20Tables%201-4.pdf" target="_blank">www.iom.edu/Activities/Nutrition/
  SummaryDRIs/~/media/Files
  /Activity%20Files/Nutrition
  /DRIs/5_Summary%20Table%20Tables%201-4.pdf.
• The Farmacy: Vitamins. http://drewramseymd.com/index.php/resources/farmacy/category/vitamins.
• Office of Dietary Supplements. National Institutes of Health. Dietary supplements fact sheets. http://ods.od.nih.gov/factsheets/list-all.
• Oregon State University. Linus Pauling Institute. Micronutrient information center. http://lpi.oregonstate.edu/infocenter/vitamins.html.

Drug Brand Names

• Isotretinoin • Accutane
• L-methylfolate • Deplin
• Omeprazole • Prilosec

Disclosure

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Discuss this article at www.facebook.com/CurrentPsychiatry

Patients today often are overfed but undernourished. A growing body of literature links dietary choices to brain health and the risk of psychiatric illness. Vitamin deficiencies can affect psychiatric patients in several ways:

• deficiencies may play a causative role in mental illness and exacerbate symptoms
• psychiatric symptoms can result in poor nutrition
• vitamin insufficiency—defined as subclinical deficiency—may compromise patient recovery.

Additionally, genetic differences may compromise vitamin and essential nutrient pathways.

Vitamins are dietary components other than carbohydrates, fats, minerals, and proteins that are necessary for life. B vitamins are required for proper functioning of the methylation cycle, monoamine production, DNA synthesis, and maintenance of phospholipids such as myelin (Figure). Fat-soluble vitamins A, D, and E play important roles in genetic transcription, antioxidant recycling, and inflammatory regulation in the brain.

Figure: The methylation cycle
Vitamins B2, B6, B9, and B12 directly impact the functioning of the methylation cycle. Deficiencies pertain to brain function, as neurotransmitters, myelin, and active glutathione are dependent on one-carbon metabolism
Illustration: Mala Nimalasuriya with permission from DrewRamseyMD.com

To help clinicians recognize and treat vitamin deficiencies among psychiatric patients, this article reviews the role of the 6 essential water-soluble vitamins (B1, B2, B6, B9, B12, and C; Table 1,¹) and 3 fat-soluble vitamins (A, D, and E; Table 2,¹) in brain metabolism and psychiatric pathology. Because numerous sources address using supplements to treat vitamin deficiencies, this article emphasizes food sources, which for many patients are adequate to sustain nutrient status.

Table 1

Water-soluble vitamins: Deficiency, insufficiency, symptoms, and dietary sources

Table 2

Fat-soluble vitamins: Deficiency, insufficiency, symptoms, and dietary sources

Water-soluble vitamins

Vitamin B1 (thiamine) is essential for glucose metabolism. Pregnancy, lactation, and fever increase the need for thiamine, and tea, coffee, and shellfish can impair its absorption. Although rare, severe B1 deficiency can lead to beriberi, Wernicke’s encephalopathy (confusion, ataxia, nystagmus), and Korsakoff’s psychosis (confabulation, lack of insight, retrograde and anterograde amnesia, and apathy). Confusion and disorientation stem from the brain’s inability to oxidize glucose for energy because B1 is a critical cofactor in glycolysis and the tricarboxylic acid cycle. Deficiency leads to an increase in reactive oxygen species, proinflammatory cytokines, and blood-brain barrier dysfunction.² Wernicke’s encephalopathy is most frequently encountered in patients with chronic alcoholism, diabetes, or eating disorders, and after bariatric surgery.³ Iatrogenic Wernicke’s encephalopathy may occur when depleted patients receive IV saline with dextrose without receiving thiamine. Top dietary sources of B1 include pork, fish, beans, lentils, nuts, rice, and wheat germ.

Vitamin B2 (riboflavin) is essential for oxidative pathways, monoamine synthesis, and the methylation cycle. B2 is needed to create the essential flavoprotein coenzymes for synthesis of L-methylfolate—the active form of folate—and for proper utilization of B6. Deficiency can occur after 4 months of inadequate intake.

Although generally B2 deficiency is rare, surveys in the United States have found that 10% to 27% of older adults (age ≥65) are deficient.⁴ Low intake of dairy products and meat and chronic, excessive alcohol intake are associated with deficiency. Marginal B2 levels are more prevalent in depressed patients, possibly because of B2’s role in the function of glutathione, an endogenous antioxidant.⁵ Top dietary sources of B2 are dairy products, meat and fish, eggs, mushrooms, almonds, leafy greens, and legumes.

Vitamin B6 refers to 3 distinct compounds: pyridoxine, pyridoxal, and pyridoxamine. B6 is essential to glycolysis, the methylation cycle, and recharging glutathione, an innate antioxidant in the brain. Higher levels of vitamin B6 are associated with a lower prevalence of depression in adolescents,⁶ and low dietary and plasma B6 increases the risk and severity of depression in geriatric patients⁷ and predicts depression in prospective trials.⁸ Deficiency is common (24% to 56%) among patients receiving hemodialysis.⁹ Women who take oral contraceptives are at increased risk of vitamin B6 deficiency.¹⁰ Top dietary sources are fish, beef, poultry, potatoes, legumes, and spinach.

Vitamin B9 (folate) is needed for proper one-carbon metabolism and thus requisite in synthesis of serotonin, norepinephrine, dopamine, and DNA and in phospholipid production. Low maternal folate status increases the risk of neural tube defects in newborns. Folate deficiency and insufficiency are common among patients with mood disorders and correlate with illness severity.¹¹ In a study of 2,682 Finnish men, those in the lowest one-third of folate consumption had a 67% increased relative risk of depression.¹² A meta-analysis of 11 studies of 15,315 persons found those who had low folate levels had a significant risk of depression.¹³ Patients without deficiency but with folate levels near the low end of the normal range also report low mood.¹⁴ Compared with controls, patients experiencing a first episode of psychosis have lower levels of folate, B12, and docosahexaenoic acid.¹⁵

Dietary folate must be converted to L-methylfolate for use in the brain. Patients with a methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism produce a less active form of the enzyme. The TT genotype is associated with major depression and bipolar disorder.¹⁶ Clinical trials have shown that several forms of folate can enhance antidepressant treatment.¹⁷ Augmentation with L-methylfolate, which bypasses the MTHFR enzyme, can be an effective strategy for treating depression in these patients.¹⁸

Leafy greens and legumes such as lentils are top dietary sources of folate; supplemental folic acid has been linked to an increased risk of cancer and overall mortality.^19,20

Vitamin B12 (cobalamin). An essential cofactor in one-carbon metabolism, B12 is needed to produce monoamine neurotransmitters and maintain myelin. Deficiency is found in up to one-third of depressed patients¹¹ and compromises antidepressant response,²¹ whereas higher vitamin B12 levels are associated with better treatment outcomes.²² B12 deficiency can cause depression, irritability, agitation, psychosis, and obsessive symptoms.^23,24 Low B12 levels and elevated homocysteine increase the risk of cognitive decline and Alzheimer’s disease and are linked to a 5-fold increase in the rate of brain atrophy.²⁶

B12 deficiencies may be seen in patients with gastrointestinal illness, older adults with achlorhydria, and vegans and vegetarians, in whom B12 intake can be low. Proton pump inhibitors such as omeprazole interfere with B12 absorption from food.

Psychiatric symptoms of B12 deficiency may present before hematologic findings.²³ Folic acid supplementation may mask a B12 deficiency by delaying anemia but will not delay psychiatric symptoms. Ten percent of patients with an insufficiency (low normal levels of 200 to 400 pg/mL) have elevated homocysteine, which increases the risk of psychiatric disorders as well as comorbid illnesses such as cardiovascular disease. Top dietary sources include fish, mollusks (oysters, mussels, and clams), meat, and dairy products.

Vitamin C is vital for the synthesis of monoamines such as serotonin and norepinephrine. Vitamin C’s primary role in the brain is as an antioxidant. As a necessary cofactor, it keeps the copper and iron in metalloenzymes reduced, and also recycles vitamin E. Proper function of the methylation cycle depends on vitamin C, as does collagen synthesis and metabolism of xenobiotics by the liver. It is concentrated in cerebrospinal fluid.

Humans cannot manufacture vitamin C. Although the need for vitamin C (90 mg/d) is thought to be met by diet, studies have found that up to 13.7% of healthy, middle class patients in the United States are depleted.²⁷ Older adults and patients with a poor diet due to drug or alcohol abuse, eating disorders, or affective symptoms are at risk.

Scurvy is caused by vitamin C deficiency and leads to bleeding gums and petechiae. Patients with insufficiency report irritability, loss of appetite, weight loss, and hypochondriasis. Vitamin C intake is significantly lower in older adults (age ≥60) with depression.²⁸ Some research indicates patients with schizophrenia have decreased vitamin C levels and dysfunction of antioxidant defenses.²⁹ Citrus, potatoes, and tomatoes are top dietary sources of vitamin C.

Fat-soluble vitamins

Vitamin A. Although vitamin A activity in the brain is poorly understood, retinol—the active form of vitamin A—is crucial for formation of opsins, which are the basis for vision. Childhood vitamin A deficiency may lead to blindness. Vitamin A also plays an important role in maintaining bone growth, reproduction, cell division, and immune system integrity.³⁰ Animal sources such as beef liver, dairy products, and eggs provide retinol, and plant sources such as carrots, sweet potatoes, and leafy greens provide provitamin A carotenoids that humans convert into retinol.

Deficiency rarely is observed in the United States but remains a common problem for developing nations. In the United States, vitamin A deficiency is most often seen with excessive alcohol use, rigorous dietary restrictions, and gastrointestinal diseases accompanied by poor fat absorption.

Excess vitamin A ingestion may result in bone abnormalities, liver damage, birth defects, and depression. Isotretinoin—a form of vitamin A used to treat severe acne—carries an FDA “black-box” warning for psychiatric adverse effects, including aggression, depression, psychosis, and suicide.

Vitamin D is produced from cholesterol in the epidermis through exposure to sunlight, namely ultraviolet B radiation. After dermal synthesis or ingestion, vitamin D is converted through a series of steps into the active form of vitamin D, calcitriol, which also is known as 25(OH)D3.

Although vitamin D is known for its role in bone growth and mineralization,³¹ increasing evidence reveals vitamin D’s role in brain function and development.³² Both glial and neuronal cells possess vitamin D receptors in the hippocampus, prefrontal cortex, hypothalamus, thalamus, and substantia nigra—all regions theorized to be linked to depression pathophysiology.³³ A review of the association of vitamin D deficiency and psychiatric illnesses will be published in a future issue of Current Psychiatry.

Vitamin D exists in food as either D2 or D3, from plant and animal sources, respectively. Concentrated sources include oily fish, sun-dried or “UVB-irradiated” mushrooms, and milk.

Vitamin E. There are 8 isoforms of vitamin E—4 tocopherols and 4 tocotrienols—that function as fat-soluble antioxidants and also promote innate antioxidant enzymes. Because vitamin E protects neuronal membranes from oxidation, low levels may affect the brain via increased inflammation. Alpha-tocopherol is the most common form of vitamin E in humans, but emerging evidence suggests tocotrienols mediate disease by modifying transcription factors in the brain, such as glutathione reductase, superoxide dismutase, and nuclear factor-kappaB.³⁴ Low plasma vitamin E levels are found in depressed patients, although some data suggest this may be caused by factors other than dietary intake.³⁵ Low vitamin status has been found in up to 70% of older adults.³⁶ Although deficiency is rare, most of the U.S. population (93%) has inadequate dietary intake of vitamin E.¹ The reasons for this discrepancy are unclear. Foods rich in vitamin E include almonds, sunflower seeds, leafy greens, and wheat germ.

Recommendations

Patients with depression, alcohol abuse, eating disorders, obsessive-compulsive disorder, or schizophrenia may neglect to care for themselves or adopt particular eating patterns. Deficiencies are more common among geriatric patients and those who are medically ill. Because dietary patterns are linked to the risk of psychiatric disorders, nutritional inquiry often identifies multiple modifiable risk factors, such as folate, vitamin B12, and vitamin D intake.^37,38 Nutritional counseling offers clinicians an intervention with minimal side effect risks and the opportunity to modify a behavior that patients engage in 3 times a day.

Psychiatrists should assess patients’ dietary patterns and vitamin status, particularly older adults and those with:

• lower socioeconomic status or food insecurity
• a history of treatment resistance
• restrictive dietary patterns such as veganism
• alcohol abuse.

On initial assessment, test or obtain from other health care providers your patient’s blood levels of folate and vitamins D and B12. In some patients, assessing B2 and B6 levels may provide etiological guidance regarding onset of psychiatric symptoms or failure to respond to pharmacologic treatment. Because treating vitamin deficiencies often includes using supplements, evaluate recent reviews of specific deficiencies and consider consulting with the patient’s primary care provider.

Conduct a simple assessment of dietary patterns by asking patients about a typical breakfast, lunch, and dinner, their favorite snacks and foods, and specific dietary habits or restrictions (eg, not consuming seafood, dairy, meat, etc.). Rudimentary nutritional recommendations can be effective in changing a patient’s eating habits, particularly when provided by a physician. Encourage patients to eat nutrient-dense foods such as leafy greens, beans and legumes, seafood, whole grains, and a variety of vegetables and fruits. For more complex patients, consult with a clinical nutritionist.

Related Resources

• Institute of Medicine. Dietary Reference Intakes: Recommended intakes for individuals. SummaryDRIs/~/media/Files
  /Activity%20Files/Nutrition
  /DRIs/5_Summary%20Table%20Tables%201-4.pdf" target="_blank">www.iom.edu/Activities/Nutrition/
  SummaryDRIs/~/media/Files
  /Activity%20Files/Nutrition
  /DRIs/5_Summary%20Table%20Tables%201-4.pdf.
• The Farmacy: Vitamins. http://drewramseymd.com/index.php/resources/farmacy/category/vitamins.
• Office of Dietary Supplements. National Institutes of Health. Dietary supplements fact sheets. http://ods.od.nih.gov/factsheets/list-all.
• Oregon State University. Linus Pauling Institute. Micronutrient information center. http://lpi.oregonstate.edu/infocenter/vitamins.html.

Drug Brand Names

• Isotretinoin • Accutane
• L-methylfolate • Deplin
• Omeprazole • Prilosec

Disclosure

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Discuss this article at www.facebook.com/CurrentPsychiatry

Patients today often are overfed but undernourished. A growing body of literature links dietary choices to brain health and the risk of psychiatric illness. Vitamin deficiencies can affect psychiatric patients in several ways:

• deficiencies may play a causative role in mental illness and exacerbate symptoms
• psychiatric symptoms can result in poor nutrition
• vitamin insufficiency—defined as subclinical deficiency—may compromise patient recovery.

Additionally, genetic differences may compromise vitamin and essential nutrient pathways.

Vitamins are dietary components other than carbohydrates, fats, minerals, and proteins that are necessary for life. B vitamins are required for proper functioning of the methylation cycle, monoamine production, DNA synthesis, and maintenance of phospholipids such as myelin (Figure). Fat-soluble vitamins A, D, and E play important roles in genetic transcription, antioxidant recycling, and inflammatory regulation in the brain.

Figure: The methylation cycle
Vitamins B2, B6, B9, and B12 directly impact the functioning of the methylation cycle. Deficiencies pertain to brain function, as neurotransmitters, myelin, and active glutathione are dependent on one-carbon metabolism
Illustration: Mala Nimalasuriya with permission from DrewRamseyMD.com

To help clinicians recognize and treat vitamin deficiencies among psychiatric patients, this article reviews the role of the 6 essential water-soluble vitamins (B1, B2, B6, B9, B12, and C; Table 1,¹) and 3 fat-soluble vitamins (A, D, and E; Table 2,¹) in brain metabolism and psychiatric pathology. Because numerous sources address using supplements to treat vitamin deficiencies, this article emphasizes food sources, which for many patients are adequate to sustain nutrient status.

Table 1

Water-soluble vitamins: Deficiency, insufficiency, symptoms, and dietary sources

Table 2

Fat-soluble vitamins: Deficiency, insufficiency, symptoms, and dietary sources

Water-soluble vitamins

Vitamin B1 (thiamine) is essential for glucose metabolism. Pregnancy, lactation, and fever increase the need for thiamine, and tea, coffee, and shellfish can impair its absorption. Although rare, severe B1 deficiency can lead to beriberi, Wernicke’s encephalopathy (confusion, ataxia, nystagmus), and Korsakoff’s psychosis (confabulation, lack of insight, retrograde and anterograde amnesia, and apathy). Confusion and disorientation stem from the brain’s inability to oxidize glucose for energy because B1 is a critical cofactor in glycolysis and the tricarboxylic acid cycle. Deficiency leads to an increase in reactive oxygen species, proinflammatory cytokines, and blood-brain barrier dysfunction.² Wernicke’s encephalopathy is most frequently encountered in patients with chronic alcoholism, diabetes, or eating disorders, and after bariatric surgery.³ Iatrogenic Wernicke’s encephalopathy may occur when depleted patients receive IV saline with dextrose without receiving thiamine. Top dietary sources of B1 include pork, fish, beans, lentils, nuts, rice, and wheat germ.

Vitamin B2 (riboflavin) is essential for oxidative pathways, monoamine synthesis, and the methylation cycle. B2 is needed to create the essential flavoprotein coenzymes for synthesis of L-methylfolate—the active form of folate—and for proper utilization of B6. Deficiency can occur after 4 months of inadequate intake.

Although generally B2 deficiency is rare, surveys in the United States have found that 10% to 27% of older adults (age ≥65) are deficient.⁴ Low intake of dairy products and meat and chronic, excessive alcohol intake are associated with deficiency. Marginal B2 levels are more prevalent in depressed patients, possibly because of B2’s role in the function of glutathione, an endogenous antioxidant.⁵ Top dietary sources of B2 are dairy products, meat and fish, eggs, mushrooms, almonds, leafy greens, and legumes.

Vitamin B6 refers to 3 distinct compounds: pyridoxine, pyridoxal, and pyridoxamine. B6 is essential to glycolysis, the methylation cycle, and recharging glutathione, an innate antioxidant in the brain. Higher levels of vitamin B6 are associated with a lower prevalence of depression in adolescents,⁶ and low dietary and plasma B6 increases the risk and severity of depression in geriatric patients⁷ and predicts depression in prospective trials.⁸ Deficiency is common (24% to 56%) among patients receiving hemodialysis.⁹ Women who take oral contraceptives are at increased risk of vitamin B6 deficiency.¹⁰ Top dietary sources are fish, beef, poultry, potatoes, legumes, and spinach.

Vitamin B9 (folate) is needed for proper one-carbon metabolism and thus requisite in synthesis of serotonin, norepinephrine, dopamine, and DNA and in phospholipid production. Low maternal folate status increases the risk of neural tube defects in newborns. Folate deficiency and insufficiency are common among patients with mood disorders and correlate with illness severity.¹¹ In a study of 2,682 Finnish men, those in the lowest one-third of folate consumption had a 67% increased relative risk of depression.¹² A meta-analysis of 11 studies of 15,315 persons found those who had low folate levels had a significant risk of depression.¹³ Patients without deficiency but with folate levels near the low end of the normal range also report low mood.¹⁴ Compared with controls, patients experiencing a first episode of psychosis have lower levels of folate, B12, and docosahexaenoic acid.¹⁵

Dietary folate must be converted to L-methylfolate for use in the brain. Patients with a methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism produce a less active form of the enzyme. The TT genotype is associated with major depression and bipolar disorder.¹⁶ Clinical trials have shown that several forms of folate can enhance antidepressant treatment.¹⁷ Augmentation with L-methylfolate, which bypasses the MTHFR enzyme, can be an effective strategy for treating depression in these patients.¹⁸

Leafy greens and legumes such as lentils are top dietary sources of folate; supplemental folic acid has been linked to an increased risk of cancer and overall mortality.^19,20

Vitamin B12 (cobalamin). An essential cofactor in one-carbon metabolism, B12 is needed to produce monoamine neurotransmitters and maintain myelin. Deficiency is found in up to one-third of depressed patients¹¹ and compromises antidepressant response,²¹ whereas higher vitamin B12 levels are associated with better treatment outcomes.²² B12 deficiency can cause depression, irritability, agitation, psychosis, and obsessive symptoms.^23,24 Low B12 levels and elevated homocysteine increase the risk of cognitive decline and Alzheimer’s disease and are linked to a 5-fold increase in the rate of brain atrophy.²⁶

B12 deficiencies may be seen in patients with gastrointestinal illness, older adults with achlorhydria, and vegans and vegetarians, in whom B12 intake can be low. Proton pump inhibitors such as omeprazole interfere with B12 absorption from food.

Psychiatric symptoms of B12 deficiency may present before hematologic findings.²³ Folic acid supplementation may mask a B12 deficiency by delaying anemia but will not delay psychiatric symptoms. Ten percent of patients with an insufficiency (low normal levels of 200 to 400 pg/mL) have elevated homocysteine, which increases the risk of psychiatric disorders as well as comorbid illnesses such as cardiovascular disease. Top dietary sources include fish, mollusks (oysters, mussels, and clams), meat, and dairy products.

