The Journal of Family Practice

In a recent letter to the editor, “25-hydroxyvitamin D concentration is key to analyzing vitamin D’s effects” (J Fam Pract. 2021;70:472), Dr. Grant links vitamin D supplementation with important health outcomes. He concludes that the positivity rate of SARS-CoV-2 was only 5.9% in people with higher concentrations of 25(OH)D vs 12.5% in those with lower concentrations. This is a flawed conclusion on the face of it, because the great confabulatory factor is behavior. Is it possible that those more likely to take supplemental vitamin D do so as a result of overall healthier lifestyles and choices (eg, vaccinations)? As health care representatives, we must be very careful about the data we publish and the commentary we attach to it, lest we advertise inadvertent follies. I see so much of that in our “peer-reviewed literature.”

I came to medicine as a chemist, and the rigors of peer review impressed upon the hard (fundamental) sciences are markedly different from those we “claim” adherence to in medicine. I find that some of the medical literature and study designs fall short of what would pass muster in the fundamental science industry. That is a shame! Such statements, as discussed here, have to be served for public consumption, and even to our colleagues, with a generous helping of skepticism and qualification.

RA Segal, MD, MPH
Gainesville, FL

In a recent letter to the editor, “25-hydroxyvitamin D concentration is key to analyzing vitamin D’s effects” (J Fam Pract. 2021;70:472), Dr. Grant links vitamin D supplementation with important health outcomes. He concludes that the positivity rate of SARS-CoV-2 was only 5.9% in people with higher concentrations of 25(OH)D vs 12.5% in those with lower concentrations. This is a flawed conclusion on the face of it, because the great confabulatory factor is behavior. Is it possible that those more likely to take supplemental vitamin D do so as a result of overall healthier lifestyles and choices (eg, vaccinations)? As health care representatives, we must be very careful about the data we publish and the commentary we attach to it, lest we advertise inadvertent follies. I see so much of that in our “peer-reviewed literature.”

I came to medicine as a chemist, and the rigors of peer review impressed upon the hard (fundamental) sciences are markedly different from those we “claim” adherence to in medicine. I find that some of the medical literature and study designs fall short of what would pass muster in the fundamental science industry. That is a shame! Such statements, as discussed here, have to be served for public consumption, and even to our colleagues, with a generous helping of skepticism and qualification.

RA Segal, MD, MPH
Gainesville, FL

In a recent letter to the editor, “25-hydroxyvitamin D concentration is key to analyzing vitamin D’s effects” (J Fam Pract. 2021;70:472), Dr. Grant links vitamin D supplementation with important health outcomes. He concludes that the positivity rate of SARS-CoV-2 was only 5.9% in people with higher concentrations of 25(OH)D vs 12.5% in those with lower concentrations. This is a flawed conclusion on the face of it, because the great confabulatory factor is behavior. Is it possible that those more likely to take supplemental vitamin D do so as a result of overall healthier lifestyles and choices (eg, vaccinations)? As health care representatives, we must be very careful about the data we publish and the commentary we attach to it, lest we advertise inadvertent follies. I see so much of that in our “peer-reviewed literature.”

I came to medicine as a chemist, and the rigors of peer review impressed upon the hard (fundamental) sciences are markedly different from those we “claim” adherence to in medicine. I find that some of the medical literature and study designs fall short of what would pass muster in the fundamental science industry. That is a shame! Such statements, as discussed here, have to be served for public consumption, and even to our colleagues, with a generous helping of skepticism and qualification.

RA Segal, MD, MPH
Gainesville, FL

A 56-year-old woman with a history of a thyroid goiter following a partial thyroidectomy presented to the emergency department with shortness of breath, progressive weakness, and fatigue. She also reported a poor appetite and unintentional weight loss of approximately 40 lbs over the past 2 months but had not sought medical care. She denied having a cough, chest pain, hemoptysis, hematemesis, fevers, chills, or night sweats.

Physical examination revealed a cachectic woman with tachycardia and tachypnea, along with diffuse coarse rales throughout both lungs. The patient’s initial heart rate was 101 beats/min; respiratory rate, 25 breaths/min; and oxygen saturation, 74% on room air. The results of a complete blood count and comprehensive metabolic panel were within normal limits. A chest radiograph was performed, showing innumerable subcentimeter- and ­pericentimeter-sized soft-tissue densities in both lungs (FIGURE 1). Computed tomography (CT) of the chest was subsequently obtained to better characterize the nodules (FIGURES 2A and 2B). The CT revealed innumerable noncalcified pulmonary nodules as well as multiple hilar masses suggestive of malignancy; however, infectious etiologies could not be ruled out.

As the patient was visiting from a tuberculosis-endemic area, she was empirically started on rifampin, isoniazid, pyrazinamide, and ethambutol (RIPE) therapy for treatment of Mycobacterium tuberculosis infection. Subsequently, polymerase chain reaction (PCR) testing and acid-fast bacillus sputum smear came back negative for M tuberculosis and RIPE therapy was stopped. Bacterial culture and fungal screens for Pneumocystis jirovecii, Coccidioides, Cryptococcus, and Histoplasma capsulatum were negative.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

A biopsy of one of the lung nodules was performed and showed strong positive staining for thyroglobulin and thyroid transcription factor-1, establishing a diagnosis of metastatic follicular thyroid carcinoma. Further imaging revealed additional metastases to the brain, liver, adrenal glands, and spine.

If follicular thyroid carcinoma is caught early (with only local involvement), 5-year relative survival rates are near 100%.

Follicular thyroid carcinoma is the second most common histologic type of thyroid cancer, comprising 10% to 15% of thyroid cancer cases.¹ Distant metastases are not uncommon in this histologic type; about 11% of patients have distant metastases at presentation.² Compared with papillary thyroid cancer, which spreads via the lymphatics, the follicular type can metastasize via vascular invasion, thus leading to its “aggressiveness” and frequent occurrence of metastasis outside the neck (most commonly to the lung).¹ For this reason, an early diagnosis is important.³ In this case, the patient revealed that she hadn’t sought medical care at the onset of her symptoms due to financial limitations and limited access to medical providers; this likely contributed to the patient’s diagnosis at a late stage of disease.

Infectious and septic diseases are part of the differential Dx

The differential diagnosis for diffuse pulmonary nodules includes various infections, silicosis, coal worker’s pneumoconiosis, septic pulmonary emboli, and pulmonary sarcoidosis. All of these diagnoses can cause constitutional, as well as pulmonary, symptoms.

Infections, such as pulmonary tuberculosis, pulmonary coccidioidomycosis, or other cavitating infections, can be ruled out with specific testing for the organism of concern and/or culture.

Silicosis and coal worker’s pneumoconiosis generally cause lesions in the upper lobes and require a significant occupational exposure to silica or coal, respectively.

Continue to: Septic pulmonary emboli

Septic pulmonary emboli are usually seen in the context of sepsis, and there are positive blood cultures at the time of imaging.

Pulmonary sarcoidosis typically manifests with hilar and mediastinal lymphadenopathy and is often accompanied by other organ involvement.

There are options for treatment if diagnosis is made early

Thyroidectomy, radioiodine treatment, and thyroid-stimulating hormone suppressive therapy are the most commonly used therapies for treatment of follicular thyroid carcinoma.⁴ If follicular thyroid carcinoma is caught early (with only local involvement), 5-year relative survival rates are near 100%.⁵ However, outcomes are generally poor in patients who are of older age and those who have macronodular lung metastases or multiple bone metastases.⁶

Our patient was started on levothyroxine. Radioiodine and targeted drug therapy with a tyrosine kinase inhibitor were attempted, but the patient was unable to tolerate them due to her poor functional status. She was thus transitioned to hospice care.

A 56-year-old woman with a history of a thyroid goiter following a partial thyroidectomy presented to the emergency department with shortness of breath, progressive weakness, and fatigue. She also reported a poor appetite and unintentional weight loss of approximately 40 lbs over the past 2 months but had not sought medical care. She denied having a cough, chest pain, hemoptysis, hematemesis, fevers, chills, or night sweats.

Physical examination revealed a cachectic woman with tachycardia and tachypnea, along with diffuse coarse rales throughout both lungs. The patient’s initial heart rate was 101 beats/min; respiratory rate, 25 breaths/min; and oxygen saturation, 74% on room air. The results of a complete blood count and comprehensive metabolic panel were within normal limits. A chest radiograph was performed, showing innumerable subcentimeter- and ­pericentimeter-sized soft-tissue densities in both lungs (FIGURE 1). Computed tomography (CT) of the chest was subsequently obtained to better characterize the nodules (FIGURES 2A and 2B). The CT revealed innumerable noncalcified pulmonary nodules as well as multiple hilar masses suggestive of malignancy; however, infectious etiologies could not be ruled out.

As the patient was visiting from a tuberculosis-endemic area, she was empirically started on rifampin, isoniazid, pyrazinamide, and ethambutol (RIPE) therapy for treatment of Mycobacterium tuberculosis infection. Subsequently, polymerase chain reaction (PCR) testing and acid-fast bacillus sputum smear came back negative for M tuberculosis and RIPE therapy was stopped. Bacterial culture and fungal screens for Pneumocystis jirovecii, Coccidioides, Cryptococcus, and Histoplasma capsulatum were negative.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

A biopsy of one of the lung nodules was performed and showed strong positive staining for thyroglobulin and thyroid transcription factor-1, establishing a diagnosis of metastatic follicular thyroid carcinoma. Further imaging revealed additional metastases to the brain, liver, adrenal glands, and spine.

If follicular thyroid carcinoma is caught early (with only local involvement), 5-year relative survival rates are near 100%.

Follicular thyroid carcinoma is the second most common histologic type of thyroid cancer, comprising 10% to 15% of thyroid cancer cases.¹ Distant metastases are not uncommon in this histologic type; about 11% of patients have distant metastases at presentation.² Compared with papillary thyroid cancer, which spreads via the lymphatics, the follicular type can metastasize via vascular invasion, thus leading to its “aggressiveness” and frequent occurrence of metastasis outside the neck (most commonly to the lung).¹ For this reason, an early diagnosis is important.³ In this case, the patient revealed that she hadn’t sought medical care at the onset of her symptoms due to financial limitations and limited access to medical providers; this likely contributed to the patient’s diagnosis at a late stage of disease.

Infectious and septic diseases are part of the differential Dx

The differential diagnosis for diffuse pulmonary nodules includes various infections, silicosis, coal worker’s pneumoconiosis, septic pulmonary emboli, and pulmonary sarcoidosis. All of these diagnoses can cause constitutional, as well as pulmonary, symptoms.

Infections, such as pulmonary tuberculosis, pulmonary coccidioidomycosis, or other cavitating infections, can be ruled out with specific testing for the organism of concern and/or culture.

Silicosis and coal worker’s pneumoconiosis generally cause lesions in the upper lobes and require a significant occupational exposure to silica or coal, respectively.

Continue to: Septic pulmonary emboli

Septic pulmonary emboli are usually seen in the context of sepsis, and there are positive blood cultures at the time of imaging.

Pulmonary sarcoidosis typically manifests with hilar and mediastinal lymphadenopathy and is often accompanied by other organ involvement.

There are options for treatment if diagnosis is made early

Thyroidectomy, radioiodine treatment, and thyroid-stimulating hormone suppressive therapy are the most commonly used therapies for treatment of follicular thyroid carcinoma.⁴ If follicular thyroid carcinoma is caught early (with only local involvement), 5-year relative survival rates are near 100%.⁵ However, outcomes are generally poor in patients who are of older age and those who have macronodular lung metastases or multiple bone metastases.⁶

Our patient was started on levothyroxine. Radioiodine and targeted drug therapy with a tyrosine kinase inhibitor were attempted, but the patient was unable to tolerate them due to her poor functional status. She was thus transitioned to hospice care.

A 56-year-old woman with a history of a thyroid goiter following a partial thyroidectomy presented to the emergency department with shortness of breath, progressive weakness, and fatigue. She also reported a poor appetite and unintentional weight loss of approximately 40 lbs over the past 2 months but had not sought medical care. She denied having a cough, chest pain, hemoptysis, hematemesis, fevers, chills, or night sweats.

