The Journal of Family Practice

THE CASE

A 27-year-old man with no past medical history presented to his primary care physician (PCP) for a routine physical. He reported experiencing muscle weakness and fatigue for the previous 1 to 2 months. Two blood pressure measurements were recorded: 138/80 mm Hg and 142/95 mm Hg. The patient was given a diagnosis of hypertension and started on ­triamterene/hydrochlorothiazide. Labwork was ordered, including a complete metabolic panel, lipid panel, urinalysis, thyroid-stimulating hormone (TSH) plus thyroxine (T4), HIV antibodies, and a complete blood count.

The samples were drawn 1 week later, and the results were notable for low-normal TSH with a T4 of 0.8 ng/dL (normal range, 0.9-2.3 ng/dL); sodium, 151 mmol/L (normal range, 136-145 mmol/L); potassium, 3.4 mmol/L (normal range, 3.6-5.2 mmol/L); and white blood cell count, 13.8 x 10³/mcL. The electrolyte abnormalities were attributed to the triamterene/hydrochlorothiazide, which was stopped. One week later, repeat labs showed a persistent potassium level of 3.0 mmol/L; sodium, 141 mmol/L; and glucose, 310 mg/dL. Follow-up A1C was measured at 7.4%.

At the next appointment (2 weeks after initial evaluation), the patient received a diagnosis of type 2 diabetes in addition to new-onset essential hypertension. He expressed surprise at his diagnoses, as he said he primarily ate a balanced diet with plenty of vegetables and lots of healthy home-cooked meals. His body mass index (BMI) was in normal range, and he said he exercised regularly.

The patient was started on metformin 500 mg/d and referred to Endocrinology. After seeing the endocrinologist, who agreed with metformin for initial management, the patient contacted his PCP with concerns about worsening “muscle wasting.” Based on these ongoing symptoms, the patient was advised to go to the emergency department (ED).

In the ED, the patient reported muscle aches and weakness, weight gain, dyspnea on exertion, and polyuria. He also said that his face had widened with his weight gain, and his weakness was greatest in his thighs compared to his distal lower extremities. Labs drawn in the ED indicated hyperglycemia (glucose, 334 mg/dL) and severe hypokalemia (potassium, 2.2 mmol/L).

THE DIAGNOSIS

The patient was admitted in the afternoon for further evaluation, and a random serum cortisol measurement was ordered. The results showed an elevated cortisol level (55.2 mcg/dL; normal range, 3-20 mcg/dL). This was followed by a profoundly positive low-dose dexamethasone suppression test with a morning cortisol level of 75.9 mcg/dL (normal range, < 1.8 mcg/dL). With these findings, the diagnosis of Cushing syndrome was made and the focus of the evaluation shifted to localization.

An adrenocorticotropic hormone (ACTH) measurement was ordered, as well as magnetic resonance imaging (MRI) of the pituitary gland and of the abdomen to assess the adrenal glands. Both MRIs were negative, prompting a high-dose 8-mg dexamethasone suppression test to be performed. The patient’s morning cortisol level remained elevated (69.9 mcg/dL), confirming the diagnosis of Cushing syndrome.

Continue to: Based on the results...

Based on the results of the dexamethasone suppression test, a pituitary adenoma was unlikely (as they are often suppressed to < 5 mcg/dL with this test). The patient’s morning ACTH results came back as elevated (356.6 pg/mL; normal range, 10-60 pg/mL), suggesting inappropriate ACTH secretion, which most often has an ectopic source. However, a nuclear medicine octreotide scan and multiple computed tomography scans failed to locate such a source.

The patient eventually underwent bilateral petrosal venous sinus sampling to definitively rule out a pituitary source. Lastly, he underwent nuclear medicine positron emission tomography, which identified a nodular opacity in the anterior left lung apex, demonstrating moderate radiotracer activity (FIGURE 1).

THE DISCUSSION

Cushing syndrome is rarely encountered—it is estimated to affect 2% of patients with uncontrolled diabetes¹ and 1% of those with uncontrolled hypertension²—and requires a high level of clinical suspicion. This case highlights the importance of considering secondary causes of diabetes in patients who present atypically. This patient presented with symptoms consistent with Cushing syndrome that went unrecognized initially; these included high blood pressure, rounded face, weak muscles, hypokalemia, and intermittent hypernatremia in addition to new-onset hyperglycemia.^2-5 Despite the atypical findings, evaluation for diabetes and potential secondary causes was neglected until an ED evaluation 1 month after initial presentation. The work-up for possible Cushing syndrome was completed in the hospital but could easily have been conducted in the outpatient setting.

Making the diagnosis. When Cushing syndrome is suspected, consider consultation with Endocrinology. It is important to exclude exogenous glucocorticoid exposure through a thorough review of the patient’s medications.² The Endocrine Society² recommends that one of the following tests be performed:

• 24-hour urine free cortisol (≥ 2 tests)
• Overnight 1-mg dexamethasone suppression test
• Late-night salivary cortisol test.

Results within normal range make Cushing syndrome an unlikely diagnosis; however, for patients with suggestive clinical features, further work-up may be warranted.

Continue to: Any abnormal result...

Any abnormal result is an indication to exclude a physiologic cause of hypercortisolism by repeating at least 1 of the previous studies. As with the initial testing, normal results may rule out Cushing syndrome, while abnormal results would be confirmatory. (Conflicting results require additional evaluation.)

Morbidity and mortality. Finding the etiology of Cushing syndrome can present a challenge but is also rewarding due to the reversible nature of most of the abnormalities. That said, Cushing syndrome can have a significant impact on morbidity and mortality.

Morbidity. The case patient developed compression fractures throughout his thoracic and lumbar spine, with a loss of 4 inches in height, attributed to the delay in curative treatment (FIGURE 2); these were identified about 2 months after his initial presentation to a health care facility. In addition to bone mineral density, cognitive function and quality of life can be impacted by untreated hypercortisolism and Cushing syndrome.²

Mortality. In the earliest studies^6,7 (from the 1930s-1950s), the average survival rate was about 4.6 years and the 5-year survival was just 50%—and yet, outcomes data from modern treatment modalities are scant. While there is limited data on outcomes in untreated disease, the Endocrine Society states that treatment of moderate-to-severe cases “clearly reduces mortality and morbidity” while early identification and treatment of mild cases “would reduce the risk of residual morbidity.”²

Our patient underwent video-assisted thoracoscopic surgery, during which a nodule in the anterior lingula was removed. In addition, lymph node dissection was performed. Two lymph nodes were positive for atypical well-differentiated carcinoid tumor. After surgical removal, the patient’s cortisol levels normalized and his diabetes resolved.

THE TAKEAWAY

In primary care, the frequency at which we evaluate and diagnose type 2 diabetes without secondary cause can lead to cognitive biases, such as anchoring bias, that impact patient care. In this case, the atypical secondary nature of the diabetes was missed at 3 outpatient appointments prior to presentation at the hospital ED. In an active patient who has a normal BMI and a healthy diet—but systemic symptoms—it is critical to consider secondary causes of diabetes, such as Cushing syndrome.

CORRESPONDENCE
Anna Murley Squibb, MD, 2145 North Fairfield Road, Suite 100, Beavercreek, OH 45385; [email protected]

THE CASE

A 27-year-old man with no past medical history presented to his primary care physician (PCP) for a routine physical. He reported experiencing muscle weakness and fatigue for the previous 1 to 2 months. Two blood pressure measurements were recorded: 138/80 mm Hg and 142/95 mm Hg. The patient was given a diagnosis of hypertension and started on ­triamterene/hydrochlorothiazide. Labwork was ordered, including a complete metabolic panel, lipid panel, urinalysis, thyroid-stimulating hormone (TSH) plus thyroxine (T4), HIV antibodies, and a complete blood count.

The samples were drawn 1 week later, and the results were notable for low-normal TSH with a T4 of 0.8 ng/dL (normal range, 0.9-2.3 ng/dL); sodium, 151 mmol/L (normal range, 136-145 mmol/L); potassium, 3.4 mmol/L (normal range, 3.6-5.2 mmol/L); and white blood cell count, 13.8 x 10³/mcL. The electrolyte abnormalities were attributed to the triamterene/hydrochlorothiazide, which was stopped. One week later, repeat labs showed a persistent potassium level of 3.0 mmol/L; sodium, 141 mmol/L; and glucose, 310 mg/dL. Follow-up A1C was measured at 7.4%.

At the next appointment (2 weeks after initial evaluation), the patient received a diagnosis of type 2 diabetes in addition to new-onset essential hypertension. He expressed surprise at his diagnoses, as he said he primarily ate a balanced diet with plenty of vegetables and lots of healthy home-cooked meals. His body mass index (BMI) was in normal range, and he said he exercised regularly.

The patient was started on metformin 500 mg/d and referred to Endocrinology. After seeing the endocrinologist, who agreed with metformin for initial management, the patient contacted his PCP with concerns about worsening “muscle wasting.” Based on these ongoing symptoms, the patient was advised to go to the emergency department (ED).

In the ED, the patient reported muscle aches and weakness, weight gain, dyspnea on exertion, and polyuria. He also said that his face had widened with his weight gain, and his weakness was greatest in his thighs compared to his distal lower extremities. Labs drawn in the ED indicated hyperglycemia (glucose, 334 mg/dL) and severe hypokalemia (potassium, 2.2 mmol/L).

THE DIAGNOSIS

The patient was admitted in the afternoon for further evaluation, and a random serum cortisol measurement was ordered. The results showed an elevated cortisol level (55.2 mcg/dL; normal range, 3-20 mcg/dL). This was followed by a profoundly positive low-dose dexamethasone suppression test with a morning cortisol level of 75.9 mcg/dL (normal range, < 1.8 mcg/dL). With these findings, the diagnosis of Cushing syndrome was made and the focus of the evaluation shifted to localization.

An adrenocorticotropic hormone (ACTH) measurement was ordered, as well as magnetic resonance imaging (MRI) of the pituitary gland and of the abdomen to assess the adrenal glands. Both MRIs were negative, prompting a high-dose 8-mg dexamethasone suppression test to be performed. The patient’s morning cortisol level remained elevated (69.9 mcg/dL), confirming the diagnosis of Cushing syndrome.

Continue to: Based on the results...

Based on the results of the dexamethasone suppression test, a pituitary adenoma was unlikely (as they are often suppressed to < 5 mcg/dL with this test). The patient’s morning ACTH results came back as elevated (356.6 pg/mL; normal range, 10-60 pg/mL), suggesting inappropriate ACTH secretion, which most often has an ectopic source. However, a nuclear medicine octreotide scan and multiple computed tomography scans failed to locate such a source.

The patient eventually underwent bilateral petrosal venous sinus sampling to definitively rule out a pituitary source. Lastly, he underwent nuclear medicine positron emission tomography, which identified a nodular opacity in the anterior left lung apex, demonstrating moderate radiotracer activity (FIGURE 1).

THE DISCUSSION

Cushing syndrome is rarely encountered—it is estimated to affect 2% of patients with uncontrolled diabetes¹ and 1% of those with uncontrolled hypertension²—and requires a high level of clinical suspicion. This case highlights the importance of considering secondary causes of diabetes in patients who present atypically. This patient presented with symptoms consistent with Cushing syndrome that went unrecognized initially; these included high blood pressure, rounded face, weak muscles, hypokalemia, and intermittent hypernatremia in addition to new-onset hyperglycemia.^2-5 Despite the atypical findings, evaluation for diabetes and potential secondary causes was neglected until an ED evaluation 1 month after initial presentation. The work-up for possible Cushing syndrome was completed in the hospital but could easily have been conducted in the outpatient setting.

Making the diagnosis. When Cushing syndrome is suspected, consider consultation with Endocrinology. It is important to exclude exogenous glucocorticoid exposure through a thorough review of the patient’s medications.² The Endocrine Society² recommends that one of the following tests be performed:

• 24-hour urine free cortisol (≥ 2 tests)
• Overnight 1-mg dexamethasone suppression test
• Late-night salivary cortisol test.

Results within normal range make Cushing syndrome an unlikely diagnosis; however, for patients with suggestive clinical features, further work-up may be warranted.

Continue to: Any abnormal result...

Any abnormal result is an indication to exclude a physiologic cause of hypercortisolism by repeating at least 1 of the previous studies. As with the initial testing, normal results may rule out Cushing syndrome, while abnormal results would be confirmatory. (Conflicting results require additional evaluation.)

Morbidity and mortality. Finding the etiology of Cushing syndrome can present a challenge but is also rewarding due to the reversible nature of most of the abnormalities. That said, Cushing syndrome can have a significant impact on morbidity and mortality.

Morbidity. The case patient developed compression fractures throughout his thoracic and lumbar spine, with a loss of 4 inches in height, attributed to the delay in curative treatment (FIGURE 2); these were identified about 2 months after his initial presentation to a health care facility. In addition to bone mineral density, cognitive function and quality of life can be impacted by untreated hypercortisolism and Cushing syndrome.²

Mortality. In the earliest studies^6,7 (from the 1930s-1950s), the average survival rate was about 4.6 years and the 5-year survival was just 50%—and yet, outcomes data from modern treatment modalities are scant. While there is limited data on outcomes in untreated disease, the Endocrine Society states that treatment of moderate-to-severe cases “clearly reduces mortality and morbidity” while early identification and treatment of mild cases “would reduce the risk of residual morbidity.”²

Our patient underwent video-assisted thoracoscopic surgery, during which a nodule in the anterior lingula was removed. In addition, lymph node dissection was performed. Two lymph nodes were positive for atypical well-differentiated carcinoid tumor. After surgical removal, the patient’s cortisol levels normalized and his diabetes resolved.

THE TAKEAWAY

In primary care, the frequency at which we evaluate and diagnose type 2 diabetes without secondary cause can lead to cognitive biases, such as anchoring bias, that impact patient care. In this case, the atypical secondary nature of the diabetes was missed at 3 outpatient appointments prior to presentation at the hospital ED. In an active patient who has a normal BMI and a healthy diet—but systemic symptoms—it is critical to consider secondary causes of diabetes, such as Cushing syndrome.

CORRESPONDENCE
Anna Murley Squibb, MD, 2145 North Fairfield Road, Suite 100, Beavercreek, OH 45385; [email protected]

THE CASE

A 27-year-old man with no past medical history presented to his primary care physician (PCP) for a routine physical. He reported experiencing muscle weakness and fatigue for the previous 1 to 2 months. Two blood pressure measurements were recorded: 138/80 mm Hg and 142/95 mm Hg. The patient was given a diagnosis of hypertension and started on ­triamterene/hydrochlorothiazide. Labwork was ordered, including a complete metabolic panel, lipid panel, urinalysis, thyroid-stimulating hormone (TSH) plus thyroxine (T4), HIV antibodies, and a complete blood count.