Vitamin C is vital for the synthesis of monoamines such as serotonin and norepinephrine. Vitamin C’s primary role in the brain is as an antioxidant. As a necessary cofactor, it keeps the copper and iron in metalloenzymes reduced, and also recycles vitamin E. Proper function of the methylation cycle depends on vitamin C, as does collagen synthesis and metabolism of xenobiotics by the liver. It is concentrated in cerebrospinal fluid.

Humans cannot manufacture vitamin C. Although the need for vitamin C (90 mg/d) is thought to be met by diet, studies have found that up to 13.7% of healthy, middle class patients in the United States are depleted.²⁷ Older adults and patients with a poor diet due to drug or alcohol abuse, eating disorders, or affective symptoms are at risk.

Scurvy is caused by vitamin C deficiency and leads to bleeding gums and petechiae. Patients with insufficiency report irritability, loss of appetite, weight loss, and hypochondriasis. Vitamin C intake is significantly lower in older adults (age ≥60) with depression.²⁸ Some research indicates patients with schizophrenia have decreased vitamin C levels and dysfunction of antioxidant defenses.²⁹ Citrus, potatoes, and tomatoes are top dietary sources of vitamin C.

Fat-soluble vitamins

Vitamin A. Although vitamin A activity in the brain is poorly understood, retinol—the active form of vitamin A—is crucial for formation of opsins, which are the basis for vision. Childhood vitamin A deficiency may lead to blindness. Vitamin A also plays an important role in maintaining bone growth, reproduction, cell division, and immune system integrity.³⁰ Animal sources such as beef liver, dairy products, and eggs provide retinol, and plant sources such as carrots, sweet potatoes, and leafy greens provide provitamin A carotenoids that humans convert into retinol.

Deficiency rarely is observed in the United States but remains a common problem for developing nations. In the United States, vitamin A deficiency is most often seen with excessive alcohol use, rigorous dietary restrictions, and gastrointestinal diseases accompanied by poor fat absorption.

Excess vitamin A ingestion may result in bone abnormalities, liver damage, birth defects, and depression. Isotretinoin—a form of vitamin A used to treat severe acne—carries an FDA “black-box” warning for psychiatric adverse effects, including aggression, depression, psychosis, and suicide.

Vitamin D is produced from cholesterol in the epidermis through exposure to sunlight, namely ultraviolet B radiation. After dermal synthesis or ingestion, vitamin D is converted through a series of steps into the active form of vitamin D, calcitriol, which also is known as 25(OH)D3.

Although vitamin D is known for its role in bone growth and mineralization,³¹ increasing evidence reveals vitamin D’s role in brain function and development.³² Both glial and neuronal cells possess vitamin D receptors in the hippocampus, prefrontal cortex, hypothalamus, thalamus, and substantia nigra—all regions theorized to be linked to depression pathophysiology.³³ A review of the association of vitamin D deficiency and psychiatric illnesses will be published in a future issue of Current Psychiatry.

Vitamin D exists in food as either D2 or D3, from plant and animal sources, respectively. Concentrated sources include oily fish, sun-dried or “UVB-irradiated” mushrooms, and milk.

Vitamin E. There are 8 isoforms of vitamin E—4 tocopherols and 4 tocotrienols—that function as fat-soluble antioxidants and also promote innate antioxidant enzymes. Because vitamin E protects neuronal membranes from oxidation, low levels may affect the brain via increased inflammation. Alpha-tocopherol is the most common form of vitamin E in humans, but emerging evidence suggests tocotrienols mediate disease by modifying transcription factors in the brain, such as glutathione reductase, superoxide dismutase, and nuclear factor-kappaB.³⁴ Low plasma vitamin E levels are found in depressed patients, although some data suggest this may be caused by factors other than dietary intake.³⁵ Low vitamin status has been found in up to 70% of older adults.³⁶ Although deficiency is rare, most of the U.S. population (93%) has inadequate dietary intake of vitamin E.¹ The reasons for this discrepancy are unclear. Foods rich in vitamin E include almonds, sunflower seeds, leafy greens, and wheat germ.

Recommendations

Patients with depression, alcohol abuse, eating disorders, obsessive-compulsive disorder, or schizophrenia may neglect to care for themselves or adopt particular eating patterns. Deficiencies are more common among geriatric patients and those who are medically ill. Because dietary patterns are linked to the risk of psychiatric disorders, nutritional inquiry often identifies multiple modifiable risk factors, such as folate, vitamin B12, and vitamin D intake.^37,38 Nutritional counseling offers clinicians an intervention with minimal side effect risks and the opportunity to modify a behavior that patients engage in 3 times a day.

Psychiatrists should assess patients’ dietary patterns and vitamin status, particularly older adults and those with:

• lower socioeconomic status or food insecurity
• a history of treatment resistance
• restrictive dietary patterns such as veganism
• alcohol abuse.

On initial assessment, test or obtain from other health care providers your patient’s blood levels of folate and vitamins D and B12. In some patients, assessing B2 and B6 levels may provide etiological guidance regarding onset of psychiatric symptoms or failure to respond to pharmacologic treatment. Because treating vitamin deficiencies often includes using supplements, evaluate recent reviews of specific deficiencies and consider consulting with the patient’s primary care provider.

Conduct a simple assessment of dietary patterns by asking patients about a typical breakfast, lunch, and dinner, their favorite snacks and foods, and specific dietary habits or restrictions (eg, not consuming seafood, dairy, meat, etc.). Rudimentary nutritional recommendations can be effective in changing a patient’s eating habits, particularly when provided by a physician. Encourage patients to eat nutrient-dense foods such as leafy greens, beans and legumes, seafood, whole grains, and a variety of vegetables and fruits. For more complex patients, consult with a clinical nutritionist.

Related Resources

• Institute of Medicine. Dietary Reference Intakes: Recommended intakes for individuals. SummaryDRIs/~/media/Files
  /Activity%20Files/Nutrition
  /DRIs/5_Summary%20Table%20Tables%201-4.pdf" target="_blank">www.iom.edu/Activities/Nutrition/
  SummaryDRIs/~/media/Files
  /Activity%20Files/Nutrition
  /DRIs/5_Summary%20Table%20Tables%201-4.pdf.
• The Farmacy: Vitamins. http://drewramseymd.com/index.php/resources/farmacy/category/vitamins.
• Office of Dietary Supplements. National Institutes of Health. Dietary supplements fact sheets. http://ods.od.nih.gov/factsheets/list-all.
• Oregon State University. Linus Pauling Institute. Micronutrient information center. http://lpi.oregonstate.edu/infocenter/vitamins.html.

Drug Brand Names

• Isotretinoin • Accutane
• L-methylfolate • Deplin
• Omeprazole • Prilosec

Disclosure

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Delirium is the most common psychiatric disorder on medical/surgical units of general hospitals and is a major cause of consultations for consultation-liaison (C-L) psychiatrists in medical centers.

It primarily afflicts older patients and is characterized by a rapid onset of confusion with hallucinations, delusions, agitation (but sometimes hypoactivity), and fluctuating severity and outcomes. It can be triggered by multiple factors, including dehydration, electrolyte imbalance, upper respiratory infection, urinary tract infections, post-surgical state, and, very commonly, iatrogenic factors. Many medications, especially those with anticholinergic activity, can cause delirium in older patients. Delirium can lead to pronged hospital stays, functional decline, cognitive impairment, and accelerated mortality.¹

So what is the evidence-based treatment for this common and serious neuropsychiatric brain disorder? None exists! Delirium is managed by identifying and addressing underlying factors, as well as supportive medical care (hydration, nutrition, sleep, monitoring vital signs, preventing aspiration, quiet rooms, orientation, and ambulation). Physical restraints are undesirable but may be hard to avoid for severely disinhibited and agitated patients who try to rip out their IV or endotracheal tube or assault staff or family members who try to calm them during their psychotic confusional state.

Doesn’t this sound similar to dementia patients in nursing homes who develop psychosis and agitation and pose management problems for their family and staff? These 2 neuropsychiatric conditions are clinically similar, and the use of antipsychotic agents is not FDA-approved for either of them. Antipsychotics have not been found efficacious for delirium² or dementia with psychosis³ but their use continues. The paradox is that C-L psychiatrists use small doses of antipsychotics routinely for delirium and generally believe that such pharmacologic intervention works in many patients, although some older agents (eg, haloperidol) have been reported to be neurotoxic⁴ and associated with higher mortality in dementia patients with psychosis.^5,6

The relationship of antipsychotic treatment with delirium and dementia is complex, paradoxical, and unsettled. Consider the following:

• Antipsychotics are not approved for the psychosis of dementia despite 17 large, placebo-controlled trials with 4 different second-generation agents.
• The FDA issued a “black-box” warning on all first- and second-generation antipsychotics because of a 1.6-times higher mortality rate among older patients with dementia.
• No placebo-controlled, FDA trials of delirium have been conducted with any antipsychotic agents.
• Clinicians frequently use first- and second-generation antipsychotics for delirium despite the lack of evidence.
• The FDA has not issued a “black-box” warning on antipsychotics for use in delirium as they did for dementia, although typically both populations are older and may be susceptible to the same complications observed in Alzheimer’s disease trials (eg, strokes, transient ischemic attack, and aspiration pneumonia). This may be because of the absence of safety data of antipsychotics in delirium based on industry-sponsored registration clinical trials. No data means no warning, although the risk factors may be present for millions of older patients who have suffered from delirium and have been treated with first-or second-generation antipsychotics.

The current convoluted state of pharmacotherapy for delirium and dementia is likely to continue: dementia patients with psychosis may or may not receive antipsychotics because of the FDA’s “black-box” warning while delirium patients readily receive various antipsychotics based on long-term practice, although not a single antipsychotic has been FDA-approved for delirium. Until a pharmaceutical company decides to conduct a large placebo-controlled trial for delirium, the current widespread, off-label use of antipsychotics in delirium will continue and “black-box” warning will apply only to 1 clinical population of older persons (those with dementia) but not another (those with delirium). Go figure!

Delirium is the most common psychiatric disorder on medical/surgical units of general hospitals and is a major cause of consultations for consultation-liaison (C-L) psychiatrists in medical centers.

It primarily afflicts older patients and is characterized by a rapid onset of confusion with hallucinations, delusions, agitation (but sometimes hypoactivity), and fluctuating severity and outcomes. It can be triggered by multiple factors, including dehydration, electrolyte imbalance, upper respiratory infection, urinary tract infections, post-surgical state, and, very commonly, iatrogenic factors. Many medications, especially those with anticholinergic activity, can cause delirium in older patients. Delirium can lead to pronged hospital stays, functional decline, cognitive impairment, and accelerated mortality.¹

So what is the evidence-based treatment for this common and serious neuropsychiatric brain disorder? None exists! Delirium is managed by identifying and addressing underlying factors, as well as supportive medical care (hydration, nutrition, sleep, monitoring vital signs, preventing aspiration, quiet rooms, orientation, and ambulation). Physical restraints are undesirable but may be hard to avoid for severely disinhibited and agitated patients who try to rip out their IV or endotracheal tube or assault staff or family members who try to calm them during their psychotic confusional state.

Doesn’t this sound similar to dementia patients in nursing homes who develop psychosis and agitation and pose management problems for their family and staff? These 2 neuropsychiatric conditions are clinically similar, and the use of antipsychotic agents is not FDA-approved for either of them. Antipsychotics have not been found efficacious for delirium² or dementia with psychosis³ but their use continues. The paradox is that C-L psychiatrists use small doses of antipsychotics routinely for delirium and generally believe that such pharmacologic intervention works in many patients, although some older agents (eg, haloperidol) have been reported to be neurotoxic⁴ and associated with higher mortality in dementia patients with psychosis.^5,6

The relationship of antipsychotic treatment with delirium and dementia is complex, paradoxical, and unsettled. Consider the following:

• Antipsychotics are not approved for the psychosis of dementia despite 17 large, placebo-controlled trials with 4 different second-generation agents.
• The FDA issued a “black-box” warning on all first- and second-generation antipsychotics because of a 1.6-times higher mortality rate among older patients with dementia.
• No placebo-controlled, FDA trials of delirium have been conducted with any antipsychotic agents.
• Clinicians frequently use first- and second-generation antipsychotics for delirium despite the lack of evidence.
• The FDA has not issued a “black-box” warning on antipsychotics for use in delirium as they did for dementia, although typically both populations are older and may be susceptible to the same complications observed in Alzheimer’s disease trials (eg, strokes, transient ischemic attack, and aspiration pneumonia). This may be because of the absence of safety data of antipsychotics in delirium based on industry-sponsored registration clinical trials. No data means no warning, although the risk factors may be present for millions of older patients who have suffered from delirium and have been treated with first-or second-generation antipsychotics.

The current convoluted state of pharmacotherapy for delirium and dementia is likely to continue: dementia patients with psychosis may or may not receive antipsychotics because of the FDA’s “black-box” warning while delirium patients readily receive various antipsychotics based on long-term practice, although not a single antipsychotic has been FDA-approved for delirium. Until a pharmaceutical company decides to conduct a large placebo-controlled trial for delirium, the current widespread, off-label use of antipsychotics in delirium will continue and “black-box” warning will apply only to 1 clinical population of older persons (those with dementia) but not another (those with delirium). Go figure!

Delirium is the most common psychiatric disorder on medical/surgical units of general hospitals and is a major cause of consultations for consultation-liaison (C-L) psychiatrists in medical centers.

It primarily afflicts older patients and is characterized by a rapid onset of confusion with hallucinations, delusions, agitation (but sometimes hypoactivity), and fluctuating severity and outcomes. It can be triggered by multiple factors, including dehydration, electrolyte imbalance, upper respiratory infection, urinary tract infections, post-surgical state, and, very commonly, iatrogenic factors. Many medications, especially those with anticholinergic activity, can cause delirium in older patients. Delirium can lead to pronged hospital stays, functional decline, cognitive impairment, and accelerated mortality.¹

So what is the evidence-based treatment for this common and serious neuropsychiatric brain disorder? None exists! Delirium is managed by identifying and addressing underlying factors, as well as supportive medical care (hydration, nutrition, sleep, monitoring vital signs, preventing aspiration, quiet rooms, orientation, and ambulation). Physical restraints are undesirable but may be hard to avoid for severely disinhibited and agitated patients who try to rip out their IV or endotracheal tube or assault staff or family members who try to calm them during their psychotic confusional state.

Doesn’t this sound similar to dementia patients in nursing homes who develop psychosis and agitation and pose management problems for their family and staff? These 2 neuropsychiatric conditions are clinically similar, and the use of antipsychotic agents is not FDA-approved for either of them. Antipsychotics have not been found efficacious for delirium² or dementia with psychosis³ but their use continues. The paradox is that C-L psychiatrists use small doses of antipsychotics routinely for delirium and generally believe that such pharmacologic intervention works in many patients, although some older agents (eg, haloperidol) have been reported to be neurotoxic⁴ and associated with higher mortality in dementia patients with psychosis.^5,6

The relationship of antipsychotic treatment with delirium and dementia is complex, paradoxical, and unsettled. Consider the following:

• Antipsychotics are not approved for the psychosis of dementia despite 17 large, placebo-controlled trials with 4 different second-generation agents.
• The FDA issued a “black-box” warning on all first- and second-generation antipsychotics because of a 1.6-times higher mortality rate among older patients with dementia.
• No placebo-controlled, FDA trials of delirium have been conducted with any antipsychotic agents.
• Clinicians frequently use first- and second-generation antipsychotics for delirium despite the lack of evidence.
• The FDA has not issued a “black-box” warning on antipsychotics for use in delirium as they did for dementia, although typically both populations are older and may be susceptible to the same complications observed in Alzheimer’s disease trials (eg, strokes, transient ischemic attack, and aspiration pneumonia). This may be because of the absence of safety data of antipsychotics in delirium based on industry-sponsored registration clinical trials. No data means no warning, although the risk factors may be present for millions of older patients who have suffered from delirium and have been treated with first-or second-generation antipsychotics.

The current convoluted state of pharmacotherapy for delirium and dementia is likely to continue: dementia patients with psychosis may or may not receive antipsychotics because of the FDA’s “black-box” warning while delirium patients readily receive various antipsychotics based on long-term practice, although not a single antipsychotic has been FDA-approved for delirium. Until a pharmaceutical company decides to conduct a large placebo-controlled trial for delirium, the current widespread, off-label use of antipsychotics in delirium will continue and “black-box” warning will apply only to 1 clinical population of older persons (those with dementia) but not another (those with delirium). Go figure!

Physicians who have high numbers of difficult patient encounters are more likely to report burnout and related stressor effects than are colleagues with fewer difficult encounters.¹ More of them also perceive that they provide suboptimal care than do colleagues who report fewer difficult patients.¹ These were some of the findings taken from the Minimizing Error, Maximizing Outcome (MEMO) Study that we conducted from 2001 to 2005.¹ But these findings prompted us to wonder: Is that perception accurate?

Whether physicians reporting high numbers of difficult patient encounters actually provide poorer care is unknown. In a recent study of physicians from one large primary care system, patient panels that were more challenging—as determined by higher rates of underinsured, minority, and non-English-speaking patients—were associated with lower quality care.² Hinchey and Jackson found that 2 weeks after initial presentation, patients involved in difficult encounters at a walk-in clinic experienced worsening physical symptoms.³ However, this study did not address whether difficult patient encounters affected the care rendered by providers to patients in general.

A detailed, rigorous model describing the interplay and relationships among difficult encounters, adverse physician outcomes (eg, burnout, dissatisfaction), and patient health outcomes has yet to be developed. To better understand the effects of these interactions, we revisited data from the MEMO study.

The findings that prompted another look at the data
When we conducted the MEMO study, we surveyed 422 physicians working in 119 primary care clinics in the upper Midwest and New York City.⁴ Almost half (49%) of the physicians reported moderately or highly stressful jobs; 27% reported burnout; and 30% were at least moderately likely to leave their practices within 2 years. Of these physicians, 113 (27%) reported high numbers of difficult encounters, which corresponds with other reports of 10% to 37% in primary care settings.^5-7 These 113 physicians were 12.2 times more likely to report burnout compared with colleagues with fewer difficult encounters.¹ They also reported lower job satisfaction, increased stress, more time pressure, and greater intent to leave practice, which are also echoed in other studies.^8-10

We found in our study (and at least one other) that physicians experiencing burnout are often younger and female, work long hours, and practice in a medicine subspecialty.^1,11 Many physicians who care for difficult patients report that they secretly hope these patients will not return.⁶

Our hypothesis
We hypothesized that frequent difficult encounters may amplify an adverse work environment, and that physicians facing time pressure and a lack of work control brought on by these encounters might be unable to sustain a high standard of care for their overall patient load.

METHODS

Participants
Physician and patient participants and design of the MEMO study are described in detail elsewhere.¹² The following, though, is a recap:

We recruited 422 general internists and family physicians from 119 ambulatory care clinics in New York City and the upper Midwest. These regions offered a diverse patient and payer mix. Physicians were asked via on-site presentations and mailed invitations to complete a survey derived from focus groups and the Physician Worklife Survey.^13,14

We also recruited up to 8 patients per participating physician via mailed invitations. Inclusion criteria were a minimum age of 18; a diagnosis of at least one target condition (hypertension, diabetes, congestive heart failure); ability to read in English, Spanish, or Chinese; and at least 2 visits with their primary physician in the previous year.

Here we report on outcomes for those patients with diabetes and hypertension.

Measures
When we initially conducted the study, physicians completed an 8-item Burden of Difficult Encounters measure designed to approximate the frequency of difficult encounters experienced. Latent cluster analyses of this survey measure defined 3 distinct groups of physicians: those who estimated a high, medium, and low frequency of difficult encounters in their practices. Via chart audits, we determined quality of care and errors related to guideline-recommended management and preventive care for hypertension and diabetes. Details of these audits are found elsewhere.⁴

We defined quality care for hypertension as successful blood pressure control (<140/90), and for diabetes, successful control of hemoglobin A1c (≤7.5) and blood pressure (<135/80). One quality point was awarded for each of these 3 measures if achieved for at least 50% of recorded visits over an 18-month period. We calculated the quality score as the proportion of total possible quality points (with 100%=best).

We defined errors as guideline non-adherence and missed opportunities for prevention or management, tailored to each patient’s age, sex, and diagnoses. We calculated the error score as the proportion of total applicable error points (maximum=15; 0%=best). We assigned an error point for each missing process of care, including missed treatment opportunities, inattention to behavioral factors, guideline nonadherence, lack of tobacco use documentation, and missed prevention activities, such as mammograms, cervical cancer screening, colon cancer screening, and depression assessment.

We normalized scores to a range of 0 to 100 by dividing the number of quality or error points by the number of applicable items and multiplying by 100. We calculated quality and error scores for hypertension or diabetes for each patient and averaged them to determine total scores per physician.