Physical examination revealed a cachectic woman with tachycardia and tachypnea, along with diffuse coarse rales throughout both lungs. The patient’s initial heart rate was 101 beats/min; respiratory rate, 25 breaths/min; and oxygen saturation, 74% on room air. The results of a complete blood count and comprehensive metabolic panel were within normal limits. A chest radiograph was performed, showing innumerable subcentimeter- and ­pericentimeter-sized soft-tissue densities in both lungs (FIGURE 1). Computed tomography (CT) of the chest was subsequently obtained to better characterize the nodules (FIGURES 2A and 2B). The CT revealed innumerable noncalcified pulmonary nodules as well as multiple hilar masses suggestive of malignancy; however, infectious etiologies could not be ruled out.

As the patient was visiting from a tuberculosis-endemic area, she was empirically started on rifampin, isoniazid, pyrazinamide, and ethambutol (RIPE) therapy for treatment of Mycobacterium tuberculosis infection. Subsequently, polymerase chain reaction (PCR) testing and acid-fast bacillus sputum smear came back negative for M tuberculosis and RIPE therapy was stopped. Bacterial culture and fungal screens for Pneumocystis jirovecii, Coccidioides, Cryptococcus, and Histoplasma capsulatum were negative.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

A biopsy of one of the lung nodules was performed and showed strong positive staining for thyroglobulin and thyroid transcription factor-1, establishing a diagnosis of metastatic follicular thyroid carcinoma. Further imaging revealed additional metastases to the brain, liver, adrenal glands, and spine.

If follicular thyroid carcinoma is caught early (with only local involvement), 5-year relative survival rates are near 100%.

Follicular thyroid carcinoma is the second most common histologic type of thyroid cancer, comprising 10% to 15% of thyroid cancer cases.¹ Distant metastases are not uncommon in this histologic type; about 11% of patients have distant metastases at presentation.² Compared with papillary thyroid cancer, which spreads via the lymphatics, the follicular type can metastasize via vascular invasion, thus leading to its “aggressiveness” and frequent occurrence of metastasis outside the neck (most commonly to the lung).¹ For this reason, an early diagnosis is important.³ In this case, the patient revealed that she hadn’t sought medical care at the onset of her symptoms due to financial limitations and limited access to medical providers; this likely contributed to the patient’s diagnosis at a late stage of disease.

Infectious and septic diseases are part of the differential Dx

The differential diagnosis for diffuse pulmonary nodules includes various infections, silicosis, coal worker’s pneumoconiosis, septic pulmonary emboli, and pulmonary sarcoidosis. All of these diagnoses can cause constitutional, as well as pulmonary, symptoms.

Infections, such as pulmonary tuberculosis, pulmonary coccidioidomycosis, or other cavitating infections, can be ruled out with specific testing for the organism of concern and/or culture.

Silicosis and coal worker’s pneumoconiosis generally cause lesions in the upper lobes and require a significant occupational exposure to silica or coal, respectively.

Continue to: Septic pulmonary emboli

Septic pulmonary emboli are usually seen in the context of sepsis, and there are positive blood cultures at the time of imaging.

Pulmonary sarcoidosis typically manifests with hilar and mediastinal lymphadenopathy and is often accompanied by other organ involvement.

There are options for treatment if diagnosis is made early

Thyroidectomy, radioiodine treatment, and thyroid-stimulating hormone suppressive therapy are the most commonly used therapies for treatment of follicular thyroid carcinoma.⁴ If follicular thyroid carcinoma is caught early (with only local involvement), 5-year relative survival rates are near 100%.⁵ However, outcomes are generally poor in patients who are of older age and those who have macronodular lung metastases or multiple bone metastases.⁶

Our patient was started on levothyroxine. Radioiodine and targeted drug therapy with a tyrosine kinase inhibitor were attempted, but the patient was unable to tolerate them due to her poor functional status. She was thus transitioned to hospice care.

THE CASE

A previously healthy 3-year-old girl presented to the emergency department with 4 days of fever and 2 days of right-side neck pain. The maximum temperature at home was 103 °F. The patient was irritable and vomited once. There were no other apparent or reported symptoms.

The neck exam was notable for nonfluctuant, swollen, and tender lymph nodes on the right side. Her sclera and conjunctiva were clear, and her oropharynx was unremarkable. Lab work revealed leukocytosis, with a white blood cell (WBC) count of 15.5 × 10³/µL (normal range, 4.0-10.0 × 10³/µL). She was given one 20 cc/kg normal saline bolus, started on intravenous clindamycin for presumed cervical lymphadenitis, and admitted to the hospital.

On Day 2, the patient developed a fine maculopapular rash on her chest, abdomen, and back. She had spiking fevers—as high as 102.2 °F—despite being on antibiotics for more than 24 hours. The erythrocyte sedimentation rate (ESR) was 39 mm/h (0-20 mm/h), and C-reactive protein (CRP) was 71.4 mg/L (0.0-4.9 mg/L). Due to concern for abscess, a neck ultrasound was performed; it showed a chain of enlarged lymph nodes in the right neck (largest, 2.3 × 1.1 × 1.4 cm) and no abscess.

On Day 3, clindamycin was switched to intravenous ampicillin/sulbactam because a nasal swab for methicillin-resistant Staphylococcus aureus was negative. A swab for respiratory viral infections was also negative. The patient then developed notable facial swelling, bilateral bulbar conjunctival injection with limbic sparing, and swelling of her hands and feet.

THE DIAGNOSIS

By the end of Day 3, the patient’s lab studies demonstrated microcytic anemia and low albumin (2.5 g/dL), but no transaminitis, thrombocytosis, or sterile pyuria. An electrocardiogram was unremarkable. A pediatric echocardiogram revealed hyperemic coronaries, indicating inflammation. The coronary arteries were measured in the upper limits of normal, and the patient’s Z-scores were < 2.5. (A Z-score < 2 indicates no involvement, 2 to < 2.5 indicates dilation, and ≥ 2.5 indicates aneurysm abnormality.¹) An ultrasound of the right upper quadrant revealed an enlarged/elongated gallbladder. The patient therefore met clinical criteria for Kawasaki disease.

DISCUSSION

Kawasaki disease is a self-limited vasculitis of childhood and the leading cause of acquired heart disease in children in developed countries.¹ The annual incidence of Kawasaki disease in North America is about 25 cases per 100,000 children < 5 years of age.¹ In the United States, incidence is highest in Asian and Pacific Islander populations (30 per 100,000) and is particularly high among those of Japanese ancestry (~200 per 100,000).² Disease prevalence is also noteworthy in Non-Hispanic African American (17 per 100,000) and Hispanic (16 per 100,000) populations.²

Diagnosis of Kawasaki disease requires presence of fever lasting at least 5 days and at least 4 of the following: bilateral bulbar conjunctival injection, oral mucous membrane changes (erythematous or cracked lips, erythematous pharynx, strawberry tongue), peripheral extremity changes (erythema of palms or soles, edema of hands or feet, and/or periungual desquamation), diffuse maculopapular rash, and cervical lymphadenopathy (≥ 1.5 cm, often unilateral). If ≥ 4 criteria are met, Kawasaki disease can be diagnosed on the fourth day of illness.¹

Continue to: Laboratory findings suggesting...

Laboratory findings suggesting ­Kawasaki disease include a WBC count ≥ 15,000/mcL, normocytic, normochromic anemia, platelets ≥ 450,000/mcL after 7 days of illness, sterile pyuria (≥ 10 WBCs/high-power field), serum alanine aminotransferase level > 50 U/L, and serum albumin ≤ 3 g/dL.

Cardiac abnormalities are not included in the diagnostic criteria for Kawasaki disease but provide evidence in cases of incomplete Kawasaki disease if ≥ 4 criteria are not met and there is strong clinical suspicion.¹ Incomplete Kawasaki disease should be considered in a patient with a CRP level ≥ 3 mg/dL and/or ESR ≥ 40 mm/h, ≥ 3 supplemental laboratory criteria, or a positive echocardiogram.¹

Ultrasound imaging may reveal cervical lymph nodes resembling a “cluster of grapes.”³ The case patient’s imaging showed a “chain of enlarged lymph nodes.” She likely had gallbladder “hydrops” due to its increased longitudinal and horizontal diameter and lack of other anatomic changes.⁴

Prompt treatment is essential

Treatment for complete and incomplete Kawasaki disease is a single high dose of intravenous immunoglobulin (IVIG) along with aspirin. Patients meeting criteria should be treated as soon as the diagnosis is established.⁵ A single high dose of IVIG (2 g/kg), administered over 10 to 12 hours, should be initiated within 5 to 10 days of disease onset. Administering IVIG in the acute phase of Kawasaki disease reduces the prevalence of coronary artery abnormalities.⁶ Corticosteroids may be used as adjunctive therapy for patients with high risk of IVIG resistance.^1,7-9

Our patient was not deemed to be at high risk for IVIG resistance (Non-Japanese patient, age at fever onset > 6 months, absence of coronary artery aneurysm⁹) and was administered IVIG on Day 4. She was also given moderate-dose aspirin, then later transitioned to low-dose aspirin. The patient’s fevers improved, she was less irritable, and she had periods of playfulness. Physical exam then showed erythematous and cracked lips with peeling skin.

Continue to: The patient was discharged...

Untreated children with Kawasaki disease have a 25% chance of developing coronary artery aneurysms.

The patient was discharged home on Day 8, after her fever resolved, with instructions to continue low-dose aspirin and to obtain a repeat echocardiogram, gallbladder ultrasound, and lab work in 2 weeks. At her follow-up appointment, periungual desquamation was noted, and ultrasound showed continued enlarged/elongated gallbladder. A repeat echocardiogram was not available. Overall, the patient recovered from Kawasaki disease after therapeutic intervention.

THE TAKEAWAY

Kawasaki disease can be relatively rare in North American populations, but it is important for physicians to be able to recognize and treat it. Untreated children have a 25% chance of developing coronary artery aneurysms.^1,10,11 Early treatment with IVIG can decrease risk to 5%, resulting in an excellent medium- to long-term prognosis for patients.¹⁰ Thorough physical examination and an appropriate degree of clinical suspicion was key in this case of Kawasaki disease.

CORRESPONDENCE
Taisha Doo, MD, 1401 Madison Street, Suite #100, Seattle, WA 98104; taisha.doo@swedish.org

THE CASE

A previously healthy 3-year-old girl presented to the emergency department with 4 days of fever and 2 days of right-side neck pain. The maximum temperature at home was 103 °F. The patient was irritable and vomited once. There were no other apparent or reported symptoms.

The neck exam was notable for nonfluctuant, swollen, and tender lymph nodes on the right side. Her sclera and conjunctiva were clear, and her oropharynx was unremarkable. Lab work revealed leukocytosis, with a white blood cell (WBC) count of 15.5 × 10³/µL (normal range, 4.0-10.0 × 10³/µL). She was given one 20 cc/kg normal saline bolus, started on intravenous clindamycin for presumed cervical lymphadenitis, and admitted to the hospital.

On Day 2, the patient developed a fine maculopapular rash on her chest, abdomen, and back. She had spiking fevers—as high as 102.2 °F—despite being on antibiotics for more than 24 hours. The erythrocyte sedimentation rate (ESR) was 39 mm/h (0-20 mm/h), and C-reactive protein (CRP) was 71.4 mg/L (0.0-4.9 mg/L). Due to concern for abscess, a neck ultrasound was performed; it showed a chain of enlarged lymph nodes in the right neck (largest, 2.3 × 1.1 × 1.4 cm) and no abscess.

On Day 3, clindamycin was switched to intravenous ampicillin/sulbactam because a nasal swab for methicillin-resistant Staphylococcus aureus was negative. A swab for respiratory viral infections was also negative. The patient then developed notable facial swelling, bilateral bulbar conjunctival injection with limbic sparing, and swelling of her hands and feet.

THE DIAGNOSIS

By the end of Day 3, the patient’s lab studies demonstrated microcytic anemia and low albumin (2.5 g/dL), but no transaminitis, thrombocytosis, or sterile pyuria. An electrocardiogram was unremarkable. A pediatric echocardiogram revealed hyperemic coronaries, indicating inflammation. The coronary arteries were measured in the upper limits of normal, and the patient’s Z-scores were < 2.5. (A Z-score < 2 indicates no involvement, 2 to < 2.5 indicates dilation, and ≥ 2.5 indicates aneurysm abnormality.¹) An ultrasound of the right upper quadrant revealed an enlarged/elongated gallbladder. The patient therefore met clinical criteria for Kawasaki disease.