The samples were drawn 1 week later, and the results were notable for low-normal TSH with a T4 of 0.8 ng/dL (normal range, 0.9-2.3 ng/dL); sodium, 151 mmol/L (normal range, 136-145 mmol/L); potassium, 3.4 mmol/L (normal range, 3.6-5.2 mmol/L); and white blood cell count, 13.8 x 10³/mcL. The electrolyte abnormalities were attributed to the triamterene/hydrochlorothiazide, which was stopped. One week later, repeat labs showed a persistent potassium level of 3.0 mmol/L; sodium, 141 mmol/L; and glucose, 310 mg/dL. Follow-up A1C was measured at 7.4%.

At the next appointment (2 weeks after initial evaluation), the patient received a diagnosis of type 2 diabetes in addition to new-onset essential hypertension. He expressed surprise at his diagnoses, as he said he primarily ate a balanced diet with plenty of vegetables and lots of healthy home-cooked meals. His body mass index (BMI) was in normal range, and he said he exercised regularly.

The patient was started on metformin 500 mg/d and referred to Endocrinology. After seeing the endocrinologist, who agreed with metformin for initial management, the patient contacted his PCP with concerns about worsening “muscle wasting.” Based on these ongoing symptoms, the patient was advised to go to the emergency department (ED).

In the ED, the patient reported muscle aches and weakness, weight gain, dyspnea on exertion, and polyuria. He also said that his face had widened with his weight gain, and his weakness was greatest in his thighs compared to his distal lower extremities. Labs drawn in the ED indicated hyperglycemia (glucose, 334 mg/dL) and severe hypokalemia (potassium, 2.2 mmol/L).

THE DIAGNOSIS

The patient was admitted in the afternoon for further evaluation, and a random serum cortisol measurement was ordered. The results showed an elevated cortisol level (55.2 mcg/dL; normal range, 3-20 mcg/dL). This was followed by a profoundly positive low-dose dexamethasone suppression test with a morning cortisol level of 75.9 mcg/dL (normal range, < 1.8 mcg/dL). With these findings, the diagnosis of Cushing syndrome was made and the focus of the evaluation shifted to localization.

An adrenocorticotropic hormone (ACTH) measurement was ordered, as well as magnetic resonance imaging (MRI) of the pituitary gland and of the abdomen to assess the adrenal glands. Both MRIs were negative, prompting a high-dose 8-mg dexamethasone suppression test to be performed. The patient’s morning cortisol level remained elevated (69.9 mcg/dL), confirming the diagnosis of Cushing syndrome.

Continue to: Based on the results...

Based on the results of the dexamethasone suppression test, a pituitary adenoma was unlikely (as they are often suppressed to < 5 mcg/dL with this test). The patient’s morning ACTH results came back as elevated (356.6 pg/mL; normal range, 10-60 pg/mL), suggesting inappropriate ACTH secretion, which most often has an ectopic source. However, a nuclear medicine octreotide scan and multiple computed tomography scans failed to locate such a source.

The patient eventually underwent bilateral petrosal venous sinus sampling to definitively rule out a pituitary source. Lastly, he underwent nuclear medicine positron emission tomography, which identified a nodular opacity in the anterior left lung apex, demonstrating moderate radiotracer activity (FIGURE 1).

THE DISCUSSION

Cushing syndrome is rarely encountered—it is estimated to affect 2% of patients with uncontrolled diabetes¹ and 1% of those with uncontrolled hypertension²—and requires a high level of clinical suspicion. This case highlights the importance of considering secondary causes of diabetes in patients who present atypically. This patient presented with symptoms consistent with Cushing syndrome that went unrecognized initially; these included high blood pressure, rounded face, weak muscles, hypokalemia, and intermittent hypernatremia in addition to new-onset hyperglycemia.^2-5 Despite the atypical findings, evaluation for diabetes and potential secondary causes was neglected until an ED evaluation 1 month after initial presentation. The work-up for possible Cushing syndrome was completed in the hospital but could easily have been conducted in the outpatient setting.

Making the diagnosis. When Cushing syndrome is suspected, consider consultation with Endocrinology. It is important to exclude exogenous glucocorticoid exposure through a thorough review of the patient’s medications.² The Endocrine Society² recommends that one of the following tests be performed:

• 24-hour urine free cortisol (≥ 2 tests)
• Overnight 1-mg dexamethasone suppression test
• Late-night salivary cortisol test.

Results within normal range make Cushing syndrome an unlikely diagnosis; however, for patients with suggestive clinical features, further work-up may be warranted.

Continue to: Any abnormal result...

Any abnormal result is an indication to exclude a physiologic cause of hypercortisolism by repeating at least 1 of the previous studies. As with the initial testing, normal results may rule out Cushing syndrome, while abnormal results would be confirmatory. (Conflicting results require additional evaluation.)

Morbidity and mortality. Finding the etiology of Cushing syndrome can present a challenge but is also rewarding due to the reversible nature of most of the abnormalities. That said, Cushing syndrome can have a significant impact on morbidity and mortality.

Morbidity. The case patient developed compression fractures throughout his thoracic and lumbar spine, with a loss of 4 inches in height, attributed to the delay in curative treatment (FIGURE 2); these were identified about 2 months after his initial presentation to a health care facility. In addition to bone mineral density, cognitive function and quality of life can be impacted by untreated hypercortisolism and Cushing syndrome.²

Mortality. In the earliest studies^6,7 (from the 1930s-1950s), the average survival rate was about 4.6 years and the 5-year survival was just 50%—and yet, outcomes data from modern treatment modalities are scant. While there is limited data on outcomes in untreated disease, the Endocrine Society states that treatment of moderate-to-severe cases “clearly reduces mortality and morbidity” while early identification and treatment of mild cases “would reduce the risk of residual morbidity.”²

Our patient underwent video-assisted thoracoscopic surgery, during which a nodule in the anterior lingula was removed. In addition, lymph node dissection was performed. Two lymph nodes were positive for atypical well-differentiated carcinoid tumor. After surgical removal, the patient’s cortisol levels normalized and his diabetes resolved.

THE TAKEAWAY

In primary care, the frequency at which we evaluate and diagnose type 2 diabetes without secondary cause can lead to cognitive biases, such as anchoring bias, that impact patient care. In this case, the atypical secondary nature of the diabetes was missed at 3 outpatient appointments prior to presentation at the hospital ED. In an active patient who has a normal BMI and a healthy diet—but systemic symptoms—it is critical to consider secondary causes of diabetes, such as Cushing syndrome.

CORRESPONDENCE
Anna Murley Squibb, MD, 2145 North Fairfield Road, Suite 100, Beavercreek, OH 45385; [email protected]

ILLUSTRATIVE CASE

A 62-year-old woman with a past medical history of type 2 diabetes, hyperlipidemia, hypertension, and remote myocardial infarction (MI) presents to her primary care office for a preventive visit. She is a nonsmoker and has been taking her daily medications as prescribed, including an angiotensin-converting enzyme inhibitor, high-intensity statin, and aspirin. Her diabetes is well controlled. What else would you consider recommending to decrease this patient’s risk for future CVEs?

Cardiovascular disease (CVD) is a major contributor to morbidity and mortality, affecting more than 50% of patients older than 60.² Despite control of risk factors with standard treatment modalities, patients with established CVD remain at high risk for future events, which makes elucidating and targeting other causative pathways essential.³

Inflammation has been identified as a key player in the development and progression of atherosclerosis and its downstream effects, with increased inflammatory markers correlating with increased risk for CVEs.⁴ Due to these findings, anti-inflammatory treatments have been under investigation as agents to further reduce risk for CVEs. In 1 such trial, the Canakinumab Antiinflammatory Thrombosis Outcome Study (CANTOS), patients with MI and elevated C-reactive protein levels treated with the interleukin-1 beta inhibitor canakinumab showed reduced risk for future CVEs compared to those receiving placebo.⁵ However, due to canakinumab’s high cost, inconvenient subcutaneous administration, and increased incidence of fatal infections, other agents are under investigation.

Colchicine is a potent anti-inflammatory agent, with approval in the United States for treatment of gout and familial Mediterranean fever. It works broadly to reduce inflammation by disrupting tubulin polymerization.^6,7 Colchicine decreases interleukin-1 beta production through inactivation of the NLRP3 inflammasome pathway, which has been associated with the inflammatory component driving atherosclerotic plaque progression and instability.^5,8 Colchicine’s oral administration, relative cost-effectiveness, and safety profile make it an attractive option for potential use in secondary prevention of CVEs.

The Low-Dose Colchicine (LoDoCo) trial, published in 2013, demonstrated a reduction in CVEs in those with CVD taking guideline-directed medical therapy (GDMT) plus colchicine 0.5 mg/d, compared with those taking GDMT alone.⁹ However, the LoDoCo study enrolled only 532 patients and was not placebo controlled. The Colchicine Cardiovascular Outcomes Trial (COLCOT), published in 2019, was a randomized, ­double-blind, placebo-controlled trial that aimed to further evaluate the effects of colchicine on CVEs on a larger scale and to assess its longer-term safety.¹⁰ In this study, the colchicine group had a significantly lower risk of CVEs vs placebo, with a comparable safety profile.¹⁰

STUDY SUMMARY

Fewer CVEs occurred when colchicine was added to the regimen

The randomized, multicenter, double-blind Low Dose Colchicine 2 (LoDoCo2) trial evaluated whether colchicine 0.5 mg daily reduces CV death, spontaneous (nonprocedural) MI, ischemic stroke, or ischemia-driven coronary revascularization in patients with chronic CAD (composite primary endpoint). This trial included 5522 patients, ages 35 to 82, in Australia and the Netherlands. Patients were eligible to participate if they had evidence of CAD by invasive coronary angiography, coronary calcium score, or computed tomography angiography, as well as evidence of clinical stability for 6 months. Exclusion criteria included moderate-to-severe renal impairment, severe heart failure, severe valvular disease, or intolerance to colchicine.

Patients (N = 6528) took colchicine 0.5 mg daily as part of a 1-month, open-label run-in phase; 1006 patients stopped taking colchicine during this time. Perceived adverse effects were observed in 611 of these patients, the most common being gastrointestinal (GI) upset (437 patients). After the run-in phase, the remaining 5522 patients were randomized to either the colchicine or placebo group. Both groups continued to receive GDMT for CVD, including antiplatelet therapy, anticoagulants, and hypertensive therapy as indicated. Lipid-lowering therapies were continued in 96.7% of the colchicine group and 96.6% of the placebo group. These patients were then followed for a minimum of 1 year (median duration, 28.6 months).

Continue to: The primary endpoint...

The primary endpoint occurred less frequently in the colchicine group than in the placebo group (6.8% vs 9.6%; P < .001; number needed to treat = 36). The incidence rates for 2 of the individual outcomes in the composite, MI (hazard ratio [HR] = 0.7; 95% CI, 0.53-0.93) and ischemia-driven coronary revascularization (HR = 0.75; 95% CI, 0.60-0.94), were significantly lower in the colchicine group. The other outcomes were no different from placebo.¹

There was a similar incidence of serious adverse events, such as noncardiovascular death, cancer diagnosis, and hospitalization for infection, pneumonia, or GI issues. High-dose statins were used by 3413 patients (61.8%). Myalgia (data collected only from the Netherlands cohort) was reported more commonly in the colchicine group than the placebo group (21.2% vs 18.5%; cumulative incidence ratio = 1.15; 95% CI, 1.01-1.31). Myotoxic effects were rare in both groups.¹

WHAT’S NEW

RCT supports potential for anti-inflammatory therapy in CAD

This large RCT demonstrated that the addition of daily colchicine reduces CVE risk in patients with known CAD while maintaining a good safety profile.¹

CAVEATS

Watch for potential drug interactions in patients with renal dysfunction

Prescribers should be aware of potential drug interactions, especially in those with renal or hepatic dysfunction, when prescribing colchicine, as it is metabolized through cytochrome P450 3A4 (CYP3A4) and excreted via the P-glycoprotein transport system, by which many statins are also metabolized and act as a competitive substrate.⁷ In addition, simvastatin, and to a lesser degree atorvastatin, are CYP3A4 inhibitors.

Also of note, the 0.5-mg colchicine tablet is not available in some countries—including the United States, where only 0.6-mg tablets are available. The 0.6-mg dose would likely have the same benefit and similar adverse effect profile but was not included in the study.

CHALLENGES TO IMPLEMENTATION

GI tolerability may be an issue

Colchicine is widely available and relatively low in cost, at approximately $32 per month for the 0.6-mg daily tablets. A major limitation is lack of tolerability, as adverse effects such as nausea, vomiting, diarrhea, and abdominal pain are frequently reported.

ILLUSTRATIVE CASE

A 62-year-old woman with a past medical history of type 2 diabetes, hyperlipidemia, hypertension, and remote myocardial infarction (MI) presents to her primary care office for a preventive visit. She is a nonsmoker and has been taking her daily medications as prescribed, including an angiotensin-converting enzyme inhibitor, high-intensity statin, and aspirin. Her diabetes is well controlled. What else would you consider recommending to decrease this patient’s risk for future CVEs?

Cardiovascular disease (CVD) is a major contributor to morbidity and mortality, affecting more than 50% of patients older than 60.² Despite control of risk factors with standard treatment modalities, patients with established CVD remain at high risk for future events, which makes elucidating and targeting other causative pathways essential.³

Inflammation has been identified as a key player in the development and progression of atherosclerosis and its downstream effects, with increased inflammatory markers correlating with increased risk for CVEs.⁴ Due to these findings, anti-inflammatory treatments have been under investigation as agents to further reduce risk for CVEs. In 1 such trial, the Canakinumab Antiinflammatory Thrombosis Outcome Study (CANTOS), patients with MI and elevated C-reactive protein levels treated with the interleukin-1 beta inhibitor canakinumab showed reduced risk for future CVEs compared to those receiving placebo.⁵ However, due to canakinumab’s high cost, inconvenient subcutaneous administration, and increased incidence of fatal infections, other agents are under investigation.

