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]

Anxiety over the U.S. economy intensified in June, with 87% of Americans reporting they are anxious or very anxious about inflation, up eight percentage points from the previous month, results from a new national report from the American Psychiatric Association show.

“The economy seems to have supplanted COVID as a major factor in Americans’ day-to-day anxiety,” APA President Rebecca W. Brendel, MD, JD, said in a news release.

“Knowing that so many Americans are concerned about finances is important because it can prepare clinicians to be ready to approach the subject, which is one that people are often reluctant or ashamed to raise on their own,” Dr. Brendel told this news organization.

What’s the best way to bring up the sensitive topic of money?

“In general, it’s best to start with open-ended questions to allow individuals in therapy to share what is on their minds, explore their concerns, and develop strategies to address these issues. Once a patient raises a concern, that is a good time to ask more about the issues they’ve raised and to explore other potential sources of anxiety or stress,” said Dr. Brendel.

The latest APA poll was conducted by Morning Consult, June 18-20, 2022, among a nationally representative sample of 2,210 adults.

In addition to an uptick in worry about inflation, the poll shows that more than half (51%) of adults are worried about a potential loss of income.

Hispanic adults (66%), mothers (65%), millennials (63%), and genZers (62%) are among the groups most likely to be concerned about income loss.

“Stress is not good for health, mental or physical. So, while it’s a reality that Americans are faced with finding ways of making ends meet, it’s more important than ever to make sure that we are all accessing the care that we need,” said Dr. Brendel.

“People should be aware that there may be low- or no-cost options such as community mental health centers or employer-sponsored resources to address mental health concerns,” she added.
 

Coping with traumatic events

The latest poll also shows that about one-third of adults are worried about gun violence (35% overall, 47% among genZers) or a natural disaster (29%) personally affecting them.

Climate change anxiety is also up slightly in June, compared with May (+4%).

The same goes for mid-term election-related anxiety (+3%) – particularly among Democrats (54% vs. 59%) compared with Republicans (48% vs. 48%).

The latest poll provides insight how Americans would cope after a traumatic event. More adults report they will turn to family and friends for support (60%) than practice self-care (42%), speak openly about their feelings (37%), or seek help from a professional (31%). Nearly one-third (30%) say they will move on from it and not dwell on their feelings.

GenZers are the least likely to say they will speak openly about their feelings (29%) and are less likely than millennials to say they would speak to a health professional (28% vs. 38%).

“While many people show resilience, it’s troubling that most Americans wouldn’t speak openly about their feelings after a traumatic event,” APA CEO and Medical Director Saul Levin, MD, said in the news release.

“In many ways, naming feelings is the most important step toward healing, and this reluctance to air our thoughts may indicate that mental health stigma is still a powerful force in our society,” Dr. Levin said.

After a traumatic current event, 41% of Americans say they consume more news and 30% say they take in more social media, but the majority say this does not impact their mental health, the poll shows.

Two in five adults (43%) say the news of a traumatic event makes them feel more informed, 32% say it makes them feel more anxious, and about one-quarter say it makes them feel overwhelmed (27%) or discouraged (24%).

Dr. Brendel noted that, after a traumatic event, “it’s expected that people may experience anxiety or other symptoms for brief periods of time. However, no two people experience things the same way. If symptoms don’t go away, are overwhelming, or get worse over time, for example, it’s critical to seek help right away.”

The June poll shows that 50% of Americans are anxious about the future of reproductive rights but the poll was conducted before the Dobbs ruling.

Anxiety around COVID-19 continues to ease, with about 47% of Americans saying they are concerned about the pandemic, down 2% among all Americans and 16% among Black Americans since May.

The APA’s Healthy Minds Monthly tracks timely mental health issues throughout the year. The APA also releases its annual Healthy Minds Poll each May in conjunction with Mental Health Awareness Month.

A version of this article first appeared on Medscape.com.

Anxiety over the U.S. economy intensified in June, with 87% of Americans reporting they are anxious or very anxious about inflation, up eight percentage points from the previous month, results from a new national report from the American Psychiatric Association show.

“The economy seems to have supplanted COVID as a major factor in Americans’ day-to-day anxiety,” APA President Rebecca W. Brendel, MD, JD, said in a news release.

“Knowing that so many Americans are concerned about finances is important because it can prepare clinicians to be ready to approach the subject, which is one that people are often reluctant or ashamed to raise on their own,” Dr. Brendel told this news organization.

What’s the best way to bring up the sensitive topic of money?

“In general, it’s best to start with open-ended questions to allow individuals in therapy to share what is on their minds, explore their concerns, and develop strategies to address these issues. Once a patient raises a concern, that is a good time to ask more about the issues they’ve raised and to explore other potential sources of anxiety or stress,” said Dr. Brendel.

The latest APA poll was conducted by Morning Consult, June 18-20, 2022, among a nationally representative sample of 2,210 adults.

In addition to an uptick in worry about inflation, the poll shows that more than half (51%) of adults are worried about a potential loss of income.

Hispanic adults (66%), mothers (65%), millennials (63%), and genZers (62%) are among the groups most likely to be concerned about income loss.

“Stress is not good for health, mental or physical. So, while it’s a reality that Americans are faced with finding ways of making ends meet, it’s more important than ever to make sure that we are all accessing the care that we need,” said Dr. Brendel.

“People should be aware that there may be low- or no-cost options such as community mental health centers or employer-sponsored resources to address mental health concerns,” she added.
 

Coping with traumatic events

The latest poll also shows that about one-third of adults are worried about gun violence (35% overall, 47% among genZers) or a natural disaster (29%) personally affecting them.

Climate change anxiety is also up slightly in June, compared with May (+4%).

The same goes for mid-term election-related anxiety (+3%) – particularly among Democrats (54% vs. 59%) compared with Republicans (48% vs. 48%).

The latest poll provides insight how Americans would cope after a traumatic event. More adults report they will turn to family and friends for support (60%) than practice self-care (42%), speak openly about their feelings (37%), or seek help from a professional (31%). Nearly one-third (30%) say they will move on from it and not dwell on their feelings.

GenZers are the least likely to say they will speak openly about their feelings (29%) and are less likely than millennials to say they would speak to a health professional (28% vs. 38%).

“While many people show resilience, it’s troubling that most Americans wouldn’t speak openly about their feelings after a traumatic event,” APA CEO and Medical Director Saul Levin, MD, said in the news release.

“In many ways, naming feelings is the most important step toward healing, and this reluctance to air our thoughts may indicate that mental health stigma is still a powerful force in our society,” Dr. Levin said.

After a traumatic current event, 41% of Americans say they consume more news and 30% say they take in more social media, but the majority say this does not impact their mental health, the poll shows.

Two in five adults (43%) say the news of a traumatic event makes them feel more informed, 32% say it makes them feel more anxious, and about one-quarter say it makes them feel overwhelmed (27%) or discouraged (24%).

Dr. Brendel noted that, after a traumatic event, “it’s expected that people may experience anxiety or other symptoms for brief periods of time. However, no two people experience things the same way. If symptoms don’t go away, are overwhelming, or get worse over time, for example, it’s critical to seek help right away.”

The June poll shows that 50% of Americans are anxious about the future of reproductive rights but the poll was conducted before the Dobbs ruling.

Anxiety around COVID-19 continues to ease, with about 47% of Americans saying they are concerned about the pandemic, down 2% among all Americans and 16% among Black Americans since May.

The APA’s Healthy Minds Monthly tracks timely mental health issues throughout the year. The APA also releases its annual Healthy Minds Poll each May in conjunction with Mental Health Awareness Month.

A version of this article first appeared on Medscape.com.

Anxiety over the U.S. economy intensified in June, with 87% of Americans reporting they are anxious or very anxious about inflation, up eight percentage points from the previous month, results from a new national report from the American Psychiatric Association show.

“The economy seems to have supplanted COVID as a major factor in Americans’ day-to-day anxiety,” APA President Rebecca W. Brendel, MD, JD, said in a news release.

“Knowing that so many Americans are concerned about finances is important because it can prepare clinicians to be ready to approach the subject, which is one that people are often reluctant or ashamed to raise on their own,” Dr. Brendel told this news organization.