DISCUSSION

Kawasaki disease is a self-limited vasculitis of childhood and the leading cause of acquired heart disease in children in developed countries.¹ The annual incidence of Kawasaki disease in North America is about 25 cases per 100,000 children < 5 years of age.¹ In the United States, incidence is highest in Asian and Pacific Islander populations (30 per 100,000) and is particularly high among those of Japanese ancestry (~200 per 100,000).² Disease prevalence is also noteworthy in Non-Hispanic African American (17 per 100,000) and Hispanic (16 per 100,000) populations.²

Diagnosis of Kawasaki disease requires presence of fever lasting at least 5 days and at least 4 of the following: bilateral bulbar conjunctival injection, oral mucous membrane changes (erythematous or cracked lips, erythematous pharynx, strawberry tongue), peripheral extremity changes (erythema of palms or soles, edema of hands or feet, and/or periungual desquamation), diffuse maculopapular rash, and cervical lymphadenopathy (≥ 1.5 cm, often unilateral). If ≥ 4 criteria are met, Kawasaki disease can be diagnosed on the fourth day of illness.¹

Continue to: Laboratory findings suggesting...

Laboratory findings suggesting ­Kawasaki disease include a WBC count ≥ 15,000/mcL, normocytic, normochromic anemia, platelets ≥ 450,000/mcL after 7 days of illness, sterile pyuria (≥ 10 WBCs/high-power field), serum alanine aminotransferase level > 50 U/L, and serum albumin ≤ 3 g/dL.

Cardiac abnormalities are not included in the diagnostic criteria for Kawasaki disease but provide evidence in cases of incomplete Kawasaki disease if ≥ 4 criteria are not met and there is strong clinical suspicion.¹ Incomplete Kawasaki disease should be considered in a patient with a CRP level ≥ 3 mg/dL and/or ESR ≥ 40 mm/h, ≥ 3 supplemental laboratory criteria, or a positive echocardiogram.¹

Ultrasound imaging may reveal cervical lymph nodes resembling a “cluster of grapes.”³ The case patient’s imaging showed a “chain of enlarged lymph nodes.” She likely had gallbladder “hydrops” due to its increased longitudinal and horizontal diameter and lack of other anatomic changes.⁴

Prompt treatment is essential

Treatment for complete and incomplete Kawasaki disease is a single high dose of intravenous immunoglobulin (IVIG) along with aspirin. Patients meeting criteria should be treated as soon as the diagnosis is established.⁵ A single high dose of IVIG (2 g/kg), administered over 10 to 12 hours, should be initiated within 5 to 10 days of disease onset. Administering IVIG in the acute phase of Kawasaki disease reduces the prevalence of coronary artery abnormalities.⁶ Corticosteroids may be used as adjunctive therapy for patients with high risk of IVIG resistance.^1,7-9

Our patient was not deemed to be at high risk for IVIG resistance (Non-Japanese patient, age at fever onset > 6 months, absence of coronary artery aneurysm⁹) and was administered IVIG on Day 4. She was also given moderate-dose aspirin, then later transitioned to low-dose aspirin. The patient’s fevers improved, she was less irritable, and she had periods of playfulness. Physical exam then showed erythematous and cracked lips with peeling skin.

Continue to: The patient was discharged...

Untreated children with Kawasaki disease have a 25% chance of developing coronary artery aneurysms.

The patient was discharged home on Day 8, after her fever resolved, with instructions to continue low-dose aspirin and to obtain a repeat echocardiogram, gallbladder ultrasound, and lab work in 2 weeks. At her follow-up appointment, periungual desquamation was noted, and ultrasound showed continued enlarged/elongated gallbladder. A repeat echocardiogram was not available. Overall, the patient recovered from Kawasaki disease after therapeutic intervention.

THE TAKEAWAY

Kawasaki disease can be relatively rare in North American populations, but it is important for physicians to be able to recognize and treat it. Untreated children have a 25% chance of developing coronary artery aneurysms.^1,10,11 Early treatment with IVIG can decrease risk to 5%, resulting in an excellent medium- to long-term prognosis for patients.¹⁰ Thorough physical examination and an appropriate degree of clinical suspicion was key in this case of Kawasaki disease.

CORRESPONDENCE
Taisha Doo, MD, 1401 Madison Street, Suite #100, Seattle, WA 98104; taisha.doo@swedish.org

THE CASE

A previously healthy 3-year-old girl presented to the emergency department with 4 days of fever and 2 days of right-side neck pain. The maximum temperature at home was 103 °F. The patient was irritable and vomited once. There were no other apparent or reported symptoms.

The neck exam was notable for nonfluctuant, swollen, and tender lymph nodes on the right side. Her sclera and conjunctiva were clear, and her oropharynx was unremarkable. Lab work revealed leukocytosis, with a white blood cell (WBC) count of 15.5 × 10³/µL (normal range, 4.0-10.0 × 10³/µL). She was given one 20 cc/kg normal saline bolus, started on intravenous clindamycin for presumed cervical lymphadenitis, and admitted to the hospital.

On Day 2, the patient developed a fine maculopapular rash on her chest, abdomen, and back. She had spiking fevers—as high as 102.2 °F—despite being on antibiotics for more than 24 hours. The erythrocyte sedimentation rate (ESR) was 39 mm/h (0-20 mm/h), and C-reactive protein (CRP) was 71.4 mg/L (0.0-4.9 mg/L). Due to concern for abscess, a neck ultrasound was performed; it showed a chain of enlarged lymph nodes in the right neck (largest, 2.3 × 1.1 × 1.4 cm) and no abscess.

On Day 3, clindamycin was switched to intravenous ampicillin/sulbactam because a nasal swab for methicillin-resistant Staphylococcus aureus was negative. A swab for respiratory viral infections was also negative. The patient then developed notable facial swelling, bilateral bulbar conjunctival injection with limbic sparing, and swelling of her hands and feet.

THE DIAGNOSIS

By the end of Day 3, the patient’s lab studies demonstrated microcytic anemia and low albumin (2.5 g/dL), but no transaminitis, thrombocytosis, or sterile pyuria. An electrocardiogram was unremarkable. A pediatric echocardiogram revealed hyperemic coronaries, indicating inflammation. The coronary arteries were measured in the upper limits of normal, and the patient’s Z-scores were < 2.5. (A Z-score < 2 indicates no involvement, 2 to < 2.5 indicates dilation, and ≥ 2.5 indicates aneurysm abnormality.¹) An ultrasound of the right upper quadrant revealed an enlarged/elongated gallbladder. The patient therefore met clinical criteria for Kawasaki disease.

DISCUSSION

Kawasaki disease is a self-limited vasculitis of childhood and the leading cause of acquired heart disease in children in developed countries.¹ The annual incidence of Kawasaki disease in North America is about 25 cases per 100,000 children < 5 years of age.¹ In the United States, incidence is highest in Asian and Pacific Islander populations (30 per 100,000) and is particularly high among those of Japanese ancestry (~200 per 100,000).² Disease prevalence is also noteworthy in Non-Hispanic African American (17 per 100,000) and Hispanic (16 per 100,000) populations.²

Diagnosis of Kawasaki disease requires presence of fever lasting at least 5 days and at least 4 of the following: bilateral bulbar conjunctival injection, oral mucous membrane changes (erythematous or cracked lips, erythematous pharynx, strawberry tongue), peripheral extremity changes (erythema of palms or soles, edema of hands or feet, and/or periungual desquamation), diffuse maculopapular rash, and cervical lymphadenopathy (≥ 1.5 cm, often unilateral). If ≥ 4 criteria are met, Kawasaki disease can be diagnosed on the fourth day of illness.¹

Continue to: Laboratory findings suggesting...

Laboratory findings suggesting ­Kawasaki disease include a WBC count ≥ 15,000/mcL, normocytic, normochromic anemia, platelets ≥ 450,000/mcL after 7 days of illness, sterile pyuria (≥ 10 WBCs/high-power field), serum alanine aminotransferase level > 50 U/L, and serum albumin ≤ 3 g/dL.

Cardiac abnormalities are not included in the diagnostic criteria for Kawasaki disease but provide evidence in cases of incomplete Kawasaki disease if ≥ 4 criteria are not met and there is strong clinical suspicion.¹ Incomplete Kawasaki disease should be considered in a patient with a CRP level ≥ 3 mg/dL and/or ESR ≥ 40 mm/h, ≥ 3 supplemental laboratory criteria, or a positive echocardiogram.¹

Ultrasound imaging may reveal cervical lymph nodes resembling a “cluster of grapes.”³ The case patient’s imaging showed a “chain of enlarged lymph nodes.” She likely had gallbladder “hydrops” due to its increased longitudinal and horizontal diameter and lack of other anatomic changes.⁴

Prompt treatment is essential

Treatment for complete and incomplete Kawasaki disease is a single high dose of intravenous immunoglobulin (IVIG) along with aspirin. Patients meeting criteria should be treated as soon as the diagnosis is established.⁵ A single high dose of IVIG (2 g/kg), administered over 10 to 12 hours, should be initiated within 5 to 10 days of disease onset. Administering IVIG in the acute phase of Kawasaki disease reduces the prevalence of coronary artery abnormalities.⁶ Corticosteroids may be used as adjunctive therapy for patients with high risk of IVIG resistance.^1,7-9

Our patient was not deemed to be at high risk for IVIG resistance (Non-Japanese patient, age at fever onset > 6 months, absence of coronary artery aneurysm⁹) and was administered IVIG on Day 4. She was also given moderate-dose aspirin, then later transitioned to low-dose aspirin. The patient’s fevers improved, she was less irritable, and she had periods of playfulness. Physical exam then showed erythematous and cracked lips with peeling skin.

Continue to: The patient was discharged...

Untreated children with Kawasaki disease have a 25% chance of developing coronary artery aneurysms.

The patient was discharged home on Day 8, after her fever resolved, with instructions to continue low-dose aspirin and to obtain a repeat echocardiogram, gallbladder ultrasound, and lab work in 2 weeks. At her follow-up appointment, periungual desquamation was noted, and ultrasound showed continued enlarged/elongated gallbladder. A repeat echocardiogram was not available. Overall, the patient recovered from Kawasaki disease after therapeutic intervention.

THE TAKEAWAY

Kawasaki disease can be relatively rare in North American populations, but it is important for physicians to be able to recognize and treat it. Untreated children have a 25% chance of developing coronary artery aneurysms.^1,10,11 Early treatment with IVIG can decrease risk to 5%, resulting in an excellent medium- to long-term prognosis for patients.¹⁰ Thorough physical examination and an appropriate degree of clinical suspicion was key in this case of Kawasaki disease.

CORRESPONDENCE
Taisha Doo, MD, 1401 Madison Street, Suite #100, Seattle, WA 98104; taisha.doo@swedish.org

ILLUSTRATIVE CASE

A 61-year-old man with hypertension and paroxysmal AF presents to your office shortly after experiencing his third episode of AF in the past 6 months. He describes these episodes, which last for several days, as “just awful,” noting that when he experiences AF, he has fatigue, palpitations, and shortness of breath and “can’t stop paying attention to my heart.” The patient, who has a body mass index of 32, consumes more than 15 alcoholic drinks per week. What can you recommend to him that will decrease his likelihood of experiencing more episodes of AF?

AF is the most common sustained cardiac arrhythmia. It is associated with significant morbidity and mortality. Known risk factors include obesity, physical inactivity, sleep apnea, diabetes, and hypertension.²

According to the Centers for Disease Control and Prevention, an estimated 12.1 million people in the United States will have AF by 2030. In 2018, AF was mentioned on more than 183,000 death certificates and was the underlying cause of more than 26,000 of those deaths.³ AF is the primary diagnosis in 450,000 hospitalizations annually,⁴ and the death rate from AF as the primary or contributing cause of death has been rising for more than 2 decades.³

More than 50% of Americans report alcohol consumption within the past month.⁵ Although alcohol use is associated with new and recurrent AF, only limited prospective data show a clear and causal association between abstaining from alcohol and decreasing AF recurrence.