Colchicine is a potent anti-inflammatory agent, with approval in the United States for treatment of gout and familial Mediterranean fever. It works broadly to reduce inflammation by disrupting tubulin polymerization.^6,7 Colchicine decreases interleukin-1 beta production through inactivation of the NLRP3 inflammasome pathway, which has been associated with the inflammatory component driving atherosclerotic plaque progression and instability.^5,8 Colchicine’s oral administration, relative cost-effectiveness, and safety profile make it an attractive option for potential use in secondary prevention of CVEs.

The Low-Dose Colchicine (LoDoCo) trial, published in 2013, demonstrated a reduction in CVEs in those with CVD taking guideline-directed medical therapy (GDMT) plus colchicine 0.5 mg/d, compared with those taking GDMT alone.⁹ However, the LoDoCo study enrolled only 532 patients and was not placebo controlled. The Colchicine Cardiovascular Outcomes Trial (COLCOT), published in 2019, was a randomized, ­double-blind, placebo-controlled trial that aimed to further evaluate the effects of colchicine on CVEs on a larger scale and to assess its longer-term safety.¹⁰ In this study, the colchicine group had a significantly lower risk of CVEs vs placebo, with a comparable safety profile.¹⁰

STUDY SUMMARY

Fewer CVEs occurred when colchicine was added to the regimen

The randomized, multicenter, double-blind Low Dose Colchicine 2 (LoDoCo2) trial evaluated whether colchicine 0.5 mg daily reduces CV death, spontaneous (nonprocedural) MI, ischemic stroke, or ischemia-driven coronary revascularization in patients with chronic CAD (composite primary endpoint). This trial included 5522 patients, ages 35 to 82, in Australia and the Netherlands. Patients were eligible to participate if they had evidence of CAD by invasive coronary angiography, coronary calcium score, or computed tomography angiography, as well as evidence of clinical stability for 6 months. Exclusion criteria included moderate-to-severe renal impairment, severe heart failure, severe valvular disease, or intolerance to colchicine.

Patients (N = 6528) took colchicine 0.5 mg daily as part of a 1-month, open-label run-in phase; 1006 patients stopped taking colchicine during this time. Perceived adverse effects were observed in 611 of these patients, the most common being gastrointestinal (GI) upset (437 patients). After the run-in phase, the remaining 5522 patients were randomized to either the colchicine or placebo group. Both groups continued to receive GDMT for CVD, including antiplatelet therapy, anticoagulants, and hypertensive therapy as indicated. Lipid-lowering therapies were continued in 96.7% of the colchicine group and 96.6% of the placebo group. These patients were then followed for a minimum of 1 year (median duration, 28.6 months).

Continue to: The primary endpoint...

The primary endpoint occurred less frequently in the colchicine group than in the placebo group (6.8% vs 9.6%; P < .001; number needed to treat = 36). The incidence rates for 2 of the individual outcomes in the composite, MI (hazard ratio [HR] = 0.7; 95% CI, 0.53-0.93) and ischemia-driven coronary revascularization (HR = 0.75; 95% CI, 0.60-0.94), were significantly lower in the colchicine group. The other outcomes were no different from placebo.¹

There was a similar incidence of serious adverse events, such as noncardiovascular death, cancer diagnosis, and hospitalization for infection, pneumonia, or GI issues. High-dose statins were used by 3413 patients (61.8%). Myalgia (data collected only from the Netherlands cohort) was reported more commonly in the colchicine group than the placebo group (21.2% vs 18.5%; cumulative incidence ratio = 1.15; 95% CI, 1.01-1.31). Myotoxic effects were rare in both groups.¹

WHAT’S NEW

RCT supports potential for anti-inflammatory therapy in CAD

This large RCT demonstrated that the addition of daily colchicine reduces CVE risk in patients with known CAD while maintaining a good safety profile.¹

CAVEATS

Watch for potential drug interactions in patients with renal dysfunction

Prescribers should be aware of potential drug interactions, especially in those with renal or hepatic dysfunction, when prescribing colchicine, as it is metabolized through cytochrome P450 3A4 (CYP3A4) and excreted via the P-glycoprotein transport system, by which many statins are also metabolized and act as a competitive substrate.⁷ In addition, simvastatin, and to a lesser degree atorvastatin, are CYP3A4 inhibitors.

Also of note, the 0.5-mg colchicine tablet is not available in some countries—including the United States, where only 0.6-mg tablets are available. The 0.6-mg dose would likely have the same benefit and similar adverse effect profile but was not included in the study.

CHALLENGES TO IMPLEMENTATION

GI tolerability may be an issue

Colchicine is widely available and relatively low in cost, at approximately $32 per month for the 0.6-mg daily tablets. A major limitation is lack of tolerability, as adverse effects such as nausea, vomiting, diarrhea, and abdominal pain are frequently reported.

ILLUSTRATIVE CASE

A 62-year-old woman with a past medical history of type 2 diabetes, hyperlipidemia, hypertension, and remote myocardial infarction (MI) presents to her primary care office for a preventive visit. She is a nonsmoker and has been taking her daily medications as prescribed, including an angiotensin-converting enzyme inhibitor, high-intensity statin, and aspirin. Her diabetes is well controlled. What else would you consider recommending to decrease this patient’s risk for future CVEs?

Cardiovascular disease (CVD) is a major contributor to morbidity and mortality, affecting more than 50% of patients older than 60.² Despite control of risk factors with standard treatment modalities, patients with established CVD remain at high risk for future events, which makes elucidating and targeting other causative pathways essential.³

Inflammation has been identified as a key player in the development and progression of atherosclerosis and its downstream effects, with increased inflammatory markers correlating with increased risk for CVEs.⁴ Due to these findings, anti-inflammatory treatments have been under investigation as agents to further reduce risk for CVEs. In 1 such trial, the Canakinumab Antiinflammatory Thrombosis Outcome Study (CANTOS), patients with MI and elevated C-reactive protein levels treated with the interleukin-1 beta inhibitor canakinumab showed reduced risk for future CVEs compared to those receiving placebo.⁵ However, due to canakinumab’s high cost, inconvenient subcutaneous administration, and increased incidence of fatal infections, other agents are under investigation.

Colchicine is a potent anti-inflammatory agent, with approval in the United States for treatment of gout and familial Mediterranean fever. It works broadly to reduce inflammation by disrupting tubulin polymerization.^6,7 Colchicine decreases interleukin-1 beta production through inactivation of the NLRP3 inflammasome pathway, which has been associated with the inflammatory component driving atherosclerotic plaque progression and instability.^5,8 Colchicine’s oral administration, relative cost-effectiveness, and safety profile make it an attractive option for potential use in secondary prevention of CVEs.

The Low-Dose Colchicine (LoDoCo) trial, published in 2013, demonstrated a reduction in CVEs in those with CVD taking guideline-directed medical therapy (GDMT) plus colchicine 0.5 mg/d, compared with those taking GDMT alone.⁹ However, the LoDoCo study enrolled only 532 patients and was not placebo controlled. The Colchicine Cardiovascular Outcomes Trial (COLCOT), published in 2019, was a randomized, ­double-blind, placebo-controlled trial that aimed to further evaluate the effects of colchicine on CVEs on a larger scale and to assess its longer-term safety.¹⁰ In this study, the colchicine group had a significantly lower risk of CVEs vs placebo, with a comparable safety profile.¹⁰

STUDY SUMMARY

Fewer CVEs occurred when colchicine was added to the regimen

The randomized, multicenter, double-blind Low Dose Colchicine 2 (LoDoCo2) trial evaluated whether colchicine 0.5 mg daily reduces CV death, spontaneous (nonprocedural) MI, ischemic stroke, or ischemia-driven coronary revascularization in patients with chronic CAD (composite primary endpoint). This trial included 5522 patients, ages 35 to 82, in Australia and the Netherlands. Patients were eligible to participate if they had evidence of CAD by invasive coronary angiography, coronary calcium score, or computed tomography angiography, as well as evidence of clinical stability for 6 months. Exclusion criteria included moderate-to-severe renal impairment, severe heart failure, severe valvular disease, or intolerance to colchicine.

Patients (N = 6528) took colchicine 0.5 mg daily as part of a 1-month, open-label run-in phase; 1006 patients stopped taking colchicine during this time. Perceived adverse effects were observed in 611 of these patients, the most common being gastrointestinal (GI) upset (437 patients). After the run-in phase, the remaining 5522 patients were randomized to either the colchicine or placebo group. Both groups continued to receive GDMT for CVD, including antiplatelet therapy, anticoagulants, and hypertensive therapy as indicated. Lipid-lowering therapies were continued in 96.7% of the colchicine group and 96.6% of the placebo group. These patients were then followed for a minimum of 1 year (median duration, 28.6 months).

Continue to: The primary endpoint...

The primary endpoint occurred less frequently in the colchicine group than in the placebo group (6.8% vs 9.6%; P < .001; number needed to treat = 36). The incidence rates for 2 of the individual outcomes in the composite, MI (hazard ratio [HR] = 0.7; 95% CI, 0.53-0.93) and ischemia-driven coronary revascularization (HR = 0.75; 95% CI, 0.60-0.94), were significantly lower in the colchicine group. The other outcomes were no different from placebo.¹

There was a similar incidence of serious adverse events, such as noncardiovascular death, cancer diagnosis, and hospitalization for infection, pneumonia, or GI issues. High-dose statins were used by 3413 patients (61.8%). Myalgia (data collected only from the Netherlands cohort) was reported more commonly in the colchicine group than the placebo group (21.2% vs 18.5%; cumulative incidence ratio = 1.15; 95% CI, 1.01-1.31). Myotoxic effects were rare in both groups.¹

WHAT’S NEW

RCT supports potential for anti-inflammatory therapy in CAD

This large RCT demonstrated that the addition of daily colchicine reduces CVE risk in patients with known CAD while maintaining a good safety profile.¹

CAVEATS

Watch for potential drug interactions in patients with renal dysfunction

Prescribers should be aware of potential drug interactions, especially in those with renal or hepatic dysfunction, when prescribing colchicine, as it is metabolized through cytochrome P450 3A4 (CYP3A4) and excreted via the P-glycoprotein transport system, by which many statins are also metabolized and act as a competitive substrate.⁷ In addition, simvastatin, and to a lesser degree atorvastatin, are CYP3A4 inhibitors.

Also of note, the 0.5-mg colchicine tablet is not available in some countries—including the United States, where only 0.6-mg tablets are available. The 0.6-mg dose would likely have the same benefit and similar adverse effect profile but was not included in the study.

CHALLENGES TO IMPLEMENTATION

GI tolerability may be an issue

Colchicine is widely available and relatively low in cost, at approximately $32 per month for the 0.6-mg daily tablets. A major limitation is lack of tolerability, as adverse effects such as nausea, vomiting, diarrhea, and abdominal pain are frequently reported.

The World Health Organization (WHO) named vaccine hesitancy as one of the top 10 threats to public health as of 2019.¹ Although the COVID-19 vaccines manufactured by Pfizer-BioNTech and Moderna, first authorized for use in November 2020 and fully approved in August 2021,² are widely available in most countries, vaccination uptake is insufficient.³

As of June 2022, 78% of the US population had received at least 1 vaccine dose and 66.8% were fully vaccinated against COVID-19.⁴ High confidence in vaccines is associated with greater uptake; thus, engendering confidence in patients is a critical area of intervention for increasing uptake of COVID-19 and other vaccines.⁵ Despite the steady increase in vaccine acceptance observed following the release of the COVID-19 vaccine, acceptance remains suboptimal.^2,6

Demographic characteristics associated with lower vaccine acceptance include younger age, female sex, lower education and/or income, and Black race or Hispanic/Latinx ethnicity (compared to white or Asian non-­Hispanic).^6,7 Moreover, patients who are skeptical of vaccine safety and efficacy are associated with lower intentions to vaccinate. In contrast, patients with a history of receiving influenza vaccinations and those with a greater concern about COVID-19 and their risk of infection have increased vaccine intentions.⁶

Numerous strategies exist to increase vaccine acceptance; however, there does not appear to be a single “best” method to overcome individual or parental vaccine hesitancy for COVID-19 or other vaccines.^8,9 There are no large-scale randomized controlled trials (RCTs) demonstrating one strategy as more effective than another. In this review, we outline a variety of evidenced-based strategies to help patients overcome vaccine hesitancy for COVID-19 and other vaccines, with a focus on practical tips for primary care physicians (PCPs).

Which talking points are likely to resonate with your patients?

Intervention strategies promote vaccine acceptance by communicating personal benefit, collective benefit, or both to vaccine-­hesitant patients. In a study sample of US undergraduate students, Kim and colleagues¹⁰ found that providing information about the benefits and risks of influenza vaccines resulted in significantly less vaccine intent compared to communicating information only on the benefits. Similarly, Shim and colleagues¹¹ investigated how game theory (acting to maximize personal payoff regardless of payoff to others) and altruism affect influenza vaccination decisions. Through a survey-based study of 427 US university employees, researchers found altruistic motivation had a significant impact on the decision to vaccinate against influenza, resulting in a shift from self-interest to that of the good of the community.¹¹

A German trial on COVID-19 vaccine acceptance by Sprengholz and colleagues¹² found that communications about the benefits of vaccination, availability of financial compensation for vaccination, or a combination of both, did not increase a person’s willingness to get vaccinated. This trial, however, did not separate out individual vs collective benefit, and it was conducted prior to widespread COVID-19 vaccine availability. 

When speaking with patients who are strongly hesitant to vaccination, emphasizing concrete personal benefit may prove more effective than stressing protection of others from illness.

In an online RCT conducted in early 2021, Freeman and colleagues¹³ randomized UK adults to 1 of 10 different “information conditions.” Participants read from 1 of 10 vaccine scripts that varied by the talking points they addressed. The topics that researchers drew from for these scripts included the personal or collective benefit from the COVID-19 vaccine, safety and effectiveness of the vaccine, and the seriousness of the pandemic. They found communications emphasizing personal benefit from vaccination and safety concerns were more effective in participants identified as being strongly hesitant (defined as those who said they would avoid getting the COVID-19 vaccine for as long as possible or who said they’d never get it). However, none of the information arms in this study decreased vaccine hesitancy among those who were doubtful of vaccination (defined as those who said they would delay vaccination or who didn’t know if they would get vaccinated).¹³

Continue to: When encountering patients who are strongly...

When encountering patients who are strongly hesitant to vaccination, an approach emphasizing concrete personal benefit may prove more effective than one stressing protection of others from illness. It is important to note, though, that findings from other countries may not be relevant to US patients due to differences in demographic factors, individual beliefs, and political climate. 