What’s the best way to bring up the sensitive topic of money?

“In general, it’s best to start with open-ended questions to allow individuals in therapy to share what is on their minds, explore their concerns, and develop strategies to address these issues. Once a patient raises a concern, that is a good time to ask more about the issues they’ve raised and to explore other potential sources of anxiety or stress,” said Dr. Brendel.

The latest APA poll was conducted by Morning Consult, June 18-20, 2022, among a nationally representative sample of 2,210 adults.

In addition to an uptick in worry about inflation, the poll shows that more than half (51%) of adults are worried about a potential loss of income.

Hispanic adults (66%), mothers (65%), millennials (63%), and genZers (62%) are among the groups most likely to be concerned about income loss.

“Stress is not good for health, mental or physical. So, while it’s a reality that Americans are faced with finding ways of making ends meet, it’s more important than ever to make sure that we are all accessing the care that we need,” said Dr. Brendel.

“People should be aware that there may be low- or no-cost options such as community mental health centers or employer-sponsored resources to address mental health concerns,” she added.
 

Coping with traumatic events

The latest poll also shows that about one-third of adults are worried about gun violence (35% overall, 47% among genZers) or a natural disaster (29%) personally affecting them.

Climate change anxiety is also up slightly in June, compared with May (+4%).

The same goes for mid-term election-related anxiety (+3%) – particularly among Democrats (54% vs. 59%) compared with Republicans (48% vs. 48%).

The latest poll provides insight how Americans would cope after a traumatic event. More adults report they will turn to family and friends for support (60%) than practice self-care (42%), speak openly about their feelings (37%), or seek help from a professional (31%). Nearly one-third (30%) say they will move on from it and not dwell on their feelings.

GenZers are the least likely to say they will speak openly about their feelings (29%) and are less likely than millennials to say they would speak to a health professional (28% vs. 38%).

“While many people show resilience, it’s troubling that most Americans wouldn’t speak openly about their feelings after a traumatic event,” APA CEO and Medical Director Saul Levin, MD, said in the news release.

“In many ways, naming feelings is the most important step toward healing, and this reluctance to air our thoughts may indicate that mental health stigma is still a powerful force in our society,” Dr. Levin said.

After a traumatic current event, 41% of Americans say they consume more news and 30% say they take in more social media, but the majority say this does not impact their mental health, the poll shows.

Two in five adults (43%) say the news of a traumatic event makes them feel more informed, 32% say it makes them feel more anxious, and about one-quarter say it makes them feel overwhelmed (27%) or discouraged (24%).

Dr. Brendel noted that, after a traumatic event, “it’s expected that people may experience anxiety or other symptoms for brief periods of time. However, no two people experience things the same way. If symptoms don’t go away, are overwhelming, or get worse over time, for example, it’s critical to seek help right away.”

The June poll shows that 50% of Americans are anxious about the future of reproductive rights but the poll was conducted before the Dobbs ruling.

Anxiety around COVID-19 continues to ease, with about 47% of Americans saying they are concerned about the pandemic, down 2% among all Americans and 16% among Black Americans since May.

The APA’s Healthy Minds Monthly tracks timely mental health issues throughout the year. The APA also releases its annual Healthy Minds Poll each May in conjunction with Mental Health Awareness Month.

A version of this article first appeared on Medscape.com.

When I began in private practice several eons ago, I employed only registered nurses (RNs) and licensed practical nurses (LPNs) in my office – as did, I think, most other physicians.

That is still the preferred way to go from an efficiency perspective, as well as the ability to delegate such tasks as blood collection and administering intramuscular injections. Unfortunately, the current state of medical practice – driven by payment reform, regulatory changes, technology costs, inflation, and other factors – has forced most independent practitioners to pivot from RNs and LPNs to medical assistants in a majority of situations.

Given this reality, it makes sense to understand how the use of medical assistants has changed private medical practice, and how the most effective MAs manage their roles and maximize their efficiency in the office.

A recent article by two physicians at the University of Michigan, Ann Arbor, is one of the few published papers to address this issue. It presents the results of a cross-sectional study examining the MA’s experience and key factors that enhance or reduce efficiencies.

The authors sent an email survey to 86 MAs working in six clinics within the department of family medicine at the University of Michigan Medical Center, and received responses from 75 of them, including 61 who completed the entire survey. They then singled out 18 individuals deemed “most efficient” by their peers and conducted face-to-face interviews with them.

The surveys and interviews looked at how MAs identified personal strategies for efficiency, dealt with barriers to implementing those strategies, and navigated interoffice relationships, as well as how all of this affected overall job satisfaction.

All 61 respondents who completed the full survey agreed that the MA role was “very important to keep the clinic functioning” and nearly all said that working in health care was “a calling” for them. About half agreed that their work was very stressful, and about the same percentage reported that there was inadequate MA staffing at their clinic. Others complained of limited pay and promotion opportunities.

The surveyed MAs described important work values that increased their efficiency. These included good communication, strong teamwork, and workload sharing, as well as individual strategies such as multitasking, limiting patient conversations, and completing tasks in a consistent way to improve accuracy.

Other strategies identified as contributing to an efficient operation included preclinic huddles, reviews of patient records before the patient’s arrival, and completing routine office duties before the start of office hours.

Respondents were then asked to identify barriers to clinic efficiency, and most of them involved physicians who barked orders at them, did not complete paperwork or sign orders in a timely manner, and agreed to see late-arriving patients. Some MAs suggested that physicians refrain from “talking down” to them, and teach rather than criticize. They also faulted decisions affecting patient flow made by other staffers without soliciting the MAs’ input.

Despite these barriers, the authors found that most of the surveyed MAs agreed that their work was valued by doctors. “Proper training of managers to provide ... support and ensure equitable workloads may be one strategy to ensure that staff members feel the workplace is fair and collegial,” they said.

“Many described the working relationships with physicians as critical to their satisfaction at work and indicated that strong partnerships motivated them to do their best to make the physician’s day easier,” they added.

At the same time, the authors noted that most survey subjects reported that their jobs were “stressful,” and believed that their stress went underrecognized by physicians. They argued that “it’s important for physicians to be cognizant of these patterns and clinic culture, as reducing a hierarchy-based environment will be appreciated by MAs.”

Since this study involved only MAs in a family practice setting, further studies will be needed to determine whether these results translate to specialty offices – and whether the unique issues inherent in various specialty environments elicit different efficiency contributors and barriers.

Overall, though, “staff job satisfaction is linked to improved quality of care, so treating staff well contributes to high-value care for patients,” the authors wrote. “Disseminating practices that staff members themselves have identified as effective, and being attentive to how staff members are treated, may increase individual efficiency while improving staff retention and satisfaction.”

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].

When I began in private practice several eons ago, I employed only registered nurses (RNs) and licensed practical nurses (LPNs) in my office – as did, I think, most other physicians.

That is still the preferred way to go from an efficiency perspective, as well as the ability to delegate such tasks as blood collection and administering intramuscular injections. Unfortunately, the current state of medical practice – driven by payment reform, regulatory changes, technology costs, inflation, and other factors – has forced most independent practitioners to pivot from RNs and LPNs to medical assistants in a majority of situations.

Given this reality, it makes sense to understand how the use of medical assistants has changed private medical practice, and how the most effective MAs manage their roles and maximize their efficiency in the office.

A recent article by two physicians at the University of Michigan, Ann Arbor, is one of the few published papers to address this issue. It presents the results of a cross-sectional study examining the MA’s experience and key factors that enhance or reduce efficiencies.

The authors sent an email survey to 86 MAs working in six clinics within the department of family medicine at the University of Michigan Medical Center, and received responses from 75 of them, including 61 who completed the entire survey. They then singled out 18 individuals deemed “most efficient” by their peers and conducted face-to-face interviews with them.

The surveys and interviews looked at how MAs identified personal strategies for efficiency, dealt with barriers to implementing those strategies, and navigated interoffice relationships, as well as how all of this affected overall job satisfaction.

All 61 respondents who completed the full survey agreed that the MA role was “very important to keep the clinic functioning” and nearly all said that working in health care was “a calling” for them. About half agreed that their work was very stressful, and about the same percentage reported that there was inadequate MA staffing at their clinic. Others complained of limited pay and promotion opportunities.