STUDY SUMMARY

Reduction in AF recurrence and total AF burden following alcohol abstinence

This multicenter, prospective, open-label, randomized controlled trial (N = 140) from 6 sites in Australia evaluated the impact of alcohol abstinence on both the recurrence of AF and the amount of time in AF. Study participants were ages 18 to 85 years, consumed 10 or more standard alcohol-containing drinks per week, had paroxysmal or persistent AF, and were in sinus rhythm at the time of enrollment, regardless of antiarrhythmic therapy. Exclusion criteria included alcohol dependence or abuse, severe left ventricular systolic dysfunction (ejection fraction < 35%), clinically significant noncardiac illness, and/or coexisting psychiatric disorder.¹

After a 4-week run-in period, patients were randomized to either an abstinence or a control group in a 1:1 fashion. Patients enrolled in the abstinence group were encouraged to abstain from alcohol consumption for 6 months and were provided with written and oral instructions to assist with abstaining. Control group patients continued their same level of alcohol consumption. Comprehensive rhythm monitoring occurred for all patients after randomization.

The largest challenge to implementation of this intervention is most likely the willingness of patients to cut their alcohol consumption.

Alcohol consumption was reported by both groups using a weekly alcohol diary, supplemented with a visual guide showing pictures of standard alcohol drinks. For the abstinence group, random urine testing for ethyl glucuronide (an alcohol metabolite) was possible if no alcohol intake was reported. Primary outcomes during the 6-month study included recurrence of AF and total AF burden (percentage of time in AF).

Continue to: Secondary outcomes included hospitalizations...

Secondary outcomes included hospitalizations for AF, AF symptom severity, and change in weight. Blood pressure, quality-of-life, and depression scores were missing for > 35% of patients.¹

Patients were randomized evenly to the control and abstinence groups. The typical patient was an overweight male in his early 60s with paroxysmal AF, who was taking an antiarrhythmic agent. Patients in the abstinence group decreased their alcohol consumption from 16.8 to 2.1 drinks per week (87.5% reduction; mean difference = –14.7; 95% CI, –12.7 to –16.7). Patients in the control group reduced their intake from 16.4 to 13.2 drinks per week (19.5% reduction; mean difference = –3.2; 95% CI, –1.9 to –4.4).¹

AF recurred in 53% vs 73% of the abstinence and control groups, respectively, with a longer period before recurrence in the abstinence group than in the control group (hazard ratio = 0.55; 95% CI, 0.36-0.84; P = .005; number needed to treat = 5). The AF burden was also lower in the abstinence group (0.5%; interquartile range [IQR] = 0.0-3.0) than in the control group (1.2%; IQR = 0.0-10.3; P = .01). The abstinence group had a lower percentage of AF hospitalizations compared with the control group (9% vs 20%), and fewer patients reporting moderate or severe AF symptoms (10% vs 32%). In addition, the abstinence group lost 3.7 kg more weight than did the control group at 6 months.¹

WHAT’S NEW

Objective new evidence for effective patient counseling

Alcohol consumption and its association with the onset and recurrence of AF has been documented previously.⁶ This study was the first to prospectively examine if abstaining from alcohol reduces paroxysmal AF episodes in moderate drinkers.

The study identified clinically meaningful findings among those who abstained from alcohol, including decreased AF recurrence rates, increased time to recurrence, and lower overall AF burden. This provides objective evidence that can be used for motivational interviewing in patients with paroxysmal AF who may be receptive to reducing or abstaining from alcohol consumption.

Continue to: CAVEATS

The narrow study population may not be widely applicable

The study population was predominantly male, in their seventh decade of life (mean age, 61), and living in Australia. Rates of AF and symptomatology differ by gender and age, making this information challenging to apply to women or older populations. The study excluded patients with alcohol dependence or abuse, left ventricular systolic dysfunction (ejection fraction < 35%), coexisting psychiatric disorders, and clinically significant noncardiac illnesses, limiting the study’s generalizability to these patient populations. Overall, AF recurrence was low in both groups despite the intervention, and the study did not evaluate the efficacy of the counseling method for abstinence.

Since publication of this article, a prospective cohort study of approximately 3800 Swiss patients with AF evaluated the effect of alcohol consumption on the rate of stroke and embolic events. That study did not find statistically significant correlations between patients who drank no alcohol per day, > 0 to < 1, 1 to < 2, or ≥ 2 drinks per day and their rate of stroke.⁷ However, this study did not specifically evaluate the rate of AF recurrence or time spent in AF among the cohort, which is clinically meaningful for patient morbidity.¹

CHALLENGES TO IMPLEMENTATION

Patient willingness to cut alcohol consumption may be limited

The largest challenge to implementation of this intervention is most likely the willingness of patients to cut their alcohol consumption. In this study population, 697 patients were screened for enrollment and met inclusion criteria; however, 491 patients (70.4%) were not willing to consider abstinence from alcohol, and after the run-in phase, another 17 declined randomization. Many primary care physicians would likely agree that while it is easy to encourage patients to drink less, patient adherence to these recommendations, particularly abstaining, is likely to be limited.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

ILLUSTRATIVE CASE

A 61-year-old man with hypertension and paroxysmal AF presents to your office shortly after experiencing his third episode of AF in the past 6 months. He describes these episodes, which last for several days, as “just awful,” noting that when he experiences AF, he has fatigue, palpitations, and shortness of breath and “can’t stop paying attention to my heart.” The patient, who has a body mass index of 32, consumes more than 15 alcoholic drinks per week. What can you recommend to him that will decrease his likelihood of experiencing more episodes of AF?

AF is the most common sustained cardiac arrhythmia. It is associated with significant morbidity and mortality. Known risk factors include obesity, physical inactivity, sleep apnea, diabetes, and hypertension.²

According to the Centers for Disease Control and Prevention, an estimated 12.1 million people in the United States will have AF by 2030. In 2018, AF was mentioned on more than 183,000 death certificates and was the underlying cause of more than 26,000 of those deaths.³ AF is the primary diagnosis in 450,000 hospitalizations annually,⁴ and the death rate from AF as the primary or contributing cause of death has been rising for more than 2 decades.³

More than 50% of Americans report alcohol consumption within the past month.⁵ Although alcohol use is associated with new and recurrent AF, only limited prospective data show a clear and causal association between abstaining from alcohol and decreasing AF recurrence.

STUDY SUMMARY

Reduction in AF recurrence and total AF burden following alcohol abstinence

This multicenter, prospective, open-label, randomized controlled trial (N = 140) from 6 sites in Australia evaluated the impact of alcohol abstinence on both the recurrence of AF and the amount of time in AF. Study participants were ages 18 to 85 years, consumed 10 or more standard alcohol-containing drinks per week, had paroxysmal or persistent AF, and were in sinus rhythm at the time of enrollment, regardless of antiarrhythmic therapy. Exclusion criteria included alcohol dependence or abuse, severe left ventricular systolic dysfunction (ejection fraction < 35%), clinically significant noncardiac illness, and/or coexisting psychiatric disorder.¹

After a 4-week run-in period, patients were randomized to either an abstinence or a control group in a 1:1 fashion. Patients enrolled in the abstinence group were encouraged to abstain from alcohol consumption for 6 months and were provided with written and oral instructions to assist with abstaining. Control group patients continued their same level of alcohol consumption. Comprehensive rhythm monitoring occurred for all patients after randomization.

The largest challenge to implementation of this intervention is most likely the willingness of patients to cut their alcohol consumption.

Alcohol consumption was reported by both groups using a weekly alcohol diary, supplemented with a visual guide showing pictures of standard alcohol drinks. For the abstinence group, random urine testing for ethyl glucuronide (an alcohol metabolite) was possible if no alcohol intake was reported. Primary outcomes during the 6-month study included recurrence of AF and total AF burden (percentage of time in AF).

Continue to: Secondary outcomes included hospitalizations...

Secondary outcomes included hospitalizations for AF, AF symptom severity, and change in weight. Blood pressure, quality-of-life, and depression scores were missing for > 35% of patients.¹

Patients were randomized evenly to the control and abstinence groups. The typical patient was an overweight male in his early 60s with paroxysmal AF, who was taking an antiarrhythmic agent. Patients in the abstinence group decreased their alcohol consumption from 16.8 to 2.1 drinks per week (87.5% reduction; mean difference = –14.7; 95% CI, –12.7 to –16.7). Patients in the control group reduced their intake from 16.4 to 13.2 drinks per week (19.5% reduction; mean difference = –3.2; 95% CI, –1.9 to –4.4).¹

AF recurred in 53% vs 73% of the abstinence and control groups, respectively, with a longer period before recurrence in the abstinence group than in the control group (hazard ratio = 0.55; 95% CI, 0.36-0.84; P = .005; number needed to treat = 5). The AF burden was also lower in the abstinence group (0.5%; interquartile range [IQR] = 0.0-3.0) than in the control group (1.2%; IQR = 0.0-10.3; P = .01). The abstinence group had a lower percentage of AF hospitalizations compared with the control group (9% vs 20%), and fewer patients reporting moderate or severe AF symptoms (10% vs 32%). In addition, the abstinence group lost 3.7 kg more weight than did the control group at 6 months.¹

WHAT’S NEW

Objective new evidence for effective patient counseling

Alcohol consumption and its association with the onset and recurrence of AF has been documented previously.⁶ This study was the first to prospectively examine if abstaining from alcohol reduces paroxysmal AF episodes in moderate drinkers.

The study identified clinically meaningful findings among those who abstained from alcohol, including decreased AF recurrence rates, increased time to recurrence, and lower overall AF burden. This provides objective evidence that can be used for motivational interviewing in patients with paroxysmal AF who may be receptive to reducing or abstaining from alcohol consumption.

Continue to: CAVEATS

The narrow study population may not be widely applicable

The study population was predominantly male, in their seventh decade of life (mean age, 61), and living in Australia. Rates of AF and symptomatology differ by gender and age, making this information challenging to apply to women or older populations. The study excluded patients with alcohol dependence or abuse, left ventricular systolic dysfunction (ejection fraction < 35%), coexisting psychiatric disorders, and clinically significant noncardiac illnesses, limiting the study’s generalizability to these patient populations. Overall, AF recurrence was low in both groups despite the intervention, and the study did not evaluate the efficacy of the counseling method for abstinence.

Since publication of this article, a prospective cohort study of approximately 3800 Swiss patients with AF evaluated the effect of alcohol consumption on the rate of stroke and embolic events. That study did not find statistically significant correlations between patients who drank no alcohol per day, > 0 to < 1, 1 to < 2, or ≥ 2 drinks per day and their rate of stroke.⁷ However, this study did not specifically evaluate the rate of AF recurrence or time spent in AF among the cohort, which is clinically meaningful for patient morbidity.¹

CHALLENGES TO IMPLEMENTATION

Patient willingness to cut alcohol consumption may be limited

The largest challenge to implementation of this intervention is most likely the willingness of patients to cut their alcohol consumption. In this study population, 697 patients were screened for enrollment and met inclusion criteria; however, 491 patients (70.4%) were not willing to consider abstinence from alcohol, and after the run-in phase, another 17 declined randomization. Many primary care physicians would likely agree that while it is easy to encourage patients to drink less, patient adherence to these recommendations, particularly abstaining, is likely to be limited.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

ILLUSTRATIVE CASE

A 61-year-old man with hypertension and paroxysmal AF presents to your office shortly after experiencing his third episode of AF in the past 6 months. He describes these episodes, which last for several days, as “just awful,” noting that when he experiences AF, he has fatigue, palpitations, and shortness of breath and “can’t stop paying attention to my heart.” The patient, who has a body mass index of 32, consumes more than 15 alcoholic drinks per week. What can you recommend to him that will decrease his likelihood of experiencing more episodes of AF?

AF is the most common sustained cardiac arrhythmia. It is associated with significant morbidity and mortality. Known risk factors include obesity, physical inactivity, sleep apnea, diabetes, and hypertension.²

According to the Centers for Disease Control and Prevention, an estimated 12.1 million people in the United States will have AF by 2030. In 2018, AF was mentioned on more than 183,000 death certificates and was the underlying cause of more than 26,000 of those deaths.³ AF is the primary diagnosis in 450,000 hospitalizations annually,⁴ and the death rate from AF as the primary or contributing cause of death has been rising for more than 2 decades.³

More than 50% of Americans report alcohol consumption within the past month.⁵ Although alcohol use is associated with new and recurrent AF, only limited prospective data show a clear and causal association between abstaining from alcohol and decreasing AF recurrence.