It helps to explain herd immunity by providing concrete examples 

Among the collective benefits of vaccination is the decreased risk of transmitting the disease to others (eg, family, friends, neighbors, colleagues), a quicker “return to normalcy,” and herd immunity.¹³ While individual health benefits may more strongly motivate people to get vaccinated than collective benefits, this may be due to a lack of understanding about herd immunity among the general public. The optimal method of communicating information on herd immunity is not known.¹⁴

Betsch and colleagues¹⁵ found that explaining herd immunity using interactive simulations increased vaccine intent, especially in countries that prioritize the self (rather than prioritizing the group over the individual). In addition to educating study participants about herd immunity, telling them how local vaccine coverage compared to the desired level of coverage helped to increase (influenza) vaccine intent among those who were least informed about herd immunity.¹⁶

Providing concrete examples of the collective benefits of vaccination (eg, protecting grandparents, children too young to be vaccinated, and those at increased risk for severe illness) or sharing stories about how other patients suffered from the disease in question may increase the likelihood of vaccination. One recent trial by Pfattheicher and colleagues¹⁷ found that empathy for those most vulnerable to COVID-19 and increased knowledge about herd immunity were 2 factors associated with greater vaccine intentions.

In this study, the authors induced empathy and increased COVID-19 vaccination intention by having participants read a short story about 2 close siblings who worked together in a nursing facility. In the story, participants learned that both siblings were given a diagnosis of COVID-19 at the same time but only 1 survived.¹⁷

Continue to: Try this 3-pronged approach

Try this 3-pronged approach. Consider explaining herd immunity to vaccine-hesitant patients, pairing this concept with information about local vaccine uptake, and appealing to the patient’s sense of empathy. You might share de-identified information on other patients in your practice or personal network who experienced severe illness, had long-term effects, or died from COVID-19 infection. Such concrete examples may help to increase motivation to vaccinate more than a general appeal to altruism.

Initiate the discussion by emphasizing that community immunity protects those who are vulnerable and lack immunity while providing specific empathetic examples (eg, newborns, cancer survivors) and asking patients to consider friends and family who might be at risk. Additionally, it is essential to explain that although community immunity can decrease the spread of infection, it can only be achieved when enough people are vaccinated. 

Proceed with caution: Addressing conspiracy theories can backfire

Accurate information is critical to improving vaccine intentions; belief in conspiracy theories or misinformation related to COVID-19 is associated with reduced vaccine intentions and uptake.⁶ For example, a study by Loomba and colleagues¹⁸ showed that after exposure to misinformation, US and UK adults reported reduced intentions to vaccinate against COVID-19 once a vaccine became available.

Unfortunately, addressing myths about vaccines can sometimes backfire and unintentionally reinforce vaccine misperceptions.^19,20 This is especially true for patients with the highest levels of concern or mistrust in vaccines. Nyhan and colleagues^21,22 observed the backfire effect in 2 US studies looking at influenza and measles, mumps, and rubella vaccine misperceptions. Although corrective information significantly reduced belief in vaccine myths, they found individuals with the most concerns more strongly endorsed misperceptions when their beliefs were challenged.^21,22

Strategies for correcting vaccine misinformation may vary by type of vaccine; however, placing emphasis on facts delivered by trusted sources appears to be beneficial.

An Australian randomized study by Steffens and colleagues²³ found repeating myths about childhood vaccines, followed by corrective text, to parents of children ages 0 to 5 years had no difference on parental intent to vaccinate their children compared to providing vaccine information as a statement or in a question/answer format. Furthermore, an RCT in Brazil by Carey and colleagues²⁴ found that myth-correction messages about Zika virus failed to reduce misperceptions about the virus and actually reduced the belief in factual information about Zika—­regardless of baseline beliefs in conspiracies. However, a similar experiment in the same study showed that myth-correction messages reduced false beliefs about yellow fever.

Continue to: The authors speculated...

The authors speculated that this may be because Zika is a relatively new virus when compared to yellow fever, and participants may have more pre-existing knowledge about yellow fever.²⁴ These findings are important to keep in mind when addressing misinformation regarding COVID-19. When addressing myth perceptions with patients, consider pivoting the conversation from vaccine myths to the disease itself, focusing on the disease risk and severity of symptoms.^19,20 

Other studies have had positive results when addressing misinformation, including a digital RCT of older adults in the Netherlands by Yousuf and colleagues.²⁵ In this study, participants were randomized to view 1 of 2 versions of an information video on vaccination featuring an informative discussion by celebrity scientists, government officials, and a cardiologist. Video 1 did not include debunking strategies, only information about vaccination; Video 2 provided the same information about vaccines but also described the myths surrounding vaccines and reiterated the truth to debunk the myths.

Findings demonstrated that a significantly higher number of participants in the Video 2 group overcame vaccination myths related to influenza and COVID-19.²⁵ Notably, this study took place prior to the widespread availability of COVID-19 vaccines and did not measure intent to vaccinate against COVID-19.

Taken together, strategies for correcting vaccine misinformation may vary by population as well as type of vaccine; however, placing emphasis on facts delivered by trusted sources appears to be beneficial. When addressing misinformation, PCPs should first focus on key details (not all supporting information) and clearly explain why the misinformation is false before pointing out the actual myth and providing an alternative explanation.²⁰ When caring for patients who express strong concerns over the vaccine in question or have avid beliefs in certain myths or conspiracy theories, it’s best to pivot the conversation back to the disease rather than address the misinformation to avoid a potential backfire effect.

Utilize these effective communication techniques

TABLE 1^{10,13,16,17,19,20} summarizes the “do’s and don’ts” of communicating with vaccine-hesitant patients. PCPs should provide strong recommendations for vaccination, approaching it presumptively—ie, framing it as normative behavior.^19,26 This approach is critical to building patient trust so that vaccine-hesitant patients feel the PCP is truly listening to them and addressing their concerns.²⁷ Additionally, implementing motivational interviewing (MI) and self-determination theory (SDT)²⁸ techniques when discussing vaccinations with patients can improve intentions and uptake.^19,29TABLE 2^19,29 outlines specific techniques based on SDT and MI that PCPs may utilize to communicate with vaccine-hesitant individuals or parents. 

Continue to: The takeaway

Strategies for increasing vaccine intentions include educating hesitant patients about the benefits and risks of vaccines, addressing misinformation, and explaining the personal and collective benefits of vaccination. These strategies appear to be more effective when delivered by a trusted source, such as a health care provider (HCP). Care should be taken when implementing vaccine-acceptance strategies to ensure that they are tailored to specific populations and vaccines.

At this stage in the COVID-19 pandemic, when several vaccines have been widely available for more than a year, we expect that the majority of patients desiring vaccination (ie, those with the greatest vaccine intent) have already received them. With the recent approval of COVID-19 vaccines for children younger than 5 years, we must now advocate for our patients to vaccinate not only themselves, but their children. Patients who remain unvaccinated may be hesitant or outright reject vaccination for a number of reasons, including fear or skepticism over the safety and efficacy of the vaccine, belief in conspiracy theories, belief that COVID-19 is not real or not severe, or mistrust of the government.⁶ Vaccine hesitation or rejection is also often political in nature.

Based on the studies included in this review, we have identified several strategies for reducing vaccine hesitancy, which can be used with vaccine-hesitant patients and parents. We suggest emphasizing the personal benefit of vaccination and focusing on specific disease risks. If time allows, you can also explain the collective benefit of vaccination through herd immunity, including the current levels of local vaccine uptake compared to the desired level for community immunity. Communicating the collective benefits of vaccination may be more effective when paired with a strategy intended to increase empathy and altruism, such as sharing actual stories about those who have suffered from a vaccine-preventable disease.

Build trust by asking your patient: What kind of information do you feel you are missing about the vaccine?

Addressing myths and misinformation related to COVID-19 and other vaccines, with emphasis placed on the correct information delivered by trusted sources may be beneficial for those who are uncertain but not strongly against vaccination. For those who remain staunchly hesitant against vaccination, we recommend focusing on the personal benefits of vaccination with a focus on delivering facts about the risk of the disease in question, rather than trying to refute misinformation.

COVID-19 vaccine acceptance in the United States is disturbingly low among health care workers, particularly nurses, technicians, and those in nonclinical roles, compared to physicians.^6,30 Many of the strategies for addressing vaccine hesitancy among the general population can also apply to health care personnel (eg, vaccine education, addressing misinformation, delivering information from a trusted source). Health care personnel may also be subject to vaccine mandates by their employers, which have demonstrated increases in vaccination rates for influenza.³¹ Given that COVID-19 vaccination recommendations made by HCPs are associated with greater vaccine intentions and uptake,⁶ reducing hesitancy among health care workers is a critical first step to achieving optimal implementation.

CORRESPONDENCE
Nicole Mayo, PhD, 236 Pearl Street, Rochester, NY 14607; [email protected]

The World Health Organization (WHO) named vaccine hesitancy as one of the top 10 threats to public health as of 2019.¹ Although the COVID-19 vaccines manufactured by Pfizer-BioNTech and Moderna, first authorized for use in November 2020 and fully approved in August 2021,² are widely available in most countries, vaccination uptake is insufficient.³

As of June 2022, 78% of the US population had received at least 1 vaccine dose and 66.8% were fully vaccinated against COVID-19.⁴ High confidence in vaccines is associated with greater uptake; thus, engendering confidence in patients is a critical area of intervention for increasing uptake of COVID-19 and other vaccines.⁵ Despite the steady increase in vaccine acceptance observed following the release of the COVID-19 vaccine, acceptance remains suboptimal.^2,6

Demographic characteristics associated with lower vaccine acceptance include younger age, female sex, lower education and/or income, and Black race or Hispanic/Latinx ethnicity (compared to white or Asian non-­Hispanic).^6,7 Moreover, patients who are skeptical of vaccine safety and efficacy are associated with lower intentions to vaccinate. In contrast, patients with a history of receiving influenza vaccinations and those with a greater concern about COVID-19 and their risk of infection have increased vaccine intentions.⁶

Numerous strategies exist to increase vaccine acceptance; however, there does not appear to be a single “best” method to overcome individual or parental vaccine hesitancy for COVID-19 or other vaccines.^8,9 There are no large-scale randomized controlled trials (RCTs) demonstrating one strategy as more effective than another. In this review, we outline a variety of evidenced-based strategies to help patients overcome vaccine hesitancy for COVID-19 and other vaccines, with a focus on practical tips for primary care physicians (PCPs).

Which talking points are likely to resonate with your patients?

Intervention strategies promote vaccine acceptance by communicating personal benefit, collective benefit, or both to vaccine-­hesitant patients. In a study sample of US undergraduate students, Kim and colleagues¹⁰ found that providing information about the benefits and risks of influenza vaccines resulted in significantly less vaccine intent compared to communicating information only on the benefits. Similarly, Shim and colleagues¹¹ investigated how game theory (acting to maximize personal payoff regardless of payoff to others) and altruism affect influenza vaccination decisions. Through a survey-based study of 427 US university employees, researchers found altruistic motivation had a significant impact on the decision to vaccinate against influenza, resulting in a shift from self-interest to that of the good of the community.¹¹

A German trial on COVID-19 vaccine acceptance by Sprengholz and colleagues¹² found that communications about the benefits of vaccination, availability of financial compensation for vaccination, or a combination of both, did not increase a person’s willingness to get vaccinated. This trial, however, did not separate out individual vs collective benefit, and it was conducted prior to widespread COVID-19 vaccine availability. 

When speaking with patients who are strongly hesitant to vaccination, emphasizing concrete personal benefit may prove more effective than stressing protection of others from illness.

In an online RCT conducted in early 2021, Freeman and colleagues¹³ randomized UK adults to 1 of 10 different “information conditions.” Participants read from 1 of 10 vaccine scripts that varied by the talking points they addressed. The topics that researchers drew from for these scripts included the personal or collective benefit from the COVID-19 vaccine, safety and effectiveness of the vaccine, and the seriousness of the pandemic. They found communications emphasizing personal benefit from vaccination and safety concerns were more effective in participants identified as being strongly hesitant (defined as those who said they would avoid getting the COVID-19 vaccine for as long as possible or who said they’d never get it). However, none of the information arms in this study decreased vaccine hesitancy among those who were doubtful of vaccination (defined as those who said they would delay vaccination or who didn’t know if they would get vaccinated).¹³

Continue to: When encountering patients who are strongly...

When encountering patients who are strongly hesitant to vaccination, an approach emphasizing concrete personal benefit may prove more effective than one stressing protection of others from illness. It is important to note, though, that findings from other countries may not be relevant to US patients due to differences in demographic factors, individual beliefs, and political climate. 

It helps to explain herd immunity by providing concrete examples 

Among the collective benefits of vaccination is the decreased risk of transmitting the disease to others (eg, family, friends, neighbors, colleagues), a quicker “return to normalcy,” and herd immunity.¹³ While individual health benefits may more strongly motivate people to get vaccinated than collective benefits, this may be due to a lack of understanding about herd immunity among the general public. The optimal method of communicating information on herd immunity is not known.¹⁴

Betsch and colleagues¹⁵ found that explaining herd immunity using interactive simulations increased vaccine intent, especially in countries that prioritize the self (rather than prioritizing the group over the individual). In addition to educating study participants about herd immunity, telling them how local vaccine coverage compared to the desired level of coverage helped to increase (influenza) vaccine intent among those who were least informed about herd immunity.¹⁶

Providing concrete examples of the collective benefits of vaccination (eg, protecting grandparents, children too young to be vaccinated, and those at increased risk for severe illness) or sharing stories about how other patients suffered from the disease in question may increase the likelihood of vaccination. One recent trial by Pfattheicher and colleagues¹⁷ found that empathy for those most vulnerable to COVID-19 and increased knowledge about herd immunity were 2 factors associated with greater vaccine intentions.

In this study, the authors induced empathy and increased COVID-19 vaccination intention by having participants read a short story about 2 close siblings who worked together in a nursing facility. In the story, participants learned that both siblings were given a diagnosis of COVID-19 at the same time but only 1 survived.¹⁷

Continue to: Try this 3-pronged approach

Try this 3-pronged approach. Consider explaining herd immunity to vaccine-hesitant patients, pairing this concept with information about local vaccine uptake, and appealing to the patient’s sense of empathy. You might share de-identified information on other patients in your practice or personal network who experienced severe illness, had long-term effects, or died from COVID-19 infection. Such concrete examples may help to increase motivation to vaccinate more than a general appeal to altruism.