The surveyed MAs described important work values that increased their efficiency. These included good communication, strong teamwork, and workload sharing, as well as individual strategies such as multitasking, limiting patient conversations, and completing tasks in a consistent way to improve accuracy.

Other strategies identified as contributing to an efficient operation included preclinic huddles, reviews of patient records before the patient’s arrival, and completing routine office duties before the start of office hours.

Respondents were then asked to identify barriers to clinic efficiency, and most of them involved physicians who barked orders at them, did not complete paperwork or sign orders in a timely manner, and agreed to see late-arriving patients. Some MAs suggested that physicians refrain from “talking down” to them, and teach rather than criticize. They also faulted decisions affecting patient flow made by other staffers without soliciting the MAs’ input.

Despite these barriers, the authors found that most of the surveyed MAs agreed that their work was valued by doctors. “Proper training of managers to provide ... support and ensure equitable workloads may be one strategy to ensure that staff members feel the workplace is fair and collegial,” they said.

“Many described the working relationships with physicians as critical to their satisfaction at work and indicated that strong partnerships motivated them to do their best to make the physician’s day easier,” they added.

At the same time, the authors noted that most survey subjects reported that their jobs were “stressful,” and believed that their stress went underrecognized by physicians. They argued that “it’s important for physicians to be cognizant of these patterns and clinic culture, as reducing a hierarchy-based environment will be appreciated by MAs.”

Since this study involved only MAs in a family practice setting, further studies will be needed to determine whether these results translate to specialty offices – and whether the unique issues inherent in various specialty environments elicit different efficiency contributors and barriers.

Overall, though, “staff job satisfaction is linked to improved quality of care, so treating staff well contributes to high-value care for patients,” the authors wrote. “Disseminating practices that staff members themselves have identified as effective, and being attentive to how staff members are treated, may increase individual efficiency while improving staff retention and satisfaction.”

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].

When I began in private practice several eons ago, I employed only registered nurses (RNs) and licensed practical nurses (LPNs) in my office – as did, I think, most other physicians.

That is still the preferred way to go from an efficiency perspective, as well as the ability to delegate such tasks as blood collection and administering intramuscular injections. Unfortunately, the current state of medical practice – driven by payment reform, regulatory changes, technology costs, inflation, and other factors – has forced most independent practitioners to pivot from RNs and LPNs to medical assistants in a majority of situations.

Given this reality, it makes sense to understand how the use of medical assistants has changed private medical practice, and how the most effective MAs manage their roles and maximize their efficiency in the office.

A recent article by two physicians at the University of Michigan, Ann Arbor, is one of the few published papers to address this issue. It presents the results of a cross-sectional study examining the MA’s experience and key factors that enhance or reduce efficiencies.

The authors sent an email survey to 86 MAs working in six clinics within the department of family medicine at the University of Michigan Medical Center, and received responses from 75 of them, including 61 who completed the entire survey. They then singled out 18 individuals deemed “most efficient” by their peers and conducted face-to-face interviews with them.

The surveys and interviews looked at how MAs identified personal strategies for efficiency, dealt with barriers to implementing those strategies, and navigated interoffice relationships, as well as how all of this affected overall job satisfaction.

All 61 respondents who completed the full survey agreed that the MA role was “very important to keep the clinic functioning” and nearly all said that working in health care was “a calling” for them. About half agreed that their work was very stressful, and about the same percentage reported that there was inadequate MA staffing at their clinic. Others complained of limited pay and promotion opportunities.

The surveyed MAs described important work values that increased their efficiency. These included good communication, strong teamwork, and workload sharing, as well as individual strategies such as multitasking, limiting patient conversations, and completing tasks in a consistent way to improve accuracy.

Other strategies identified as contributing to an efficient operation included preclinic huddles, reviews of patient records before the patient’s arrival, and completing routine office duties before the start of office hours.

Respondents were then asked to identify barriers to clinic efficiency, and most of them involved physicians who barked orders at them, did not complete paperwork or sign orders in a timely manner, and agreed to see late-arriving patients. Some MAs suggested that physicians refrain from “talking down” to them, and teach rather than criticize. They also faulted decisions affecting patient flow made by other staffers without soliciting the MAs’ input.

Despite these barriers, the authors found that most of the surveyed MAs agreed that their work was valued by doctors. “Proper training of managers to provide ... support and ensure equitable workloads may be one strategy to ensure that staff members feel the workplace is fair and collegial,” they said.

“Many described the working relationships with physicians as critical to their satisfaction at work and indicated that strong partnerships motivated them to do their best to make the physician’s day easier,” they added.

At the same time, the authors noted that most survey subjects reported that their jobs were “stressful,” and believed that their stress went underrecognized by physicians. They argued that “it’s important for physicians to be cognizant of these patterns and clinic culture, as reducing a hierarchy-based environment will be appreciated by MAs.”

Since this study involved only MAs in a family practice setting, further studies will be needed to determine whether these results translate to specialty offices – and whether the unique issues inherent in various specialty environments elicit different efficiency contributors and barriers.

Overall, though, “staff job satisfaction is linked to improved quality of care, so treating staff well contributes to high-value care for patients,” the authors wrote. “Disseminating practices that staff members themselves have identified as effective, and being attentive to how staff members are treated, may increase individual efficiency while improving staff retention and satisfaction.”

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].

Walking 10,000 steps per day may reduce the risk of death for those who have trouble regulating their blood sugar, according to the findings from a study of almost 1,700 American adults with prediabetes or diabetes.

Researchers from the University of Seville, Spain, evaluated U.S. adults with prediabetes and diabetes using data from the Centers for Disease Control and Prevention’s National Health and Nutrition Examination Survey, collected between 2005 and 2006.

The findings were published this month in Diabetes Care.

Ariel Skelley/Getty Images

Of the total, 1,194 adults had prediabetes, and 493 had diabetes. People with diabetes in the study were diagnosed by a doctor or had a fasting blood glucose level higher than 126 mg/dL. People with prediabetes in the study were also diagnosed by a doctor or had a fasting glucose level from 100 to 125 mg/dL.

Over half (56%) of prediabetic adults were male (average age 55 years), and they took an average of 8,500 steps per day. Half (51%) of the diabetic adults were also male (average age 61 years), and they took fewer steps per day – about 6,300.

The people in the study wore an accelerometer on their waist to count their steps for 7 consecutive days. The researchers adjusted for age, sex, ethnicity, smoking, alcohol use, diet, and use of diabetes medications.

Over 9 years, 200 people with prediabetes and 138 with diabetes died. Based on those who survived after follow-up, walking nearly 10,000 steps per day was best for reducing the risk of death from any cause for people with prediabetes and diabetes.

But about 20% of people in the study were removed from the analysis because they had invalid accelerometry data. Adults who are healthy enough to walk 10,000 steps may have different rates of death from those who aren’t, according to the study authors, who called for more research to compare these two groups.

If 10,000 steps seem like a daunting task, talking to a doctor about finding a routine that works for your physical ability could be helpful, the study authors suggest.

A version of this article first appeared on Medscape.com.

Walking 10,000 steps per day may reduce the risk of death for those who have trouble regulating their blood sugar, according to the findings from a study of almost 1,700 American adults with prediabetes or diabetes.

Researchers from the University of Seville, Spain, evaluated U.S. adults with prediabetes and diabetes using data from the Centers for Disease Control and Prevention’s National Health and Nutrition Examination Survey, collected between 2005 and 2006.

The findings were published this month in Diabetes Care.

Ariel Skelley/Getty Images

Of the total, 1,194 adults had prediabetes, and 493 had diabetes. People with diabetes in the study were diagnosed by a doctor or had a fasting blood glucose level higher than 126 mg/dL. People with prediabetes in the study were also diagnosed by a doctor or had a fasting glucose level from 100 to 125 mg/dL.

Over half (56%) of prediabetic adults were male (average age 55 years), and they took an average of 8,500 steps per day. Half (51%) of the diabetic adults were also male (average age 61 years), and they took fewer steps per day – about 6,300.