STUDY SUMMARY

Reduction in AF recurrence and total AF burden following alcohol abstinence

This multicenter, prospective, open-label, randomized controlled trial (N = 140) from 6 sites in Australia evaluated the impact of alcohol abstinence on both the recurrence of AF and the amount of time in AF. Study participants were ages 18 to 85 years, consumed 10 or more standard alcohol-containing drinks per week, had paroxysmal or persistent AF, and were in sinus rhythm at the time of enrollment, regardless of antiarrhythmic therapy. Exclusion criteria included alcohol dependence or abuse, severe left ventricular systolic dysfunction (ejection fraction < 35%), clinically significant noncardiac illness, and/or coexisting psychiatric disorder.¹

After a 4-week run-in period, patients were randomized to either an abstinence or a control group in a 1:1 fashion. Patients enrolled in the abstinence group were encouraged to abstain from alcohol consumption for 6 months and were provided with written and oral instructions to assist with abstaining. Control group patients continued their same level of alcohol consumption. Comprehensive rhythm monitoring occurred for all patients after randomization.

The largest challenge to implementation of this intervention is most likely the willingness of patients to cut their alcohol consumption.

Alcohol consumption was reported by both groups using a weekly alcohol diary, supplemented with a visual guide showing pictures of standard alcohol drinks. For the abstinence group, random urine testing for ethyl glucuronide (an alcohol metabolite) was possible if no alcohol intake was reported. Primary outcomes during the 6-month study included recurrence of AF and total AF burden (percentage of time in AF).

Continue to: Secondary outcomes included hospitalizations...

Secondary outcomes included hospitalizations for AF, AF symptom severity, and change in weight. Blood pressure, quality-of-life, and depression scores were missing for > 35% of patients.¹

Patients were randomized evenly to the control and abstinence groups. The typical patient was an overweight male in his early 60s with paroxysmal AF, who was taking an antiarrhythmic agent. Patients in the abstinence group decreased their alcohol consumption from 16.8 to 2.1 drinks per week (87.5% reduction; mean difference = –14.7; 95% CI, –12.7 to –16.7). Patients in the control group reduced their intake from 16.4 to 13.2 drinks per week (19.5% reduction; mean difference = –3.2; 95% CI, –1.9 to –4.4).¹

AF recurred in 53% vs 73% of the abstinence and control groups, respectively, with a longer period before recurrence in the abstinence group than in the control group (hazard ratio = 0.55; 95% CI, 0.36-0.84; P = .005; number needed to treat = 5). The AF burden was also lower in the abstinence group (0.5%; interquartile range [IQR] = 0.0-3.0) than in the control group (1.2%; IQR = 0.0-10.3; P = .01). The abstinence group had a lower percentage of AF hospitalizations compared with the control group (9% vs 20%), and fewer patients reporting moderate or severe AF symptoms (10% vs 32%). In addition, the abstinence group lost 3.7 kg more weight than did the control group at 6 months.¹

WHAT’S NEW

Objective new evidence for effective patient counseling

Alcohol consumption and its association with the onset and recurrence of AF has been documented previously.⁶ This study was the first to prospectively examine if abstaining from alcohol reduces paroxysmal AF episodes in moderate drinkers.

The study identified clinically meaningful findings among those who abstained from alcohol, including decreased AF recurrence rates, increased time to recurrence, and lower overall AF burden. This provides objective evidence that can be used for motivational interviewing in patients with paroxysmal AF who may be receptive to reducing or abstaining from alcohol consumption.

Continue to: CAVEATS

The narrow study population may not be widely applicable

The study population was predominantly male, in their seventh decade of life (mean age, 61), and living in Australia. Rates of AF and symptomatology differ by gender and age, making this information challenging to apply to women or older populations. The study excluded patients with alcohol dependence or abuse, left ventricular systolic dysfunction (ejection fraction < 35%), coexisting psychiatric disorders, and clinically significant noncardiac illnesses, limiting the study’s generalizability to these patient populations. Overall, AF recurrence was low in both groups despite the intervention, and the study did not evaluate the efficacy of the counseling method for abstinence.

Since publication of this article, a prospective cohort study of approximately 3800 Swiss patients with AF evaluated the effect of alcohol consumption on the rate of stroke and embolic events. That study did not find statistically significant correlations between patients who drank no alcohol per day, > 0 to < 1, 1 to < 2, or ≥ 2 drinks per day and their rate of stroke.⁷ However, this study did not specifically evaluate the rate of AF recurrence or time spent in AF among the cohort, which is clinically meaningful for patient morbidity.¹

CHALLENGES TO IMPLEMENTATION

Patient willingness to cut alcohol consumption may be limited

The largest challenge to implementation of this intervention is most likely the willingness of patients to cut their alcohol consumption. In this study population, 697 patients were screened for enrollment and met inclusion criteria; however, 491 patients (70.4%) were not willing to consider abstinence from alcohol, and after the run-in phase, another 17 declined randomization. Many primary care physicians would likely agree that while it is easy to encourage patients to drink less, patient adherence to these recommendations, particularly abstaining, is likely to be limited.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

As the geriatric population continues to grow and treatment advances blur the lines between improving the length of life vs improving its quality, end-of-life (EOL) conversations are becoming increasingly important. These discussions are a crucial part of the advance care planning (ACP) process, in which patients discuss their treatment preferences and values with their caregiver/surrogate decision maker and health care provider to ultimately improve EOL decision-making and care. ^1,2

EOL conversations are most helpful when incorporated in the outpatient setting as part of the patient’s ongoing health care plan or when initiating treatment for a chronic or life-threatening disease. Because family physicians promote general wellness, understand the patient’s health status and medical history, and have an ongoing—and often longstanding—relationship with patients and their families, we are ideally positioned to engage patients in EOL discussions. However, these conversations can be challenging in the outpatient setting, and often clinicians struggle not only to find ways to raise the subject, but also to find the time to have these supportive, meaningful conversations.³

In this article, we will address the importance of having EOL discussions in the outpatient setting, specifically about advance directives (ADs), and the reasons why patients and physicians might avoid these discussions. The role of palliative care in EOL care, along with its benefits and methods for overcoming patient and physician barriers to its successful use, are reviewed. Finally, we examine specific challenges associated with discussing EOL care with patients with decreased mental capacity, such as those with dementia, and provide strategies to successfully facilitate EOL discussions in these populations. 

Moving patients toward completion of advance directives

Although many older patients express a desire to document their wishes before EOL situations arise, they may not fully understand the benefits of an AD or how to complete one. ⁴ Often the family physician is best equipped to address the patient’s concerns and discuss their goals for EOL care, as well as the potential situations that might arise.

Managing an aging population. Projections suggest that primary care physicians will encounter increasing numbers of geriatric patients in the next 2 decades. Thus it is essential for those in primary care to receive proper training during their residency for the care of this group of patients. According to a group of academic educators and geriatricians from internal medicine and family medicine whose goal was to define a set of minimal and essential competencies in the care of older adults, this includes training on how to discuss and document “advance care planning and goals of care with all patients with chronic or complex illness,” as well as how to differentiate among “types of code status, health care proxies, and advanced directives” within the state in which training occurs. ⁵

Educate patients and ease fears. Patients often avoid EOL conversations or wait for their family physician to start the conversation. They may not understand how ADs can help guide care or they may believe they are “too healthy” to have these conversations at this time. ⁴ Simply asking about existing ADs or providing forms to patients during an outpatient visit can open the door to more in-depth discussions. Some examples of opening phrases include:

• Do you have a living will or durable power of attorney for health care?
• Have you ever discussed your health care wishes with your loved ones?
• Who would you want to speak for you regarding your health care if you could not speak for yourself? Have you discussed your health care wishes with that person?

By normalizing the conversation as a routine part of comprehensive, patient-centered care, the family physician can allay patient fears, foster open and honest conversations, and encourage ongoing discussions with loved ones as situations arise.⁶

Continue to: When ADs are executed...

As many as 90% of patients with a life-threatening illness report never having discussed EOL care issues with their clinician.

When ADs are executed, patients often fail to have meaningful conversations with their surrogates about specific treatment wishes or EOL scenarios. As a result, the surrogate may not feel prepared to serve as a proxy decision maker or may find the role extremely stressful.⁷ Physicians should encourage open conversations between patients and their surrogates about potential EOL scenarios when possible. When possible and appropriate, it is also important to encourage the patient to include the surrogate in future outpatient visits so that the surrogate can understand the patient’s health status and potential decisions they may need to make.

Don’t overlook clinician barriers. Family physicians also might avoid AD discussions because they do not understand laws that govern ADs, which vary from state to state. Various online resources for patients and physicians exist that clarify state-specific regulations and provide state-specific forms (TABLE).

Time constraints present another challenge for family physicians. This can be addressed by establishing workflows that include EOL elements. Also, the Centers for Medicare and Medicaid Services (CMS) has provided separate billing codes for AD discussion based on time spent explaining and discussing how to complete forms.⁸ CPT codes 99497 and 99498 are time-based codes that cover the first 30 minutes and each additional 30 minutes, respectively, of time spent explaining and discussing how to complete standard forms in a face-to-face setting (TABLE).⁹ CMS also includes discussion of AD documents as an optional element of the annual Medicare wellness visit.⁸ 

Improve quality of life for patients with any serious illness

Unlike hospice, which focuses on providing comfort rather than cure in the final months of a patient’s life, palliative care strives to prevent and relieve the patient’s suffering from a serious illness that is not immediately life-threatening. Palliative care focuses on the early identification, careful assessment, and treatment of the physical, psychosocial, and spiritual symptoms associated with a patient’s condition(s).^10,11 It has been well established that palliative care has a positive effect on many clinical outcomes including symptom burden, quality of life, satisfaction with care, and survival.^12-14 Patients who receive palliative care consultation also tend to perceive a higher quality of care.¹⁵

Conversations lead to better outcomes. Palliative care consultation is being increasingly used in the outpatient setting and can be introduced early in a disease process. Doing so provides an additional opportunity for the family physician to introduce an EOL discussion. A comparison of outcomes between patients who had initial inpatient palliative care consultation vs outpatient palliative care referral found that outpatient referral improved quality EOL care and was associated with significantly fewer emergency department visits (68% vs 48%; P < .001) and hospital admissions (86% vs 52%; P < .001), as well as shorter hospital stays in the last 30 days of life (3-11 vs 5-14 days; P = .01).¹⁴ Despite these benefits, 60% to 90% of patients with a serious illness report never having discussed EOL care issues with their clinician.^16,17

Continue to: Early EOL discussions...

Early EOL discussions have also been shown to have a positive impact on families. In a US study, family members stated that timely EOL care discussions allowed them to make use of hospice and palliative care services sooner and to make the most of their time with the patient.¹⁸

Timing and communication are key

Logistically it can be difficult to gather the right people (patient, family, etc) in the right place and at the right time. For physicians, the most often cited barriers include inadequate time to conduct an EOL discussion, ¹⁹ a perceived lack of competence in EOL conversations, ^1,20 difficulty navigating patient readiness, ²¹ and a fear of destroying hope due to prognostic uncertainty. ^19,20

A prospective, observational study used the Quality of Communication (QOC) questionnaire to assess life-sustaining treatment preferences, ACP, and the quality of EOL care communication in Dutch outpatients with clinically stable but severe chronic obstructive pulmonary disease (n = 105) or congestive heart failure (n = 80). The QOC questionnaire is a validated instrument that asks patients to rate their physician on several communication skills from 0 (“the very worst” or “My doctor didn’t do this”) to 10 (“the very best”). In this study, quality communication was identified by patients as one of the most important skills for physicians to provide adequate EOL care. ²² While QOC ratings were high for general communication skills (median, 8.0 points), quality EOL care communication was rated very low (median, 0.0 points). Researchers say that this was primarily because most EOL topics were not discussed—especially spirituality, prognosis, and what dying might be like. ²² In a secondary analysis that evaluated quality of EOL care communication during 1-year follow-up of patients with advanced chronic organ failure (n = 265) with the QOC questionnaire, patient ratings improved to moderate to good (medians, 6-8 points) when these topics were addressed. ²³  

Pick a strategy and prepare. As the older population continues to grow, the demands of palliative care management cannot be met by specialists alone and the responsibility of discussing EOL care with patients and their families will increasingly fall to family physicians as well. ²⁴ Several strategies and approaches have evolved to assist family physicians with acquiring the skills to conduct productive EOL discussions. These include widely referenced resources, such as VitalTalk ²⁵ and the ABCDE Plan. ²⁶ VitalTalk teaches skills to help clinicians navigate difficult conversations, ²⁵ and the “ABCDE” method provides a pneumonic for recommendations for how to deliver bad news ( A dvance preparation; B uild a therapeutic environment/relationship; C ommunicate well; D eal with patient and family reactions; E ncourage and validate emotions). ²⁶

Researchers found that timely EOL care discussions allowed family members to make use of hospice and palliative care services sooner and maximize their time with the patient.