Initiate the discussion by emphasizing that community immunity protects those who are vulnerable and lack immunity while providing specific empathetic examples (eg, newborns, cancer survivors) and asking patients to consider friends and family who might be at risk. Additionally, it is essential to explain that although community immunity can decrease the spread of infection, it can only be achieved when enough people are vaccinated. 

Proceed with caution: Addressing conspiracy theories can backfire

Accurate information is critical to improving vaccine intentions; belief in conspiracy theories or misinformation related to COVID-19 is associated with reduced vaccine intentions and uptake.⁶ For example, a study by Loomba and colleagues¹⁸ showed that after exposure to misinformation, US and UK adults reported reduced intentions to vaccinate against COVID-19 once a vaccine became available.

Unfortunately, addressing myths about vaccines can sometimes backfire and unintentionally reinforce vaccine misperceptions.^19,20 This is especially true for patients with the highest levels of concern or mistrust in vaccines. Nyhan and colleagues^21,22 observed the backfire effect in 2 US studies looking at influenza and measles, mumps, and rubella vaccine misperceptions. Although corrective information significantly reduced belief in vaccine myths, they found individuals with the most concerns more strongly endorsed misperceptions when their beliefs were challenged.^21,22

Strategies for correcting vaccine misinformation may vary by type of vaccine; however, placing emphasis on facts delivered by trusted sources appears to be beneficial.

An Australian randomized study by Steffens and colleagues²³ found repeating myths about childhood vaccines, followed by corrective text, to parents of children ages 0 to 5 years had no difference on parental intent to vaccinate their children compared to providing vaccine information as a statement or in a question/answer format. Furthermore, an RCT in Brazil by Carey and colleagues²⁴ found that myth-correction messages about Zika virus failed to reduce misperceptions about the virus and actually reduced the belief in factual information about Zika—­regardless of baseline beliefs in conspiracies. However, a similar experiment in the same study showed that myth-correction messages reduced false beliefs about yellow fever.

Continue to: The authors speculated...

The authors speculated that this may be because Zika is a relatively new virus when compared to yellow fever, and participants may have more pre-existing knowledge about yellow fever.²⁴ These findings are important to keep in mind when addressing misinformation regarding COVID-19. When addressing myth perceptions with patients, consider pivoting the conversation from vaccine myths to the disease itself, focusing on the disease risk and severity of symptoms.^19,20 

Other studies have had positive results when addressing misinformation, including a digital RCT of older adults in the Netherlands by Yousuf and colleagues.²⁵ In this study, participants were randomized to view 1 of 2 versions of an information video on vaccination featuring an informative discussion by celebrity scientists, government officials, and a cardiologist. Video 1 did not include debunking strategies, only information about vaccination; Video 2 provided the same information about vaccines but also described the myths surrounding vaccines and reiterated the truth to debunk the myths.

Findings demonstrated that a significantly higher number of participants in the Video 2 group overcame vaccination myths related to influenza and COVID-19.²⁵ Notably, this study took place prior to the widespread availability of COVID-19 vaccines and did not measure intent to vaccinate against COVID-19.

Taken together, strategies for correcting vaccine misinformation may vary by population as well as type of vaccine; however, placing emphasis on facts delivered by trusted sources appears to be beneficial. When addressing misinformation, PCPs should first focus on key details (not all supporting information) and clearly explain why the misinformation is false before pointing out the actual myth and providing an alternative explanation.²⁰ When caring for patients who express strong concerns over the vaccine in question or have avid beliefs in certain myths or conspiracy theories, it’s best to pivot the conversation back to the disease rather than address the misinformation to avoid a potential backfire effect.

Utilize these effective communication techniques

TABLE 1^{10,13,16,17,19,20} summarizes the “do’s and don’ts” of communicating with vaccine-hesitant patients. PCPs should provide strong recommendations for vaccination, approaching it presumptively—ie, framing it as normative behavior.^19,26 This approach is critical to building patient trust so that vaccine-hesitant patients feel the PCP is truly listening to them and addressing their concerns.²⁷ Additionally, implementing motivational interviewing (MI) and self-determination theory (SDT)²⁸ techniques when discussing vaccinations with patients can improve intentions and uptake.^19,29TABLE 2^19,29 outlines specific techniques based on SDT and MI that PCPs may utilize to communicate with vaccine-hesitant individuals or parents. 

Continue to: The takeaway

Strategies for increasing vaccine intentions include educating hesitant patients about the benefits and risks of vaccines, addressing misinformation, and explaining the personal and collective benefits of vaccination. These strategies appear to be more effective when delivered by a trusted source, such as a health care provider (HCP). Care should be taken when implementing vaccine-acceptance strategies to ensure that they are tailored to specific populations and vaccines.

At this stage in the COVID-19 pandemic, when several vaccines have been widely available for more than a year, we expect that the majority of patients desiring vaccination (ie, those with the greatest vaccine intent) have already received them. With the recent approval of COVID-19 vaccines for children younger than 5 years, we must now advocate for our patients to vaccinate not only themselves, but their children. Patients who remain unvaccinated may be hesitant or outright reject vaccination for a number of reasons, including fear or skepticism over the safety and efficacy of the vaccine, belief in conspiracy theories, belief that COVID-19 is not real or not severe, or mistrust of the government.⁶ Vaccine hesitation or rejection is also often political in nature.

Based on the studies included in this review, we have identified several strategies for reducing vaccine hesitancy, which can be used with vaccine-hesitant patients and parents. We suggest emphasizing the personal benefit of vaccination and focusing on specific disease risks. If time allows, you can also explain the collective benefit of vaccination through herd immunity, including the current levels of local vaccine uptake compared to the desired level for community immunity. Communicating the collective benefits of vaccination may be more effective when paired with a strategy intended to increase empathy and altruism, such as sharing actual stories about those who have suffered from a vaccine-preventable disease.

Build trust by asking your patient: What kind of information do you feel you are missing about the vaccine?

Addressing myths and misinformation related to COVID-19 and other vaccines, with emphasis placed on the correct information delivered by trusted sources may be beneficial for those who are uncertain but not strongly against vaccination. For those who remain staunchly hesitant against vaccination, we recommend focusing on the personal benefits of vaccination with a focus on delivering facts about the risk of the disease in question, rather than trying to refute misinformation.

COVID-19 vaccine acceptance in the United States is disturbingly low among health care workers, particularly nurses, technicians, and those in nonclinical roles, compared to physicians.^6,30 Many of the strategies for addressing vaccine hesitancy among the general population can also apply to health care personnel (eg, vaccine education, addressing misinformation, delivering information from a trusted source). Health care personnel may also be subject to vaccine mandates by their employers, which have demonstrated increases in vaccination rates for influenza.³¹ Given that COVID-19 vaccination recommendations made by HCPs are associated with greater vaccine intentions and uptake,⁶ reducing hesitancy among health care workers is a critical first step to achieving optimal implementation.

CORRESPONDENCE
Nicole Mayo, PhD, 236 Pearl Street, Rochester, NY 14607; [email protected]

The World Health Organization (WHO) named vaccine hesitancy as one of the top 10 threats to public health as of 2019.¹ Although the COVID-19 vaccines manufactured by Pfizer-BioNTech and Moderna, first authorized for use in November 2020 and fully approved in August 2021,² are widely available in most countries, vaccination uptake is insufficient.³

As of June 2022, 78% of the US population had received at least 1 vaccine dose and 66.8% were fully vaccinated against COVID-19.⁴ High confidence in vaccines is associated with greater uptake; thus, engendering confidence in patients is a critical area of intervention for increasing uptake of COVID-19 and other vaccines.⁵ Despite the steady increase in vaccine acceptance observed following the release of the COVID-19 vaccine, acceptance remains suboptimal.^2,6

Demographic characteristics associated with lower vaccine acceptance include younger age, female sex, lower education and/or income, and Black race or Hispanic/Latinx ethnicity (compared to white or Asian non-­Hispanic).^6,7 Moreover, patients who are skeptical of vaccine safety and efficacy are associated with lower intentions to vaccinate. In contrast, patients with a history of receiving influenza vaccinations and those with a greater concern about COVID-19 and their risk of infection have increased vaccine intentions.⁶

Numerous strategies exist to increase vaccine acceptance; however, there does not appear to be a single “best” method to overcome individual or parental vaccine hesitancy for COVID-19 or other vaccines.^8,9 There are no large-scale randomized controlled trials (RCTs) demonstrating one strategy as more effective than another. In this review, we outline a variety of evidenced-based strategies to help patients overcome vaccine hesitancy for COVID-19 and other vaccines, with a focus on practical tips for primary care physicians (PCPs).

Which talking points are likely to resonate with your patients?

Intervention strategies promote vaccine acceptance by communicating personal benefit, collective benefit, or both to vaccine-­hesitant patients. In a study sample of US undergraduate students, Kim and colleagues¹⁰ found that providing information about the benefits and risks of influenza vaccines resulted in significantly less vaccine intent compared to communicating information only on the benefits. Similarly, Shim and colleagues¹¹ investigated how game theory (acting to maximize personal payoff regardless of payoff to others) and altruism affect influenza vaccination decisions. Through a survey-based study of 427 US university employees, researchers found altruistic motivation had a significant impact on the decision to vaccinate against influenza, resulting in a shift from self-interest to that of the good of the community.¹¹

A German trial on COVID-19 vaccine acceptance by Sprengholz and colleagues¹² found that communications about the benefits of vaccination, availability of financial compensation for vaccination, or a combination of both, did not increase a person’s willingness to get vaccinated. This trial, however, did not separate out individual vs collective benefit, and it was conducted prior to widespread COVID-19 vaccine availability. 

When speaking with patients who are strongly hesitant to vaccination, emphasizing concrete personal benefit may prove more effective than stressing protection of others from illness.

In an online RCT conducted in early 2021, Freeman and colleagues¹³ randomized UK adults to 1 of 10 different “information conditions.” Participants read from 1 of 10 vaccine scripts that varied by the talking points they addressed. The topics that researchers drew from for these scripts included the personal or collective benefit from the COVID-19 vaccine, safety and effectiveness of the vaccine, and the seriousness of the pandemic. They found communications emphasizing personal benefit from vaccination and safety concerns were more effective in participants identified as being strongly hesitant (defined as those who said they would avoid getting the COVID-19 vaccine for as long as possible or who said they’d never get it). However, none of the information arms in this study decreased vaccine hesitancy among those who were doubtful of vaccination (defined as those who said they would delay vaccination or who didn’t know if they would get vaccinated).¹³

Continue to: When encountering patients who are strongly...

When encountering patients who are strongly hesitant to vaccination, an approach emphasizing concrete personal benefit may prove more effective than one stressing protection of others from illness. It is important to note, though, that findings from other countries may not be relevant to US patients due to differences in demographic factors, individual beliefs, and political climate. 

It helps to explain herd immunity by providing concrete examples 

Among the collective benefits of vaccination is the decreased risk of transmitting the disease to others (eg, family, friends, neighbors, colleagues), a quicker “return to normalcy,” and herd immunity.¹³ While individual health benefits may more strongly motivate people to get vaccinated than collective benefits, this may be due to a lack of understanding about herd immunity among the general public. The optimal method of communicating information on herd immunity is not known.¹⁴

Betsch and colleagues¹⁵ found that explaining herd immunity using interactive simulations increased vaccine intent, especially in countries that prioritize the self (rather than prioritizing the group over the individual). In addition to educating study participants about herd immunity, telling them how local vaccine coverage compared to the desired level of coverage helped to increase (influenza) vaccine intent among those who were least informed about herd immunity.¹⁶

Providing concrete examples of the collective benefits of vaccination (eg, protecting grandparents, children too young to be vaccinated, and those at increased risk for severe illness) or sharing stories about how other patients suffered from the disease in question may increase the likelihood of vaccination. One recent trial by Pfattheicher and colleagues¹⁷ found that empathy for those most vulnerable to COVID-19 and increased knowledge about herd immunity were 2 factors associated with greater vaccine intentions.

In this study, the authors induced empathy and increased COVID-19 vaccination intention by having participants read a short story about 2 close siblings who worked together in a nursing facility. In the story, participants learned that both siblings were given a diagnosis of COVID-19 at the same time but only 1 survived.¹⁷

Continue to: Try this 3-pronged approach

Try this 3-pronged approach. Consider explaining herd immunity to vaccine-hesitant patients, pairing this concept with information about local vaccine uptake, and appealing to the patient’s sense of empathy. You might share de-identified information on other patients in your practice or personal network who experienced severe illness, had long-term effects, or died from COVID-19 infection. Such concrete examples may help to increase motivation to vaccinate more than a general appeal to altruism.

Initiate the discussion by emphasizing that community immunity protects those who are vulnerable and lack immunity while providing specific empathetic examples (eg, newborns, cancer survivors) and asking patients to consider friends and family who might be at risk. Additionally, it is essential to explain that although community immunity can decrease the spread of infection, it can only be achieved when enough people are vaccinated. 

Proceed with caution: Addressing conspiracy theories can backfire

Accurate information is critical to improving vaccine intentions; belief in conspiracy theories or misinformation related to COVID-19 is associated with reduced vaccine intentions and uptake.⁶ For example, a study by Loomba and colleagues¹⁸ showed that after exposure to misinformation, US and UK adults reported reduced intentions to vaccinate against COVID-19 once a vaccine became available.

Unfortunately, addressing myths about vaccines can sometimes backfire and unintentionally reinforce vaccine misperceptions.^19,20 This is especially true for patients with the highest levels of concern or mistrust in vaccines. Nyhan and colleagues^21,22 observed the backfire effect in 2 US studies looking at influenza and measles, mumps, and rubella vaccine misperceptions. Although corrective information significantly reduced belief in vaccine myths, they found individuals with the most concerns more strongly endorsed misperceptions when their beliefs were challenged.^21,22

Strategies for correcting vaccine misinformation may vary by type of vaccine; however, placing emphasis on facts delivered by trusted sources appears to be beneficial.

An Australian randomized study by Steffens and colleagues²³ found repeating myths about childhood vaccines, followed by corrective text, to parents of children ages 0 to 5 years had no difference on parental intent to vaccinate their children compared to providing vaccine information as a statement or in a question/answer format. Furthermore, an RCT in Brazil by Carey and colleagues²⁴ found that myth-correction messages about Zika virus failed to reduce misperceptions about the virus and actually reduced the belief in factual information about Zika—­regardless of baseline beliefs in conspiracies. However, a similar experiment in the same study showed that myth-correction messages reduced false beliefs about yellow fever.