The people in the study wore an accelerometer on their waist to count their steps for 7 consecutive days. The researchers adjusted for age, sex, ethnicity, smoking, alcohol use, diet, and use of diabetes medications.

Over 9 years, 200 people with prediabetes and 138 with diabetes died. Based on those who survived after follow-up, walking nearly 10,000 steps per day was best for reducing the risk of death from any cause for people with prediabetes and diabetes.

But about 20% of people in the study were removed from the analysis because they had invalid accelerometry data. Adults who are healthy enough to walk 10,000 steps may have different rates of death from those who aren’t, according to the study authors, who called for more research to compare these two groups.

If 10,000 steps seem like a daunting task, talking to a doctor about finding a routine that works for your physical ability could be helpful, the study authors suggest.

A version of this article first appeared on Medscape.com.

Walking 10,000 steps per day may reduce the risk of death for those who have trouble regulating their blood sugar, according to the findings from a study of almost 1,700 American adults with prediabetes or diabetes.

Researchers from the University of Seville, Spain, evaluated U.S. adults with prediabetes and diabetes using data from the Centers for Disease Control and Prevention’s National Health and Nutrition Examination Survey, collected between 2005 and 2006.

The findings were published this month in Diabetes Care.

Ariel Skelley/Getty Images

Of the total, 1,194 adults had prediabetes, and 493 had diabetes. People with diabetes in the study were diagnosed by a doctor or had a fasting blood glucose level higher than 126 mg/dL. People with prediabetes in the study were also diagnosed by a doctor or had a fasting glucose level from 100 to 125 mg/dL.

Over half (56%) of prediabetic adults were male (average age 55 years), and they took an average of 8,500 steps per day. Half (51%) of the diabetic adults were also male (average age 61 years), and they took fewer steps per day – about 6,300.

The people in the study wore an accelerometer on their waist to count their steps for 7 consecutive days. The researchers adjusted for age, sex, ethnicity, smoking, alcohol use, diet, and use of diabetes medications.

Over 9 years, 200 people with prediabetes and 138 with diabetes died. Based on those who survived after follow-up, walking nearly 10,000 steps per day was best for reducing the risk of death from any cause for people with prediabetes and diabetes.

But about 20% of people in the study were removed from the analysis because they had invalid accelerometry data. Adults who are healthy enough to walk 10,000 steps may have different rates of death from those who aren’t, according to the study authors, who called for more research to compare these two groups.

If 10,000 steps seem like a daunting task, talking to a doctor about finding a routine that works for your physical ability could be helpful, the study authors suggest.

A version of this article first appeared on Medscape.com.

MUSCATINE, IOWA – Bailee Tordai, who was 33 weeks into her pregnancy, barely made it to the prenatal checkup. Her clunky old Jeep couldn’t complete the 2-mile trip from her house to the University of Iowa’s outreach clinic in her southeastern Iowa hometown. It was a hot June day, and a wiring problem made the Jeep conk out in the street.

A passerby helped Ms.Tordai, 22, push her stricken vehicle off the road and into a parking lot. Then she called her stepdad for a ride to the clinic.

Jaclyn Roman, a nurse-midwife, walked into the exam room. “I heard your car broke down.”

“Yup. You want to buy it? Five bucks!” Ms. Tordai joked.

Her lack of reliable transportation won’t be a laughing matter in August, when her baby is due. She will need to arrange for someone to drive her about 40 miles northwest to the University of Iowa Hospitals and Clinics in Iowa City. She can’t give birth at Muscatine’s hospital because it shuttered its birthing unit in 2020.

Ms. Roman is part of an unusual effort to minimize the harm caused by such closures. She’s one of 11 certified nurse-midwives from the University of Iowa who travel regularly to Muscatine and Washington, another southeastern Iowa town where the local hospital closed its birthing unit. The university’s pilot project, which is supported by a federal grant, doesn’t aim to reopen shuttered birthing units. Instead, the midwife team helps ensure area women receive related services. Last year, it served more than 500 patients in Muscatine and Washington.

Muscatine is one of hundreds of rural areas in the United States where hospitals have dropped birthing services during the past 2 decades, often because they lack obstetricians and other specialized staff members.

Hospital industry leaders say birthing units also tend to lose money, largely because of low payments from Medicaid, the public health insurance program that covers more than 40% of births in the United States and an even greater share in many rural areas.

The loss of labor-and-delivery services hits especially hard for women who lack resources and time to travel for care.

Muscatine, which is on the Mississippi River, has more than 23,000 residents, making it a relatively large town by Iowa standards. But its hospital is one of 41 Iowa facilities that have closed their birthing units since 2000, according to the Iowa Department of Public Health. Most were in rural areas. Just one has reopened, and only 56 Iowa hospitals now have birthing units.

The nurse-midwife team’s work includes crucial prenatal checkups. Most pregnant people are supposed to have a dozen or more such appointments before giving birth. Health care providers use the checkups to track how a pregnancy is progressing and to watch for signs of high blood pressure and other problems that can lead to premature births, stillbirths, or even maternal deaths. The midwives also advise women on how to keep themselves and their babies healthy after birth.

Karen Jefferson, DM, director of midwifery practice for the American College of Nurse-Midwives, said the University of Iowa team’s approach is an innovative way to address needs in rural areas that have lost hospital birthing units. “How wonderful would it be to see a provider in your town, instead of driving 40 miles for your prenatal visits – especially toward the end of pregnancy, when you’re going every week,” said Dr. Jefferson, who lives in rural New York.

Midwives can provide many other types of care for women and for babies. In theory, they could even open rural birthing centers outside of hospitals, Dr. Jefferson said. But they would need to overcome concerns about financing and about the availability of surgeons to do emergency cesarean sections, which she said are rarely needed in low-risk births.

The University of Iowa midwives focus on low-risk pregnancies, referring patients with significant health issues to physician specialists in Iowa City. Often, those specialists can visit with the patients and the midwives via video conference in the small-town clinics.

The loss of a hospital obstetrics unit can make finding local maternity care harder for rural families.

Ms. Tordai can attest that if patients must travel far for prenatal appointments, they’re less likely to get to them all. If she had to go to Iowa City for each of hers, repeatedly taking 3 hours off from her job managing a pizza restaurant would be tough, she said. On that June day her Jeep broke down, she would have canceled her appointment.

Instead, she wound up on an exam table at the Muscatine clinic listening to her baby’s heartbeat on a monitor and watching as Ms. Roman measured her belly.

“Nice job being perfect,” the midwife told her during the checkup.

Ms. Roman asked Ms. Tordai to describe her baby’s movements. “Constant,” she replied with a smile.

Ms. Roman asked whether she planned to breastfeed. Ms. Tordai said she didn’t have much luck with her first daughter, Aspen, now 4.

“Have you thought about a breastfeeding class?” the midwife asked.

“I don’t have time for that,” Ms. Tordai replied. Ms. Roman continued to coax her, noting where a breastfeeding class is available online.

Near the end of the appointment, Ms. Tordai asked Ms. Roman whether she could schedule an induced birth at the University of Iowa hospital. The midwife told her that, in general, letting labor begin on its own is better than artificially starting it.

But there was the matter of unreliable transportation. Ms. Tordai explained that scheduling the birth would help her arrange to have her mother drive her to the hospital in Iowa City. Ms. Roman agreed that transportation is a legitimate reason and arranged for an induced labor on Aug. 10.

The University of Iowa midwife team started offering services in 2020 in a clinic about 2 miles from Trinity Muscatine hospital. The hospital is owned by UnityPoint Health, a large nonprofit hospital system that blamed a lack of available obstetricians for the closure of the Muscatine birthing unit. At the time, UnityPoint leaders said they hoped to reopen the unit if they could recruit new obstetricians to the area.

Kristy Phillipson, a UnityPoint Health spokesperson, told KHN in June that the company has continued to try to recruit physicians, including for the Muscatine hospital. Although it has not reopened the birthing unit, the company regularly sends an obstetrician and other staff members to provide prenatal care and related services, she said.

Most pregnant patients from the area who choose UnityPoint for their care wind up giving birth at the system’s hospital in Bettendorf, a 45-minute drive to the east.