Other strategies include familiarizing oneself with the patient’s medical history and present situation (eg, What are the patient’s symptoms? What do other involved clinicians think and recommend? What therapies have been attempted? What are the relevant social and emotional dynamics?); asking the patient who they want present for the EOL conversation; scheduling the conversation for when you can set aside an appropriate amount of time and in a private place where there will be no interruptions; and going into the meeting with your goal in mind, whether it is to deliver bad news, clarify the prognosis, establish goals of care, or communicate the patient’s goals and wishes for the EOL to those in attendance. ²⁷ It can be very helpful to begin the conversation by clarifying what the patient and their family/surrogate understand about the current diagnosis and prognosis. From there, the family physician can present a “headline” that prepares them for the current conversation (eg, “I have your latest test results, and I need to share some serious news”). This can facilitate a more detailed discussion of the patient’s and surrogate’s goals of care. Using these strategies, family physicians can lead a productive EOL discussion that benefits everyone.  

Continue to: How to navigate EOL discussions with patients with dementia

How to navigate EOL discussions with patients with dementia

EOL discussions with patients with dementia become even more complex and warrant specific discussion because one must consider the timing of such discussions, ^2,28,29 the trajectory of the disease and how that affects the patient’s capacity for EOL conversations, and the critical importance of engaging caregivers/surrogate decision makers in these discussions. ² ACP provides an opportunity for the physician, patient, and caregiver/­surrogate to jointly explore the patient’s values, beliefs, and preferences for care through the EOL as the disease progresses and the patient’s decisional capacity declines.

Ensure meaningful participation with timing. EOL discussions should occur while the patient has the cognitive capacity to actively participate in the planning process. A National Institutes of Health stage I behavioral intervention development trial evaluated a structured psychoeducational intervention, known as SPIRIT (Sharing Patient’s Illness Representation to Increase Trust), that aimed to promote cognitive and emotional preparation for EOL decisions for patients and their surrogates.²⁸ It was found to be effective in patients, including those with end-stage renal disease and advanced heart failure, and their surrogates.²⁸ Preliminary results from the trial confirmed that people with mild-to-­moderate dementia (recent Montreal Cognitive Assessment score ≥ 13) are able to participate meaningfully in EOL discussions and ACP.²⁸

Song et al²⁹ adapted SPIRIT for use with patients with dementia and conducted a feasibility study with 23 patient-surrogate dyads.The mixed-methods study involved an expert panel review of the adapted SPIRIT, followed by a randomized trial with qualitative interviews. All 23 patients with dementia, including 14 with moderate dementia, were able to articulate their values and EOL preferences somewhat or very coherently (91.3% inter-rater reliability).²⁹ In addition, dyad care goal congruence (agreement between patient’s EOL preferences and surrogate’s understanding of those preferences) and surrogate decision-making confidence (comfort in performing as a surrogate) were high and patient decisional conflict (patient difficulty in weighing the benefits and burdens of life-sustaining treatments and decision-making) was low, both at baseline as well as post ­intervention.²⁹ Although preparedness for EOL decision-making outcome measures did not change, people with dementia and their surrogates perceived SPIRIT to be beneficial, particularly in helping them be on the same page.²⁹

Patient ratings of physician communication improved when EOL topics such as spirituality, prognosis, and what dying might be like were discussed.

The randomized trial portion of the study (phase 2) continues to recruit 120 patient-surrogate dyads. Patient and surrogate self-reported preparedness for EOL decision-making are the primary outcomes, measured at baseline and 2 to 3 days post intervention. The estimated study completion date is May 31, 2022.³⁰

Evidence-based clinical guidance can improve the process. Following the Belgian Centre for Evidence-Based Medicine’s procedures as a sample methodology, Piers et al² developed evidence-based clinical recommendations for providers to use in the practical application of ACP in their care of patients with dementia.The researchers searched the literature; developed recommendations based on the evidence obtained, as well as their collective expert opinion; and performed validation using expert and end-user feedback and peer review. The study resulted in 32 recommendations focused on 8 domains that ranged from the beginning of the process (preconditions for optimal implementation of ACP) to later stages (ACP when it is difficult/no longer possible to communicate).²Specific guidance for ACP in dementia care include the following: 

• ACP initiation. Begin conversations around the time of diagnosis, continue them throughout ongoing care, and revisit them when changes occur in the patient’s health, financial, or residential status.
• ACP conversations. Use conversations to identify significant others in the patient’s life (potential caregivers and/or surrogate decision makers) and explore the patient’s awareness of the disease and its trajectory. Discuss the patient’s values and beliefs, as well as their fears about, and preferences for, future care and the EOL.  
• Role of significant others in the ACP process. Involve a patient’s significant others early in the ACP process, educate them about the surrogate ­decision-maker role, assess their disease awareness, and inform them about the disease trajectory and anticipated EOL decisions. ²

Continue to: Incorporate and document patients' values and preferences with LEAD

Incorporate and document patients’ values and preferences with LEAD. Dassel et al³¹ developed the Life-planning in Early Alzheimer’s and Dementia (LEAD) tool, which is a validated dementia-focused EOL planning tool that can be used to promote discussion and document a patient’s care preferences and values within the context of their changing cognitive ability.Dassel et al³¹ used a 4-phase mixed-method design that included (1) focus groups of patients with early-stage dementia and family caregivers, (2) clinical utility evaluation by content experts, (3) instrument completion sampling to evaluate its psychometric properties, and (4) additional focus groups to inform how the instrument should be used by families and in clinical practice.Six scales with high internal consistency and high test-retest reliability were identified: 3 scales represented patient values (concern about being a burden, the importance of quality [vs length] of life, and the preference for autonomy in decision-making) and 3 scales represented patient preferences (use of life-prolonging measures, controlling the timing of death, and the location of EOL care).³¹

When having EOL discussions with patients with dementia, one needs to consider the timing of such discussions and the trajectory of the disease.

The LEAD Guide can be used as a self-­assessment tool that is completed individually and then shared with the surrogate decision maker and health care provider.³² It also can be used to guide conversations with the surrogate and physician, as well as with trusted family and friends. Using this framework, family physicians can facilitate EOL planning with the patient and their surrogate that is based on the patient’s values and preferences for EOL care prior to, and in anticipation of, the patient’s loss of decisional capacity.³¹

Facilitate discussions that improve outcomes

Conversations about EOL care are taking on increased importance as the population ages and treatments advance. Understanding the concerns of patients and their surrogate decision makers, as well as the resources available to guide these difficult discussions ( TABLE ), will help family physicians conduct effective conversations that enhance care, reduce the burden on surrogate decision makers, and have a positive impact on many clinical outcomes.

CORRESPONDENCE
Shirley Bodi, MD, 3000 Arlington Avenue, Department of Family Medicine, Dowling Hall, Suite 2200, University of Toledo College of Medicine and Life Sciences, Toledo, OH 43614; Shirley.Bodi2@utoledo.edu

As the geriatric population continues to grow and treatment advances blur the lines between improving the length of life vs improving its quality, end-of-life (EOL) conversations are becoming increasingly important. These discussions are a crucial part of the advance care planning (ACP) process, in which patients discuss their treatment preferences and values with their caregiver/surrogate decision maker and health care provider to ultimately improve EOL decision-making and care. ^1,2

EOL conversations are most helpful when incorporated in the outpatient setting as part of the patient’s ongoing health care plan or when initiating treatment for a chronic or life-threatening disease. Because family physicians promote general wellness, understand the patient’s health status and medical history, and have an ongoing—and often longstanding—relationship with patients and their families, we are ideally positioned to engage patients in EOL discussions. However, these conversations can be challenging in the outpatient setting, and often clinicians struggle not only to find ways to raise the subject, but also to find the time to have these supportive, meaningful conversations.³

In this article, we will address the importance of having EOL discussions in the outpatient setting, specifically about advance directives (ADs), and the reasons why patients and physicians might avoid these discussions. The role of palliative care in EOL care, along with its benefits and methods for overcoming patient and physician barriers to its successful use, are reviewed. Finally, we examine specific challenges associated with discussing EOL care with patients with decreased mental capacity, such as those with dementia, and provide strategies to successfully facilitate EOL discussions in these populations. 

Moving patients toward completion of advance directives

Although many older patients express a desire to document their wishes before EOL situations arise, they may not fully understand the benefits of an AD or how to complete one. ⁴ Often the family physician is best equipped to address the patient’s concerns and discuss their goals for EOL care, as well as the potential situations that might arise.

Managing an aging population. Projections suggest that primary care physicians will encounter increasing numbers of geriatric patients in the next 2 decades. Thus it is essential for those in primary care to receive proper training during their residency for the care of this group of patients. According to a group of academic educators and geriatricians from internal medicine and family medicine whose goal was to define a set of minimal and essential competencies in the care of older adults, this includes training on how to discuss and document “advance care planning and goals of care with all patients with chronic or complex illness,” as well as how to differentiate among “types of code status, health care proxies, and advanced directives” within the state in which training occurs. ⁵

Educate patients and ease fears. Patients often avoid EOL conversations or wait for their family physician to start the conversation. They may not understand how ADs can help guide care or they may believe they are “too healthy” to have these conversations at this time. ⁴ Simply asking about existing ADs or providing forms to patients during an outpatient visit can open the door to more in-depth discussions. Some examples of opening phrases include:

• Do you have a living will or durable power of attorney for health care?
• Have you ever discussed your health care wishes with your loved ones?
• Who would you want to speak for you regarding your health care if you could not speak for yourself? Have you discussed your health care wishes with that person?

By normalizing the conversation as a routine part of comprehensive, patient-centered care, the family physician can allay patient fears, foster open and honest conversations, and encourage ongoing discussions with loved ones as situations arise.⁶

Continue to: When ADs are executed...

As many as 90% of patients with a life-threatening illness report never having discussed EOL care issues with their clinician.

When ADs are executed, patients often fail to have meaningful conversations with their surrogates about specific treatment wishes or EOL scenarios. As a result, the surrogate may not feel prepared to serve as a proxy decision maker or may find the role extremely stressful.⁷ Physicians should encourage open conversations between patients and their surrogates about potential EOL scenarios when possible. When possible and appropriate, it is also important to encourage the patient to include the surrogate in future outpatient visits so that the surrogate can understand the patient’s health status and potential decisions they may need to make.

Don’t overlook clinician barriers. Family physicians also might avoid AD discussions because they do not understand laws that govern ADs, which vary from state to state. Various online resources for patients and physicians exist that clarify state-specific regulations and provide state-specific forms (TABLE).

Time constraints present another challenge for family physicians. This can be addressed by establishing workflows that include EOL elements. Also, the Centers for Medicare and Medicaid Services (CMS) has provided separate billing codes for AD discussion based on time spent explaining and discussing how to complete forms.⁸ CPT codes 99497 and 99498 are time-based codes that cover the first 30 minutes and each additional 30 minutes, respectively, of time spent explaining and discussing how to complete standard forms in a face-to-face setting (TABLE).⁹ CMS also includes discussion of AD documents as an optional element of the annual Medicare wellness visit.⁸ 

Improve quality of life for patients with any serious illness

Unlike hospice, which focuses on providing comfort rather than cure in the final months of a patient’s life, palliative care strives to prevent and relieve the patient’s suffering from a serious illness that is not immediately life-threatening. Palliative care focuses on the early identification, careful assessment, and treatment of the physical, psychosocial, and spiritual symptoms associated with a patient’s condition(s).^10,11 It has been well established that palliative care has a positive effect on many clinical outcomes including symptom burden, quality of life, satisfaction with care, and survival.^12-14 Patients who receive palliative care consultation also tend to perceive a higher quality of care.¹⁵

Conversations lead to better outcomes. Palliative care consultation is being increasingly used in the outpatient setting and can be introduced early in a disease process. Doing so provides an additional opportunity for the family physician to introduce an EOL discussion. A comparison of outcomes between patients who had initial inpatient palliative care consultation vs outpatient palliative care referral found that outpatient referral improved quality EOL care and was associated with significantly fewer emergency department visits (68% vs 48%; P < .001) and hospital admissions (86% vs 52%; P < .001), as well as shorter hospital stays in the last 30 days of life (3-11 vs 5-14 days; P = .01).¹⁴ Despite these benefits, 60% to 90% of patients with a serious illness report never having discussed EOL care issues with their clinician.^16,17

Continue to: Early EOL discussions...