Continue to: The authors speculated...

The authors speculated that this may be because Zika is a relatively new virus when compared to yellow fever, and participants may have more pre-existing knowledge about yellow fever.²⁴ These findings are important to keep in mind when addressing misinformation regarding COVID-19. When addressing myth perceptions with patients, consider pivoting the conversation from vaccine myths to the disease itself, focusing on the disease risk and severity of symptoms.^19,20 

Other studies have had positive results when addressing misinformation, including a digital RCT of older adults in the Netherlands by Yousuf and colleagues.²⁵ In this study, participants were randomized to view 1 of 2 versions of an information video on vaccination featuring an informative discussion by celebrity scientists, government officials, and a cardiologist. Video 1 did not include debunking strategies, only information about vaccination; Video 2 provided the same information about vaccines but also described the myths surrounding vaccines and reiterated the truth to debunk the myths.

Findings demonstrated that a significantly higher number of participants in the Video 2 group overcame vaccination myths related to influenza and COVID-19.²⁵ Notably, this study took place prior to the widespread availability of COVID-19 vaccines and did not measure intent to vaccinate against COVID-19.

Taken together, strategies for correcting vaccine misinformation may vary by population as well as type of vaccine; however, placing emphasis on facts delivered by trusted sources appears to be beneficial. When addressing misinformation, PCPs should first focus on key details (not all supporting information) and clearly explain why the misinformation is false before pointing out the actual myth and providing an alternative explanation.²⁰ When caring for patients who express strong concerns over the vaccine in question or have avid beliefs in certain myths or conspiracy theories, it’s best to pivot the conversation back to the disease rather than address the misinformation to avoid a potential backfire effect.

Utilize these effective communication techniques

TABLE 1^{10,13,16,17,19,20} summarizes the “do’s and don’ts” of communicating with vaccine-hesitant patients. PCPs should provide strong recommendations for vaccination, approaching it presumptively—ie, framing it as normative behavior.^19,26 This approach is critical to building patient trust so that vaccine-hesitant patients feel the PCP is truly listening to them and addressing their concerns.²⁷ Additionally, implementing motivational interviewing (MI) and self-determination theory (SDT)²⁸ techniques when discussing vaccinations with patients can improve intentions and uptake.^19,29TABLE 2^19,29 outlines specific techniques based on SDT and MI that PCPs may utilize to communicate with vaccine-hesitant individuals or parents. 

Continue to: The takeaway

Strategies for increasing vaccine intentions include educating hesitant patients about the benefits and risks of vaccines, addressing misinformation, and explaining the personal and collective benefits of vaccination. These strategies appear to be more effective when delivered by a trusted source, such as a health care provider (HCP). Care should be taken when implementing vaccine-acceptance strategies to ensure that they are tailored to specific populations and vaccines.

At this stage in the COVID-19 pandemic, when several vaccines have been widely available for more than a year, we expect that the majority of patients desiring vaccination (ie, those with the greatest vaccine intent) have already received them. With the recent approval of COVID-19 vaccines for children younger than 5 years, we must now advocate for our patients to vaccinate not only themselves, but their children. Patients who remain unvaccinated may be hesitant or outright reject vaccination for a number of reasons, including fear or skepticism over the safety and efficacy of the vaccine, belief in conspiracy theories, belief that COVID-19 is not real or not severe, or mistrust of the government.⁶ Vaccine hesitation or rejection is also often political in nature.

Based on the studies included in this review, we have identified several strategies for reducing vaccine hesitancy, which can be used with vaccine-hesitant patients and parents. We suggest emphasizing the personal benefit of vaccination and focusing on specific disease risks. If time allows, you can also explain the collective benefit of vaccination through herd immunity, including the current levels of local vaccine uptake compared to the desired level for community immunity. Communicating the collective benefits of vaccination may be more effective when paired with a strategy intended to increase empathy and altruism, such as sharing actual stories about those who have suffered from a vaccine-preventable disease.

Build trust by asking your patient: What kind of information do you feel you are missing about the vaccine?

Addressing myths and misinformation related to COVID-19 and other vaccines, with emphasis placed on the correct information delivered by trusted sources may be beneficial for those who are uncertain but not strongly against vaccination. For those who remain staunchly hesitant against vaccination, we recommend focusing on the personal benefits of vaccination with a focus on delivering facts about the risk of the disease in question, rather than trying to refute misinformation.

COVID-19 vaccine acceptance in the United States is disturbingly low among health care workers, particularly nurses, technicians, and those in nonclinical roles, compared to physicians.^6,30 Many of the strategies for addressing vaccine hesitancy among the general population can also apply to health care personnel (eg, vaccine education, addressing misinformation, delivering information from a trusted source). Health care personnel may also be subject to vaccine mandates by their employers, which have demonstrated increases in vaccination rates for influenza.³¹ Given that COVID-19 vaccination recommendations made by HCPs are associated with greater vaccine intentions and uptake,⁶ reducing hesitancy among health care workers is a critical first step to achieving optimal implementation.

CORRESPONDENCE
Nicole Mayo, PhD, 236 Pearl Street, Rochester, NY 14607; [email protected]

A 24-YEAR-OLD WOMAN with a history of guttate psoriasis, for which she was taking adalimumab, presented with a 2-week history of diffuse papules and plaques on her neck, back, torso, and upper and lower extremities (FIGURE 1). She said that the lesions were pruritic and seemed similar to those that erupted during past outbreaks of psoriasis—although they were more numerous and progressive. So, the patient (a nurse) decided to take her biweekly dose (40 mg) of adalimumab 1 week early. After administration, the rash significantly worsened, spreading to the rest of her trunk and extremities.

Physical exam was notable for multiple erythematous papules and plaques with central clearing and light peripheral scaling on both arms and legs, as well as her chest and back. The patient also indicated she’d adopted a stray cat 2 weeks prior. Given the patient’s pet exposure and the annular nature of the lesions, a potassium hydroxide (KOH) preparation was done.

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

The KOH preparation was positive for hyphae in 4 separate sites (trunk, left arm, left leg, and left neck), confirming the diagnosis of severe extensive tinea corporis (FIGURE 2).

Dermatophyte (tinea) infections are caused by fungi that invade and reproduce in the skin, hair, and nails. Dermatophytes, which include the genera Trichophyton, Microsporum, and Epidermophyton, are the most common cause of superficial mycotic infections. As of 2016, the worldwide prevalence of superficial mycotic infections was 20% to 25%.¹ Tinea corporis can result from contact with people, animals, or soil. Infections resulting from animal-to-human contact are often transmitted by domestic animals. In this case, the patient’s exposure was from her new cat.

Tinea corporis classically manifests as pruritic, erythematous patches or plaques with central clearing, giving it an annular appearance. The response to a tinea infection depends on the immune system of the host and can range in severity from superficial to severe.² There are 2 forms of severe dermatophytosis: invasive, which involves localized perifollicular sites or deep dermatophytosis, and extensive, which is confined to the stratum corneum but results in numerous lesions.³

The diagnosis of tinea corporis is commonly confirmed using direct microscopic examination with 10% to 20% KOH preparation, which will show branching and septate hyphal filaments.⁴

Several conditions with annular lesions comprise the differential

The findings of pruritic annular erythematous lesions on the patient’s neck, chest, trunk, and bilateral extremities led the patient to suspect this was a worsening case of her guttate psoriasis. Other possible diagnoses included pityriasis rosea, subacute cutaneous lupus erythematosus (SCLE), and secondary syphilis.

Continue to: Guttate psoriasis

Guttate psoriasis would not typically progress during treatment with adalimumab, although tumor necrosis factor (TNF) inhibitors have been associated with worsening psoriasis. Guttate psoriasis manifests with small, pink to red, scaly raindrop-shaped patches over the trunk and extremities.

Pityriasis rosea, a rash that resembles branches of a Christmas tree, was strongly considered given the appearance of the lesions on the patient’s back. It commonly manifests as round to oval lesions with a subtle advancing border and central fine scaling, similar in shape and color to the lesions seen in tinea corporis.

SCLE has been associated with use of TNF inhibitors, but our patient had no other lupus-like symptoms, such as fatigue, fever, headaches, or joint pain. SCLE lesions are often annular with raised pink to red borders similar in appearance to tinea corporis.

Secondary syphilis was ruled out in this patient because she had a negative rapid plasma reagin test. Secondary syphilis most commonly manifests with diffuse, nonpruritic pink to red-brown lesions on the palms and soles of patients. Patients often have prodromal symptoms that include fever, weight loss, myalgias, headache, and sore throat.

Terbinafine, Yes, but for how long?

Historically, terbinafine has been prescribed at 250 mg once daily for 2 weeks for extensive tinea corporis. However, recent studies in India suggest that terbinafine should be dosed at 250 mg twice daily, with longer durations of treatment, due to resistance.⁵ In the United States, it is reasonable to prescribe oral terbinafine 250 mg once daily for 4 weeks and then re-evaluate the patient in a case of extensive tinea corporis.

Other oral antifungals that can effectively treat extensive tinea corporis include itraconazole, fluconazole, and griseofulvin.¹ Itraconazole and terbinafine are equally effective and safe in the treatment of tinea corporis, although itraconazole is significantly more expensive.⁶ Furthermore, a recent study found that combination therapy with oral terbinafine and itraconazole is as safe as monotherapy and is an option when terbinafine resistance is suspected.⁷

Our patient was initially started on oral terbinafine 250 mg/d. After the first dose, the patient requested a change in medication because there was no improvement in the rash. The patient was then prescribed oral fluconazole 300 mg daily and the tinea cleared after 2 months of daily therapy. (We surmise the treatment course may have been prolonged due to the possible immunosuppressant effects of adalimumab.) At the completion of treatment for the tinea corporis, the patient was restarted on adalimumab 40 mg biweekly for her psoriasis. 

A 24-YEAR-OLD WOMAN with a history of guttate psoriasis, for which she was taking adalimumab, presented with a 2-week history of diffuse papules and plaques on her neck, back, torso, and upper and lower extremities (FIGURE 1). She said that the lesions were pruritic and seemed similar to those that erupted during past outbreaks of psoriasis—although they were more numerous and progressive. So, the patient (a nurse) decided to take her biweekly dose (40 mg) of adalimumab 1 week early. After administration, the rash significantly worsened, spreading to the rest of her trunk and extremities.

Physical exam was notable for multiple erythematous papules and plaques with central clearing and light peripheral scaling on both arms and legs, as well as her chest and back. The patient also indicated she’d adopted a stray cat 2 weeks prior. Given the patient’s pet exposure and the annular nature of the lesions, a potassium hydroxide (KOH) preparation was done.

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

The KOH preparation was positive for hyphae in 4 separate sites (trunk, left arm, left leg, and left neck), confirming the diagnosis of severe extensive tinea corporis (FIGURE 2).

Dermatophyte (tinea) infections are caused by fungi that invade and reproduce in the skin, hair, and nails. Dermatophytes, which include the genera Trichophyton, Microsporum, and Epidermophyton, are the most common cause of superficial mycotic infections. As of 2016, the worldwide prevalence of superficial mycotic infections was 20% to 25%.¹ Tinea corporis can result from contact with people, animals, or soil. Infections resulting from animal-to-human contact are often transmitted by domestic animals. In this case, the patient’s exposure was from her new cat.

Tinea corporis classically manifests as pruritic, erythematous patches or plaques with central clearing, giving it an annular appearance. The response to a tinea infection depends on the immune system of the host and can range in severity from superficial to severe.² There are 2 forms of severe dermatophytosis: invasive, which involves localized perifollicular sites or deep dermatophytosis, and extensive, which is confined to the stratum corneum but results in numerous lesions.³

The diagnosis of tinea corporis is commonly confirmed using direct microscopic examination with 10% to 20% KOH preparation, which will show branching and septate hyphal filaments.⁴

Several conditions with annular lesions comprise the differential

The findings of pruritic annular erythematous lesions on the patient’s neck, chest, trunk, and bilateral extremities led the patient to suspect this was a worsening case of her guttate psoriasis. Other possible diagnoses included pityriasis rosea, subacute cutaneous lupus erythematosus (SCLE), and secondary syphilis.

Continue to: Guttate psoriasis

Guttate psoriasis would not typically progress during treatment with adalimumab, although tumor necrosis factor (TNF) inhibitors have been associated with worsening psoriasis. Guttate psoriasis manifests with small, pink to red, scaly raindrop-shaped patches over the trunk and extremities.

Pityriasis rosea, a rash that resembles branches of a Christmas tree, was strongly considered given the appearance of the lesions on the patient’s back. It commonly manifests as round to oval lesions with a subtle advancing border and central fine scaling, similar in shape and color to the lesions seen in tinea corporis.

SCLE has been associated with use of TNF inhibitors, but our patient had no other lupus-like symptoms, such as fatigue, fever, headaches, or joint pain. SCLE lesions are often annular with raised pink to red borders similar in appearance to tinea corporis.

Secondary syphilis was ruled out in this patient because she had a negative rapid plasma reagin test. Secondary syphilis most commonly manifests with diffuse, nonpruritic pink to red-brown lesions on the palms and soles of patients. Patients often have prodromal symptoms that include fever, weight loss, myalgias, headache, and sore throat.

Terbinafine, Yes, but for how long?

Historically, terbinafine has been prescribed at 250 mg once daily for 2 weeks for extensive tinea corporis. However, recent studies in India suggest that terbinafine should be dosed at 250 mg twice daily, with longer durations of treatment, due to resistance.⁵ In the United States, it is reasonable to prescribe oral terbinafine 250 mg once daily for 4 weeks and then re-evaluate the patient in a case of extensive tinea corporis.

Other oral antifungals that can effectively treat extensive tinea corporis include itraconazole, fluconazole, and griseofulvin.¹ Itraconazole and terbinafine are equally effective and safe in the treatment of tinea corporis, although itraconazole is significantly more expensive.⁶ Furthermore, a recent study found that combination therapy with oral terbinafine and itraconazole is as safe as monotherapy and is an option when terbinafine resistance is suspected.⁷

Our patient was initially started on oral terbinafine 250 mg/d. After the first dose, the patient requested a change in medication because there was no improvement in the rash. The patient was then prescribed oral fluconazole 300 mg daily and the tinea cleared after 2 months of daily therapy. (We surmise the treatment course may have been prolonged due to the possible immunosuppressant effects of adalimumab.) At the completion of treatment for the tinea corporis, the patient was restarted on adalimumab 40 mg biweekly for her psoriasis. 