Data analysis
Latent cluster analyses identified 3 distinct clusters of physicians based on their reported frequency of difficult encounters.¹ We used a 2-level hierarchical linear model of patients nested under physicians to assess if a higher number of perceived difficult patients was associated with poorer patient care, as measured by quality of care and medical errors, controlling for physician age, sex, and racial/ethnic minority status. To further adjust for negatively biased standard errors (physicians recruited from the same clinics, for example), we applied the Huber-White sandwich estimator.^15,16

We analyzed the association between levels of difficult patients and patient outcomes following a conceptual model. Using Cluster 3 (low frequency of difficult encounters) as the reference group, we tested the direct association of Cluster 1 (high frequency of difficult encounters) and Cluster 2 (medium frequency of encounters) with patient outcomes (eg, errors in diabetes and hypertension management, missed prevention activities, quality benchmarks met). We also tested the adjusted influence of Clusters 1 and 2 on patient outcomes, controlling for the mediators of burnout and satisfaction. Finally, we examined the direct influence of Clusters 1 and 2 on the mediators of burnout and satisfaction.

RESULTS

A total of 449 physicians from 119 clinics consented to participate in MEMO (59.8% of those approached), and 94% of these (n=422) completed the survey.⁴ Compared with participants, nonparticipants did not differ significantly by specialty or sex. Physicians were evenly divided between general internists (51.9%) and family physicians (48.1%). The mean age was 43 (range, 29-89), 44.4% were women, most (83.3%) worked full-time, and 22.0% were from a racial or ethnic minority group. Specific results of the Burden of Encounters measure, depicted in TABLE 1, have been reported previously.¹

TABLE 1
Burden of Difficult Encounters measure¹
Latent cluster analyses of this survey measure were used to assign physicians to one of 3 clusters: those who estimated a low, medium, or high frequency of difficult encounters in their practice.

Physicians were more likely to sort into the high (n=113) and medium (n=268) frequency of difficult encounter clusters as opposed to the low-frequency cluster (n=41) (TABLE 2). Of the 1384 patients whose records were audited, 359 were cared for by high-cluster physicians, 871 by medium-cluster physicians, and 154 by low-cluster physicians. Patients had a mean age of 59.6, 65.6% were women, and they had an average of 4.5 chronic medical conditions. A greater percentage of patients with physicians in the high-frequency cluster had a diagnosis of hypertension, compared with the medium cluster (92.4% vs 87.7%; P<.05). Patients did not differ across physician clusters by age, sex, prevalence of diabetes, or number of chronic diagnoses.

TABLE 2
Physician characteristics across frequency clusters (n=422)¹

We examined the relationship between perceived frequency of difficult encounters and patient outcomes using a double-mediation model with physician burnout and satisfaction as mediators. We found that the greater the perceived number of difficult encounters, the greater the burnout and job dissatisfaction. For example, on a 5-point Likert scale measuring burnout where 1 = no burnout and 5 = significant and persistent burnout, medium-cluster physicians scored 0.48 points higher than the low-cluster physician cohort. High-cluster physicians scored 0.84 points higher than their low-cluster colleagues (both P<.05). Similarly, high-cluster physicians were less satisfied with their jobs; on a 5-point scale where 1 = low satisfaction and 5 = high satisfaction, high-cluster physicians scored 0.60 points lower than low-cluster physicians (P<.05).

Yet, there was no clear association between perceived frequency of difficult encounters and patient outcomes. High-cluster physicians had a 5.57% lower overall error rate compared with low-cluster physicians (P<.05), although this was not true for specific errors, such as those in hypertension or diabetes management, where rates were similar. High-cluster physicians also had a 7.68% lower overall quality rate (P<.05), although, again, this was not true for management of specific conditions such as hypertension and diabetes, where rates were similar. In sum, in our double-mediation model, there was no consistent influence of a physician’s difficult-encounter cluster on patient outcomes, even when including physician burnout and level of satisfaction as mediators.

DISCUSSION

Our principal finding is that the perception of frequent difficult encounters—while associated with significant physician burnout and dissatisfaction—was not associated with worse quality of patient care or higher rates of error. Physicians with a high volume of difficult encounters and burnout maintained standards of care for their patients comparable to those of their peers who experienced less frequent difficult encounters. We propose several hypotheses to explain this observation.

First, the Conservation of Resources (COR) Theory suggests that when resources are depleted or stressed by work demands (difficult encounters), burnout will result.¹⁷ In response, burned-out individuals will reduce their resource expenditure (attention, time) and focus their resources on the most important aspects of their work—in our case, measured quality of care. In the physician-patient communication literature, Williams et al suggest that burned-out physicians use a strictly biomedical style of communication,¹⁸ which is less resource intensive than more patient-centered forms of communication.¹⁹ Thus, while a physician may be burned out and dissatisfied, she or he will focus communication on key clinical aspects of the encounter (the presenting complaint, necessary preventive care) while de-emphasizing the psychosocial aspects of care. Consequently, a physician may be burned out by difficult encounters, but may continue to provide adequate patient care.

Second, these results may reflect (in part) the professional socialization of physicians. The rigors of medical school and residency training provide physicians with a high level of personal hardiness. The nursing literature defines hardiness as the interrelatedness of 3 factors controlled by the individual through lifestyle: control of the environment, commitment to self-fulfilling goals, and reasonable levels of challenge in daily life. Thomsens et al found that these traits serve as buffers to protect individuals from the psychological repercussions of stress.²⁰

Nikou designed a study to investigate the relationships among hardiness, stress, and health-promoting behaviors in students attending a nursing student conference.²¹ The results indicated that hardiness was inversely related to stress and positively related to health-promoting behaviors. Thus, while physicians face challenging and difficult encounters and become burned out and dissatisfied, they are able to deliver acceptable patient care due to the buffering effect of their professional socialization.

Third, physicians’ responses to performance measurement pressures—ubiquitous in the culture of primary care medicine today—may also contribute to our findings. Physicians are called on to meet both national and local standards of care, and are expected to keep patients satisfied. Such objectives may be tied to financial incentives.²² In this environment, many doctors are likely to respond so that quality measures are met, even when faced with a challenging patient encounter. Higashi et al found that the quality of care delivered to patients was better as the number of chronic conditions increased.²³ Others have argued that current clinical practice guidelines, which have driven quality measurement, have led to unintended consequences—for example, polypharmacy with inadequate consideration of adverse drug-drug interactions.^22,24,25

Study limitations. This study is limited by its sample size, which may have restricted our ability to discern small but meaningful differences in quality and errors. In addition, enrollment bias—given that a small number of patients per physician were enrolled—could have muted potential positive findings. If possible, future studies should include outcomes from entire patient panels.

While the objective recording of quality and errors is a strength of this study, data on the frequency of difficult encounters were cross-sectional. As a result, causal relationships between physician-experienced difficulty and patient outcomes were not possible to determine.

Lastly, throughout this study the term “patient outcomes” has been limited to the particular medical outcomes used in our investigation. But it is well recognized that important patient outcomes could also include measures such as satisfaction, trust, medication adherence, and costs.

More to explore. We found that the perception of frequent difficult patient encounters was not associated with poorer patient outcomes, even in the setting of physician dissatisfaction and burnout. Although difficult encounters were associated with physician burnout and job dissatisfaction, it appears that physicians who perceived very frequent difficult patient encounters had comparable standards of care relative to their peers who reported fewer difficult encounters.

Future research should examine additional patient outcomes related to chronic conditions and acute care and their relationship to difficult encounters. Furthermore, other potential consequences of difficult encounters need to be explored, especially those that may result from poor physician-patient communication such as medication adherence, patient satisfaction, and trust.

CORRESPONDENCE
Perry G. An, MD, Newton-Wellesley Hospital, 2014 Washington Street, 2nd Floor, Newton, MA 02462; [email protected]

Physicians who have high numbers of difficult patient encounters are more likely to report burnout and related stressor effects than are colleagues with fewer difficult encounters.¹ More of them also perceive that they provide suboptimal care than do colleagues who report fewer difficult patients.¹ These were some of the findings taken from the Minimizing Error, Maximizing Outcome (MEMO) Study that we conducted from 2001 to 2005.¹ But these findings prompted us to wonder: Is that perception accurate?

Whether physicians reporting high numbers of difficult patient encounters actually provide poorer care is unknown. In a recent study of physicians from one large primary care system, patient panels that were more challenging—as determined by higher rates of underinsured, minority, and non-English-speaking patients—were associated with lower quality care.² Hinchey and Jackson found that 2 weeks after initial presentation, patients involved in difficult encounters at a walk-in clinic experienced worsening physical symptoms.³ However, this study did not address whether difficult patient encounters affected the care rendered by providers to patients in general.

A detailed, rigorous model describing the interplay and relationships among difficult encounters, adverse physician outcomes (eg, burnout, dissatisfaction), and patient health outcomes has yet to be developed. To better understand the effects of these interactions, we revisited data from the MEMO study.

The findings that prompted another look at the data
When we conducted the MEMO study, we surveyed 422 physicians working in 119 primary care clinics in the upper Midwest and New York City.⁴ Almost half (49%) of the physicians reported moderately or highly stressful jobs; 27% reported burnout; and 30% were at least moderately likely to leave their practices within 2 years. Of these physicians, 113 (27%) reported high numbers of difficult encounters, which corresponds with other reports of 10% to 37% in primary care settings.^5-7 These 113 physicians were 12.2 times more likely to report burnout compared with colleagues with fewer difficult encounters.¹ They also reported lower job satisfaction, increased stress, more time pressure, and greater intent to leave practice, which are also echoed in other studies.^8-10

We found in our study (and at least one other) that physicians experiencing burnout are often younger and female, work long hours, and practice in a medicine subspecialty.^1,11 Many physicians who care for difficult patients report that they secretly hope these patients will not return.⁶

Our hypothesis
We hypothesized that frequent difficult encounters may amplify an adverse work environment, and that physicians facing time pressure and a lack of work control brought on by these encounters might be unable to sustain a high standard of care for their overall patient load.

METHODS

Participants
Physician and patient participants and design of the MEMO study are described in detail elsewhere.¹² The following, though, is a recap:

We recruited 422 general internists and family physicians from 119 ambulatory care clinics in New York City and the upper Midwest. These regions offered a diverse patient and payer mix. Physicians were asked via on-site presentations and mailed invitations to complete a survey derived from focus groups and the Physician Worklife Survey.^13,14

We also recruited up to 8 patients per participating physician via mailed invitations. Inclusion criteria were a minimum age of 18; a diagnosis of at least one target condition (hypertension, diabetes, congestive heart failure); ability to read in English, Spanish, or Chinese; and at least 2 visits with their primary physician in the previous year.

Here we report on outcomes for those patients with diabetes and hypertension.

Measures
When we initially conducted the study, physicians completed an 8-item Burden of Difficult Encounters measure designed to approximate the frequency of difficult encounters experienced. Latent cluster analyses of this survey measure defined 3 distinct groups of physicians: those who estimated a high, medium, and low frequency of difficult encounters in their practices. Via chart audits, we determined quality of care and errors related to guideline-recommended management and preventive care for hypertension and diabetes. Details of these audits are found elsewhere.⁴

We defined quality care for hypertension as successful blood pressure control (<140/90), and for diabetes, successful control of hemoglobin A1c (≤7.5) and blood pressure (<135/80). One quality point was awarded for each of these 3 measures if achieved for at least 50% of recorded visits over an 18-month period. We calculated the quality score as the proportion of total possible quality points (with 100%=best).

We defined errors as guideline non-adherence and missed opportunities for prevention or management, tailored to each patient’s age, sex, and diagnoses. We calculated the error score as the proportion of total applicable error points (maximum=15; 0%=best). We assigned an error point for each missing process of care, including missed treatment opportunities, inattention to behavioral factors, guideline nonadherence, lack of tobacco use documentation, and missed prevention activities, such as mammograms, cervical cancer screening, colon cancer screening, and depression assessment.

We normalized scores to a range of 0 to 100 by dividing the number of quality or error points by the number of applicable items and multiplying by 100. We calculated quality and error scores for hypertension or diabetes for each patient and averaged them to determine total scores per physician.

Data analysis
Latent cluster analyses identified 3 distinct clusters of physicians based on their reported frequency of difficult encounters.¹ We used a 2-level hierarchical linear model of patients nested under physicians to assess if a higher number of perceived difficult patients was associated with poorer patient care, as measured by quality of care and medical errors, controlling for physician age, sex, and racial/ethnic minority status. To further adjust for negatively biased standard errors (physicians recruited from the same clinics, for example), we applied the Huber-White sandwich estimator.^15,16

We analyzed the association between levels of difficult patients and patient outcomes following a conceptual model. Using Cluster 3 (low frequency of difficult encounters) as the reference group, we tested the direct association of Cluster 1 (high frequency of difficult encounters) and Cluster 2 (medium frequency of encounters) with patient outcomes (eg, errors in diabetes and hypertension management, missed prevention activities, quality benchmarks met). We also tested the adjusted influence of Clusters 1 and 2 on patient outcomes, controlling for the mediators of burnout and satisfaction. Finally, we examined the direct influence of Clusters 1 and 2 on the mediators of burnout and satisfaction.

RESULTS

A total of 449 physicians from 119 clinics consented to participate in MEMO (59.8% of those approached), and 94% of these (n=422) completed the survey.⁴ Compared with participants, nonparticipants did not differ significantly by specialty or sex. Physicians were evenly divided between general internists (51.9%) and family physicians (48.1%). The mean age was 43 (range, 29-89), 44.4% were women, most (83.3%) worked full-time, and 22.0% were from a racial or ethnic minority group. Specific results of the Burden of Encounters measure, depicted in TABLE 1, have been reported previously.¹

TABLE 1
Burden of Difficult Encounters measure¹
Latent cluster analyses of this survey measure were used to assign physicians to one of 3 clusters: those who estimated a low, medium, or high frequency of difficult encounters in their practice.

Physicians were more likely to sort into the high (n=113) and medium (n=268) frequency of difficult encounter clusters as opposed to the low-frequency cluster (n=41) (TABLE 2). Of the 1384 patients whose records were audited, 359 were cared for by high-cluster physicians, 871 by medium-cluster physicians, and 154 by low-cluster physicians. Patients had a mean age of 59.6, 65.6% were women, and they had an average of 4.5 chronic medical conditions. A greater percentage of patients with physicians in the high-frequency cluster had a diagnosis of hypertension, compared with the medium cluster (92.4% vs 87.7%; P<.05). Patients did not differ across physician clusters by age, sex, prevalence of diabetes, or number of chronic diagnoses.

TABLE 2
Physician characteristics across frequency clusters (n=422)¹

We examined the relationship between perceived frequency of difficult encounters and patient outcomes using a double-mediation model with physician burnout and satisfaction as mediators. We found that the greater the perceived number of difficult encounters, the greater the burnout and job dissatisfaction. For example, on a 5-point Likert scale measuring burnout where 1 = no burnout and 5 = significant and persistent burnout, medium-cluster physicians scored 0.48 points higher than the low-cluster physician cohort. High-cluster physicians scored 0.84 points higher than their low-cluster colleagues (both P<.05). Similarly, high-cluster physicians were less satisfied with their jobs; on a 5-point scale where 1 = low satisfaction and 5 = high satisfaction, high-cluster physicians scored 0.60 points lower than low-cluster physicians (P<.05).

Yet, there was no clear association between perceived frequency of difficult encounters and patient outcomes. High-cluster physicians had a 5.57% lower overall error rate compared with low-cluster physicians (P<.05), although this was not true for specific errors, such as those in hypertension or diabetes management, where rates were similar. High-cluster physicians also had a 7.68% lower overall quality rate (P<.05), although, again, this was not true for management of specific conditions such as hypertension and diabetes, where rates were similar. In sum, in our double-mediation model, there was no consistent influence of a physician’s difficult-encounter cluster on patient outcomes, even when including physician burnout and level of satisfaction as mediators.

DISCUSSION

Our principal finding is that the perception of frequent difficult encounters—while associated with significant physician burnout and dissatisfaction—was not associated with worse quality of patient care or higher rates of error. Physicians with a high volume of difficult encounters and burnout maintained standards of care for their patients comparable to those of their peers who experienced less frequent difficult encounters. We propose several hypotheses to explain this observation.

First, the Conservation of Resources (COR) Theory suggests that when resources are depleted or stressed by work demands (difficult encounters), burnout will result.¹⁷ In response, burned-out individuals will reduce their resource expenditure (attention, time) and focus their resources on the most important aspects of their work—in our case, measured quality of care. In the physician-patient communication literature, Williams et al suggest that burned-out physicians use a strictly biomedical style of communication,¹⁸ which is less resource intensive than more patient-centered forms of communication.¹⁹ Thus, while a physician may be burned out and dissatisfied, she or he will focus communication on key clinical aspects of the encounter (the presenting complaint, necessary preventive care) while de-emphasizing the psychosocial aspects of care. Consequently, a physician may be burned out by difficult encounters, but may continue to provide adequate patient care.

Second, these results may reflect (in part) the professional socialization of physicians. The rigors of medical school and residency training provide physicians with a high level of personal hardiness. The nursing literature defines hardiness as the interrelatedness of 3 factors controlled by the individual through lifestyle: control of the environment, commitment to self-fulfilling goals, and reasonable levels of challenge in daily life. Thomsens et al found that these traits serve as buffers to protect individuals from the psychological repercussions of stress.²⁰

Nikou designed a study to investigate the relationships among hardiness, stress, and health-promoting behaviors in students attending a nursing student conference.²¹ The results indicated that hardiness was inversely related to stress and positively related to health-promoting behaviors. Thus, while physicians face challenging and difficult encounters and become burned out and dissatisfied, they are able to deliver acceptable patient care due to the buffering effect of their professional socialization.

Third, physicians’ responses to performance measurement pressures—ubiquitous in the culture of primary care medicine today—may also contribute to our findings. Physicians are called on to meet both national and local standards of care, and are expected to keep patients satisfied. Such objectives may be tied to financial incentives.²² In this environment, many doctors are likely to respond so that quality measures are met, even when faced with a challenging patient encounter. Higashi et al found that the quality of care delivered to patients was better as the number of chronic conditions increased.²³ Others have argued that current clinical practice guidelines, which have driven quality measurement, have led to unintended consequences—for example, polypharmacy with inadequate consideration of adverse drug-drug interactions.^22,24,25

Study limitations. This study is limited by its sample size, which may have restricted our ability to discern small but meaningful differences in quality and errors. In addition, enrollment bias—given that a small number of patients per physician were enrolled—could have muted potential positive findings. If possible, future studies should include outcomes from entire patient panels.

While the objective recording of quality and errors is a strength of this study, data on the frequency of difficult encounters were cross-sectional. As a result, causal relationships between physician-experienced difficulty and patient outcomes were not possible to determine.

Lastly, throughout this study the term “patient outcomes” has been limited to the particular medical outcomes used in our investigation. But it is well recognized that important patient outcomes could also include measures such as satisfaction, trust, medication adherence, and costs.

More to explore. We found that the perception of frequent difficult patient encounters was not associated with poorer patient outcomes, even in the setting of physician dissatisfaction and burnout. Although difficult encounters were associated with physician burnout and job dissatisfaction, it appears that physicians who perceived very frequent difficult patient encounters had comparable standards of care relative to their peers who reported fewer difficult encounters.

Future research should examine additional patient outcomes related to chronic conditions and acute care and their relationship to difficult encounters. Furthermore, other potential consequences of difficult encounters need to be explored, especially those that may result from poor physician-patient communication such as medication adherence, patient satisfaction, and trust.

CORRESPONDENCE
Perry G. An, MD, Newton-Wellesley Hospital, 2014 Washington Street, 2nd Floor, Newton, MA 02462; [email protected]

Physicians who have high numbers of difficult patient encounters are more likely to report burnout and related stressor effects than are colleagues with fewer difficult encounters.¹ More of them also perceive that they provide suboptimal care than do colleagues who report fewer difficult patients.¹ These were some of the findings taken from the Minimizing Error, Maximizing Outcome (MEMO) Study that we conducted from 2001 to 2005.¹ But these findings prompted us to wonder: Is that perception accurate?

Whether physicians reporting high numbers of difficult patient encounters actually provide poorer care is unknown. In a recent study of physicians from one large primary care system, patient panels that were more challenging—as determined by higher rates of underinsured, minority, and non-English-speaking patients—were associated with lower quality care.² Hinchey and Jackson found that 2 weeks after initial presentation, patients involved in difficult encounters at a walk-in clinic experienced worsening physical symptoms.³ However, this study did not address whether difficult patient encounters affected the care rendered by providers to patients in general.

A detailed, rigorous model describing the interplay and relationships among difficult encounters, adverse physician outcomes (eg, burnout, dissatisfaction), and patient health outcomes has yet to be developed. To better understand the effects of these interactions, we revisited data from the MEMO study.