The University of Iowa midwife team has no plans to open its own birthing centers, but it hopes to expand its rural clinic service to other underserved towns. To do so, the university would need to hire more nurse-midwives, which could be a challenge. According to the Iowa Board of Nursing, 120 licensed nurse-midwives live in the state of 3 million people.

The University of Iowa plans to address that by starting the state’s first nurse-midwife training program in 2023. The master’s degree program, which will emphasize rural service, will train registered nurses to become nurse-midwives. It eventually could graduate eight people per year, said Amber Goodrich, a University of Iowa midwife helping lead the effort.

Those graduates could fill gaps throughout rural areas, where even more hospitals may shutter their birthing units in the coming years.

“This crisis is going nowhere fast,” Ms. Goodrich said.

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

MUSCATINE, IOWA – Bailee Tordai, who was 33 weeks into her pregnancy, barely made it to the prenatal checkup. Her clunky old Jeep couldn’t complete the 2-mile trip from her house to the University of Iowa’s outreach clinic in her southeastern Iowa hometown. It was a hot June day, and a wiring problem made the Jeep conk out in the street.

A passerby helped Ms.Tordai, 22, push her stricken vehicle off the road and into a parking lot. Then she called her stepdad for a ride to the clinic.

Jaclyn Roman, a nurse-midwife, walked into the exam room. “I heard your car broke down.”

“Yup. You want to buy it? Five bucks!” Ms. Tordai joked.

Her lack of reliable transportation won’t be a laughing matter in August, when her baby is due. She will need to arrange for someone to drive her about 40 miles northwest to the University of Iowa Hospitals and Clinics in Iowa City. She can’t give birth at Muscatine’s hospital because it shuttered its birthing unit in 2020.

Ms. Roman is part of an unusual effort to minimize the harm caused by such closures. She’s one of 11 certified nurse-midwives from the University of Iowa who travel regularly to Muscatine and Washington, another southeastern Iowa town where the local hospital closed its birthing unit. The university’s pilot project, which is supported by a federal grant, doesn’t aim to reopen shuttered birthing units. Instead, the midwife team helps ensure area women receive related services. Last year, it served more than 500 patients in Muscatine and Washington.

Muscatine is one of hundreds of rural areas in the United States where hospitals have dropped birthing services during the past 2 decades, often because they lack obstetricians and other specialized staff members.

Hospital industry leaders say birthing units also tend to lose money, largely because of low payments from Medicaid, the public health insurance program that covers more than 40% of births in the United States and an even greater share in many rural areas.

The loss of labor-and-delivery services hits especially hard for women who lack resources and time to travel for care.

Muscatine, which is on the Mississippi River, has more than 23,000 residents, making it a relatively large town by Iowa standards. But its hospital is one of 41 Iowa facilities that have closed their birthing units since 2000, according to the Iowa Department of Public Health. Most were in rural areas. Just one has reopened, and only 56 Iowa hospitals now have birthing units.

The nurse-midwife team’s work includes crucial prenatal checkups. Most pregnant people are supposed to have a dozen or more such appointments before giving birth. Health care providers use the checkups to track how a pregnancy is progressing and to watch for signs of high blood pressure and other problems that can lead to premature births, stillbirths, or even maternal deaths. The midwives also advise women on how to keep themselves and their babies healthy after birth.

Karen Jefferson, DM, director of midwifery practice for the American College of Nurse-Midwives, said the University of Iowa team’s approach is an innovative way to address needs in rural areas that have lost hospital birthing units. “How wonderful would it be to see a provider in your town, instead of driving 40 miles for your prenatal visits – especially toward the end of pregnancy, when you’re going every week,” said Dr. Jefferson, who lives in rural New York.

Midwives can provide many other types of care for women and for babies. In theory, they could even open rural birthing centers outside of hospitals, Dr. Jefferson said. But they would need to overcome concerns about financing and about the availability of surgeons to do emergency cesarean sections, which she said are rarely needed in low-risk births.

The University of Iowa midwives focus on low-risk pregnancies, referring patients with significant health issues to physician specialists in Iowa City. Often, those specialists can visit with the patients and the midwives via video conference in the small-town clinics.

The loss of a hospital obstetrics unit can make finding local maternity care harder for rural families.

Ms. Tordai can attest that if patients must travel far for prenatal appointments, they’re less likely to get to them all. If she had to go to Iowa City for each of hers, repeatedly taking 3 hours off from her job managing a pizza restaurant would be tough, she said. On that June day her Jeep broke down, she would have canceled her appointment.

Instead, she wound up on an exam table at the Muscatine clinic listening to her baby’s heartbeat on a monitor and watching as Ms. Roman measured her belly.

“Nice job being perfect,” the midwife told her during the checkup.

Ms. Roman asked Ms. Tordai to describe her baby’s movements. “Constant,” she replied with a smile.

Ms. Roman asked whether she planned to breastfeed. Ms. Tordai said she didn’t have much luck with her first daughter, Aspen, now 4.

“Have you thought about a breastfeeding class?” the midwife asked.

“I don’t have time for that,” Ms. Tordai replied. Ms. Roman continued to coax her, noting where a breastfeeding class is available online.

Near the end of the appointment, Ms. Tordai asked Ms. Roman whether she could schedule an induced birth at the University of Iowa hospital. The midwife told her that, in general, letting labor begin on its own is better than artificially starting it.

But there was the matter of unreliable transportation. Ms. Tordai explained that scheduling the birth would help her arrange to have her mother drive her to the hospital in Iowa City. Ms. Roman agreed that transportation is a legitimate reason and arranged for an induced labor on Aug. 10.

The University of Iowa midwife team started offering services in 2020 in a clinic about 2 miles from Trinity Muscatine hospital. The hospital is owned by UnityPoint Health, a large nonprofit hospital system that blamed a lack of available obstetricians for the closure of the Muscatine birthing unit. At the time, UnityPoint leaders said they hoped to reopen the unit if they could recruit new obstetricians to the area.

Kristy Phillipson, a UnityPoint Health spokesperson, told KHN in June that the company has continued to try to recruit physicians, including for the Muscatine hospital. Although it has not reopened the birthing unit, the company regularly sends an obstetrician and other staff members to provide prenatal care and related services, she said.

Most pregnant patients from the area who choose UnityPoint for their care wind up giving birth at the system’s hospital in Bettendorf, a 45-minute drive to the east.

The University of Iowa midwife team has no plans to open its own birthing centers, but it hopes to expand its rural clinic service to other underserved towns. To do so, the university would need to hire more nurse-midwives, which could be a challenge. According to the Iowa Board of Nursing, 120 licensed nurse-midwives live in the state of 3 million people.

The University of Iowa plans to address that by starting the state’s first nurse-midwife training program in 2023. The master’s degree program, which will emphasize rural service, will train registered nurses to become nurse-midwives. It eventually could graduate eight people per year, said Amber Goodrich, a University of Iowa midwife helping lead the effort.

Those graduates could fill gaps throughout rural areas, where even more hospitals may shutter their birthing units in the coming years.

“This crisis is going nowhere fast,” Ms. Goodrich said.

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

MUSCATINE, IOWA – Bailee Tordai, who was 33 weeks into her pregnancy, barely made it to the prenatal checkup. Her clunky old Jeep couldn’t complete the 2-mile trip from her house to the University of Iowa’s outreach clinic in her southeastern Iowa hometown. It was a hot June day, and a wiring problem made the Jeep conk out in the street.

A passerby helped Ms.Tordai, 22, push her stricken vehicle off the road and into a parking lot. Then she called her stepdad for a ride to the clinic.

Jaclyn Roman, a nurse-midwife, walked into the exam room. “I heard your car broke down.”

“Yup. You want to buy it? Five bucks!” Ms. Tordai joked.

Her lack of reliable transportation won’t be a laughing matter in August, when her baby is due. She will need to arrange for someone to drive her about 40 miles northwest to the University of Iowa Hospitals and Clinics in Iowa City. She can’t give birth at Muscatine’s hospital because it shuttered its birthing unit in 2020.