A 24-YEAR-OLD WOMAN with a history of guttate psoriasis, for which she was taking adalimumab, presented with a 2-week history of diffuse papules and plaques on her neck, back, torso, and upper and lower extremities (FIGURE 1). She said that the lesions were pruritic and seemed similar to those that erupted during past outbreaks of psoriasis—although they were more numerous and progressive. So, the patient (a nurse) decided to take her biweekly dose (40 mg) of adalimumab 1 week early. After administration, the rash significantly worsened, spreading to the rest of her trunk and extremities.

Physical exam was notable for multiple erythematous papules and plaques with central clearing and light peripheral scaling on both arms and legs, as well as her chest and back. The patient also indicated she’d adopted a stray cat 2 weeks prior. Given the patient’s pet exposure and the annular nature of the lesions, a potassium hydroxide (KOH) preparation was done.

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

The KOH preparation was positive for hyphae in 4 separate sites (trunk, left arm, left leg, and left neck), confirming the diagnosis of severe extensive tinea corporis (FIGURE 2).

Dermatophyte (tinea) infections are caused by fungi that invade and reproduce in the skin, hair, and nails. Dermatophytes, which include the genera Trichophyton, Microsporum, and Epidermophyton, are the most common cause of superficial mycotic infections. As of 2016, the worldwide prevalence of superficial mycotic infections was 20% to 25%.¹ Tinea corporis can result from contact with people, animals, or soil. Infections resulting from animal-to-human contact are often transmitted by domestic animals. In this case, the patient’s exposure was from her new cat.

Tinea corporis classically manifests as pruritic, erythematous patches or plaques with central clearing, giving it an annular appearance. The response to a tinea infection depends on the immune system of the host and can range in severity from superficial to severe.² There are 2 forms of severe dermatophytosis: invasive, which involves localized perifollicular sites or deep dermatophytosis, and extensive, which is confined to the stratum corneum but results in numerous lesions.³

The diagnosis of tinea corporis is commonly confirmed using direct microscopic examination with 10% to 20% KOH preparation, which will show branching and septate hyphal filaments.⁴

Several conditions with annular lesions comprise the differential

The findings of pruritic annular erythematous lesions on the patient’s neck, chest, trunk, and bilateral extremities led the patient to suspect this was a worsening case of her guttate psoriasis. Other possible diagnoses included pityriasis rosea, subacute cutaneous lupus erythematosus (SCLE), and secondary syphilis.

Continue to: Guttate psoriasis

Guttate psoriasis would not typically progress during treatment with adalimumab, although tumor necrosis factor (TNF) inhibitors have been associated with worsening psoriasis. Guttate psoriasis manifests with small, pink to red, scaly raindrop-shaped patches over the trunk and extremities.

Pityriasis rosea, a rash that resembles branches of a Christmas tree, was strongly considered given the appearance of the lesions on the patient’s back. It commonly manifests as round to oval lesions with a subtle advancing border and central fine scaling, similar in shape and color to the lesions seen in tinea corporis.

SCLE has been associated with use of TNF inhibitors, but our patient had no other lupus-like symptoms, such as fatigue, fever, headaches, or joint pain. SCLE lesions are often annular with raised pink to red borders similar in appearance to tinea corporis.

Secondary syphilis was ruled out in this patient because she had a negative rapid plasma reagin test. Secondary syphilis most commonly manifests with diffuse, nonpruritic pink to red-brown lesions on the palms and soles of patients. Patients often have prodromal symptoms that include fever, weight loss, myalgias, headache, and sore throat.

Terbinafine, Yes, but for how long?

Historically, terbinafine has been prescribed at 250 mg once daily for 2 weeks for extensive tinea corporis. However, recent studies in India suggest that terbinafine should be dosed at 250 mg twice daily, with longer durations of treatment, due to resistance.⁵ In the United States, it is reasonable to prescribe oral terbinafine 250 mg once daily for 4 weeks and then re-evaluate the patient in a case of extensive tinea corporis.

Other oral antifungals that can effectively treat extensive tinea corporis include itraconazole, fluconazole, and griseofulvin.¹ Itraconazole and terbinafine are equally effective and safe in the treatment of tinea corporis, although itraconazole is significantly more expensive.⁶ Furthermore, a recent study found that combination therapy with oral terbinafine and itraconazole is as safe as monotherapy and is an option when terbinafine resistance is suspected.⁷

Our patient was initially started on oral terbinafine 250 mg/d. After the first dose, the patient requested a change in medication because there was no improvement in the rash. The patient was then prescribed oral fluconazole 300 mg daily and the tinea cleared after 2 months of daily therapy. (We surmise the treatment course may have been prolonged due to the possible immunosuppressant effects of adalimumab.) At the completion of treatment for the tinea corporis, the patient was restarted on adalimumab 40 mg biweekly for her psoriasis. 

THE CASE

A 52-year-old man requested medicine to help him with erectile dysfunction. After obtaining a medical history and performing a physical exam, the family physician (FP) asked for more details about the patient’s situation. He reported that his wife, who had recently seen the same FP for counseling related to her frustrations with her husband, was uninterested in sex. He then added that he was having an affair with a 32-year-old female co-worker and wanted to improve his sexual function.

He admitted to feeling guilty about this situation and was conflicted about whether to end the affair. He also stated that since the affair, his insomnia had worsened, he was drinking more alcohol, and he was having migraine headaches. As the FP for both patients, and with the knowledge that the wife was worried about possible infidelity, the physician felt some level of conflict about the situation. The following is a discussion of the issues that this patient encounter raised.

DISCUSSION

Issues related to infidelity are common to both men and women. They are also common in same-sex relationships; in general, however, lesbian couples have fewer outside partners, whereas gay men are more likely to seek variety by having multiple partners.¹

It is widely understood that successfully committed couples spend quality time together, emphasize each other’s strengths, show respect, accept influence, and nurture their friendship. However, many couples experience infidelity at some time in the course of their marriage. It is difficult to put an exact estimate on rates of infidelity due to problems with research methodology, inaccurate reporting, and a lack of agreement on a definition for infidelity.² General categories of infidelity include emotional only, sexual only, and combined sexual and emotional infidelity.^3,4 In terms of sexual infidelity, one study found that 25% of married men and 15% of married women admitted to having had extramarital sex at least once during their relationship.⁵ However, other studies suggest that women are closing the “sexual infidelity” gap and engaging in sexual affairs at a similar rate to men.⁶ There are websites that, in fact, have made it easier for married individuals to engage in affairs.

Reasons for infidelity. Men and women often have different motives in engaging in infidelity. In general, men’s motivations are more often related to sexual dissatisfaction and women’s to emotional dissatisfaction.^7,8 However, infidelity may not always be the result of marital unhappiness.

Some studies suggest that the presence of opportunity may override the positive aspects of a relationship.⁹ Opportunity is heightened in the work environment, as reflected by the finding that 50% of infidelity occurs in the office.¹⁰ Research suggests that all relationships may be vulnerable to infidelity if the right opportunities present themselves.¹¹

In general, health care providers are encouraged to use caution in generalizing about infidelity, as the subject is extremely complex, nuanced, and difficult to measure with exactitude.¹²

Continue to: The impact of infidelity

The impact of infidelity on couples varies due to factors such as the pre-morbid health of the marriage,¹³ the depth of involvement with the affair partner,¹⁴ and pre-­existing attitudes about infidelity.¹³

Infidelity is a common cause of divorce in America. However, in a sample, Schneider et al¹⁵ found that despite initial threats to leave the marriage after infidelity, less than one-quarter of partners divorced. Other studies have found that disclosure of the infidelity and a commitment to work on the marriage may be an essential component of healing.¹⁶

One study found that 25% of married men and 15% of married women admitted to having had extramarital sex at least once during their relationship.

Emotionally focused couples therapy, with its emphasis on attachment and bonding, may hold promise for helping couples successfully work through the trauma brought on by extramarital relationships.¹⁷ Psychologist and infidelity researcher Shirley Glass found that of the two-thirds of couples who chose to stay together after an affair, 80% of them reported a better marriage after treatment.¹¹

Initial steps to take, and questions to ask

Both male and female patients need to feel comfortable surfacing sexual concerns with their clinicians. In this case, the concerns of the husband are interwoven with broader marital issues, which are the source of emotional and psychosomatic distress. His decision regarding his affair carried with it potentially life-altering consequences for his wife, 3 children, and affair partner and her family. It also raised ethical issues for the FP, who was providing care to both the husband and the wife. Appropriate care requires that a physician in this situation

• demonstrate a nonjudgmental approach
• clarify personal ethics in response to patient behaviors
• maintain confidentiality
• apply an ethical framework to resolve value dilemmas
• avoid actions that would be harmful to patients.

Interviewing can help to elicit information that may be clarifying not only to the physician but also to the patient. When interviewing a patient such as the one in this case, it would be wise to ask:

• How long has the affair been going on?
• Why is the patient engaging in the affair?
• Is abuse (emotional or physical) a factor in the marriage?
• Does the patient still have feelings for their spouse? Does the patient want to work on the marriage?
• Has the patient talked to a friend or therapist about the situation?
• Would the patient be willing to talk to a therapist?

Continue to: Ethical and legal considerations

Some therapists espouse the view that being “neutral” in the presence of an affair is as much a value judgment as taking one side or the other. In the presence of emotional or physical abuse, it might indeed be best to support a marital separation. However, in other situations when there are young children involved and the patient is undecided about what to do, the FP can discuss the pros and cons of working on a marriage that suffers from more treatable types of disrepair (ie, stress, disconnection, repetitive arguments).

Provision of care. If the patient is unwilling to end the affair, the physician needs to decide whether they feel ethically at ease with prescribing sexually enhancing performance medication, given that the patient’s wife is also a patient. A physician in this situation might feel that they are betraying the wife by providing such medications to the husband. In such cases, it might be appropriate to refer the husband to a colleague.

In all cases of infidelity, however, it is wise to discuss safe-sex practices in order to limit the risk of transmitting a sexually transmitted infection (STI) to the spouse (or affair partner) and offer testing for STIs.

Confidentiality. Despite feelings the physician might have about betraying the wife’s trust by providing the performance-enhancing medicine to the husband, there is very little justification for revealing the affair to the wife. In general, confidentiality can only be broken if there is a high level of imminent danger associated with nondisclosure. The physician needs to realize the serious legal implications of breaking confidentiality in this situation, as such disclosure may prompt the initiation of divorce proceedings.

Real-world recommendations

Check your own biases. Infidelity can trigger a whole host of emotional reactions in physicians based on their own personal and professional history. It is important to be aware of such emotions and if sufficiently triggered, discuss the case with a colleague.

Continue to: Encourage bibliotherapy and marriage therapy

Encourage bibliotherapy and marriage therapy. The conversation might go something like this:

“I would recommend you do some reading about infidelity. If you are interested in working on your marriage, you might want to consider a couples counselor who can help you. Research shows that while such counseling can help couples work through infidelity, disclosure needs to occur as part of that process. Research also indicates that about two-thirds of marriages stay together after the revelation of an affair and that such couples can experience healing if they commit to a therapeutic process. If you are unsure how you want to proceed, it might be helpful for you to explore your situation with an individual therapist. What would you like to do next?”

There are also written resources that the patient might find helpful; see “3 bibliotherapy resources for infidelity” for recommendations.

Referral to an individual or marriage counselor is warranted if the patient wants to work through the issues alone or with their partner. Disclosure of infidelity may not always be necessary for successful reconciliation if the affair has ended. A marriage therapist to whom you refer needs to be competent in working with infidelity.

Our patient. At the completion of the initial consultation—and after a discussion focused on the issues described, including encouragement to seek counseling—the FP acceded to the patient’s request for sexual performance-enhancing medication.

Continue to: The patient returned a few months...

The patient returned a few months later. His wife had found texts between him and his affair partner and told the patient that they had to enter into couples therapy or she was going to file for divorce. The patient told his physician that he had ended the extramarital relationship and was working on his marriage with a qualified marriage therapist; however, he felt lingering feelings of loss, discomfort in the workplace, and confusion about his choices. The physician was supportive and encouraged him to share these feelings, if possible, with an individual therapist or to find a friend who could listen while being supportive of his marriage. The physician also offered his services as a sounding board.

A year later, the patient had found another job and was still working on his marriage.

THE TAKEAWAY

This case underscores the importance of some basic health care tenets. It reminds us that maintaining patient confidentiality is paramount, and that nonjudgmental interviewing can help us to help our patients navigate challenging situations. The particulars of this case also highlight the importance of referring patients out for individual or marriage counseling and making a referral to a colleague when a situation makes us feel as if we are betraying a patient’s trust.

CORRESPONDENCE
David C. Slawson, MD, 2001 Vail Avenue, Suite 400B, Mercy Medical Plaza, Charlotte, NC 28207; [email protected]

THE CASE

A 52-year-old man requested medicine to help him with erectile dysfunction. After obtaining a medical history and performing a physical exam, the family physician (FP) asked for more details about the patient’s situation. He reported that his wife, who had recently seen the same FP for counseling related to her frustrations with her husband, was uninterested in sex. He then added that he was having an affair with a 32-year-old female co-worker and wanted to improve his sexual function.

He admitted to feeling guilty about this situation and was conflicted about whether to end the affair. He also stated that since the affair, his insomnia had worsened, he was drinking more alcohol, and he was having migraine headaches. As the FP for both patients, and with the knowledge that the wife was worried about possible infidelity, the physician felt some level of conflict about the situation. The following is a discussion of the issues that this patient encounter raised.

DISCUSSION

Issues related to infidelity are common to both men and women. They are also common in same-sex relationships; in general, however, lesbian couples have fewer outside partners, whereas gay men are more likely to seek variety by having multiple partners.¹

It is widely understood that successfully committed couples spend quality time together, emphasize each other’s strengths, show respect, accept influence, and nurture their friendship. However, many couples experience infidelity at some time in the course of their marriage. It is difficult to put an exact estimate on rates of infidelity due to problems with research methodology, inaccurate reporting, and a lack of agreement on a definition for infidelity.² General categories of infidelity include emotional only, sexual only, and combined sexual and emotional infidelity.^3,4 In terms of sexual infidelity, one study found that 25% of married men and 15% of married women admitted to having had extramarital sex at least once during their relationship.⁵ However, other studies suggest that women are closing the “sexual infidelity” gap and engaging in sexual affairs at a similar rate to men.⁶ There are websites that, in fact, have made it easier for married individuals to engage in affairs.