The findings that prompted another look at the data
When we conducted the MEMO study, we surveyed 422 physicians working in 119 primary care clinics in the upper Midwest and New York City.⁴ Almost half (49%) of the physicians reported moderately or highly stressful jobs; 27% reported burnout; and 30% were at least moderately likely to leave their practices within 2 years. Of these physicians, 113 (27%) reported high numbers of difficult encounters, which corresponds with other reports of 10% to 37% in primary care settings.^5-7 These 113 physicians were 12.2 times more likely to report burnout compared with colleagues with fewer difficult encounters.¹ They also reported lower job satisfaction, increased stress, more time pressure, and greater intent to leave practice, which are also echoed in other studies.^8-10

We found in our study (and at least one other) that physicians experiencing burnout are often younger and female, work long hours, and practice in a medicine subspecialty.^1,11 Many physicians who care for difficult patients report that they secretly hope these patients will not return.⁶

Our hypothesis
We hypothesized that frequent difficult encounters may amplify an adverse work environment, and that physicians facing time pressure and a lack of work control brought on by these encounters might be unable to sustain a high standard of care for their overall patient load.

METHODS

Participants
Physician and patient participants and design of the MEMO study are described in detail elsewhere.¹² The following, though, is a recap:

We recruited 422 general internists and family physicians from 119 ambulatory care clinics in New York City and the upper Midwest. These regions offered a diverse patient and payer mix. Physicians were asked via on-site presentations and mailed invitations to complete a survey derived from focus groups and the Physician Worklife Survey.^13,14

We also recruited up to 8 patients per participating physician via mailed invitations. Inclusion criteria were a minimum age of 18; a diagnosis of at least one target condition (hypertension, diabetes, congestive heart failure); ability to read in English, Spanish, or Chinese; and at least 2 visits with their primary physician in the previous year.

Here we report on outcomes for those patients with diabetes and hypertension.

Measures
When we initially conducted the study, physicians completed an 8-item Burden of Difficult Encounters measure designed to approximate the frequency of difficult encounters experienced. Latent cluster analyses of this survey measure defined 3 distinct groups of physicians: those who estimated a high, medium, and low frequency of difficult encounters in their practices. Via chart audits, we determined quality of care and errors related to guideline-recommended management and preventive care for hypertension and diabetes. Details of these audits are found elsewhere.⁴

We defined quality care for hypertension as successful blood pressure control (<140/90), and for diabetes, successful control of hemoglobin A1c (≤7.5) and blood pressure (<135/80). One quality point was awarded for each of these 3 measures if achieved for at least 50% of recorded visits over an 18-month period. We calculated the quality score as the proportion of total possible quality points (with 100%=best).

We defined errors as guideline non-adherence and missed opportunities for prevention or management, tailored to each patient’s age, sex, and diagnoses. We calculated the error score as the proportion of total applicable error points (maximum=15; 0%=best). We assigned an error point for each missing process of care, including missed treatment opportunities, inattention to behavioral factors, guideline nonadherence, lack of tobacco use documentation, and missed prevention activities, such as mammograms, cervical cancer screening, colon cancer screening, and depression assessment.

We normalized scores to a range of 0 to 100 by dividing the number of quality or error points by the number of applicable items and multiplying by 100. We calculated quality and error scores for hypertension or diabetes for each patient and averaged them to determine total scores per physician.

Data analysis
Latent cluster analyses identified 3 distinct clusters of physicians based on their reported frequency of difficult encounters.¹ We used a 2-level hierarchical linear model of patients nested under physicians to assess if a higher number of perceived difficult patients was associated with poorer patient care, as measured by quality of care and medical errors, controlling for physician age, sex, and racial/ethnic minority status. To further adjust for negatively biased standard errors (physicians recruited from the same clinics, for example), we applied the Huber-White sandwich estimator.^15,16

We analyzed the association between levels of difficult patients and patient outcomes following a conceptual model. Using Cluster 3 (low frequency of difficult encounters) as the reference group, we tested the direct association of Cluster 1 (high frequency of difficult encounters) and Cluster 2 (medium frequency of encounters) with patient outcomes (eg, errors in diabetes and hypertension management, missed prevention activities, quality benchmarks met). We also tested the adjusted influence of Clusters 1 and 2 on patient outcomes, controlling for the mediators of burnout and satisfaction. Finally, we examined the direct influence of Clusters 1 and 2 on the mediators of burnout and satisfaction.

RESULTS

A total of 449 physicians from 119 clinics consented to participate in MEMO (59.8% of those approached), and 94% of these (n=422) completed the survey.⁴ Compared with participants, nonparticipants did not differ significantly by specialty or sex. Physicians were evenly divided between general internists (51.9%) and family physicians (48.1%). The mean age was 43 (range, 29-89), 44.4% were women, most (83.3%) worked full-time, and 22.0% were from a racial or ethnic minority group. Specific results of the Burden of Encounters measure, depicted in TABLE 1, have been reported previously.¹

TABLE 1
Burden of Difficult Encounters measure¹
Latent cluster analyses of this survey measure were used to assign physicians to one of 3 clusters: those who estimated a low, medium, or high frequency of difficult encounters in their practice.

Physicians were more likely to sort into the high (n=113) and medium (n=268) frequency of difficult encounter clusters as opposed to the low-frequency cluster (n=41) (TABLE 2). Of the 1384 patients whose records were audited, 359 were cared for by high-cluster physicians, 871 by medium-cluster physicians, and 154 by low-cluster physicians. Patients had a mean age of 59.6, 65.6% were women, and they had an average of 4.5 chronic medical conditions. A greater percentage of patients with physicians in the high-frequency cluster had a diagnosis of hypertension, compared with the medium cluster (92.4% vs 87.7%; P<.05). Patients did not differ across physician clusters by age, sex, prevalence of diabetes, or number of chronic diagnoses.

TABLE 2
Physician characteristics across frequency clusters (n=422)¹

We examined the relationship between perceived frequency of difficult encounters and patient outcomes using a double-mediation model with physician burnout and satisfaction as mediators. We found that the greater the perceived number of difficult encounters, the greater the burnout and job dissatisfaction. For example, on a 5-point Likert scale measuring burnout where 1 = no burnout and 5 = significant and persistent burnout, medium-cluster physicians scored 0.48 points higher than the low-cluster physician cohort. High-cluster physicians scored 0.84 points higher than their low-cluster colleagues (both P<.05). Similarly, high-cluster physicians were less satisfied with their jobs; on a 5-point scale where 1 = low satisfaction and 5 = high satisfaction, high-cluster physicians scored 0.60 points lower than low-cluster physicians (P<.05).

Yet, there was no clear association between perceived frequency of difficult encounters and patient outcomes. High-cluster physicians had a 5.57% lower overall error rate compared with low-cluster physicians (P<.05), although this was not true for specific errors, such as those in hypertension or diabetes management, where rates were similar. High-cluster physicians also had a 7.68% lower overall quality rate (P<.05), although, again, this was not true for management of specific conditions such as hypertension and diabetes, where rates were similar. In sum, in our double-mediation model, there was no consistent influence of a physician’s difficult-encounter cluster on patient outcomes, even when including physician burnout and level of satisfaction as mediators.

DISCUSSION

Our principal finding is that the perception of frequent difficult encounters—while associated with significant physician burnout and dissatisfaction—was not associated with worse quality of patient care or higher rates of error. Physicians with a high volume of difficult encounters and burnout maintained standards of care for their patients comparable to those of their peers who experienced less frequent difficult encounters. We propose several hypotheses to explain this observation.

First, the Conservation of Resources (COR) Theory suggests that when resources are depleted or stressed by work demands (difficult encounters), burnout will result.¹⁷ In response, burned-out individuals will reduce their resource expenditure (attention, time) and focus their resources on the most important aspects of their work—in our case, measured quality of care. In the physician-patient communication literature, Williams et al suggest that burned-out physicians use a strictly biomedical style of communication,¹⁸ which is less resource intensive than more patient-centered forms of communication.¹⁹ Thus, while a physician may be burned out and dissatisfied, she or he will focus communication on key clinical aspects of the encounter (the presenting complaint, necessary preventive care) while de-emphasizing the psychosocial aspects of care. Consequently, a physician may be burned out by difficult encounters, but may continue to provide adequate patient care.

Second, these results may reflect (in part) the professional socialization of physicians. The rigors of medical school and residency training provide physicians with a high level of personal hardiness. The nursing literature defines hardiness as the interrelatedness of 3 factors controlled by the individual through lifestyle: control of the environment, commitment to self-fulfilling goals, and reasonable levels of challenge in daily life. Thomsens et al found that these traits serve as buffers to protect individuals from the psychological repercussions of stress.²⁰

Nikou designed a study to investigate the relationships among hardiness, stress, and health-promoting behaviors in students attending a nursing student conference.²¹ The results indicated that hardiness was inversely related to stress and positively related to health-promoting behaviors. Thus, while physicians face challenging and difficult encounters and become burned out and dissatisfied, they are able to deliver acceptable patient care due to the buffering effect of their professional socialization.

Third, physicians’ responses to performance measurement pressures—ubiquitous in the culture of primary care medicine today—may also contribute to our findings. Physicians are called on to meet both national and local standards of care, and are expected to keep patients satisfied. Such objectives may be tied to financial incentives.²² In this environment, many doctors are likely to respond so that quality measures are met, even when faced with a challenging patient encounter. Higashi et al found that the quality of care delivered to patients was better as the number of chronic conditions increased.²³ Others have argued that current clinical practice guidelines, which have driven quality measurement, have led to unintended consequences—for example, polypharmacy with inadequate consideration of adverse drug-drug interactions.^22,24,25

Study limitations. This study is limited by its sample size, which may have restricted our ability to discern small but meaningful differences in quality and errors. In addition, enrollment bias—given that a small number of patients per physician were enrolled—could have muted potential positive findings. If possible, future studies should include outcomes from entire patient panels.

While the objective recording of quality and errors is a strength of this study, data on the frequency of difficult encounters were cross-sectional. As a result, causal relationships between physician-experienced difficulty and patient outcomes were not possible to determine.

Lastly, throughout this study the term “patient outcomes” has been limited to the particular medical outcomes used in our investigation. But it is well recognized that important patient outcomes could also include measures such as satisfaction, trust, medication adherence, and costs.

More to explore. We found that the perception of frequent difficult patient encounters was not associated with poorer patient outcomes, even in the setting of physician dissatisfaction and burnout. Although difficult encounters were associated with physician burnout and job dissatisfaction, it appears that physicians who perceived very frequent difficult patient encounters had comparable standards of care relative to their peers who reported fewer difficult encounters.

Future research should examine additional patient outcomes related to chronic conditions and acute care and their relationship to difficult encounters. Furthermore, other potential consequences of difficult encounters need to be explored, especially those that may result from poor physician-patient communication such as medication adherence, patient satisfaction, and trust.

CORRESPONDENCE
Perry G. An, MD, Newton-Wellesley Hospital, 2014 Washington Street, 2nd Floor, Newton, MA 02462; [email protected]

CASE Larry R, a 77-year-old retired college professor, comes in for a checkup because he is planning a trip to Kenya—on a safari he describes excitedly as “the trip of a lifetime.” He’ll be going with a group, but before he signs on he wants to be sure you think he can manage the tour’s “moderate pace.” He also thinks that he’ll “need to get some shots.”

The patient is overweight (BMI 29) and smokes a pipe daily. He has a history of hypertension, hyperlipidemia, and mild osteoarthritis in both knees and hips, all of which are well controlled.

What would you advise Professor R about the health care preparations needed for his big trip?

Chances are you have patients like Professor R—retired and relatively healthy, and endowed with a sense of adventure and the financial resources that make it possible to visit distant lands. With the nation’s 78 million baby boomers starting to reach retirement age—the oldest cohort turned 65 in 2011—you’re likely to see increasing numbers of older patients with plans for international travel in the years ahead.¹

Like their younger counterparts, older people travel for a variety of reasons: Some have planned for decades to take the “trip of a lifetime” when they retire. Others plan longer excursions, sometimes referred to as an adult “gap year,” to relive a long-ago experience, volunteer in an underdeveloped country, or hike and bird watch in a rainforest. Many more are immigrants who travel to visit relatives or friends in their country of origin, usually a lower-income, environmentally depressed locale with a higher incidence of infectious diseases like malaria, typhoid, and hepatitis A. ²

And while the older traveler will have to take many of the same steps to stay healthy as his or her younger counterpart, it is the older traveler who is more likely to have chronic conditions and special needs that require additional preparation. With careful planning, however, even those with decreased faculties, ranging from impaired vision or hearing to mild cognitive impairment, can safely travel abroad.³

A pretravel visit is your opportunity to assess the patient’s fitness to make the trip being planned, ensure optimal management of chronic conditions while traveling, and identify (and recommend steps to mitigate) travel-related risks.

Morbidity and mortality abroad: A review of the risks

Although much pretravel advice centers on the prevention of tropical infectious diseases, such infections account for a very small percentage of deaths of Americans outside of the United States.¹ In fact, the major health risks facing older adults traveling abroad are similar to those they face at home: Cardiovascular events are responsible for the preponderance of deaths and for half of all travel-related illnesses.¹

International travel can be physically demanding for older individuals and injuries are common, accounting for a large proportion of deaths of Americans overseas⁴ and an estimated 25% to 38% of travel-related incidents.^1,5 A third of injury-related deaths of US citizens traveling abroad involve traffic accidents, followed by homicide (17% of cases) and drowning (13%).^1,5 Thus, injury prevention and management of chronic conditions are key issues to address in a pretravel consult.

Even small steps help safeguard older travelers
Older patients planning to travel abroad should schedule an appointment at least 4 to 6 weeks before their departure.² Ask about the locale, political and environmental climate, length of stay, location and type of accommodations, accessibility to health care, and activities planned,⁶ which will enable you to offer both general and destination-specific health and safety tips. When advising older adults with complex comorbidities and/or particularly high-risk itineraries, referral to a travel medicine specialist should be strongly considered.

Exercise. Encourage older patients to initiate a graduated exercise program, starting several months before the trip.³ Even a modest improvement in endurance, strength, and flexibility can reduce the likelihood of injury.

Luggage. The right luggage can benefit your patients. Recommend that older patients purchase lightweight suitcases with wheels, which are easier to maneuver in and out of airports⁶ and less likely to cause muscle strain or musculoskeletal injury.

Insurance. If an individual becomes ill or sustains an injury overseas, the right insurance can be crucial. Advise older adults to review their health insurance policy to see whether it provides overseas coverage. If not, suggest they consider a short-term supplemental policy to cover medical care and evacuation, if needed. Recommend trip cancellation insurance, as well.

Patients should pack pills, medical supplies in a carry-on kit
Encourage all older travelers to compile a personalized travel health kit equipped with common over-the-counter (OTC) medications, prescription drugs, and any personal medical supplies they’ll need, such as a continuous positive airway pressure (CPAP) machine.^1,3 Remind patients to take an ample supply of both prescription and OTC drugs, each in its original labeled container.^3,6 Buying medications outside the United States is not advisable, given the variation in international regulatory standards. Stress the importance of keeping the kit in a carry-on bag.

The health kit should also include descriptions of the patient’s preexisting medical conditions, which you or a nurse or medical assistant in the practice can help to prepare; a list of prescription drugs he or she takes (using both the generic and brand names); and a copy of a recent electrocardiogram, if available, along with contact information in case of an emergency.^1,3,6 A patient who uses injectable medication, such as insulin, should obtain a letter (on the practice’s letterhead) from the prescribing physician and be prepared to show the letter to airport security personnel.^3,6

Staying safe in the air

The lower barometric and oxygen partial pressures found in aircraft cabins, which are pressurized at 5000 to 8000 feet, can affect both the respiratory and cardiovascular systems of older adults—particularly those with pulmonary or cardiac disorders.^6,7 Individuals who do not routinely require oxygen and are able to walk the equivalent of one city block or climb one flight of stairs without shortness of breath should have little trouble compensating for the reduced oxygen in the cabin.³ Patients with stable heart failure, including New York Heart Association grades III and IV, can tolerate flights of up to one hour without additional oxygen.⁷

Advise older adults who will require oxygen that they are not permitted to bring their own oxygen canisters onboard an airplane.¹ In-flight oxygen needs to be ordered at least 7 days before departure, and there may be a charge.⁷ Most airlines have medical consultants available to help patients who will need oxygen or other medical provisions.⁷ In addition, tour companies or travel consultants can help older patients with special needs ensure that they have access to oxygen or other medical supplies at their destination.

Thrombosis—the other in-flight risk
Sometimes referred to as “economy class syndrome” or “traveler’s thrombosis,” the venous stasis of air travel is responsible for a 3-fold increase in the risk of venous thromboembolism (VTE).⁸ While fatal pulmonary embolism is rare, duration of travel and risk of VTE follow a dose-response relationship, with each 2-hour increase in flight time conferring an additional 18% risk.⁸ Other risk factors for VTE include varicose veins, metastatic cancer, major surgery within the past 2 weeks, prior VTE, and BMI >40. Advanced age increases travelers’ risk of VTE, as well.^7,8 The absolute risk, however, is low.

Among travelers older than 50 years, symptomatic VTE occurs at an estimated rate of one in 600 for flights >4 hours and one in 500 for flights >12 hours.^9,10 While there is no evidence that first-class seating lowers the risk, there are preventive measures that patients can take.¹¹

Tell patients to stay hydrated, drinking plenty of fluids but avoiding alcohol during flights of ≥4 hours’ duration. Sedating drugs should be avoided, as well. Advise anyone planning a long flight to either do seated exercises (intermittent calf contractions) or to periodically get up and walk about the cabin.⁹ You may also want to recommend that patients purchase below-the-knee elastic compression stockings to help decrease venous stasis.¹²

There is no evidence to recommend the use of aspirin to prevent VTE.^12,13 But you may consider prescribing a single 40-mg dose of enoxaparin for a patient who has multiple risk factors and will be airborne for >6 hours.¹³

Promote safety and comfort on the ground

It is crucial to remind all travelers about the risks associated with traveling in motor vehicles in other countries. Remind patients to wear seat belts whenever they’re available; exercise caution regarding public transportation, which may be overcrowded and have an increased risk of pickpockets and robbery; and avoid riding on motorcycles and scooters. If they do opt to ride on a scooter, tell them that it’s imperative that they wear a helmet.

Minimize the effects of jet lag
Travelers of any age may experience jet lag, which occurs when the individual’s circadian clock cannot keep pace with travel across time zones.¹⁴ Notably, however, older people appear to suffer less than their younger counterparts.³ Patients traveling great distances are not likely to avoid jet lag completely, of course. Recommend the following strategies:

Start adjusting your schedule in the week before you depart, gradually shifting 2 hours toward congruence with the time zone at your destination.¹⁴

Help reset your circadian rhythm through exposure to bright light, in the morning after eastward travel and in the evening after westward travel.¹⁴

Take it easy at first. An itinerary that accounts for initial fatigue is an important nonpharmacologic management strategy.¹⁴

Avoid sedating medications, including antihistamines, tranquilizers, anti-motion sickness agents, and benzodiazepines, as these can increase falls and confusion in older adults and make jet lag worse.³

Take melatonin. A dose of 0.5 to 5 mg, taken at bedtime, may promote sleep and decrease jet lag symptoms in travelers crossing multiple time zones.¹⁴

Prepare patients to cope with heat …
Unusually hot, humid weather increases morbidity and mortality in the elderly,^3,15 and older patients traveling to such climates will need to take extra precautions. Strenuous exercise in the heat should be avoided, because both thirst and the capacity to conserve salt and water decrease with age.¹⁶ Acclimatization is helped by rest, air-conditioning, loose cotton clothing, brimmed hats, and cool baths or showers.³ Diuretics may have to be adjusted for fluids lost by increased perspiration, and a discussion about a dose reduction should be included in the pretravel consult for patients who take diuretics and will be traveling to a hot, humid climate.

… and increases in altitude
For older adults, exposure to a moderate altitude (<2500 meters) is initially associated with hypoxemia and a reduced exercise capacity, until acclimatization occurs by Day 5.^17,18 Although older adults generally acclimatize well, advise them to limit their activities for the first few days at a higher altitude. This is especially important for patients with coronary artery disease (CAD).

To further ease the effects of a higher altitude, advise patients to drink plenty of fluids, but little or no alcohol.¹⁹ Review the medications of an older patient who will be spending time at very high altitude. Rarely, antihypertensive medication may need to be adjusted. The body compensates for lower oxygen with a faster heart rate, and some antihypertensives may interfere with this compensatory mechanism.³

Precautions (and prophylaxis) may prevent travelers’ diarrhea

Diarrhea—among the most common travel-related conditions²⁰—affects an estimated 30% to 70% of international travelers.² The incidence is highest among visitors to developing countries. Most (80%-90%) of travelers’ diarrhea is due to bacterial infection,²¹ 10% of cases are caused by parasites, and 5% to 8% by viral infection.^2,22

Although increasing age lowers the risk of travelers’ diarrhea,¹ older patients traveling to developing areas should be cautioned to only eat food that is served hot or fruit they can peel themselves; drink only bottled water and sealed liquids; and avoid salad, ice, and food from street vendors.¹ Studies have shown, however, that tourists often get diarrhea despite these safety measures.²

Treatment and prophylaxis. Prophylactic antibiotics can prevent travelers’ diarrhea. But the increased sun sensitivity, drug-drug interactions, and gastrointestinal (GI) adverse effects associated with antibiotics limit their usefulness. Prophylaxis is indicated, however, for older adults for whom the complications of dehydration would likely be so severe that the benefits of using antibiotics to prevent diarrhea clearly outweigh the risks.²³

Fluoroquinolones are a first-line treatment for travelers’ diarrhea. But increasing microbial resistance to this class of drugs, especially among Campylobacter isolates,²⁴ may limit their usefulness in some destinations.²⁵ Azithromycin is recommended in such cases, and has been shown to be equally effective.^26,27 Single-dose therapy is well established with fluoroquinolones, but the best regimen for azithromycin (1 vs 3 days) is still under evaluation.^28,29 Along with instructions on when to take an antibiotic, travelers should be given prescriptions for treatment of travelers’ diarrhea before the start of their trip. Suggest that patients purchase oral rehydration packets to take on their trip, and stress the importance of using them and staying hydrated if diarrhea develops.