Ms. Roman is part of an unusual effort to minimize the harm caused by such closures. She’s one of 11 certified nurse-midwives from the University of Iowa who travel regularly to Muscatine and Washington, another southeastern Iowa town where the local hospital closed its birthing unit. The university’s pilot project, which is supported by a federal grant, doesn’t aim to reopen shuttered birthing units. Instead, the midwife team helps ensure area women receive related services. Last year, it served more than 500 patients in Muscatine and Washington.

Muscatine is one of hundreds of rural areas in the United States where hospitals have dropped birthing services during the past 2 decades, often because they lack obstetricians and other specialized staff members.

Hospital industry leaders say birthing units also tend to lose money, largely because of low payments from Medicaid, the public health insurance program that covers more than 40% of births in the United States and an even greater share in many rural areas.

The loss of labor-and-delivery services hits especially hard for women who lack resources and time to travel for care.

Muscatine, which is on the Mississippi River, has more than 23,000 residents, making it a relatively large town by Iowa standards. But its hospital is one of 41 Iowa facilities that have closed their birthing units since 2000, according to the Iowa Department of Public Health. Most were in rural areas. Just one has reopened, and only 56 Iowa hospitals now have birthing units.

The nurse-midwife team’s work includes crucial prenatal checkups. Most pregnant people are supposed to have a dozen or more such appointments before giving birth. Health care providers use the checkups to track how a pregnancy is progressing and to watch for signs of high blood pressure and other problems that can lead to premature births, stillbirths, or even maternal deaths. The midwives also advise women on how to keep themselves and their babies healthy after birth.

Karen Jefferson, DM, director of midwifery practice for the American College of Nurse-Midwives, said the University of Iowa team’s approach is an innovative way to address needs in rural areas that have lost hospital birthing units. “How wonderful would it be to see a provider in your town, instead of driving 40 miles for your prenatal visits – especially toward the end of pregnancy, when you’re going every week,” said Dr. Jefferson, who lives in rural New York.

Midwives can provide many other types of care for women and for babies. In theory, they could even open rural birthing centers outside of hospitals, Dr. Jefferson said. But they would need to overcome concerns about financing and about the availability of surgeons to do emergency cesarean sections, which she said are rarely needed in low-risk births.

The University of Iowa midwives focus on low-risk pregnancies, referring patients with significant health issues to physician specialists in Iowa City. Often, those specialists can visit with the patients and the midwives via video conference in the small-town clinics.

The loss of a hospital obstetrics unit can make finding local maternity care harder for rural families.

Ms. Tordai can attest that if patients must travel far for prenatal appointments, they’re less likely to get to them all. If she had to go to Iowa City for each of hers, repeatedly taking 3 hours off from her job managing a pizza restaurant would be tough, she said. On that June day her Jeep broke down, she would have canceled her appointment.

Instead, she wound up on an exam table at the Muscatine clinic listening to her baby’s heartbeat on a monitor and watching as Ms. Roman measured her belly.

“Nice job being perfect,” the midwife told her during the checkup.

Ms. Roman asked Ms. Tordai to describe her baby’s movements. “Constant,” she replied with a smile.

Ms. Roman asked whether she planned to breastfeed. Ms. Tordai said she didn’t have much luck with her first daughter, Aspen, now 4.

“Have you thought about a breastfeeding class?” the midwife asked.

“I don’t have time for that,” Ms. Tordai replied. Ms. Roman continued to coax her, noting where a breastfeeding class is available online.

Near the end of the appointment, Ms. Tordai asked Ms. Roman whether she could schedule an induced birth at the University of Iowa hospital. The midwife told her that, in general, letting labor begin on its own is better than artificially starting it.

But there was the matter of unreliable transportation. Ms. Tordai explained that scheduling the birth would help her arrange to have her mother drive her to the hospital in Iowa City. Ms. Roman agreed that transportation is a legitimate reason and arranged for an induced labor on Aug. 10.

The University of Iowa midwife team started offering services in 2020 in a clinic about 2 miles from Trinity Muscatine hospital. The hospital is owned by UnityPoint Health, a large nonprofit hospital system that blamed a lack of available obstetricians for the closure of the Muscatine birthing unit. At the time, UnityPoint leaders said they hoped to reopen the unit if they could recruit new obstetricians to the area.

Kristy Phillipson, a UnityPoint Health spokesperson, told KHN in June that the company has continued to try to recruit physicians, including for the Muscatine hospital. Although it has not reopened the birthing unit, the company regularly sends an obstetrician and other staff members to provide prenatal care and related services, she said.

Most pregnant patients from the area who choose UnityPoint for their care wind up giving birth at the system’s hospital in Bettendorf, a 45-minute drive to the east.

The University of Iowa midwife team has no plans to open its own birthing centers, but it hopes to expand its rural clinic service to other underserved towns. To do so, the university would need to hire more nurse-midwives, which could be a challenge. According to the Iowa Board of Nursing, 120 licensed nurse-midwives live in the state of 3 million people.

The University of Iowa plans to address that by starting the state’s first nurse-midwife training program in 2023. The master’s degree program, which will emphasize rural service, will train registered nurses to become nurse-midwives. It eventually could graduate eight people per year, said Amber Goodrich, a University of Iowa midwife helping lead the effort.

Those graduates could fill gaps throughout rural areas, where even more hospitals may shutter their birthing units in the coming years.

“This crisis is going nowhere fast,” Ms. Goodrich said.

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

The addition of social determinants of health (SDOH) to machine-learning risk-prediction models improved forecasts of in-hospital mortality in Black adults hospitalized for heart failure (HF) but didn’t show similar ability in non-Black patients, in a study based in part on the American Heart Association–sponsored Get with the Guidelines in Heart Failure (GWTG-HF) registry.

The novel risk-prediction tool bolstered by SDOH at the zip-code level – including household income, number of adults without a high-school degree, poverty and unemployment rates, and other factors – stratified risk more sharply in Black patients than more standard models, including some based on multivariable logistic regression.

“Traditional risk models that exist for heart failure assign lower risks to Black individuals if everything else is held constant,” Ambarish Pandey, MD, MSCS, University of Texas Southwestern Medical Center, Dallas, told this news organization.

“I think that is problematic, because if Black patients are considered lower risk, they may not get appropriate risk-based therapies that are being provided. We wanted to move away from this approach and use a more race-agnostic approach,” said Dr. Pandey, who is senior author on the study published  in JAMA Cardiology, with lead author Matthew W. Segar, MD, Texas Heart Institute, Houston.

The training dataset for the prediction model consisted of 123,634 patients hospitalized with HF (mean age, 71 years), of whom 47% were women, enrolled in the GWTG-HF registry from 2010 through 2020.

The machine-learning models showed “excellent performance” when applied to an internal subset cohort of 82,420 patients, with a C statistic of 0.81 for Black patients and 0.82 for non-Black patients, the authors report, and in a real-world cohort of 553,506 patients, with C statistics of 0.74 and 0.75, respectively. The models performed similarly well, they write, in an external validation cohort derived from the ARIC registry, with C statistics of 0.79 and 0.80, respectively.

The machine-learning models’ performance surpassed that of the GWTG-HF risk-score model, C statistics 0.69 for both Black and non-Black patients, and other logistic regression models in which race was a covariate, the authors state.

“We also observed significant race-specific differences in the population-attributable risk of in-hospital mortality associated with the SDOH, with a significantly greater contribution of these parameters to the overall in-hospital mortality risk in Black patients versus non-Black patients,” they write.

For Black patients, five of the SDOH parameters were among the top 20 covariate predictors of in-hospital mortality: mean income level, vacancy and unemployment rates, proportion of the population without a high school degree, and proportion older than 65 years. Together they accounted for 11.6% of population-attributable risk for in-hospital death.

Only one SDOH parameter – percentage of population older than 65 years – made the top 20 for non-Black patients, with a population-attributable risk of 0.5%, the group reports.

“I hope our work spurs future investigations to better understand how social determinants contribute to risk and how they can be incorporated in management of these patients,” Dr. Pandey said.

“I commend the authors for attempting to address SDOH as a potential contributor to some of the differences in outcomes among patients with heart failure,” writes Eldrin F. Lewis, MD, MPH, Stanford University School of Medicine, Palo Alto, Calif., in an accompanying editorial.

“It is imperative that we use these newer techniques to go beyond simply predicting which groups are at heightened risk and leverage the data to create solutions that will reduce those risks for the individual patient,” Dr. Lewis states.