Reasons for infidelity. Men and women often have different motives in engaging in infidelity. In general, men’s motivations are more often related to sexual dissatisfaction and women’s to emotional dissatisfaction.^7,8 However, infidelity may not always be the result of marital unhappiness.

Some studies suggest that the presence of opportunity may override the positive aspects of a relationship.⁹ Opportunity is heightened in the work environment, as reflected by the finding that 50% of infidelity occurs in the office.¹⁰ Research suggests that all relationships may be vulnerable to infidelity if the right opportunities present themselves.¹¹

In general, health care providers are encouraged to use caution in generalizing about infidelity, as the subject is extremely complex, nuanced, and difficult to measure with exactitude.¹²

Continue to: The impact of infidelity

The impact of infidelity on couples varies due to factors such as the pre-morbid health of the marriage,¹³ the depth of involvement with the affair partner,¹⁴ and pre-­existing attitudes about infidelity.¹³

Infidelity is a common cause of divorce in America. However, in a sample, Schneider et al¹⁵ found that despite initial threats to leave the marriage after infidelity, less than one-quarter of partners divorced. Other studies have found that disclosure of the infidelity and a commitment to work on the marriage may be an essential component of healing.¹⁶

One study found that 25% of married men and 15% of married women admitted to having had extramarital sex at least once during their relationship.

Emotionally focused couples therapy, with its emphasis on attachment and bonding, may hold promise for helping couples successfully work through the trauma brought on by extramarital relationships.¹⁷ Psychologist and infidelity researcher Shirley Glass found that of the two-thirds of couples who chose to stay together after an affair, 80% of them reported a better marriage after treatment.¹¹

Initial steps to take, and questions to ask

Both male and female patients need to feel comfortable surfacing sexual concerns with their clinicians. In this case, the concerns of the husband are interwoven with broader marital issues, which are the source of emotional and psychosomatic distress. His decision regarding his affair carried with it potentially life-altering consequences for his wife, 3 children, and affair partner and her family. It also raised ethical issues for the FP, who was providing care to both the husband and the wife. Appropriate care requires that a physician in this situation

• demonstrate a nonjudgmental approach
• clarify personal ethics in response to patient behaviors
• maintain confidentiality
• apply an ethical framework to resolve value dilemmas
• avoid actions that would be harmful to patients.

Interviewing can help to elicit information that may be clarifying not only to the physician but also to the patient. When interviewing a patient such as the one in this case, it would be wise to ask:

• How long has the affair been going on?
• Why is the patient engaging in the affair?
• Is abuse (emotional or physical) a factor in the marriage?
• Does the patient still have feelings for their spouse? Does the patient want to work on the marriage?
• Has the patient talked to a friend or therapist about the situation?
• Would the patient be willing to talk to a therapist?

Continue to: Ethical and legal considerations

Some therapists espouse the view that being “neutral” in the presence of an affair is as much a value judgment as taking one side or the other. In the presence of emotional or physical abuse, it might indeed be best to support a marital separation. However, in other situations when there are young children involved and the patient is undecided about what to do, the FP can discuss the pros and cons of working on a marriage that suffers from more treatable types of disrepair (ie, stress, disconnection, repetitive arguments).

Provision of care. If the patient is unwilling to end the affair, the physician needs to decide whether they feel ethically at ease with prescribing sexually enhancing performance medication, given that the patient’s wife is also a patient. A physician in this situation might feel that they are betraying the wife by providing such medications to the husband. In such cases, it might be appropriate to refer the husband to a colleague.

In all cases of infidelity, however, it is wise to discuss safe-sex practices in order to limit the risk of transmitting a sexually transmitted infection (STI) to the spouse (or affair partner) and offer testing for STIs.

Confidentiality. Despite feelings the physician might have about betraying the wife’s trust by providing the performance-enhancing medicine to the husband, there is very little justification for revealing the affair to the wife. In general, confidentiality can only be broken if there is a high level of imminent danger associated with nondisclosure. The physician needs to realize the serious legal implications of breaking confidentiality in this situation, as such disclosure may prompt the initiation of divorce proceedings.

Real-world recommendations

Check your own biases. Infidelity can trigger a whole host of emotional reactions in physicians based on their own personal and professional history. It is important to be aware of such emotions and if sufficiently triggered, discuss the case with a colleague.

Continue to: Encourage bibliotherapy and marriage therapy

Encourage bibliotherapy and marriage therapy. The conversation might go something like this:

“I would recommend you do some reading about infidelity. If you are interested in working on your marriage, you might want to consider a couples counselor who can help you. Research shows that while such counseling can help couples work through infidelity, disclosure needs to occur as part of that process. Research also indicates that about two-thirds of marriages stay together after the revelation of an affair and that such couples can experience healing if they commit to a therapeutic process. If you are unsure how you want to proceed, it might be helpful for you to explore your situation with an individual therapist. What would you like to do next?”

There are also written resources that the patient might find helpful; see “3 bibliotherapy resources for infidelity” for recommendations.

Referral to an individual or marriage counselor is warranted if the patient wants to work through the issues alone or with their partner. Disclosure of infidelity may not always be necessary for successful reconciliation if the affair has ended. A marriage therapist to whom you refer needs to be competent in working with infidelity.

Our patient. At the completion of the initial consultation—and after a discussion focused on the issues described, including encouragement to seek counseling—the FP acceded to the patient’s request for sexual performance-enhancing medication.

Continue to: The patient returned a few months...

The patient returned a few months later. His wife had found texts between him and his affair partner and told the patient that they had to enter into couples therapy or she was going to file for divorce. The patient told his physician that he had ended the extramarital relationship and was working on his marriage with a qualified marriage therapist; however, he felt lingering feelings of loss, discomfort in the workplace, and confusion about his choices. The physician was supportive and encouraged him to share these feelings, if possible, with an individual therapist or to find a friend who could listen while being supportive of his marriage. The physician also offered his services as a sounding board.

A year later, the patient had found another job and was still working on his marriage.

THE TAKEAWAY

This case underscores the importance of some basic health care tenets. It reminds us that maintaining patient confidentiality is paramount, and that nonjudgmental interviewing can help us to help our patients navigate challenging situations. The particulars of this case also highlight the importance of referring patients out for individual or marriage counseling and making a referral to a colleague when a situation makes us feel as if we are betraying a patient’s trust.

CORRESPONDENCE
David C. Slawson, MD, 2001 Vail Avenue, Suite 400B, Mercy Medical Plaza, Charlotte, NC 28207; [email protected]

THE CASE

A 52-year-old man requested medicine to help him with erectile dysfunction. After obtaining a medical history and performing a physical exam, the family physician (FP) asked for more details about the patient’s situation. He reported that his wife, who had recently seen the same FP for counseling related to her frustrations with her husband, was uninterested in sex. He then added that he was having an affair with a 32-year-old female co-worker and wanted to improve his sexual function.

He admitted to feeling guilty about this situation and was conflicted about whether to end the affair. He also stated that since the affair, his insomnia had worsened, he was drinking more alcohol, and he was having migraine headaches. As the FP for both patients, and with the knowledge that the wife was worried about possible infidelity, the physician felt some level of conflict about the situation. The following is a discussion of the issues that this patient encounter raised.

DISCUSSION

Issues related to infidelity are common to both men and women. They are also common in same-sex relationships; in general, however, lesbian couples have fewer outside partners, whereas gay men are more likely to seek variety by having multiple partners.¹

It is widely understood that successfully committed couples spend quality time together, emphasize each other’s strengths, show respect, accept influence, and nurture their friendship. However, many couples experience infidelity at some time in the course of their marriage. It is difficult to put an exact estimate on rates of infidelity due to problems with research methodology, inaccurate reporting, and a lack of agreement on a definition for infidelity.² General categories of infidelity include emotional only, sexual only, and combined sexual and emotional infidelity.^3,4 In terms of sexual infidelity, one study found that 25% of married men and 15% of married women admitted to having had extramarital sex at least once during their relationship.⁵ However, other studies suggest that women are closing the “sexual infidelity” gap and engaging in sexual affairs at a similar rate to men.⁶ There are websites that, in fact, have made it easier for married individuals to engage in affairs.

Reasons for infidelity. Men and women often have different motives in engaging in infidelity. In general, men’s motivations are more often related to sexual dissatisfaction and women’s to emotional dissatisfaction.^7,8 However, infidelity may not always be the result of marital unhappiness.

Some studies suggest that the presence of opportunity may override the positive aspects of a relationship.⁹ Opportunity is heightened in the work environment, as reflected by the finding that 50% of infidelity occurs in the office.¹⁰ Research suggests that all relationships may be vulnerable to infidelity if the right opportunities present themselves.¹¹

In general, health care providers are encouraged to use caution in generalizing about infidelity, as the subject is extremely complex, nuanced, and difficult to measure with exactitude.¹²

Continue to: The impact of infidelity

The impact of infidelity on couples varies due to factors such as the pre-morbid health of the marriage,¹³ the depth of involvement with the affair partner,¹⁴ and pre-­existing attitudes about infidelity.¹³

Infidelity is a common cause of divorce in America. However, in a sample, Schneider et al¹⁵ found that despite initial threats to leave the marriage after infidelity, less than one-quarter of partners divorced. Other studies have found that disclosure of the infidelity and a commitment to work on the marriage may be an essential component of healing.¹⁶

One study found that 25% of married men and 15% of married women admitted to having had extramarital sex at least once during their relationship.

Emotionally focused couples therapy, with its emphasis on attachment and bonding, may hold promise for helping couples successfully work through the trauma brought on by extramarital relationships.¹⁷ Psychologist and infidelity researcher Shirley Glass found that of the two-thirds of couples who chose to stay together after an affair, 80% of them reported a better marriage after treatment.¹¹

Initial steps to take, and questions to ask

Both male and female patients need to feel comfortable surfacing sexual concerns with their clinicians. In this case, the concerns of the husband are interwoven with broader marital issues, which are the source of emotional and psychosomatic distress. His decision regarding his affair carried with it potentially life-altering consequences for his wife, 3 children, and affair partner and her family. It also raised ethical issues for the FP, who was providing care to both the husband and the wife. Appropriate care requires that a physician in this situation

• demonstrate a nonjudgmental approach
• clarify personal ethics in response to patient behaviors
• maintain confidentiality
• apply an ethical framework to resolve value dilemmas
• avoid actions that would be harmful to patients.

Interviewing can help to elicit information that may be clarifying not only to the physician but also to the patient. When interviewing a patient such as the one in this case, it would be wise to ask:

• How long has the affair been going on?
• Why is the patient engaging in the affair?
• Is abuse (emotional or physical) a factor in the marriage?
• Does the patient still have feelings for their spouse? Does the patient want to work on the marriage?
• Has the patient talked to a friend or therapist about the situation?
• Would the patient be willing to talk to a therapist?

Continue to: Ethical and legal considerations

Some therapists espouse the view that being “neutral” in the presence of an affair is as much a value judgment as taking one side or the other. In the presence of emotional or physical abuse, it might indeed be best to support a marital separation. However, in other situations when there are young children involved and the patient is undecided about what to do, the FP can discuss the pros and cons of working on a marriage that suffers from more treatable types of disrepair (ie, stress, disconnection, repetitive arguments).

Provision of care. If the patient is unwilling to end the affair, the physician needs to decide whether they feel ethically at ease with prescribing sexually enhancing performance medication, given that the patient’s wife is also a patient. A physician in this situation might feel that they are betraying the wife by providing such medications to the husband. In such cases, it might be appropriate to refer the husband to a colleague.

In all cases of infidelity, however, it is wise to discuss safe-sex practices in order to limit the risk of transmitting a sexually transmitted infection (STI) to the spouse (or affair partner) and offer testing for STIs.

Confidentiality. Despite feelings the physician might have about betraying the wife’s trust by providing the performance-enhancing medicine to the husband, there is very little justification for revealing the affair to the wife. In general, confidentiality can only be broken if there is a high level of imminent danger associated with nondisclosure. The physician needs to realize the serious legal implications of breaking confidentiality in this situation, as such disclosure may prompt the initiation of divorce proceedings.

Real-world recommendations

Check your own biases. Infidelity can trigger a whole host of emotional reactions in physicians based on their own personal and professional history. It is important to be aware of such emotions and if sufficiently triggered, discuss the case with a colleague.

Continue to: Encourage bibliotherapy and marriage therapy

Encourage bibliotherapy and marriage therapy. The conversation might go something like this:

“I would recommend you do some reading about infidelity. If you are interested in working on your marriage, you might want to consider a couples counselor who can help you. Research shows that while such counseling can help couples work through infidelity, disclosure needs to occur as part of that process. Research also indicates that about two-thirds of marriages stay together after the revelation of an affair and that such couples can experience healing if they commit to a therapeutic process. If you are unsure how you want to proceed, it might be helpful for you to explore your situation with an individual therapist. What would you like to do next?”

There are also written resources that the patient might find helpful; see “3 bibliotherapy resources for infidelity” for recommendations.

Referral to an individual or marriage counselor is warranted if the patient wants to work through the issues alone or with their partner. Disclosure of infidelity may not always be necessary for successful reconciliation if the affair has ended. A marriage therapist to whom you refer needs to be competent in working with infidelity.

Our patient. At the completion of the initial consultation—and after a discussion focused on the issues described, including encouragement to seek counseling—the FP acceded to the patient’s request for sexual performance-enhancing medication.

Continue to: The patient returned a few months...

The patient returned a few months later. His wife had found texts between him and his affair partner and told the patient that they had to enter into couples therapy or she was going to file for divorce. The patient told his physician that he had ended the extramarital relationship and was working on his marriage with a qualified marriage therapist; however, he felt lingering feelings of loss, discomfort in the workplace, and confusion about his choices. The physician was supportive and encouraged him to share these feelings, if possible, with an individual therapist or to find a friend who could listen while being supportive of his marriage. The physician also offered his services as a sounding board.

A year later, the patient had found another job and was still working on his marriage.

THE TAKEAWAY

This case underscores the importance of some basic health care tenets. It reminds us that maintaining patient confidentiality is paramount, and that nonjudgmental interviewing can help us to help our patients navigate challenging situations. The particulars of this case also highlight the importance of referring patients out for individual or marriage counseling and making a referral to a colleague when a situation makes us feel as if we are betraying a patient’s trust.

CORRESPONDENCE
David C. Slawson, MD, 2001 Vail Avenue, Suite 400B, Mercy Medical Plaza, Charlotte, NC 28207; [email protected]