Decreased upper GI acidity due to acid-blocking medications such as proton-pump inhibitors can increase the risk for many infections, including salmonella and cholera. Patients taking such medications should be made aware of the risk, and the risks vs benefits of temporarily stopping them should be discussed. Vaccination against cholera should not routinely be recommended.^29,30

Vaccines and pills protect against preventable diseases

An impending trip abroad also presents an opportunity to review the patient’s immunization status, catch up on recommended vaccines, and determine whether any additional vaccinations are needed.

Herpes zoster (HZ). Patients older than 60 years should receive a single dose of the HZ vaccine, whether or not they have a history of this condition. Because this is a live virus-containing vaccine, however, it should not be given to anyone who is immunocompromised.³¹

MMR booster. Adults born before 1957 can be considered immune from both measles and mumps, but not rubella. There is no data on immunization to rubella, but guidelines do not recommend MMR vaccination in the elderly.¹

Pneumococcal polyvalent-23 (PPV-23). One dose of the PPV-23 vaccine is indicated for all adults at age 65. This is especially important for travelers, as the prevalence of pneumococcal disease is likely higher in crowded, urban environments within less developed countries.³¹

Tetanus. Although tetanus is mainly a disease of the elderly, only 45% of men ages 70 years or older and 21% of women in this age group were found to have protective antibodies.^1,32 In 2011, the Advisory Committee on Immunization Practices (ACIP) recommended one dose of tetanus and diphtheria toxoid (Td) every 10 years, with a single dose of tetanus toxoid, diphtheria toxoid, and acellular pertussis (Tdap) vaccine given in place of Td for adults older than 65.³³ Despite ACIP’s recommendation, the vaccine’s use in adults 65 years and older is an off-label indication, as Tdap is only approved for use in those 11 to 64 years of age.³³

Additional vaccines are recommended for travelers, with some indicated for all travelers and others that are destination-specific (TABLE).

TABLE
Which travel-related vaccines does your patient need?

Meds and safety measures can minimize malaria risk
The risk of acquiring malaria differs significantly among travelers, based on destination, duration and type of travel, and season. Choice of antimalarial agents (eg, atovaquone/proguanil, chloroquine, doxycycline, mefloquine, and primaquine) should be made on an individual basis after considering these factors, as well as the resistance patterns of the countries on the patient’s itinerary, his or her medical history, and the adverse effects profile of potential agents. Because many older adults take multiple medications, the possibility of drug-drug interactions must be considered.¹ You’ll find destination-specific recommendations on malaria prevention on the Centers for Disease Control and Prevention’s Travelers’ Health Web site, listed in “Travel and health: Resources for patients and physicians”. For guidance on the best drug to prescribe, you can also consult a travel medicine specialist.²

Patients should be mindful of mosquitos. Stress the importance of preventing mosquito bites (as much as possible). Advise patients traveling to mosquito-infested areas to use insect repellents containing 30% N-diethyl-meta-toluamide (DEET) and permethrin-treated clothing.³⁴ Tell them, too, to wear long sleeves, pants, and footwear that provides full coverage.³⁵ Ensuring that sleeping areas are properly screened or air-conditioned will further reduce the likelihood of mosquito bites.³⁶

CASE After seeing the chief complaint listed as “Traveling to Kenya” on Professor R’s chart, you quickly review the CDC’s Travelers’ Health Web site. You encourage him to stay with his tour group and to wear a seatbelt whenever possible. You also review how to make a personalized travel health kit, and encourage him to register with the Smart Traveler Enrollment Program (STEP) (detailed at https://step.state.gov/rep) before leaving for the safari. You strongly suggest that he consider purchasing additional medical evacuation insurance, as well.

Given the prevalence of travelers’ diarrhea, along with dengue and malaria, in Kenya, you review food and water safety and avoidance of insect-transmitted diseases with the patient, and write a prescription for ciprofloxacin to be taken if he develops diarrhea. Professor R is not at high risk for VTE, but you encourage him to stay hydrated, avoid sedating medications, and be diligent about mobilization during lengthy flights. You recommend melatonin for jet lag.

To adjust to the heat, you recommend that he avoid strenuous exercise in the first few days and drink sufficient fluids throughout the trip. You administer the Tdap vaccine, an adult polio booster, and the hepatitis A vaccine, verify that he has received his pneumococcal and influenza vaccines, and prescribe an antimalarial medication.

And as you walk him toward the door, you offer him one final piece of advice: Take plenty of pictures.

CORRESPONDENCE
Jeffrey D. Schlaudecker, MD, The Christ Hospital/University of Cincinnati Family Medicine Residency Program, 2123 Auburn Avenue #340, Cincinnati, OH 45219; [email protected]

CASE Larry R, a 77-year-old retired college professor, comes in for a checkup because he is planning a trip to Kenya—on a safari he describes excitedly as “the trip of a lifetime.” He’ll be going with a group, but before he signs on he wants to be sure you think he can manage the tour’s “moderate pace.” He also thinks that he’ll “need to get some shots.”

The patient is overweight (BMI 29) and smokes a pipe daily. He has a history of hypertension, hyperlipidemia, and mild osteoarthritis in both knees and hips, all of which are well controlled.

What would you advise Professor R about the health care preparations needed for his big trip?

Chances are you have patients like Professor R—retired and relatively healthy, and endowed with a sense of adventure and the financial resources that make it possible to visit distant lands. With the nation’s 78 million baby boomers starting to reach retirement age—the oldest cohort turned 65 in 2011—you’re likely to see increasing numbers of older patients with plans for international travel in the years ahead.¹

Like their younger counterparts, older people travel for a variety of reasons: Some have planned for decades to take the “trip of a lifetime” when they retire. Others plan longer excursions, sometimes referred to as an adult “gap year,” to relive a long-ago experience, volunteer in an underdeveloped country, or hike and bird watch in a rainforest. Many more are immigrants who travel to visit relatives or friends in their country of origin, usually a lower-income, environmentally depressed locale with a higher incidence of infectious diseases like malaria, typhoid, and hepatitis A. ²

And while the older traveler will have to take many of the same steps to stay healthy as his or her younger counterpart, it is the older traveler who is more likely to have chronic conditions and special needs that require additional preparation. With careful planning, however, even those with decreased faculties, ranging from impaired vision or hearing to mild cognitive impairment, can safely travel abroad.³

A pretravel visit is your opportunity to assess the patient’s fitness to make the trip being planned, ensure optimal management of chronic conditions while traveling, and identify (and recommend steps to mitigate) travel-related risks.

Morbidity and mortality abroad: A review of the risks

Although much pretravel advice centers on the prevention of tropical infectious diseases, such infections account for a very small percentage of deaths of Americans outside of the United States.¹ In fact, the major health risks facing older adults traveling abroad are similar to those they face at home: Cardiovascular events are responsible for the preponderance of deaths and for half of all travel-related illnesses.¹

International travel can be physically demanding for older individuals and injuries are common, accounting for a large proportion of deaths of Americans overseas⁴ and an estimated 25% to 38% of travel-related incidents.^1,5 A third of injury-related deaths of US citizens traveling abroad involve traffic accidents, followed by homicide (17% of cases) and drowning (13%).^1,5 Thus, injury prevention and management of chronic conditions are key issues to address in a pretravel consult.

Even small steps help safeguard older travelers
Older patients planning to travel abroad should schedule an appointment at least 4 to 6 weeks before their departure.² Ask about the locale, political and environmental climate, length of stay, location and type of accommodations, accessibility to health care, and activities planned,⁶ which will enable you to offer both general and destination-specific health and safety tips. When advising older adults with complex comorbidities and/or particularly high-risk itineraries, referral to a travel medicine specialist should be strongly considered.

Exercise. Encourage older patients to initiate a graduated exercise program, starting several months before the trip.³ Even a modest improvement in endurance, strength, and flexibility can reduce the likelihood of injury.

Luggage. The right luggage can benefit your patients. Recommend that older patients purchase lightweight suitcases with wheels, which are easier to maneuver in and out of airports⁶ and less likely to cause muscle strain or musculoskeletal injury.

Insurance. If an individual becomes ill or sustains an injury overseas, the right insurance can be crucial. Advise older adults to review their health insurance policy to see whether it provides overseas coverage. If not, suggest they consider a short-term supplemental policy to cover medical care and evacuation, if needed. Recommend trip cancellation insurance, as well.

Patients should pack pills, medical supplies in a carry-on kit
Encourage all older travelers to compile a personalized travel health kit equipped with common over-the-counter (OTC) medications, prescription drugs, and any personal medical supplies they’ll need, such as a continuous positive airway pressure (CPAP) machine.^1,3 Remind patients to take an ample supply of both prescription and OTC drugs, each in its original labeled container.^3,6 Buying medications outside the United States is not advisable, given the variation in international regulatory standards. Stress the importance of keeping the kit in a carry-on bag.

The health kit should also include descriptions of the patient’s preexisting medical conditions, which you or a nurse or medical assistant in the practice can help to prepare; a list of prescription drugs he or she takes (using both the generic and brand names); and a copy of a recent electrocardiogram, if available, along with contact information in case of an emergency.^1,3,6 A patient who uses injectable medication, such as insulin, should obtain a letter (on the practice’s letterhead) from the prescribing physician and be prepared to show the letter to airport security personnel.^3,6

Staying safe in the air

The lower barometric and oxygen partial pressures found in aircraft cabins, which are pressurized at 5000 to 8000 feet, can affect both the respiratory and cardiovascular systems of older adults—particularly those with pulmonary or cardiac disorders.^6,7 Individuals who do not routinely require oxygen and are able to walk the equivalent of one city block or climb one flight of stairs without shortness of breath should have little trouble compensating for the reduced oxygen in the cabin.³ Patients with stable heart failure, including New York Heart Association grades III and IV, can tolerate flights of up to one hour without additional oxygen.⁷

Advise older adults who will require oxygen that they are not permitted to bring their own oxygen canisters onboard an airplane.¹ In-flight oxygen needs to be ordered at least 7 days before departure, and there may be a charge.⁷ Most airlines have medical consultants available to help patients who will need oxygen or other medical provisions.⁷ In addition, tour companies or travel consultants can help older patients with special needs ensure that they have access to oxygen or other medical supplies at their destination.

Thrombosis—the other in-flight risk
Sometimes referred to as “economy class syndrome” or “traveler’s thrombosis,” the venous stasis of air travel is responsible for a 3-fold increase in the risk of venous thromboembolism (VTE).⁸ While fatal pulmonary embolism is rare, duration of travel and risk of VTE follow a dose-response relationship, with each 2-hour increase in flight time conferring an additional 18% risk.⁸ Other risk factors for VTE include varicose veins, metastatic cancer, major surgery within the past 2 weeks, prior VTE, and BMI >40. Advanced age increases travelers’ risk of VTE, as well.^7,8 The absolute risk, however, is low.

Among travelers older than 50 years, symptomatic VTE occurs at an estimated rate of one in 600 for flights >4 hours and one in 500 for flights >12 hours.^9,10 While there is no evidence that first-class seating lowers the risk, there are preventive measures that patients can take.¹¹

Tell patients to stay hydrated, drinking plenty of fluids but avoiding alcohol during flights of ≥4 hours’ duration. Sedating drugs should be avoided, as well. Advise anyone planning a long flight to either do seated exercises (intermittent calf contractions) or to periodically get up and walk about the cabin.⁹ You may also want to recommend that patients purchase below-the-knee elastic compression stockings to help decrease venous stasis.¹²

There is no evidence to recommend the use of aspirin to prevent VTE.^12,13 But you may consider prescribing a single 40-mg dose of enoxaparin for a patient who has multiple risk factors and will be airborne for >6 hours.¹³

Promote safety and comfort on the ground

It is crucial to remind all travelers about the risks associated with traveling in motor vehicles in other countries. Remind patients to wear seat belts whenever they’re available; exercise caution regarding public transportation, which may be overcrowded and have an increased risk of pickpockets and robbery; and avoid riding on motorcycles and scooters. If they do opt to ride on a scooter, tell them that it’s imperative that they wear a helmet.

Minimize the effects of jet lag
Travelers of any age may experience jet lag, which occurs when the individual’s circadian clock cannot keep pace with travel across time zones.¹⁴ Notably, however, older people appear to suffer less than their younger counterparts.³ Patients traveling great distances are not likely to avoid jet lag completely, of course. Recommend the following strategies:

Start adjusting your schedule in the week before you depart, gradually shifting 2 hours toward congruence with the time zone at your destination.¹⁴

Help reset your circadian rhythm through exposure to bright light, in the morning after eastward travel and in the evening after westward travel.¹⁴

Take it easy at first. An itinerary that accounts for initial fatigue is an important nonpharmacologic management strategy.¹⁴

Avoid sedating medications, including antihistamines, tranquilizers, anti-motion sickness agents, and benzodiazepines, as these can increase falls and confusion in older adults and make jet lag worse.³

Take melatonin. A dose of 0.5 to 5 mg, taken at bedtime, may promote sleep and decrease jet lag symptoms in travelers crossing multiple time zones.¹⁴

Prepare patients to cope with heat …
Unusually hot, humid weather increases morbidity and mortality in the elderly,^3,15 and older patients traveling to such climates will need to take extra precautions. Strenuous exercise in the heat should be avoided, because both thirst and the capacity to conserve salt and water decrease with age.¹⁶ Acclimatization is helped by rest, air-conditioning, loose cotton clothing, brimmed hats, and cool baths or showers.³ Diuretics may have to be adjusted for fluids lost by increased perspiration, and a discussion about a dose reduction should be included in the pretravel consult for patients who take diuretics and will be traveling to a hot, humid climate.

… and increases in altitude
For older adults, exposure to a moderate altitude (<2500 meters) is initially associated with hypoxemia and a reduced exercise capacity, until acclimatization occurs by Day 5.^17,18 Although older adults generally acclimatize well, advise them to limit their activities for the first few days at a higher altitude. This is especially important for patients with coronary artery disease (CAD).

To further ease the effects of a higher altitude, advise patients to drink plenty of fluids, but little or no alcohol.¹⁹ Review the medications of an older patient who will be spending time at very high altitude. Rarely, antihypertensive medication may need to be adjusted. The body compensates for lower oxygen with a faster heart rate, and some antihypertensives may interfere with this compensatory mechanism.³

Precautions (and prophylaxis) may prevent travelers’ diarrhea

Diarrhea—among the most common travel-related conditions²⁰—affects an estimated 30% to 70% of international travelers.² The incidence is highest among visitors to developing countries. Most (80%-90%) of travelers’ diarrhea is due to bacterial infection,²¹ 10% of cases are caused by parasites, and 5% to 8% by viral infection.^2,22

Although increasing age lowers the risk of travelers’ diarrhea,¹ older patients traveling to developing areas should be cautioned to only eat food that is served hot or fruit they can peel themselves; drink only bottled water and sealed liquids; and avoid salad, ice, and food from street vendors.¹ Studies have shown, however, that tourists often get diarrhea despite these safety measures.²

Treatment and prophylaxis. Prophylactic antibiotics can prevent travelers’ diarrhea. But the increased sun sensitivity, drug-drug interactions, and gastrointestinal (GI) adverse effects associated with antibiotics limit their usefulness. Prophylaxis is indicated, however, for older adults for whom the complications of dehydration would likely be so severe that the benefits of using antibiotics to prevent diarrhea clearly outweigh the risks.²³

Fluoroquinolones are a first-line treatment for travelers’ diarrhea. But increasing microbial resistance to this class of drugs, especially among Campylobacter isolates,²⁴ may limit their usefulness in some destinations.²⁵ Azithromycin is recommended in such cases, and has been shown to be equally effective.^26,27 Single-dose therapy is well established with fluoroquinolones, but the best regimen for azithromycin (1 vs 3 days) is still under evaluation.^28,29 Along with instructions on when to take an antibiotic, travelers should be given prescriptions for treatment of travelers’ diarrhea before the start of their trip. Suggest that patients purchase oral rehydration packets to take on their trip, and stress the importance of using them and staying hydrated if diarrhea develops.

Decreased upper GI acidity due to acid-blocking medications such as proton-pump inhibitors can increase the risk for many infections, including salmonella and cholera. Patients taking such medications should be made aware of the risk, and the risks vs benefits of temporarily stopping them should be discussed. Vaccination against cholera should not routinely be recommended.^29,30

Vaccines and pills protect against preventable diseases

An impending trip abroad also presents an opportunity to review the patient’s immunization status, catch up on recommended vaccines, and determine whether any additional vaccinations are needed.

Herpes zoster (HZ). Patients older than 60 years should receive a single dose of the HZ vaccine, whether or not they have a history of this condition. Because this is a live virus-containing vaccine, however, it should not be given to anyone who is immunocompromised.³¹

MMR booster. Adults born before 1957 can be considered immune from both measles and mumps, but not rubella. There is no data on immunization to rubella, but guidelines do not recommend MMR vaccination in the elderly.¹

Pneumococcal polyvalent-23 (PPV-23). One dose of the PPV-23 vaccine is indicated for all adults at age 65. This is especially important for travelers, as the prevalence of pneumococcal disease is likely higher in crowded, urban environments within less developed countries.³¹

Tetanus. Although tetanus is mainly a disease of the elderly, only 45% of men ages 70 years or older and 21% of women in this age group were found to have protective antibodies.^1,32 In 2011, the Advisory Committee on Immunization Practices (ACIP) recommended one dose of tetanus and diphtheria toxoid (Td) every 10 years, with a single dose of tetanus toxoid, diphtheria toxoid, and acellular pertussis (Tdap) vaccine given in place of Td for adults older than 65.³³ Despite ACIP’s recommendation, the vaccine’s use in adults 65 years and older is an off-label indication, as Tdap is only approved for use in those 11 to 64 years of age.³³

Additional vaccines are recommended for travelers, with some indicated for all travelers and others that are destination-specific (TABLE).

TABLE
Which travel-related vaccines does your patient need?

Meds and safety measures can minimize malaria risk
The risk of acquiring malaria differs significantly among travelers, based on destination, duration and type of travel, and season. Choice of antimalarial agents (eg, atovaquone/proguanil, chloroquine, doxycycline, mefloquine, and primaquine) should be made on an individual basis after considering these factors, as well as the resistance patterns of the countries on the patient’s itinerary, his or her medical history, and the adverse effects profile of potential agents. Because many older adults take multiple medications, the possibility of drug-drug interactions must be considered.¹ You’ll find destination-specific recommendations on malaria prevention on the Centers for Disease Control and Prevention’s Travelers’ Health Web site, listed in “Travel and health: Resources for patients and physicians”. For guidance on the best drug to prescribe, you can also consult a travel medicine specialist.²

Patients should be mindful of mosquitos. Stress the importance of preventing mosquito bites (as much as possible). Advise patients traveling to mosquito-infested areas to use insect repellents containing 30% N-diethyl-meta-toluamide (DEET) and permethrin-treated clothing.³⁴ Tell them, too, to wear long sleeves, pants, and footwear that provides full coverage.³⁵ Ensuring that sleeping areas are properly screened or air-conditioned will further reduce the likelihood of mosquito bites.³⁶

CASE After seeing the chief complaint listed as “Traveling to Kenya” on Professor R’s chart, you quickly review the CDC’s Travelers’ Health Web site. You encourage him to stay with his tour group and to wear a seatbelt whenever possible. You also review how to make a personalized travel health kit, and encourage him to register with the Smart Traveler Enrollment Program (STEP) (detailed at https://step.state.gov/rep) before leaving for the safari. You strongly suggest that he consider purchasing additional medical evacuation insurance, as well.

Given the prevalence of travelers’ diarrhea, along with dengue and malaria, in Kenya, you review food and water safety and avoidance of insect-transmitted diseases with the patient, and write a prescription for ciprofloxacin to be taken if he develops diarrhea. Professor R is not at high risk for VTE, but you encourage him to stay hydrated, avoid sedating medications, and be diligent about mobilization during lengthy flights. You recommend melatonin for jet lag.

To adjust to the heat, you recommend that he avoid strenuous exercise in the first few days and drink sufficient fluids throughout the trip. You administer the Tdap vaccine, an adult polio booster, and the hepatitis A vaccine, verify that he has received his pneumococcal and influenza vaccines, and prescribe an antimalarial medication.

And as you walk him toward the door, you offer him one final piece of advice: Take plenty of pictures.