“We should use these tools to reduce racial and ethnic differences in the operations of health care systems, potential bias in management decisions, and inactivity due to the difficulty in getting guideline-directed medical therapy into the hands of people who may have limited resources with minimal out-of-pocket costs,” he writes.

The models assessed in the current report “set a new bar for risk prediction: Integration of a comprehensive set of demographics, comorbidities, and social determinants with machine learning obviates race and ethnicity in risk prediction,” contend JAMA Cardiology deputy editor Clyde W. Yancy, MD, and associate editor Sadiya S. Khan, MD, both from Northwestern University Feinberg School of Medicine, Chicago, in an accompanying editor’s note.

“This more careful incorporation of individual-level, neighborhood-level, and hospital-level social factors,” they conclude, “is now a candidate template for future risk models.”

Dr. Pandey discloses grant funding from Applied Therapeutics and Gilead Sciences; consulting for or serving as an advisor to Tricog Health, Eli Lilly, Rivus, and Roche Diagnostics; receiving nonfinancial support from Pfizer and Merck; and research support from the Texas Health Resources Clinical Scholarship, the Gilead Sciences Research Scholar Program, the National Institute on Aging GEMSSTAR Grant, and Applied Therapeutics. Dr. Segar discloses receiving nonfinancial support from Pfizer and Merck. Other disclosures are in the report. Dr. Lewis reported no disclosures. Dr. Yancy and Dr. Khan had no relevant disclosures.

A version of this article first appeared on Medscape.com.

The addition of social determinants of health (SDOH) to machine-learning risk-prediction models improved forecasts of in-hospital mortality in Black adults hospitalized for heart failure (HF) but didn’t show similar ability in non-Black patients, in a study based in part on the American Heart Association–sponsored Get with the Guidelines in Heart Failure (GWTG-HF) registry.

The novel risk-prediction tool bolstered by SDOH at the zip-code level – including household income, number of adults without a high-school degree, poverty and unemployment rates, and other factors – stratified risk more sharply in Black patients than more standard models, including some based on multivariable logistic regression.

“Traditional risk models that exist for heart failure assign lower risks to Black individuals if everything else is held constant,” Ambarish Pandey, MD, MSCS, University of Texas Southwestern Medical Center, Dallas, told this news organization.

“I think that is problematic, because if Black patients are considered lower risk, they may not get appropriate risk-based therapies that are being provided. We wanted to move away from this approach and use a more race-agnostic approach,” said Dr. Pandey, who is senior author on the study published  in JAMA Cardiology, with lead author Matthew W. Segar, MD, Texas Heart Institute, Houston.

The training dataset for the prediction model consisted of 123,634 patients hospitalized with HF (mean age, 71 years), of whom 47% were women, enrolled in the GWTG-HF registry from 2010 through 2020.

The machine-learning models showed “excellent performance” when applied to an internal subset cohort of 82,420 patients, with a C statistic of 0.81 for Black patients and 0.82 for non-Black patients, the authors report, and in a real-world cohort of 553,506 patients, with C statistics of 0.74 and 0.75, respectively. The models performed similarly well, they write, in an external validation cohort derived from the ARIC registry, with C statistics of 0.79 and 0.80, respectively.

The machine-learning models’ performance surpassed that of the GWTG-HF risk-score model, C statistics 0.69 for both Black and non-Black patients, and other logistic regression models in which race was a covariate, the authors state.

“We also observed significant race-specific differences in the population-attributable risk of in-hospital mortality associated with the SDOH, with a significantly greater contribution of these parameters to the overall in-hospital mortality risk in Black patients versus non-Black patients,” they write.

For Black patients, five of the SDOH parameters were among the top 20 covariate predictors of in-hospital mortality: mean income level, vacancy and unemployment rates, proportion of the population without a high school degree, and proportion older than 65 years. Together they accounted for 11.6% of population-attributable risk for in-hospital death.

Only one SDOH parameter – percentage of population older than 65 years – made the top 20 for non-Black patients, with a population-attributable risk of 0.5%, the group reports.

“I hope our work spurs future investigations to better understand how social determinants contribute to risk and how they can be incorporated in management of these patients,” Dr. Pandey said.

“I commend the authors for attempting to address SDOH as a potential contributor to some of the differences in outcomes among patients with heart failure,” writes Eldrin F. Lewis, MD, MPH, Stanford University School of Medicine, Palo Alto, Calif., in an accompanying editorial.

“It is imperative that we use these newer techniques to go beyond simply predicting which groups are at heightened risk and leverage the data to create solutions that will reduce those risks for the individual patient,” Dr. Lewis states.

“We should use these tools to reduce racial and ethnic differences in the operations of health care systems, potential bias in management decisions, and inactivity due to the difficulty in getting guideline-directed medical therapy into the hands of people who may have limited resources with minimal out-of-pocket costs,” he writes.

The models assessed in the current report “set a new bar for risk prediction: Integration of a comprehensive set of demographics, comorbidities, and social determinants with machine learning obviates race and ethnicity in risk prediction,” contend JAMA Cardiology deputy editor Clyde W. Yancy, MD, and associate editor Sadiya S. Khan, MD, both from Northwestern University Feinberg School of Medicine, Chicago, in an accompanying editor’s note.

“This more careful incorporation of individual-level, neighborhood-level, and hospital-level social factors,” they conclude, “is now a candidate template for future risk models.”

Dr. Pandey discloses grant funding from Applied Therapeutics and Gilead Sciences; consulting for or serving as an advisor to Tricog Health, Eli Lilly, Rivus, and Roche Diagnostics; receiving nonfinancial support from Pfizer and Merck; and research support from the Texas Health Resources Clinical Scholarship, the Gilead Sciences Research Scholar Program, the National Institute on Aging GEMSSTAR Grant, and Applied Therapeutics. Dr. Segar discloses receiving nonfinancial support from Pfizer and Merck. Other disclosures are in the report. Dr. Lewis reported no disclosures. Dr. Yancy and Dr. Khan had no relevant disclosures.

A version of this article first appeared on Medscape.com.

The addition of social determinants of health (SDOH) to machine-learning risk-prediction models improved forecasts of in-hospital mortality in Black adults hospitalized for heart failure (HF) but didn’t show similar ability in non-Black patients, in a study based in part on the American Heart Association–sponsored Get with the Guidelines in Heart Failure (GWTG-HF) registry.

The novel risk-prediction tool bolstered by SDOH at the zip-code level – including household income, number of adults without a high-school degree, poverty and unemployment rates, and other factors – stratified risk more sharply in Black patients than more standard models, including some based on multivariable logistic regression.

“Traditional risk models that exist for heart failure assign lower risks to Black individuals if everything else is held constant,” Ambarish Pandey, MD, MSCS, University of Texas Southwestern Medical Center, Dallas, told this news organization.

“I think that is problematic, because if Black patients are considered lower risk, they may not get appropriate risk-based therapies that are being provided. We wanted to move away from this approach and use a more race-agnostic approach,” said Dr. Pandey, who is senior author on the study published  in JAMA Cardiology, with lead author Matthew W. Segar, MD, Texas Heart Institute, Houston.

The training dataset for the prediction model consisted of 123,634 patients hospitalized with HF (mean age, 71 years), of whom 47% were women, enrolled in the GWTG-HF registry from 2010 through 2020.

The machine-learning models showed “excellent performance” when applied to an internal subset cohort of 82,420 patients, with a C statistic of 0.81 for Black patients and 0.82 for non-Black patients, the authors report, and in a real-world cohort of 553,506 patients, with C statistics of 0.74 and 0.75, respectively. The models performed similarly well, they write, in an external validation cohort derived from the ARIC registry, with C statistics of 0.79 and 0.80, respectively.

The machine-learning models’ performance surpassed that of the GWTG-HF risk-score model, C statistics 0.69 for both Black and non-Black patients, and other logistic regression models in which race was a covariate, the authors state.

“We also observed significant race-specific differences in the population-attributable risk of in-hospital mortality associated with the SDOH, with a significantly greater contribution of these parameters to the overall in-hospital mortality risk in Black patients versus non-Black patients,” they write.