Early EOL discussions have also been shown to have a positive impact on families. In a US study, family members stated that timely EOL care discussions allowed them to make use of hospice and palliative care services sooner and to make the most of their time with the patient.¹⁸

Timing and communication are key

Logistically it can be difficult to gather the right people (patient, family, etc) in the right place and at the right time. For physicians, the most often cited barriers include inadequate time to conduct an EOL discussion, ¹⁹ a perceived lack of competence in EOL conversations, ^1,20 difficulty navigating patient readiness, ²¹ and a fear of destroying hope due to prognostic uncertainty. ^19,20

A prospective, observational study used the Quality of Communication (QOC) questionnaire to assess life-sustaining treatment preferences, ACP, and the quality of EOL care communication in Dutch outpatients with clinically stable but severe chronic obstructive pulmonary disease (n = 105) or congestive heart failure (n = 80). The QOC questionnaire is a validated instrument that asks patients to rate their physician on several communication skills from 0 (“the very worst” or “My doctor didn’t do this”) to 10 (“the very best”). In this study, quality communication was identified by patients as one of the most important skills for physicians to provide adequate EOL care. ²² While QOC ratings were high for general communication skills (median, 8.0 points), quality EOL care communication was rated very low (median, 0.0 points). Researchers say that this was primarily because most EOL topics were not discussed—especially spirituality, prognosis, and what dying might be like. ²² In a secondary analysis that evaluated quality of EOL care communication during 1-year follow-up of patients with advanced chronic organ failure (n = 265) with the QOC questionnaire, patient ratings improved to moderate to good (medians, 6-8 points) when these topics were addressed. ²³  

Pick a strategy and prepare. As the older population continues to grow, the demands of palliative care management cannot be met by specialists alone and the responsibility of discussing EOL care with patients and their families will increasingly fall to family physicians as well. ²⁴ Several strategies and approaches have evolved to assist family physicians with acquiring the skills to conduct productive EOL discussions. These include widely referenced resources, such as VitalTalk ²⁵ and the ABCDE Plan. ²⁶ VitalTalk teaches skills to help clinicians navigate difficult conversations, ²⁵ and the “ABCDE” method provides a pneumonic for recommendations for how to deliver bad news ( A dvance preparation; B uild a therapeutic environment/relationship; C ommunicate well; D eal with patient and family reactions; E ncourage and validate emotions). ²⁶

Researchers found that timely EOL care discussions allowed family members to make use of hospice and palliative care services sooner and maximize their time with the patient.

Other strategies include familiarizing oneself with the patient’s medical history and present situation (eg, What are the patient’s symptoms? What do other involved clinicians think and recommend? What therapies have been attempted? What are the relevant social and emotional dynamics?); asking the patient who they want present for the EOL conversation; scheduling the conversation for when you can set aside an appropriate amount of time and in a private place where there will be no interruptions; and going into the meeting with your goal in mind, whether it is to deliver bad news, clarify the prognosis, establish goals of care, or communicate the patient’s goals and wishes for the EOL to those in attendance. ²⁷ It can be very helpful to begin the conversation by clarifying what the patient and their family/surrogate understand about the current diagnosis and prognosis. From there, the family physician can present a “headline” that prepares them for the current conversation (eg, “I have your latest test results, and I need to share some serious news”). This can facilitate a more detailed discussion of the patient’s and surrogate’s goals of care. Using these strategies, family physicians can lead a productive EOL discussion that benefits everyone.  

Continue to: How to navigate EOL discussions with patients with dementia

How to navigate EOL discussions with patients with dementia

EOL discussions with patients with dementia become even more complex and warrant specific discussion because one must consider the timing of such discussions, ^2,28,29 the trajectory of the disease and how that affects the patient’s capacity for EOL conversations, and the critical importance of engaging caregivers/surrogate decision makers in these discussions. ² ACP provides an opportunity for the physician, patient, and caregiver/­surrogate to jointly explore the patient’s values, beliefs, and preferences for care through the EOL as the disease progresses and the patient’s decisional capacity declines.

Ensure meaningful participation with timing. EOL discussions should occur while the patient has the cognitive capacity to actively participate in the planning process. A National Institutes of Health stage I behavioral intervention development trial evaluated a structured psychoeducational intervention, known as SPIRIT (Sharing Patient’s Illness Representation to Increase Trust), that aimed to promote cognitive and emotional preparation for EOL decisions for patients and their surrogates.²⁸ It was found to be effective in patients, including those with end-stage renal disease and advanced heart failure, and their surrogates.²⁸ Preliminary results from the trial confirmed that people with mild-to-­moderate dementia (recent Montreal Cognitive Assessment score ≥ 13) are able to participate meaningfully in EOL discussions and ACP.²⁸

Song et al²⁹ adapted SPIRIT for use with patients with dementia and conducted a feasibility study with 23 patient-surrogate dyads.The mixed-methods study involved an expert panel review of the adapted SPIRIT, followed by a randomized trial with qualitative interviews. All 23 patients with dementia, including 14 with moderate dementia, were able to articulate their values and EOL preferences somewhat or very coherently (91.3% inter-rater reliability).²⁹ In addition, dyad care goal congruence (agreement between patient’s EOL preferences and surrogate’s understanding of those preferences) and surrogate decision-making confidence (comfort in performing as a surrogate) were high and patient decisional conflict (patient difficulty in weighing the benefits and burdens of life-sustaining treatments and decision-making) was low, both at baseline as well as post ­intervention.²⁹ Although preparedness for EOL decision-making outcome measures did not change, people with dementia and their surrogates perceived SPIRIT to be beneficial, particularly in helping them be on the same page.²⁹

Patient ratings of physician communication improved when EOL topics such as spirituality, prognosis, and what dying might be like were discussed.

The randomized trial portion of the study (phase 2) continues to recruit 120 patient-surrogate dyads. Patient and surrogate self-reported preparedness for EOL decision-making are the primary outcomes, measured at baseline and 2 to 3 days post intervention. The estimated study completion date is May 31, 2022.³⁰

Evidence-based clinical guidance can improve the process. Following the Belgian Centre for Evidence-Based Medicine’s procedures as a sample methodology, Piers et al² developed evidence-based clinical recommendations for providers to use in the practical application of ACP in their care of patients with dementia.The researchers searched the literature; developed recommendations based on the evidence obtained, as well as their collective expert opinion; and performed validation using expert and end-user feedback and peer review. The study resulted in 32 recommendations focused on 8 domains that ranged from the beginning of the process (preconditions for optimal implementation of ACP) to later stages (ACP when it is difficult/no longer possible to communicate).²Specific guidance for ACP in dementia care include the following: 

• ACP initiation. Begin conversations around the time of diagnosis, continue them throughout ongoing care, and revisit them when changes occur in the patient’s health, financial, or residential status.
• ACP conversations. Use conversations to identify significant others in the patient’s life (potential caregivers and/or surrogate decision makers) and explore the patient’s awareness of the disease and its trajectory. Discuss the patient’s values and beliefs, as well as their fears about, and preferences for, future care and the EOL.  
• Role of significant others in the ACP process. Involve a patient’s significant others early in the ACP process, educate them about the surrogate ­decision-maker role, assess their disease awareness, and inform them about the disease trajectory and anticipated EOL decisions. ²

Continue to: Incorporate and document patients' values and preferences with LEAD

Incorporate and document patients’ values and preferences with LEAD. Dassel et al³¹ developed the Life-planning in Early Alzheimer’s and Dementia (LEAD) tool, which is a validated dementia-focused EOL planning tool that can be used to promote discussion and document a patient’s care preferences and values within the context of their changing cognitive ability.Dassel et al³¹ used a 4-phase mixed-method design that included (1) focus groups of patients with early-stage dementia and family caregivers, (2) clinical utility evaluation by content experts, (3) instrument completion sampling to evaluate its psychometric properties, and (4) additional focus groups to inform how the instrument should be used by families and in clinical practice.Six scales with high internal consistency and high test-retest reliability were identified: 3 scales represented patient values (concern about being a burden, the importance of quality [vs length] of life, and the preference for autonomy in decision-making) and 3 scales represented patient preferences (use of life-prolonging measures, controlling the timing of death, and the location of EOL care).³¹

When having EOL discussions with patients with dementia, one needs to consider the timing of such discussions and the trajectory of the disease.

The LEAD Guide can be used as a self-­assessment tool that is completed individually and then shared with the surrogate decision maker and health care provider.³² It also can be used to guide conversations with the surrogate and physician, as well as with trusted family and friends. Using this framework, family physicians can facilitate EOL planning with the patient and their surrogate that is based on the patient’s values and preferences for EOL care prior to, and in anticipation of, the patient’s loss of decisional capacity.³¹

Facilitate discussions that improve outcomes

Conversations about EOL care are taking on increased importance as the population ages and treatments advance. Understanding the concerns of patients and their surrogate decision makers, as well as the resources available to guide these difficult discussions ( TABLE ), will help family physicians conduct effective conversations that enhance care, reduce the burden on surrogate decision makers, and have a positive impact on many clinical outcomes.

CORRESPONDENCE
Shirley Bodi, MD, 3000 Arlington Avenue, Department of Family Medicine, Dowling Hall, Suite 2200, University of Toledo College of Medicine and Life Sciences, Toledo, OH 43614; Shirley.Bodi2@utoledo.edu

As the geriatric population continues to grow and treatment advances blur the lines between improving the length of life vs improving its quality, end-of-life (EOL) conversations are becoming increasingly important. These discussions are a crucial part of the advance care planning (ACP) process, in which patients discuss their treatment preferences and values with their caregiver/surrogate decision maker and health care provider to ultimately improve EOL decision-making and care. ^1,2

EOL conversations are most helpful when incorporated in the outpatient setting as part of the patient’s ongoing health care plan or when initiating treatment for a chronic or life-threatening disease. Because family physicians promote general wellness, understand the patient’s health status and medical history, and have an ongoing—and often longstanding—relationship with patients and their families, we are ideally positioned to engage patients in EOL discussions. However, these conversations can be challenging in the outpatient setting, and often clinicians struggle not only to find ways to raise the subject, but also to find the time to have these supportive, meaningful conversations.³

In this article, we will address the importance of having EOL discussions in the outpatient setting, specifically about advance directives (ADs), and the reasons why patients and physicians might avoid these discussions. The role of palliative care in EOL care, along with its benefits and methods for overcoming patient and physician barriers to its successful use, are reviewed. Finally, we examine specific challenges associated with discussing EOL care with patients with decreased mental capacity, such as those with dementia, and provide strategies to successfully facilitate EOL discussions in these populations. 

Moving patients toward completion of advance directives

Although many older patients express a desire to document their wishes before EOL situations arise, they may not fully understand the benefits of an AD or how to complete one. ⁴ Often the family physician is best equipped to address the patient’s concerns and discuss their goals for EOL care, as well as the potential situations that might arise.

Managing an aging population. Projections suggest that primary care physicians will encounter increasing numbers of geriatric patients in the next 2 decades. Thus it is essential for those in primary care to receive proper training during their residency for the care of this group of patients. According to a group of academic educators and geriatricians from internal medicine and family medicine whose goal was to define a set of minimal and essential competencies in the care of older adults, this includes training on how to discuss and document “advance care planning and goals of care with all patients with chronic or complex illness,” as well as how to differentiate among “types of code status, health care proxies, and advanced directives” within the state in which training occurs. ⁵

Educate patients and ease fears. Patients often avoid EOL conversations or wait for their family physician to start the conversation. They may not understand how ADs can help guide care or they may believe they are “too healthy” to have these conversations at this time. ⁴ Simply asking about existing ADs or providing forms to patients during an outpatient visit can open the door to more in-depth discussions. Some examples of opening phrases include:

• Do you have a living will or durable power of attorney for health care?
• Have you ever discussed your health care wishes with your loved ones?
• Who would you want to speak for you regarding your health care if you could not speak for yourself? Have you discussed your health care wishes with that person?