CORRESPONDENCE
Jeffrey D. Schlaudecker, MD, The Christ Hospital/University of Cincinnati Family Medicine Residency Program, 2123 Auburn Avenue #340, Cincinnati, OH 45219; [email protected]

CASE Larry R, a 77-year-old retired college professor, comes in for a checkup because he is planning a trip to Kenya—on a safari he describes excitedly as “the trip of a lifetime.” He’ll be going with a group, but before he signs on he wants to be sure you think he can manage the tour’s “moderate pace.” He also thinks that he’ll “need to get some shots.”

The patient is overweight (BMI 29) and smokes a pipe daily. He has a history of hypertension, hyperlipidemia, and mild osteoarthritis in both knees and hips, all of which are well controlled.

What would you advise Professor R about the health care preparations needed for his big trip?

Chances are you have patients like Professor R—retired and relatively healthy, and endowed with a sense of adventure and the financial resources that make it possible to visit distant lands. With the nation’s 78 million baby boomers starting to reach retirement age—the oldest cohort turned 65 in 2011—you’re likely to see increasing numbers of older patients with plans for international travel in the years ahead.¹

Like their younger counterparts, older people travel for a variety of reasons: Some have planned for decades to take the “trip of a lifetime” when they retire. Others plan longer excursions, sometimes referred to as an adult “gap year,” to relive a long-ago experience, volunteer in an underdeveloped country, or hike and bird watch in a rainforest. Many more are immigrants who travel to visit relatives or friends in their country of origin, usually a lower-income, environmentally depressed locale with a higher incidence of infectious diseases like malaria, typhoid, and hepatitis A. ²

And while the older traveler will have to take many of the same steps to stay healthy as his or her younger counterpart, it is the older traveler who is more likely to have chronic conditions and special needs that require additional preparation. With careful planning, however, even those with decreased faculties, ranging from impaired vision or hearing to mild cognitive impairment, can safely travel abroad.³

A pretravel visit is your opportunity to assess the patient’s fitness to make the trip being planned, ensure optimal management of chronic conditions while traveling, and identify (and recommend steps to mitigate) travel-related risks.

Morbidity and mortality abroad: A review of the risks

Although much pretravel advice centers on the prevention of tropical infectious diseases, such infections account for a very small percentage of deaths of Americans outside of the United States.¹ In fact, the major health risks facing older adults traveling abroad are similar to those they face at home: Cardiovascular events are responsible for the preponderance of deaths and for half of all travel-related illnesses.¹

International travel can be physically demanding for older individuals and injuries are common, accounting for a large proportion of deaths of Americans overseas⁴ and an estimated 25% to 38% of travel-related incidents.^1,5 A third of injury-related deaths of US citizens traveling abroad involve traffic accidents, followed by homicide (17% of cases) and drowning (13%).^1,5 Thus, injury prevention and management of chronic conditions are key issues to address in a pretravel consult.

Even small steps help safeguard older travelers
Older patients planning to travel abroad should schedule an appointment at least 4 to 6 weeks before their departure.² Ask about the locale, political and environmental climate, length of stay, location and type of accommodations, accessibility to health care, and activities planned,⁶ which will enable you to offer both general and destination-specific health and safety tips. When advising older adults with complex comorbidities and/or particularly high-risk itineraries, referral to a travel medicine specialist should be strongly considered.

Exercise. Encourage older patients to initiate a graduated exercise program, starting several months before the trip.³ Even a modest improvement in endurance, strength, and flexibility can reduce the likelihood of injury.

Luggage. The right luggage can benefit your patients. Recommend that older patients purchase lightweight suitcases with wheels, which are easier to maneuver in and out of airports⁶ and less likely to cause muscle strain or musculoskeletal injury.

Insurance. If an individual becomes ill or sustains an injury overseas, the right insurance can be crucial. Advise older adults to review their health insurance policy to see whether it provides overseas coverage. If not, suggest they consider a short-term supplemental policy to cover medical care and evacuation, if needed. Recommend trip cancellation insurance, as well.

Patients should pack pills, medical supplies in a carry-on kit
Encourage all older travelers to compile a personalized travel health kit equipped with common over-the-counter (OTC) medications, prescription drugs, and any personal medical supplies they’ll need, such as a continuous positive airway pressure (CPAP) machine.^1,3 Remind patients to take an ample supply of both prescription and OTC drugs, each in its original labeled container.^3,6 Buying medications outside the United States is not advisable, given the variation in international regulatory standards. Stress the importance of keeping the kit in a carry-on bag.

The health kit should also include descriptions of the patient’s preexisting medical conditions, which you or a nurse or medical assistant in the practice can help to prepare; a list of prescription drugs he or she takes (using both the generic and brand names); and a copy of a recent electrocardiogram, if available, along with contact information in case of an emergency.^1,3,6 A patient who uses injectable medication, such as insulin, should obtain a letter (on the practice’s letterhead) from the prescribing physician and be prepared to show the letter to airport security personnel.^3,6

Staying safe in the air

The lower barometric and oxygen partial pressures found in aircraft cabins, which are pressurized at 5000 to 8000 feet, can affect both the respiratory and cardiovascular systems of older adults—particularly those with pulmonary or cardiac disorders.^6,7 Individuals who do not routinely require oxygen and are able to walk the equivalent of one city block or climb one flight of stairs without shortness of breath should have little trouble compensating for the reduced oxygen in the cabin.³ Patients with stable heart failure, including New York Heart Association grades III and IV, can tolerate flights of up to one hour without additional oxygen.⁷

Advise older adults who will require oxygen that they are not permitted to bring their own oxygen canisters onboard an airplane.¹ In-flight oxygen needs to be ordered at least 7 days before departure, and there may be a charge.⁷ Most airlines have medical consultants available to help patients who will need oxygen or other medical provisions.⁷ In addition, tour companies or travel consultants can help older patients with special needs ensure that they have access to oxygen or other medical supplies at their destination.

Thrombosis—the other in-flight risk
Sometimes referred to as “economy class syndrome” or “traveler’s thrombosis,” the venous stasis of air travel is responsible for a 3-fold increase in the risk of venous thromboembolism (VTE).⁸ While fatal pulmonary embolism is rare, duration of travel and risk of VTE follow a dose-response relationship, with each 2-hour increase in flight time conferring an additional 18% risk.⁸ Other risk factors for VTE include varicose veins, metastatic cancer, major surgery within the past 2 weeks, prior VTE, and BMI >40. Advanced age increases travelers’ risk of VTE, as well.^7,8 The absolute risk, however, is low.

Among travelers older than 50 years, symptomatic VTE occurs at an estimated rate of one in 600 for flights >4 hours and one in 500 for flights >12 hours.^9,10 While there is no evidence that first-class seating lowers the risk, there are preventive measures that patients can take.¹¹

Tell patients to stay hydrated, drinking plenty of fluids but avoiding alcohol during flights of ≥4 hours’ duration. Sedating drugs should be avoided, as well. Advise anyone planning a long flight to either do seated exercises (intermittent calf contractions) or to periodically get up and walk about the cabin.⁹ You may also want to recommend that patients purchase below-the-knee elastic compression stockings to help decrease venous stasis.¹²

There is no evidence to recommend the use of aspirin to prevent VTE.^12,13 But you may consider prescribing a single 40-mg dose of enoxaparin for a patient who has multiple risk factors and will be airborne for >6 hours.¹³

Promote safety and comfort on the ground

It is crucial to remind all travelers about the risks associated with traveling in motor vehicles in other countries. Remind patients to wear seat belts whenever they’re available; exercise caution regarding public transportation, which may be overcrowded and have an increased risk of pickpockets and robbery; and avoid riding on motorcycles and scooters. If they do opt to ride on a scooter, tell them that it’s imperative that they wear a helmet.

Minimize the effects of jet lag
Travelers of any age may experience jet lag, which occurs when the individual’s circadian clock cannot keep pace with travel across time zones.¹⁴ Notably, however, older people appear to suffer less than their younger counterparts.³ Patients traveling great distances are not likely to avoid jet lag completely, of course. Recommend the following strategies:

Start adjusting your schedule in the week before you depart, gradually shifting 2 hours toward congruence with the time zone at your destination.¹⁴

Help reset your circadian rhythm through exposure to bright light, in the morning after eastward travel and in the evening after westward travel.¹⁴

Take it easy at first. An itinerary that accounts for initial fatigue is an important nonpharmacologic management strategy.¹⁴

Avoid sedating medications, including antihistamines, tranquilizers, anti-motion sickness agents, and benzodiazepines, as these can increase falls and confusion in older adults and make jet lag worse.³

Take melatonin. A dose of 0.5 to 5 mg, taken at bedtime, may promote sleep and decrease jet lag symptoms in travelers crossing multiple time zones.¹⁴

Prepare patients to cope with heat …
Unusually hot, humid weather increases morbidity and mortality in the elderly,^3,15 and older patients traveling to such climates will need to take extra precautions. Strenuous exercise in the heat should be avoided, because both thirst and the capacity to conserve salt and water decrease with age.¹⁶ Acclimatization is helped by rest, air-conditioning, loose cotton clothing, brimmed hats, and cool baths or showers.³ Diuretics may have to be adjusted for fluids lost by increased perspiration, and a discussion about a dose reduction should be included in the pretravel consult for patients who take diuretics and will be traveling to a hot, humid climate.

… and increases in altitude
For older adults, exposure to a moderate altitude (<2500 meters) is initially associated with hypoxemia and a reduced exercise capacity, until acclimatization occurs by Day 5.^17,18 Although older adults generally acclimatize well, advise them to limit their activities for the first few days at a higher altitude. This is especially important for patients with coronary artery disease (CAD).

To further ease the effects of a higher altitude, advise patients to drink plenty of fluids, but little or no alcohol.¹⁹ Review the medications of an older patient who will be spending time at very high altitude. Rarely, antihypertensive medication may need to be adjusted. The body compensates for lower oxygen with a faster heart rate, and some antihypertensives may interfere with this compensatory mechanism.³

Precautions (and prophylaxis) may prevent travelers’ diarrhea

Diarrhea—among the most common travel-related conditions²⁰—affects an estimated 30% to 70% of international travelers.² The incidence is highest among visitors to developing countries. Most (80%-90%) of travelers’ diarrhea is due to bacterial infection,²¹ 10% of cases are caused by parasites, and 5% to 8% by viral infection.^2,22

Although increasing age lowers the risk of travelers’ diarrhea,¹ older patients traveling to developing areas should be cautioned to only eat food that is served hot or fruit they can peel themselves; drink only bottled water and sealed liquids; and avoid salad, ice, and food from street vendors.¹ Studies have shown, however, that tourists often get diarrhea despite these safety measures.²

Treatment and prophylaxis. Prophylactic antibiotics can prevent travelers’ diarrhea. But the increased sun sensitivity, drug-drug interactions, and gastrointestinal (GI) adverse effects associated with antibiotics limit their usefulness. Prophylaxis is indicated, however, for older adults for whom the complications of dehydration would likely be so severe that the benefits of using antibiotics to prevent diarrhea clearly outweigh the risks.²³

Fluoroquinolones are a first-line treatment for travelers’ diarrhea. But increasing microbial resistance to this class of drugs, especially among Campylobacter isolates,²⁴ may limit their usefulness in some destinations.²⁵ Azithromycin is recommended in such cases, and has been shown to be equally effective.^26,27 Single-dose therapy is well established with fluoroquinolones, but the best regimen for azithromycin (1 vs 3 days) is still under evaluation.^28,29 Along with instructions on when to take an antibiotic, travelers should be given prescriptions for treatment of travelers’ diarrhea before the start of their trip. Suggest that patients purchase oral rehydration packets to take on their trip, and stress the importance of using them and staying hydrated if diarrhea develops.

Decreased upper GI acidity due to acid-blocking medications such as proton-pump inhibitors can increase the risk for many infections, including salmonella and cholera. Patients taking such medications should be made aware of the risk, and the risks vs benefits of temporarily stopping them should be discussed. Vaccination against cholera should not routinely be recommended.^29,30

Vaccines and pills protect against preventable diseases

An impending trip abroad also presents an opportunity to review the patient’s immunization status, catch up on recommended vaccines, and determine whether any additional vaccinations are needed.

Herpes zoster (HZ). Patients older than 60 years should receive a single dose of the HZ vaccine, whether or not they have a history of this condition. Because this is a live virus-containing vaccine, however, it should not be given to anyone who is immunocompromised.³¹

MMR booster. Adults born before 1957 can be considered immune from both measles and mumps, but not rubella. There is no data on immunization to rubella, but guidelines do not recommend MMR vaccination in the elderly.¹

Pneumococcal polyvalent-23 (PPV-23). One dose of the PPV-23 vaccine is indicated for all adults at age 65. This is especially important for travelers, as the prevalence of pneumococcal disease is likely higher in crowded, urban environments within less developed countries.³¹

Tetanus. Although tetanus is mainly a disease of the elderly, only 45% of men ages 70 years or older and 21% of women in this age group were found to have protective antibodies.^1,32 In 2011, the Advisory Committee on Immunization Practices (ACIP) recommended one dose of tetanus and diphtheria toxoid (Td) every 10 years, with a single dose of tetanus toxoid, diphtheria toxoid, and acellular pertussis (Tdap) vaccine given in place of Td for adults older than 65.³³ Despite ACIP’s recommendation, the vaccine’s use in adults 65 years and older is an off-label indication, as Tdap is only approved for use in those 11 to 64 years of age.³³

Additional vaccines are recommended for travelers, with some indicated for all travelers and others that are destination-specific (TABLE).

TABLE
Which travel-related vaccines does your patient need?

Meds and safety measures can minimize malaria risk
The risk of acquiring malaria differs significantly among travelers, based on destination, duration and type of travel, and season. Choice of antimalarial agents (eg, atovaquone/proguanil, chloroquine, doxycycline, mefloquine, and primaquine) should be made on an individual basis after considering these factors, as well as the resistance patterns of the countries on the patient’s itinerary, his or her medical history, and the adverse effects profile of potential agents. Because many older adults take multiple medications, the possibility of drug-drug interactions must be considered.¹ You’ll find destination-specific recommendations on malaria prevention on the Centers for Disease Control and Prevention’s Travelers’ Health Web site, listed in “Travel and health: Resources for patients and physicians”. For guidance on the best drug to prescribe, you can also consult a travel medicine specialist.²

Patients should be mindful of mosquitos. Stress the importance of preventing mosquito bites (as much as possible). Advise patients traveling to mosquito-infested areas to use insect repellents containing 30% N-diethyl-meta-toluamide (DEET) and permethrin-treated clothing.³⁴ Tell them, too, to wear long sleeves, pants, and footwear that provides full coverage.³⁵ Ensuring that sleeping areas are properly screened or air-conditioned will further reduce the likelihood of mosquito bites.³⁶

CASE After seeing the chief complaint listed as “Traveling to Kenya” on Professor R’s chart, you quickly review the CDC’s Travelers’ Health Web site. You encourage him to stay with his tour group and to wear a seatbelt whenever possible. You also review how to make a personalized travel health kit, and encourage him to register with the Smart Traveler Enrollment Program (STEP) (detailed at https://step.state.gov/rep) before leaving for the safari. You strongly suggest that he consider purchasing additional medical evacuation insurance, as well.

Given the prevalence of travelers’ diarrhea, along with dengue and malaria, in Kenya, you review food and water safety and avoidance of insect-transmitted diseases with the patient, and write a prescription for ciprofloxacin to be taken if he develops diarrhea. Professor R is not at high risk for VTE, but you encourage him to stay hydrated, avoid sedating medications, and be diligent about mobilization during lengthy flights. You recommend melatonin for jet lag.

To adjust to the heat, you recommend that he avoid strenuous exercise in the first few days and drink sufficient fluids throughout the trip. You administer the Tdap vaccine, an adult polio booster, and the hepatitis A vaccine, verify that he has received his pneumococcal and influenza vaccines, and prescribe an antimalarial medication.

And as you walk him toward the door, you offer him one final piece of advice: Take plenty of pictures.

CORRESPONDENCE
Jeffrey D. Schlaudecker, MD, The Christ Hospital/University of Cincinnati Family Medicine Residency Program, 2123 Auburn Avenue #340, Cincinnati, OH 45219; [email protected]

CASE Dionne J, a 38-year-old woman with a BMI of 32, presents with a 2-month history of right upper abdominal pain. The pain is intermittent and often begins after eating, she reports, particularly when a meal includes fatty foods. She has no nausea, vomiting, diarrhea, constipation, or fever, and the pain is not getting progressively worse.

When the pain comes on, Ms. J says, it lasts about an hour, sometimes less. It is colicky in nature, and not relieved with bowel movements or position change. The patient tried ranitidine 150 mg twice a day for 2 weeks, with no relief. You suspect functional gallbladder disorder. But is Ms. J a candidate for a cholecystectomy? What would you do next?

Over the past 2 decades, the incidence of cholecystectomies due to functional gallbladder disorder (FGBD) has multiplied, going from about 5% to 20% to 25%.¹ But definitive information about the etiology of FGBD has not kept pace.

Although the Rome III diagnostic guidelines for FGBD, published in 2006,² remain the standard of care, a number of more recent studies have added to our understanding of this disorder. This review of the diagnosis and treatment of FGBD incorporates both the Rome III guidelines and the latest findings. The text and tables that follow can help you recognize this clinical entity earlier, minimize the number of tests needed to arrive at a definitive diagnosis, and establish a plan of care that is consistent with both the guidelines and the evidence.

As obesity rates rise, so does gallbladder dysfunction

Obesity has been shown to produce a chronic proinflammatory state throughout the body,^3-6 which has been linked to fatty infiltration of the gallbladder (among other organs) and impaired contractility.^3,6-9

A study by Al-Azzawi et al highlighted the importance of increased fat in the gallbladder wall as a key cause of dysmotility.¹⁰ The researchers compared wall thickness, inflammation, and the amount of fat in the walls of gallbladders that had been removed for both acalculous and calculous disease with the characteristics of gallbladders removed for reasons unrelated to organ dysfunction (the controls). Those with dysmotility, they found, had more fat in the wall but the same wall thickness as the controls. The amount of fat in the walls was similar for the acalculous and the calculous groups, but the gallbladders in which stones were found had more inflammation and increased wall thickness.¹⁰

Several other studies have found evidence of both inflammation and fatty deposits in the walls of gallbladders removed for acalculous disease.^2,4,11-13

In one study, researchers found chronic inflammation in 99% of gallbladders removed from patients who had classic biliary symptoms but no gallstones.¹¹

FGBD appears to be initiated by fatty infiltration of the gallbladder wall, causing increasing levels of inflammation and steatocholecystitis that lead to poor motility.^3,4,6-10 This in turn alters bile composition, which can lead to sludge and stone formation.^2,6,10 The finding by Al-Azzawi et al of greater thickness and inflammation in the walls of gallbladders with calculi suggests that gallstones result from progressively worsening inflammation and dysmotility.¹⁰

Steps to take for a definitive diagnosis

A diagnosis of FGBD requires a history of classic gallbladder symptoms, many but not all of which are specified in the Rome III diagnostic criteria (TABLE). Classic symptoms include nausea, vomiting, right upper quadrant pain, pain after eating, and reproduction of pain with cholecystokinin (CCK) injection. Cramping, bloating, reflux, diarrhea, fullness, and epigastric pain are atypical symptoms.^2,11

TABLE
Rome III diagnostic criteria for functional gallbladder disorder

Rule out structural causes
There is no single test for FGBD, and a definitive diagnosis can be made only after structural causes of the symptoms (eg, gallstones, tumor, sclerosis, and cirrhosis) have been ruled out (ALGORITHM).² Initial tests include liver and pancreatic enzyme laboratory screening and an ultrasound of the upper right quadrant. In patients with FGBD, both the lab tests and the ultrasound will be normal.

ALGORITHM
Diagnostic workup and management of functional gallbladder disorder (Rome III)

CCK, cholecystokinin; EGD, esophagogastroduodenoscopy; GBEF, gallbladder ejection fraction; HIDA, hepatobiliary iminodiacetic acid; LFTs, liver function tests; US, ultrasound.
Source: Behar J et al. Gastroenterology. 2006;130:1498-1509.² Used with permission from Elsevier.

The Rome III guidelines also call for an esophagogastroduodenoscopy (EGD) to rule out esophagitis, gastritis, and duodenitis, although some researchers have held that if the other tests are normal, this test need not be done.¹² If the EGD is also normal—or not done—a hepatobiliary iminodiacetic acid (HIDA) scan is the next step in the diagnostic pathway. The scan tests the gallbladder’s ejection fraction (EF), revealing the percentage of radioactive dye ejected from the organ after CCK is injected (FIGURE).² The injection of CCK should be done over a minimum of 30 minutes, the guidelines specify. The shorter the time frame used for the injection, the less likely that the pain will be reproduced or that the EF findings will be reliable.¹⁴

FIGURE
Abnormal vs normal HIDA scans: What you’ll see

The larger amount of contrast dye retained in the abnormal scan (A) compared with the normal scan (B) is evidence of a poor ejection fraction.