By normalizing the conversation as a routine part of comprehensive, patient-centered care, the family physician can allay patient fears, foster open and honest conversations, and encourage ongoing discussions with loved ones as situations arise.⁶

Continue to: When ADs are executed...

As many as 90% of patients with a life-threatening illness report never having discussed EOL care issues with their clinician.

When ADs are executed, patients often fail to have meaningful conversations with their surrogates about specific treatment wishes or EOL scenarios. As a result, the surrogate may not feel prepared to serve as a proxy decision maker or may find the role extremely stressful.⁷ Physicians should encourage open conversations between patients and their surrogates about potential EOL scenarios when possible. When possible and appropriate, it is also important to encourage the patient to include the surrogate in future outpatient visits so that the surrogate can understand the patient’s health status and potential decisions they may need to make.

Don’t overlook clinician barriers. Family physicians also might avoid AD discussions because they do not understand laws that govern ADs, which vary from state to state. Various online resources for patients and physicians exist that clarify state-specific regulations and provide state-specific forms (TABLE).

Time constraints present another challenge for family physicians. This can be addressed by establishing workflows that include EOL elements. Also, the Centers for Medicare and Medicaid Services (CMS) has provided separate billing codes for AD discussion based on time spent explaining and discussing how to complete forms.⁸ CPT codes 99497 and 99498 are time-based codes that cover the first 30 minutes and each additional 30 minutes, respectively, of time spent explaining and discussing how to complete standard forms in a face-to-face setting (TABLE).⁹ CMS also includes discussion of AD documents as an optional element of the annual Medicare wellness visit.⁸ 

Improve quality of life for patients with any serious illness

Unlike hospice, which focuses on providing comfort rather than cure in the final months of a patient’s life, palliative care strives to prevent and relieve the patient’s suffering from a serious illness that is not immediately life-threatening. Palliative care focuses on the early identification, careful assessment, and treatment of the physical, psychosocial, and spiritual symptoms associated with a patient’s condition(s).^10,11 It has been well established that palliative care has a positive effect on many clinical outcomes including symptom burden, quality of life, satisfaction with care, and survival.^12-14 Patients who receive palliative care consultation also tend to perceive a higher quality of care.¹⁵

Conversations lead to better outcomes. Palliative care consultation is being increasingly used in the outpatient setting and can be introduced early in a disease process. Doing so provides an additional opportunity for the family physician to introduce an EOL discussion. A comparison of outcomes between patients who had initial inpatient palliative care consultation vs outpatient palliative care referral found that outpatient referral improved quality EOL care and was associated with significantly fewer emergency department visits (68% vs 48%; P < .001) and hospital admissions (86% vs 52%; P < .001), as well as shorter hospital stays in the last 30 days of life (3-11 vs 5-14 days; P = .01).¹⁴ Despite these benefits, 60% to 90% of patients with a serious illness report never having discussed EOL care issues with their clinician.^16,17

Continue to: Early EOL discussions...

Early EOL discussions have also been shown to have a positive impact on families. In a US study, family members stated that timely EOL care discussions allowed them to make use of hospice and palliative care services sooner and to make the most of their time with the patient.¹⁸

Timing and communication are key

Logistically it can be difficult to gather the right people (patient, family, etc) in the right place and at the right time. For physicians, the most often cited barriers include inadequate time to conduct an EOL discussion, ¹⁹ a perceived lack of competence in EOL conversations, ^1,20 difficulty navigating patient readiness, ²¹ and a fear of destroying hope due to prognostic uncertainty. ^19,20

A prospective, observational study used the Quality of Communication (QOC) questionnaire to assess life-sustaining treatment preferences, ACP, and the quality of EOL care communication in Dutch outpatients with clinically stable but severe chronic obstructive pulmonary disease (n = 105) or congestive heart failure (n = 80). The QOC questionnaire is a validated instrument that asks patients to rate their physician on several communication skills from 0 (“the very worst” or “My doctor didn’t do this”) to 10 (“the very best”). In this study, quality communication was identified by patients as one of the most important skills for physicians to provide adequate EOL care. ²² While QOC ratings were high for general communication skills (median, 8.0 points), quality EOL care communication was rated very low (median, 0.0 points). Researchers say that this was primarily because most EOL topics were not discussed—especially spirituality, prognosis, and what dying might be like. ²² In a secondary analysis that evaluated quality of EOL care communication during 1-year follow-up of patients with advanced chronic organ failure (n = 265) with the QOC questionnaire, patient ratings improved to moderate to good (medians, 6-8 points) when these topics were addressed. ²³  

Pick a strategy and prepare. As the older population continues to grow, the demands of palliative care management cannot be met by specialists alone and the responsibility of discussing EOL care with patients and their families will increasingly fall to family physicians as well. ²⁴ Several strategies and approaches have evolved to assist family physicians with acquiring the skills to conduct productive EOL discussions. These include widely referenced resources, such as VitalTalk ²⁵ and the ABCDE Plan. ²⁶ VitalTalk teaches skills to help clinicians navigate difficult conversations, ²⁵ and the “ABCDE” method provides a pneumonic for recommendations for how to deliver bad news ( A dvance preparation; B uild a therapeutic environment/relationship; C ommunicate well; D eal with patient and family reactions; E ncourage and validate emotions). ²⁶

Researchers found that timely EOL care discussions allowed family members to make use of hospice and palliative care services sooner and maximize their time with the patient.

Other strategies include familiarizing oneself with the patient’s medical history and present situation (eg, What are the patient’s symptoms? What do other involved clinicians think and recommend? What therapies have been attempted? What are the relevant social and emotional dynamics?); asking the patient who they want present for the EOL conversation; scheduling the conversation for when you can set aside an appropriate amount of time and in a private place where there will be no interruptions; and going into the meeting with your goal in mind, whether it is to deliver bad news, clarify the prognosis, establish goals of care, or communicate the patient’s goals and wishes for the EOL to those in attendance. ²⁷ It can be very helpful to begin the conversation by clarifying what the patient and their family/surrogate understand about the current diagnosis and prognosis. From there, the family physician can present a “headline” that prepares them for the current conversation (eg, “I have your latest test results, and I need to share some serious news”). This can facilitate a more detailed discussion of the patient’s and surrogate’s goals of care. Using these strategies, family physicians can lead a productive EOL discussion that benefits everyone.  

Continue to: How to navigate EOL discussions with patients with dementia

How to navigate EOL discussions with patients with dementia

EOL discussions with patients with dementia become even more complex and warrant specific discussion because one must consider the timing of such discussions, ^2,28,29 the trajectory of the disease and how that affects the patient’s capacity for EOL conversations, and the critical importance of engaging caregivers/surrogate decision makers in these discussions. ² ACP provides an opportunity for the physician, patient, and caregiver/­surrogate to jointly explore the patient’s values, beliefs, and preferences for care through the EOL as the disease progresses and the patient’s decisional capacity declines.

Ensure meaningful participation with timing. EOL discussions should occur while the patient has the cognitive capacity to actively participate in the planning process. A National Institutes of Health stage I behavioral intervention development trial evaluated a structured psychoeducational intervention, known as SPIRIT (Sharing Patient’s Illness Representation to Increase Trust), that aimed to promote cognitive and emotional preparation for EOL decisions for patients and their surrogates.²⁸ It was found to be effective in patients, including those with end-stage renal disease and advanced heart failure, and their surrogates.²⁸ Preliminary results from the trial confirmed that people with mild-to-­moderate dementia (recent Montreal Cognitive Assessment score ≥ 13) are able to participate meaningfully in EOL discussions and ACP.²⁸

Song et al²⁹ adapted SPIRIT for use with patients with dementia and conducted a feasibility study with 23 patient-surrogate dyads.The mixed-methods study involved an expert panel review of the adapted SPIRIT, followed by a randomized trial with qualitative interviews. All 23 patients with dementia, including 14 with moderate dementia, were able to articulate their values and EOL preferences somewhat or very coherently (91.3% inter-rater reliability).²⁹ In addition, dyad care goal congruence (agreement between patient’s EOL preferences and surrogate’s understanding of those preferences) and surrogate decision-making confidence (comfort in performing as a surrogate) were high and patient decisional conflict (patient difficulty in weighing the benefits and burdens of life-sustaining treatments and decision-making) was low, both at baseline as well as post ­intervention.²⁹ Although preparedness for EOL decision-making outcome measures did not change, people with dementia and their surrogates perceived SPIRIT to be beneficial, particularly in helping them be on the same page.²⁹

Patient ratings of physician communication improved when EOL topics such as spirituality, prognosis, and what dying might be like were discussed.

The randomized trial portion of the study (phase 2) continues to recruit 120 patient-surrogate dyads. Patient and surrogate self-reported preparedness for EOL decision-making are the primary outcomes, measured at baseline and 2 to 3 days post intervention. The estimated study completion date is May 31, 2022.³⁰

Evidence-based clinical guidance can improve the process. Following the Belgian Centre for Evidence-Based Medicine’s procedures as a sample methodology, Piers et al² developed evidence-based clinical recommendations for providers to use in the practical application of ACP in their care of patients with dementia.The researchers searched the literature; developed recommendations based on the evidence obtained, as well as their collective expert opinion; and performed validation using expert and end-user feedback and peer review. The study resulted in 32 recommendations focused on 8 domains that ranged from the beginning of the process (preconditions for optimal implementation of ACP) to later stages (ACP when it is difficult/no longer possible to communicate).²Specific guidance for ACP in dementia care include the following: 

• ACP initiation. Begin conversations around the time of diagnosis, continue them throughout ongoing care, and revisit them when changes occur in the patient’s health, financial, or residential status.
• ACP conversations. Use conversations to identify significant others in the patient’s life (potential caregivers and/or surrogate decision makers) and explore the patient’s awareness of the disease and its trajectory. Discuss the patient’s values and beliefs, as well as their fears about, and preferences for, future care and the EOL.  
• Role of significant others in the ACP process. Involve a patient’s significant others early in the ACP process, educate them about the surrogate ­decision-maker role, assess their disease awareness, and inform them about the disease trajectory and anticipated EOL decisions. ²

Continue to: Incorporate and document patients' values and preferences with LEAD

Incorporate and document patients’ values and preferences with LEAD. Dassel et al³¹ developed the Life-planning in Early Alzheimer’s and Dementia (LEAD) tool, which is a validated dementia-focused EOL planning tool that can be used to promote discussion and document a patient’s care preferences and values within the context of their changing cognitive ability.Dassel et al³¹ used a 4-phase mixed-method design that included (1) focus groups of patients with early-stage dementia and family caregivers, (2) clinical utility evaluation by content experts, (3) instrument completion sampling to evaluate its psychometric properties, and (4) additional focus groups to inform how the instrument should be used by families and in clinical practice.Six scales with high internal consistency and high test-retest reliability were identified: 3 scales represented patient values (concern about being a burden, the importance of quality [vs length] of life, and the preference for autonomy in decision-making) and 3 scales represented patient preferences (use of life-prolonging measures, controlling the timing of death, and the location of EOL care).³¹

When having EOL discussions with patients with dementia, one needs to consider the timing of such discussions and the trajectory of the disease.

The LEAD Guide can be used as a self-­assessment tool that is completed individually and then shared with the surrogate decision maker and health care provider.³² It also can be used to guide conversations with the surrogate and physician, as well as with trusted family and friends. Using this framework, family physicians can facilitate EOL planning with the patient and their surrogate that is based on the patient’s values and preferences for EOL care prior to, and in anticipation of, the patient’s loss of decisional capacity.³¹

Facilitate discussions that improve outcomes

Conversations about EOL care are taking on increased importance as the population ages and treatments advance. Understanding the concerns of patients and their surrogate decision makers, as well as the resources available to guide these difficult discussions ( TABLE ), will help family physicians conduct effective conversations that enhance care, reduce the burden on surrogate decision makers, and have a positive impact on many clinical outcomes.

CORRESPONDENCE
Shirley Bodi, MD, 3000 Arlington Avenue, Department of Family Medicine, Dowling Hall, Suite 2200, University of Toledo College of Medicine and Life Sciences, Toledo, OH 43614; Shirley.Bodi2@utoledo.edu