Most researchers define a normal EF as >35%,^10,11,13 but the Rome III criteria use a cutoff of 40%. A patient who has an EF <40% and meets the other guideline criteria is diagnosed with FGBD.

CASE On physical examination, Ms. J has pain in the right upper quadrant, with no guarding or rebound, and normal bowel sounds. Her liver and pancreatic enzyme tests are normal, and an ultrasound shows no sludge, no stones, and mild edema of the gallbladder wall. The patient declines an EGD because of the cost but undergoes a HIDA scan—which reveals that she has an EF of 25%.

Will cholecystectomy bring long-term relief?

There are 2 options for a patient diagnosed with FGBD—medical management, consisting of lifestyle modifications such as dietary change and weight loss and medication for symptom relief—or cholecystectomy. Surgery should be offered to any individual who, like Ms. J, meets the Rome III diagnostic criteria and has an abnormal HIDA scan. Recent studies have raised questions about the correlation between HIDA results and postoperative relief,^11,12 however, and indicate that patients who have classic biliary symptoms and a normal HIDA scan often have good postoperative outcomes, as well.^11,15

A careful workup is key to ensuring maximal benefit from surgery. The resolution of symptoms with a cholecystectomy when the Rome III criteria are followed for patient selection has been found to be close to 90%.^11,15-20 Two recent studies have examined the resolution rate for FGBD, with conflicting results.^11,12 Both studies were based on long-term postoperative follow-up, ranging from 6 to 24 months. The main difference was the selection bias used in determining eligibility for the study.

The initial selection criteria for the study by Carr et al (N=93) were presenting symptoms (either classic or atypical), followed by a typical workup. The long-term resolution rate for those with classic gallbladder symptoms was 88%¹¹—close to the 90% associated with the Rome III guidelines. The study by Singhal et al (N=141)¹² was done retrospectively, using objective data from tests (ie, normal ultrasound and liver biochemistries and abnormal HIDA) rather than patient history as the criteria for inclusion. Among participants in the Singhal study, the long-term resolution rate was just 57%.

Ironically, the patients in the Carr study who had atypical symptoms had mixed postoperative results. The rate of long-term resolution for this cohort was 57%—the same as the overall resolution rate found by Singhal et al.^11,12 The fact that a group of patients who presented atypically had the same postoperative resolution rate as those for whom tests (rather than symptoms) were used as the selection criteria illustrates the importance of presenting symptoms as a prognostic indicator.

CASE Ms. J opts for a cholecystectomy and you refer her to a general surgeon. At her annual exam the following year, she reports that she has been symptom free since the surgery.

CORRESPONDENCE
David I. Croteau, MD, FAAFP, LRMC Family Medical Center, 300 Parkview Place, Lakeland, FL 33805; [email protected]

CASE Dionne J, a 38-year-old woman with a BMI of 32, presents with a 2-month history of right upper abdominal pain. The pain is intermittent and often begins after eating, she reports, particularly when a meal includes fatty foods. She has no nausea, vomiting, diarrhea, constipation, or fever, and the pain is not getting progressively worse.

When the pain comes on, Ms. J says, it lasts about an hour, sometimes less. It is colicky in nature, and not relieved with bowel movements or position change. The patient tried ranitidine 150 mg twice a day for 2 weeks, with no relief. You suspect functional gallbladder disorder. But is Ms. J a candidate for a cholecystectomy? What would you do next?

Over the past 2 decades, the incidence of cholecystectomies due to functional gallbladder disorder (FGBD) has multiplied, going from about 5% to 20% to 25%.¹ But definitive information about the etiology of FGBD has not kept pace.

Although the Rome III diagnostic guidelines for FGBD, published in 2006,² remain the standard of care, a number of more recent studies have added to our understanding of this disorder. This review of the diagnosis and treatment of FGBD incorporates both the Rome III guidelines and the latest findings. The text and tables that follow can help you recognize this clinical entity earlier, minimize the number of tests needed to arrive at a definitive diagnosis, and establish a plan of care that is consistent with both the guidelines and the evidence.

As obesity rates rise, so does gallbladder dysfunction

Obesity has been shown to produce a chronic proinflammatory state throughout the body,^3-6 which has been linked to fatty infiltration of the gallbladder (among other organs) and impaired contractility.^3,6-9

A study by Al-Azzawi et al highlighted the importance of increased fat in the gallbladder wall as a key cause of dysmotility.¹⁰ The researchers compared wall thickness, inflammation, and the amount of fat in the walls of gallbladders that had been removed for both acalculous and calculous disease with the characteristics of gallbladders removed for reasons unrelated to organ dysfunction (the controls). Those with dysmotility, they found, had more fat in the wall but the same wall thickness as the controls. The amount of fat in the walls was similar for the acalculous and the calculous groups, but the gallbladders in which stones were found had more inflammation and increased wall thickness.¹⁰

Several other studies have found evidence of both inflammation and fatty deposits in the walls of gallbladders removed for acalculous disease.^2,4,11-13

In one study, researchers found chronic inflammation in 99% of gallbladders removed from patients who had classic biliary symptoms but no gallstones.¹¹

FGBD appears to be initiated by fatty infiltration of the gallbladder wall, causing increasing levels of inflammation and steatocholecystitis that lead to poor motility.^3,4,6-10 This in turn alters bile composition, which can lead to sludge and stone formation.^2,6,10 The finding by Al-Azzawi et al of greater thickness and inflammation in the walls of gallbladders with calculi suggests that gallstones result from progressively worsening inflammation and dysmotility.¹⁰

Steps to take for a definitive diagnosis

A diagnosis of FGBD requires a history of classic gallbladder symptoms, many but not all of which are specified in the Rome III diagnostic criteria (TABLE). Classic symptoms include nausea, vomiting, right upper quadrant pain, pain after eating, and reproduction of pain with cholecystokinin (CCK) injection. Cramping, bloating, reflux, diarrhea, fullness, and epigastric pain are atypical symptoms.^2,11

TABLE
Rome III diagnostic criteria for functional gallbladder disorder

Rule out structural causes
There is no single test for FGBD, and a definitive diagnosis can be made only after structural causes of the symptoms (eg, gallstones, tumor, sclerosis, and cirrhosis) have been ruled out (ALGORITHM).² Initial tests include liver and pancreatic enzyme laboratory screening and an ultrasound of the upper right quadrant. In patients with FGBD, both the lab tests and the ultrasound will be normal.

ALGORITHM
Diagnostic workup and management of functional gallbladder disorder (Rome III)

CCK, cholecystokinin; EGD, esophagogastroduodenoscopy; GBEF, gallbladder ejection fraction; HIDA, hepatobiliary iminodiacetic acid; LFTs, liver function tests; US, ultrasound.
Source: Behar J et al. Gastroenterology. 2006;130:1498-1509.² Used with permission from Elsevier.

The Rome III guidelines also call for an esophagogastroduodenoscopy (EGD) to rule out esophagitis, gastritis, and duodenitis, although some researchers have held that if the other tests are normal, this test need not be done.¹² If the EGD is also normal—or not done—a hepatobiliary iminodiacetic acid (HIDA) scan is the next step in the diagnostic pathway. The scan tests the gallbladder’s ejection fraction (EF), revealing the percentage of radioactive dye ejected from the organ after CCK is injected (FIGURE).² The injection of CCK should be done over a minimum of 30 minutes, the guidelines specify. The shorter the time frame used for the injection, the less likely that the pain will be reproduced or that the EF findings will be reliable.¹⁴

FIGURE
Abnormal vs normal HIDA scans: What you’ll see

The larger amount of contrast dye retained in the abnormal scan (A) compared with the normal scan (B) is evidence of a poor ejection fraction.

Most researchers define a normal EF as >35%,^10,11,13 but the Rome III criteria use a cutoff of 40%. A patient who has an EF <40% and meets the other guideline criteria is diagnosed with FGBD.

CASE On physical examination, Ms. J has pain in the right upper quadrant, with no guarding or rebound, and normal bowel sounds. Her liver and pancreatic enzyme tests are normal, and an ultrasound shows no sludge, no stones, and mild edema of the gallbladder wall. The patient declines an EGD because of the cost but undergoes a HIDA scan—which reveals that she has an EF of 25%.

Will cholecystectomy bring long-term relief?

There are 2 options for a patient diagnosed with FGBD—medical management, consisting of lifestyle modifications such as dietary change and weight loss and medication for symptom relief—or cholecystectomy. Surgery should be offered to any individual who, like Ms. J, meets the Rome III diagnostic criteria and has an abnormal HIDA scan. Recent studies have raised questions about the correlation between HIDA results and postoperative relief,^11,12 however, and indicate that patients who have classic biliary symptoms and a normal HIDA scan often have good postoperative outcomes, as well.^11,15

A careful workup is key to ensuring maximal benefit from surgery. The resolution of symptoms with a cholecystectomy when the Rome III criteria are followed for patient selection has been found to be close to 90%.^11,15-20 Two recent studies have examined the resolution rate for FGBD, with conflicting results.^11,12 Both studies were based on long-term postoperative follow-up, ranging from 6 to 24 months. The main difference was the selection bias used in determining eligibility for the study.

The initial selection criteria for the study by Carr et al (N=93) were presenting symptoms (either classic or atypical), followed by a typical workup. The long-term resolution rate for those with classic gallbladder symptoms was 88%¹¹—close to the 90% associated with the Rome III guidelines. The study by Singhal et al (N=141)¹² was done retrospectively, using objective data from tests (ie, normal ultrasound and liver biochemistries and abnormal HIDA) rather than patient history as the criteria for inclusion. Among participants in the Singhal study, the long-term resolution rate was just 57%.

Ironically, the patients in the Carr study who had atypical symptoms had mixed postoperative results. The rate of long-term resolution for this cohort was 57%—the same as the overall resolution rate found by Singhal et al.^11,12 The fact that a group of patients who presented atypically had the same postoperative resolution rate as those for whom tests (rather than symptoms) were used as the selection criteria illustrates the importance of presenting symptoms as a prognostic indicator.

CASE Ms. J opts for a cholecystectomy and you refer her to a general surgeon. At her annual exam the following year, she reports that she has been symptom free since the surgery.

CORRESPONDENCE
David I. Croteau, MD, FAAFP, LRMC Family Medical Center, 300 Parkview Place, Lakeland, FL 33805; [email protected]

CASE Dionne J, a 38-year-old woman with a BMI of 32, presents with a 2-month history of right upper abdominal pain. The pain is intermittent and often begins after eating, she reports, particularly when a meal includes fatty foods. She has no nausea, vomiting, diarrhea, constipation, or fever, and the pain is not getting progressively worse.

When the pain comes on, Ms. J says, it lasts about an hour, sometimes less. It is colicky in nature, and not relieved with bowel movements or position change. The patient tried ranitidine 150 mg twice a day for 2 weeks, with no relief. You suspect functional gallbladder disorder. But is Ms. J a candidate for a cholecystectomy? What would you do next?

Over the past 2 decades, the incidence of cholecystectomies due to functional gallbladder disorder (FGBD) has multiplied, going from about 5% to 20% to 25%.¹ But definitive information about the etiology of FGBD has not kept pace.

Although the Rome III diagnostic guidelines for FGBD, published in 2006,² remain the standard of care, a number of more recent studies have added to our understanding of this disorder. This review of the diagnosis and treatment of FGBD incorporates both the Rome III guidelines and the latest findings. The text and tables that follow can help you recognize this clinical entity earlier, minimize the number of tests needed to arrive at a definitive diagnosis, and establish a plan of care that is consistent with both the guidelines and the evidence.

As obesity rates rise, so does gallbladder dysfunction

Obesity has been shown to produce a chronic proinflammatory state throughout the body,^3-6 which has been linked to fatty infiltration of the gallbladder (among other organs) and impaired contractility.^3,6-9

A study by Al-Azzawi et al highlighted the importance of increased fat in the gallbladder wall as a key cause of dysmotility.¹⁰ The researchers compared wall thickness, inflammation, and the amount of fat in the walls of gallbladders that had been removed for both acalculous and calculous disease with the characteristics of gallbladders removed for reasons unrelated to organ dysfunction (the controls). Those with dysmotility, they found, had more fat in the wall but the same wall thickness as the controls. The amount of fat in the walls was similar for the acalculous and the calculous groups, but the gallbladders in which stones were found had more inflammation and increased wall thickness.¹⁰

Several other studies have found evidence of both inflammation and fatty deposits in the walls of gallbladders removed for acalculous disease.^2,4,11-13

In one study, researchers found chronic inflammation in 99% of gallbladders removed from patients who had classic biliary symptoms but no gallstones.¹¹

FGBD appears to be initiated by fatty infiltration of the gallbladder wall, causing increasing levels of inflammation and steatocholecystitis that lead to poor motility.^3,4,6-10 This in turn alters bile composition, which can lead to sludge and stone formation.^2,6,10 The finding by Al-Azzawi et al of greater thickness and inflammation in the walls of gallbladders with calculi suggests that gallstones result from progressively worsening inflammation and dysmotility.¹⁰

Steps to take for a definitive diagnosis

A diagnosis of FGBD requires a history of classic gallbladder symptoms, many but not all of which are specified in the Rome III diagnostic criteria (TABLE). Classic symptoms include nausea, vomiting, right upper quadrant pain, pain after eating, and reproduction of pain with cholecystokinin (CCK) injection. Cramping, bloating, reflux, diarrhea, fullness, and epigastric pain are atypical symptoms.^2,11

TABLE
Rome III diagnostic criteria for functional gallbladder disorder

Rule out structural causes
There is no single test for FGBD, and a definitive diagnosis can be made only after structural causes of the symptoms (eg, gallstones, tumor, sclerosis, and cirrhosis) have been ruled out (ALGORITHM).² Initial tests include liver and pancreatic enzyme laboratory screening and an ultrasound of the upper right quadrant. In patients with FGBD, both the lab tests and the ultrasound will be normal.

ALGORITHM
Diagnostic workup and management of functional gallbladder disorder (Rome III)

CCK, cholecystokinin; EGD, esophagogastroduodenoscopy; GBEF, gallbladder ejection fraction; HIDA, hepatobiliary iminodiacetic acid; LFTs, liver function tests; US, ultrasound.
Source: Behar J et al. Gastroenterology. 2006;130:1498-1509.² Used with permission from Elsevier.

The Rome III guidelines also call for an esophagogastroduodenoscopy (EGD) to rule out esophagitis, gastritis, and duodenitis, although some researchers have held that if the other tests are normal, this test need not be done.¹² If the EGD is also normal—or not done—a hepatobiliary iminodiacetic acid (HIDA) scan is the next step in the diagnostic pathway. The scan tests the gallbladder’s ejection fraction (EF), revealing the percentage of radioactive dye ejected from the organ after CCK is injected (FIGURE).² The injection of CCK should be done over a minimum of 30 minutes, the guidelines specify. The shorter the time frame used for the injection, the less likely that the pain will be reproduced or that the EF findings will be reliable.¹⁴

FIGURE
Abnormal vs normal HIDA scans: What you’ll see

The larger amount of contrast dye retained in the abnormal scan (A) compared with the normal scan (B) is evidence of a poor ejection fraction.

Most researchers define a normal EF as >35%,^10,11,13 but the Rome III criteria use a cutoff of 40%. A patient who has an EF <40% and meets the other guideline criteria is diagnosed with FGBD.

CASE On physical examination, Ms. J has pain in the right upper quadrant, with no guarding or rebound, and normal bowel sounds. Her liver and pancreatic enzyme tests are normal, and an ultrasound shows no sludge, no stones, and mild edema of the gallbladder wall. The patient declines an EGD because of the cost but undergoes a HIDA scan—which reveals that she has an EF of 25%.

Will cholecystectomy bring long-term relief?

There are 2 options for a patient diagnosed with FGBD—medical management, consisting of lifestyle modifications such as dietary change and weight loss and medication for symptom relief—or cholecystectomy. Surgery should be offered to any individual who, like Ms. J, meets the Rome III diagnostic criteria and has an abnormal HIDA scan. Recent studies have raised questions about the correlation between HIDA results and postoperative relief,^11,12 however, and indicate that patients who have classic biliary symptoms and a normal HIDA scan often have good postoperative outcomes, as well.^11,15

A careful workup is key to ensuring maximal benefit from surgery. The resolution of symptoms with a cholecystectomy when the Rome III criteria are followed for patient selection has been found to be close to 90%.^11,15-20 Two recent studies have examined the resolution rate for FGBD, with conflicting results.^11,12 Both studies were based on long-term postoperative follow-up, ranging from 6 to 24 months. The main difference was the selection bias used in determining eligibility for the study.

The initial selection criteria for the study by Carr et al (N=93) were presenting symptoms (either classic or atypical), followed by a typical workup. The long-term resolution rate for those with classic gallbladder symptoms was 88%¹¹—close to the 90% associated with the Rome III guidelines. The study by Singhal et al (N=141)¹² was done retrospectively, using objective data from tests (ie, normal ultrasound and liver biochemistries and abnormal HIDA) rather than patient history as the criteria for inclusion. Among participants in the Singhal study, the long-term resolution rate was just 57%.

Ironically, the patients in the Carr study who had atypical symptoms had mixed postoperative results. The rate of long-term resolution for this cohort was 57%—the same as the overall resolution rate found by Singhal et al.^11,12 The fact that a group of patients who presented atypically had the same postoperative resolution rate as those for whom tests (rather than symptoms) were used as the selection criteria illustrates the importance of presenting symptoms as a prognostic indicator.

CASE Ms. J opts for a cholecystectomy and you refer her to a general surgeon. At her annual exam the following year, she reports that she has been symptom free since the surgery.

CORRESPONDENCE
David I. Croteau, MD, FAAFP, LRMC Family Medical Center, 300 Parkview Place, Lakeland, FL 33805; [email protected]

ANSWER
The radiograph demonstrates evidence of previous surgery on the sternum. There also is evidence of scarring or discoid atelectasis along the left mid lung.

Of note, though, is a soft tissue mass (about 5 to 6 cm) within the left pulmonary apex. This lesion could represent a rounded infiltrate, an atypical infection such as a mycetoma, or possibly a pulmonary neoplasm.

Since the patient was stable, he was placed on antibiotics with instructions to follow up with his primary care provider for further work-up on the mass. The patient did follow up; the lesion persisted and subsequent biopsy confirmed carcinoma.

ANSWER
The radiograph demonstrates evidence of previous surgery on the sternum. There also is evidence of scarring or discoid atelectasis along the left mid lung.

Of note, though, is a soft tissue mass (about 5 to 6 cm) within the left pulmonary apex. This lesion could represent a rounded infiltrate, an atypical infection such as a mycetoma, or possibly a pulmonary neoplasm.

Since the patient was stable, he was placed on antibiotics with instructions to follow up with his primary care provider for further work-up on the mass. The patient did follow up; the lesion persisted and subsequent biopsy confirmed carcinoma.

ANSWER
The radiograph demonstrates evidence of previous surgery on the sternum. There also is evidence of scarring or discoid atelectasis along the left mid lung.

Of note, though, is a soft tissue mass (about 5 to 6 cm) within the left pulmonary apex. This lesion could represent a rounded infiltrate, an atypical infection such as a mycetoma, or possibly a pulmonary neoplasm.

Since the patient was stable, he was placed on antibiotics with instructions to follow up with his primary care provider for further work-up on the mass. The patient did follow up; the lesion persisted and subsequent biopsy confirmed carcinoma.

ANSWER
The ECG is diagnostic for a septal and anterolateral ST-elevated myocardial infarction (STEMI), suggestive of a recent MI versus left ventricular aneurysm. The ECG is also diagnostic for a recent inferior wall STEMI.

There are Q waves in leads V₁ to V₅ and a 2-mm ST elevation in V₂ to V₆, as well as a T-wave inversion (TWI) in V₂ to V₆ and lead 1. A 1-mm ST elevation, TWI, and small Q waves are noted in leads II, III, and aVF (inferior leads). 

The patient’s abnormal troponin T level assisted with the differential diagnosis. The patient’s normal CK-MB pattern, combined with an elevated troponin T with ECG changes and chest pain reported about one week earlier, supported the diagnosis of a recent acute MI (within the past week). 

The stress test was canceled. Cardiac catheterization was performed and showed a 100% mid left anterior descending (LAD) stenosis, with left to left collaterals, and an 80% right coronary artery (RCA) stenosis. No left ventricular aneurysm was noted.

Interventions included an urgent percutaneous intervention (PCI) coronary stent placement to the LAD and a staged PCI to the RCA at a later date.

ANSWER
The ECG is diagnostic for a septal and anterolateral ST-elevated myocardial infarction (STEMI), suggestive of a recent MI versus left ventricular aneurysm. The ECG is also diagnostic for a recent inferior wall STEMI.

There are Q waves in leads V₁ to V₅ and a 2-mm ST elevation in V₂ to V₆, as well as a T-wave inversion (TWI) in V₂ to V₆ and lead 1. A 1-mm ST elevation, TWI, and small Q waves are noted in leads II, III, and aVF (inferior leads). 

The patient’s abnormal troponin T level assisted with the differential diagnosis. The patient’s normal CK-MB pattern, combined with an elevated troponin T with ECG changes and chest pain reported about one week earlier, supported the diagnosis of a recent acute MI (within the past week). 

The stress test was canceled. Cardiac catheterization was performed and showed a 100% mid left anterior descending (LAD) stenosis, with left to left collaterals, and an 80% right coronary artery (RCA) stenosis. No left ventricular aneurysm was noted.

Interventions included an urgent percutaneous intervention (PCI) coronary stent placement to the LAD and a staged PCI to the RCA at a later date.

ANSWER
The ECG is diagnostic for a septal and anterolateral ST-elevated myocardial infarction (STEMI), suggestive of a recent MI versus left ventricular aneurysm. The ECG is also diagnostic for a recent inferior wall STEMI.

There are Q waves in leads V₁ to V₅ and a 2-mm ST elevation in V₂ to V₆, as well as a T-wave inversion (TWI) in V₂ to V₆ and lead 1. A 1-mm ST elevation, TWI, and small Q waves are noted in leads II, III, and aVF (inferior leads). 

The patient’s abnormal troponin T level assisted with the differential diagnosis. The patient’s normal CK-MB pattern, combined with an elevated troponin T with ECG changes and chest pain reported about one week earlier, supported the diagnosis of a recent acute MI (within the past week). 

The stress test was canceled. Cardiac catheterization was performed and showed a 100% mid left anterior descending (LAD) stenosis, with left to left collaterals, and an 80% right coronary artery (RCA) stenosis. No left ventricular aneurysm was noted.

Interventions included an urgent percutaneous intervention (PCI) coronary stent placement to the LAD and a staged PCI to the RCA at a later date.

ANSWER
The correct answer is gram-negative bacteria (choice “d”); Pseudomonas is the most likely culprit. Candida albicans (choice “a”), a yeast, is an unlikely cause of this problem and even more unlikely to show up on a bacterial culture. Coagulase-positive staph aureus (choice “b”) is typically associated with infections involving the acute onset of redness, pain, swelling, and pus formation, not the indolent, chronic, low-grade process seen in this case. Trichophyton rubrum (choice “c”) is a dermatophyte, the most common fungal cause of athlete’s feet. The bacterial culture could not have grown a dermatophyte, which needs special media and conditions to grow.

DISCUSSSION
Gram-negative interweb impetigo is a relatively common dermatologic entity, which can be caused by any number of organisms found in fecal material. Pseudomonas, Klebsiella, Proteus, and Acinetobacter are among the more common culprits. These types of infections tend to be much more indolent than the more common staph- and strep-caused cellulitis, which are more likely to create acute redness, swelling, pain, and pus. 

Both types of bacterial infections need certain conditions in order to develop. These include excessive heat, sweat, and perhaps most significantly, a break in the skin barrier. Ironically, these fissures are often caused by dermatophytes, in the form of tinea pedis, which is, of course, far better known for causing rashes of the foot.

But tinea pedis is more likely to be found between the third and fourth or the fourth and fifth toes. It creates itching and maceration but rarely causes diffuse redness or edema, and even more rarely leads to pain (unless there is a secondary bacterial infection). As mentioned, given the indolence of this infective process, a culture result showing staph or strep was unlikely.

The culture in this case showed Proteus, for which the minocycline was predictably effective. The rationale for obtaining the acid-fast culture was the possibility of finding Mycobacteria species such as M fortuitum, which is known to cause chronic indolent infections in feet and legs. These, however, more typically manifest with solitary eroded or ulcerated lesions. (Minocycline would have been effective against this organism.)

The use of the topical econazole served two purposes: While this was clearly not classic tinea pedis, it was still possible a dermatophyte or a yeast could have played a role in the creation of the initial fissuring; econazole will help control this, long term. Econazole also has significant antibacterial action and is particularly useful to help prevent future flares.          

ANSWER
The correct answer is gram-negative bacteria (choice “d”); Pseudomonas is the most likely culprit. Candida albicans (choice “a”), a yeast, is an unlikely cause of this problem and even more unlikely to show up on a bacterial culture. Coagulase-positive staph aureus (choice “b”) is typically associated with infections involving the acute onset of redness, pain, swelling, and pus formation, not the indolent, chronic, low-grade process seen in this case. Trichophyton rubrum (choice “c”) is a dermatophyte, the most common fungal cause of athlete’s feet. The bacterial culture could not have grown a dermatophyte, which needs special media and conditions to grow.

DISCUSSSION
Gram-negative interweb impetigo is a relatively common dermatologic entity, which can be caused by any number of organisms found in fecal material. Pseudomonas, Klebsiella, Proteus, and Acinetobacter are among the more common culprits. These types of infections tend to be much more indolent than the more common staph- and strep-caused cellulitis, which are more likely to create acute redness, swelling, pain, and pus. 

Both types of bacterial infections need certain conditions in order to develop. These include excessive heat, sweat, and perhaps most significantly, a break in the skin barrier. Ironically, these fissures are often caused by dermatophytes, in the form of tinea pedis, which is, of course, far better known for causing rashes of the foot.

But tinea pedis is more likely to be found between the third and fourth or the fourth and fifth toes. It creates itching and maceration but rarely causes diffuse redness or edema, and even more rarely leads to pain (unless there is a secondary bacterial infection). As mentioned, given the indolence of this infective process, a culture result showing staph or strep was unlikely.

The culture in this case showed Proteus, for which the minocycline was predictably effective. The rationale for obtaining the acid-fast culture was the possibility of finding Mycobacteria species such as M fortuitum, which is known to cause chronic indolent infections in feet and legs. These, however, more typically manifest with solitary eroded or ulcerated lesions. (Minocycline would have been effective against this organism.)

The use of the topical econazole served two purposes: While this was clearly not classic tinea pedis, it was still possible a dermatophyte or a yeast could have played a role in the creation of the initial fissuring; econazole will help control this, long term. Econazole also has significant antibacterial action and is particularly useful to help prevent future flares.          

ANSWER
The correct answer is gram-negative bacteria (choice “d”); Pseudomonas is the most likely culprit. Candida albicans (choice “a”), a yeast, is an unlikely cause of this problem and even more unlikely to show up on a bacterial culture. Coagulase-positive staph aureus (choice “b”) is typically associated with infections involving the acute onset of redness, pain, swelling, and pus formation, not the indolent, chronic, low-grade process seen in this case. Trichophyton rubrum (choice “c”) is a dermatophyte, the most common fungal cause of athlete’s feet. The bacterial culture could not have grown a dermatophyte, which needs special media and conditions to grow.

DISCUSSSION
Gram-negative interweb impetigo is a relatively common dermatologic entity, which can be caused by any number of organisms found in fecal material. Pseudomonas, Klebsiella, Proteus, and Acinetobacter are among the more common culprits. These types of infections tend to be much more indolent than the more common staph- and strep-caused cellulitis, which are more likely to create acute redness, swelling, pain, and pus. 

Both types of bacterial infections need certain conditions in order to develop. These include excessive heat, sweat, and perhaps most significantly, a break in the skin barrier. Ironically, these fissures are often caused by dermatophytes, in the form of tinea pedis, which is, of course, far better known for causing rashes of the foot.

But tinea pedis is more likely to be found between the third and fourth or the fourth and fifth toes. It creates itching and maceration but rarely causes diffuse redness or edema, and even more rarely leads to pain (unless there is a secondary bacterial infection). As mentioned, given the indolence of this infective process, a culture result showing staph or strep was unlikely.

The culture in this case showed Proteus, for which the minocycline was predictably effective. The rationale for obtaining the acid-fast culture was the possibility of finding Mycobacteria species such as M fortuitum, which is known to cause chronic indolent infections in feet and legs. These, however, more typically manifest with solitary eroded or ulcerated lesions. (Minocycline would have been effective against this organism.)

The use of the topical econazole served two purposes: While this was clearly not classic tinea pedis, it was still possible a dermatophyte or a yeast could have played a role in the creation of the initial fissuring; econazole will help control this, long term. Econazole also has significant antibacterial action and is particularly useful to help prevent future flares.          

A new report finds that 49% of surveyed primary care physicians expect to participate in an accountable care organization in the next year. Twenty percent already are in ACOs, and most of them are contracting with commercial payers and Medicaid.

Why this dramatic jump? At the end of the day, it is all about the shift from volume-based reimbursement (fee for service) to value-based reimbursement. ACOs are a means to an end, not the end itself. If we will get paid for squeezing waste out of our current system and look at the best way to do it, the elements of an ACO logically fall into place.²

We attribute the big jump in primary care participation to three main factors:

1. Primary care will drive value.

The highest-impact targets for ACOs are:

• Prevention and wellness.

• Chronic disease management.

• Care transitions and navigation.

• Reduced hospitalizations.

• Multispecialty care coordination of complex patients.

While not a monopoly of primary care, all of these opportunities are in your wheelhouse. That is why the Medicare Shared Savings Program ACO regulations correctly require every ACO to include primary care providers. Consequently, primary care providers are being heavily recruited by ACOs.

2. Primary care will derive benefits.

Most ACOs are compensated by receiving some percentage, usually 50%, of savings for a patient population if quality and patient satisfaction metrics are also met. For an ACO to be successful, distribution of savings should be in proportion to their contribution. Primary care physicians should contract only with ACOs that recognize this fundamental connection.

The distribution must be an incentive for every participant to contribute as much value as possible. That will not happen unless the savings distribution is based on merit. As noted, primary care stands to contribute more value, and thus merit more distributions, than any other ACO participant.

The dysfunctions of the fee-for-service system have left primary care underpaid. Now, with the compensation model shifting leverage from costs to savings, primary care physicians are stepping up to close this gap.

3. Primary care is realizing that ACOs are for real.

The move to value-based reimbursement is being driven by unsustainable health care costs, not "Obamacare" or the U.S. Supreme Court. The "fiscal cliff" will have more impact on the growth of ACOs than the Affordable Care Act, as it is forcing us to look at the main drivers of the deficit – entitlements such as Social Security, Medicaid, and Medicare. Notwithstanding, many physicians were waiting until after the election to get serious about ACOs.

3a. This column

(Just kidding!)

So, for these reasons, it is not surprising that primary care physicians are now jumping into ACOs. That said, it is still pretty startling to see a 250% increase in 1 year, which was probably a 250% jump from the year before. Thank you for stepping up to help save American health care.

References

1. Accountable Care Organizations: How Will Payer and Provider Adoption of This Model Impact Prescribing Trends in Cardiometabolic Diseases? Decision Resources, October 2012.

2. As covered in prior articles, besides value-based reimbursement, there are seven other essential elements for a successful ACO: primary care, culture, administration, information technology, patient engagement, scale, and best practices.

Mr. Bobbitt is a senior partner and head of the Health Law Group at the Smith Anderson law firm in Raleigh, N.C. He has many years’ experience assisting physicians to form integrated delivery systems. He has spoken and written nationally to primary care physicians on the strategies and practicalities of forming or joining ACOs. This article is meant to be educational and does not constitute legal advice. For additional information, readers may contact the author at [email protected] or 919-821-6612.

A new report finds that 49% of surveyed primary care physicians expect to participate in an accountable care organization in the next year. Twenty percent already are in ACOs, and most of them are contracting with commercial payers and Medicaid.

Why this dramatic jump? At the end of the day, it is all about the shift from volume-based reimbursement (fee for service) to value-based reimbursement. ACOs are a means to an end, not the end itself. If we will get paid for squeezing waste out of our current system and look at the best way to do it, the elements of an ACO logically fall into place.²

We attribute the big jump in primary care participation to three main factors:

1. Primary care will drive value.

The highest-impact targets for ACOs are:

• Prevention and wellness.

• Chronic disease management.

• Care transitions and navigation.

• Reduced hospitalizations.

• Multispecialty care coordination of complex patients.

While not a monopoly of primary care, all of these opportunities are in your wheelhouse. That is why the Medicare Shared Savings Program ACO regulations correctly require every ACO to include primary care providers. Consequently, primary care providers are being heavily recruited by ACOs.

2. Primary care will derive benefits.

Most ACOs are compensated by receiving some percentage, usually 50%, of savings for a patient population if quality and patient satisfaction metrics are also met. For an ACO to be successful, distribution of savings should be in proportion to their contribution. Primary care physicians should contract only with ACOs that recognize this fundamental connection.

The distribution must be an incentive for every participant to contribute as much value as possible. That will not happen unless the savings distribution is based on merit. As noted, primary care stands to contribute more value, and thus merit more distributions, than any other ACO participant.

The dysfunctions of the fee-for-service system have left primary care underpaid. Now, with the compensation model shifting leverage from costs to savings, primary care physicians are stepping up to close this gap.

3. Primary care is realizing that ACOs are for real.

The move to value-based reimbursement is being driven by unsustainable health care costs, not "Obamacare" or the U.S. Supreme Court. The "fiscal cliff" will have more impact on the growth of ACOs than the Affordable Care Act, as it is forcing us to look at the main drivers of the deficit – entitlements such as Social Security, Medicaid, and Medicare. Notwithstanding, many physicians were waiting until after the election to get serious about ACOs.

3a. This column

(Just kidding!)

So, for these reasons, it is not surprising that primary care physicians are now jumping into ACOs. That said, it is still pretty startling to see a 250% increase in 1 year, which was probably a 250% jump from the year before. Thank you for stepping up to help save American health care.

References

1. Accountable Care Organizations: How Will Payer and Provider Adoption of This Model Impact Prescribing Trends in Cardiometabolic Diseases? Decision Resources, October 2012.

2. As covered in prior articles, besides value-based reimbursement, there are seven other essential elements for a successful ACO: primary care, culture, administration, information technology, patient engagement, scale, and best practices.

Mr. Bobbitt is a senior partner and head of the Health Law Group at the Smith Anderson law firm in Raleigh, N.C. He has many years’ experience assisting physicians to form integrated delivery systems. He has spoken and written nationally to primary care physicians on the strategies and practicalities of forming or joining ACOs. This article is meant to be educational and does not constitute legal advice. For additional information, readers may contact the author at [email protected] or 919-821-6612.

A new report finds that 49% of surveyed primary care physicians expect to participate in an accountable care organization in the next year. Twenty percent already are in ACOs, and most of them are contracting with commercial payers and Medicaid.

Why this dramatic jump? At the end of the day, it is all about the shift from volume-based reimbursement (fee for service) to value-based reimbursement. ACOs are a means to an end, not the end itself. If we will get paid for squeezing waste out of our current system and look at the best way to do it, the elements of an ACO logically fall into place.²

We attribute the big jump in primary care participation to three main factors:

1. Primary care will drive value.

The highest-impact targets for ACOs are:

• Prevention and wellness.

• Chronic disease management.

• Care transitions and navigation.

• Reduced hospitalizations.

• Multispecialty care coordination of complex patients.

While not a monopoly of primary care, all of these opportunities are in your wheelhouse. That is why the Medicare Shared Savings Program ACO regulations correctly require every ACO to include primary care providers. Consequently, primary care providers are being heavily recruited by ACOs.

2. Primary care will derive benefits.

Most ACOs are compensated by receiving some percentage, usually 50%, of savings for a patient population if quality and patient satisfaction metrics are also met. For an ACO to be successful, distribution of savings should be in proportion to their contribution. Primary care physicians should contract only with ACOs that recognize this fundamental connection.

The distribution must be an incentive for every participant to contribute as much value as possible. That will not happen unless the savings distribution is based on merit. As noted, primary care stands to contribute more value, and thus merit more distributions, than any other ACO participant.

The dysfunctions of the fee-for-service system have left primary care underpaid. Now, with the compensation model shifting leverage from costs to savings, primary care physicians are stepping up to close this gap.

3. Primary care is realizing that ACOs are for real.

The move to value-based reimbursement is being driven by unsustainable health care costs, not "Obamacare" or the U.S. Supreme Court. The "fiscal cliff" will have more impact on the growth of ACOs than the Affordable Care Act, as it is forcing us to look at the main drivers of the deficit – entitlements such as Social Security, Medicaid, and Medicare. Notwithstanding, many physicians were waiting until after the election to get serious about ACOs.

3a. This column

(Just kidding!)

So, for these reasons, it is not surprising that primary care physicians are now jumping into ACOs. That said, it is still pretty startling to see a 250% increase in 1 year, which was probably a 250% jump from the year before. Thank you for stepping up to help save American health care.

References

1. Accountable Care Organizations: How Will Payer and Provider Adoption of This Model Impact Prescribing Trends in Cardiometabolic Diseases? Decision Resources, October 2012.

2. As covered in prior articles, besides value-based reimbursement, there are seven other essential elements for a successful ACO: primary care, culture, administration, information technology, patient engagement, scale, and best practices.

Mr. Bobbitt is a senior partner and head of the Health Law Group at the Smith Anderson law firm in Raleigh, N.C. He has many years’ experience assisting physicians to form integrated delivery systems. He has spoken and written nationally to primary care physicians on the strategies and practicalities of forming or joining ACOs. This article is meant to be educational and does not constitute legal advice. For additional information, readers may contact the author at [email protected] or 919-821-6612.

Electronic decision support significantly improves VTE prophylaxis and hospital-acquired VTE rates, according to a new study in the Journal of Hospital Medicine.

The report, "Improving Hospital Venous Thromboembolism Prophylaxis With Electronic Decision Report," saw overall medical service prophylaxis rise to 82.1% from 61.9% (P<0.001) and pharmacologic VTE prophylaxis increase to 74.5% from 59% (P<0.001).

"Healthcare leaders talk about information technology (IT) as a means toward effecting improvements in quality and patient safety and, most of the time, they view that and discuss that in terms of the actual IT system being implemented," says lead author Rohit Bhalla, MD, MPH, associate professor of clinical medicine at Albert Einstein College of Medicine in New York City. "What our intervention really got to was once you've implemented an IT system ... how can it be modified, vis-à-vis decision support, so that it provides an even better result than you get with the product that comes out of the box."

Tailoring a health IT system to improve outcomes requires interdisciplinary work that includes quality officers, physicians, IT staff, and programmers. Hospitalist and fellow author Jason Adelman, MD, MS, patient safety officer at Montefiore Medical Center in the Bronx, N.Y., where the study was conducted, says that the research can help generate future buy-in from physicians who don't value electronic decision support tools.

It can "ease the swallowing of the bitter pill to know that it really makes a difference," Dr. Adelman says. "Don't be up in arms when you're forced to do something a little bit extra, because it really works."

Visit our website for more information about health information technology.

Electronic decision support significantly improves VTE prophylaxis and hospital-acquired VTE rates, according to a new study in the Journal of Hospital Medicine.

The report, "Improving Hospital Venous Thromboembolism Prophylaxis With Electronic Decision Report," saw overall medical service prophylaxis rise to 82.1% from 61.9% (P<0.001) and pharmacologic VTE prophylaxis increase to 74.5% from 59% (P<0.001).

"Healthcare leaders talk about information technology (IT) as a means toward effecting improvements in quality and patient safety and, most of the time, they view that and discuss that in terms of the actual IT system being implemented," says lead author Rohit Bhalla, MD, MPH, associate professor of clinical medicine at Albert Einstein College of Medicine in New York City. "What our intervention really got to was once you've implemented an IT system ... how can it be modified, vis-à-vis decision support, so that it provides an even better result than you get with the product that comes out of the box."

Tailoring a health IT system to improve outcomes requires interdisciplinary work that includes quality officers, physicians, IT staff, and programmers. Hospitalist and fellow author Jason Adelman, MD, MS, patient safety officer at Montefiore Medical Center in the Bronx, N.Y., where the study was conducted, says that the research can help generate future buy-in from physicians who don't value electronic decision support tools.

It can "ease the swallowing of the bitter pill to know that it really makes a difference," Dr. Adelman says. "Don't be up in arms when you're forced to do something a little bit extra, because it really works."

Visit our website for more information about health information technology.

Electronic decision support significantly improves VTE prophylaxis and hospital-acquired VTE rates, according to a new study in the Journal of Hospital Medicine.

The report, "Improving Hospital Venous Thromboembolism Prophylaxis With Electronic Decision Report," saw overall medical service prophylaxis rise to 82.1% from 61.9% (P<0.001) and pharmacologic VTE prophylaxis increase to 74.5% from 59% (P<0.001).

"Healthcare leaders talk about information technology (IT) as a means toward effecting improvements in quality and patient safety and, most of the time, they view that and discuss that in terms of the actual IT system being implemented," says lead author Rohit Bhalla, MD, MPH, associate professor of clinical medicine at Albert Einstein College of Medicine in New York City. "What our intervention really got to was once you've implemented an IT system ... how can it be modified, vis-à-vis decision support, so that it provides an even better result than you get with the product that comes out of the box."

Tailoring a health IT system to improve outcomes requires interdisciplinary work that includes quality officers, physicians, IT staff, and programmers. Hospitalist and fellow author Jason Adelman, MD, MS, patient safety officer at Montefiore Medical Center in the Bronx, N.Y., where the study was conducted, says that the research can help generate future buy-in from physicians who don't value electronic decision support tools.

It can "ease the swallowing of the bitter pill to know that it really makes a difference," Dr. Adelman says. "Don't be up in arms when you're forced to do something a little bit extra, because it really works."

Visit our website for more information about health information technology.