For Black patients, five of the SDOH parameters were among the top 20 covariate predictors of in-hospital mortality: mean income level, vacancy and unemployment rates, proportion of the population without a high school degree, and proportion older than 65 years. Together they accounted for 11.6% of population-attributable risk for in-hospital death.

Only one SDOH parameter – percentage of population older than 65 years – made the top 20 for non-Black patients, with a population-attributable risk of 0.5%, the group reports.

“I hope our work spurs future investigations to better understand how social determinants contribute to risk and how they can be incorporated in management of these patients,” Dr. Pandey said.

“I commend the authors for attempting to address SDOH as a potential contributor to some of the differences in outcomes among patients with heart failure,” writes Eldrin F. Lewis, MD, MPH, Stanford University School of Medicine, Palo Alto, Calif., in an accompanying editorial.

“It is imperative that we use these newer techniques to go beyond simply predicting which groups are at heightened risk and leverage the data to create solutions that will reduce those risks for the individual patient,” Dr. Lewis states.

“We should use these tools to reduce racial and ethnic differences in the operations of health care systems, potential bias in management decisions, and inactivity due to the difficulty in getting guideline-directed medical therapy into the hands of people who may have limited resources with minimal out-of-pocket costs,” he writes.

The models assessed in the current report “set a new bar for risk prediction: Integration of a comprehensive set of demographics, comorbidities, and social determinants with machine learning obviates race and ethnicity in risk prediction,” contend JAMA Cardiology deputy editor Clyde W. Yancy, MD, and associate editor Sadiya S. Khan, MD, both from Northwestern University Feinberg School of Medicine, Chicago, in an accompanying editor’s note.

“This more careful incorporation of individual-level, neighborhood-level, and hospital-level social factors,” they conclude, “is now a candidate template for future risk models.”

Dr. Pandey discloses grant funding from Applied Therapeutics and Gilead Sciences; consulting for or serving as an advisor to Tricog Health, Eli Lilly, Rivus, and Roche Diagnostics; receiving nonfinancial support from Pfizer and Merck; and research support from the Texas Health Resources Clinical Scholarship, the Gilead Sciences Research Scholar Program, the National Institute on Aging GEMSSTAR Grant, and Applied Therapeutics. Dr. Segar discloses receiving nonfinancial support from Pfizer and Merck. Other disclosures are in the report. Dr. Lewis reported no disclosures. Dr. Yancy and Dr. Khan had no relevant disclosures.

A version of this article first appeared on Medscape.com.

Medically reviewed by Jennifer Casarella, MD

Dan Miller has parked his Nissan Altima on the side of the road near a field outside Chicago and is holding a gun to his head. 

Haunted for years by the compounded trauma of tours of duty in the Middle East and his work as a police officer in Chicago, at that moment, Dr. Miller saw no reason to live. And there were troubles at home with his wife and children, who had grown fearful of his behavior.

“My whole world was falling apart,” he says of that dark night in 2014. “It left a hole I didn’t know how to fill.”

He chose not to pull the trigger after a brochure on the passenger seat of his car gave him an unexpected perspective – and launched him on a path to help others in his situation.

Had Mr. Miller taken his life that night, he would have joined thousands of other veterans who died by suicide. About 17 U.S. veterans lose their lives this way each day, on average, according to the Department of Veterans Affairs. In 2019, the last year for which records are available, 6,261 veterans took their own lives – and the suicide rate for veterans was 52% higher than for nonveterans, the agency’s records show. 

The problem has become so severe that the Veterans Health Administration now uses artificial intelligence (AI) to help identify veterans at the highest risk of suicide – and reach out to them before a crisis strikes.

But that wasn’t available when Dan Miller’s life was unraveling.

In the years leading up to his near-suicide, his wife had pushed him to get help. “She said, ‘You’re not the same person you were when you left. The kids are scared of you. The pets are scared of you,” he recalls.

He resisted, even when his wife threatened divorce. Rising through the ranks of the Marines, Mr. Miller had become more emotionally isolated. He feared losing his job and the respect of others if he let anyone know what he was going through.

Finally, he gave the VHA a chance. He went in for an initial consultation in 2010 and didn’t find it helpful. He didn’t like being told what to do. So he stopped. He turned to obsessive exercise and excessive drinking.

That day in 2014, Mr. Miller’s wife told him she was taking the kids out for a playdate. After she left, he was served with divorce papers. Less than an hour later, he was parked in his car with his gun, ready to end his life.

But if it all had happened just a few years later, things might never have gotten to that point.
 

Scanning for suicide risk

In 2017, the VHA piloted its AI program, called REACH VET, that aims to help prevent veterans from dying by suicide.

Every month, a computer scans the electronic health records of all VHA patients who’ve had a health care visit for any reason in the last 2 years. It checks more than 140 variables and weights them to estimate someone’s overall suicide risk at that moment in time.

To build the risk algorithm, a computer combed through the medical records of 6,360 veterans confirmed to have died by suicide between 2009 and 2011. (The VHA continually updates the list of variables from the health records of VHA patients, including those who have died by suicide since then and others.)

Some variables are things you’d expect:

• A past suicide attempt.
• A diagnosis of depression or other mental illness.
• A diagnosis of a terminal illness.

Others are more surprising. For example, a diagnosis of arthritis or diabetes adds weight.

REACH VET flags the riskiest cases – the top 0.1% – for a mental health or primary care provider to review. They reach out to the patient to tell them how and why their record was flagged, discuss any recommended treatment changes, and ask them to come in for a visit.

“It’s an opportunity to talk about their risk factors, which is designed to lead to a conversation about safety planning,” says clinical psychologist Matthew Miller, PhD, national director of the U.S. Department of Veterans Affairs’ Suicide Prevention Program. He’s not related to Dan Miller.

Making a suicide safety plan

A safety plan is a document that outlines how a person can help prevent their own suicide in a crisis. 

The plan may include:

• A list of personal triggers or warning signs.
• What’s helped them in the past.
• Names of people or organizations who can support them.
• Plans to remove means of suicide, such as guns, from their environment.
• Their reasons for living.

In people at risk for suicide, research shows that having a safety plan reduces suicidal thoughts and attempts, lowers rates of depression and hopelessness, and boosts veterans’ engagement with the health care system. It may also help people manage things that trigger their suicidal thoughts.
 

Getting the call

What if REACH VET had been around when Dan Miller was in crisis – and he’d gotten a call from the VHA?

“It absolutely, positively would have helped because one of the biggest things on that day when I got served was feeling completely alone and that I had no one to turn to,” Mr. Miller says. He’s now a speaker for the Wounded Warrior Project, a nonprofit that serves veterans and active-duty service people.

Vets’ reactions to the unexpected VHA phone call, psychologist Dr. Miller says, “run the gamut from ‘Thank you for contacting me. Let’s talk,’ to ‘What are you talking about? Leave me alone!’ ”

Nothing stops all suicides. But REACH VET is having an impact. In a clinical trial, vets contacted through REACH VET had more doctor visits, were more likely to have a written suicide prevention safety plan, and had fewer hospital admissions for mental health, ER visits, and suicide attempts.
 

An assist from AI

Even simple outreach can make a big difference. And there’s research to prove it.

One study included 4,730 veterans recently discharged from psychiatric care at the VHA, a group considered at high risk for suicide. 

Half of them got 13 caring emails from hospital staff in the weeks after leaving the hospital. The emails mentioned personal things the patient had shared, like a love of hiking, and wished them well. The other veterans got routine follow-up but no emails.

Two years later, those who got the caring emails were less likely to have died by suicide than the other vets. The study was published in 2014 in Contemporary Clinical Trials.

Researchers have done studies like this many times: with handwritten notes from the primary care doctor, postcards from the ER, and so forth. The results never vary: The notes reduce suicide risk.

“If we could use AI to identify people to receive notes or phone calls, it would be a very effective and inexpensive way to guide follow-up care,” says Rebecca Bernert, PhD, director and founder of the Suicide Prevention Research Laboratory at Stanford (Calif.) University.
 

AI doesn’t replace clinical judgment.

“AI can capture data that we miss due to the limits of our humanity,” psychologist Dr. Miller says. “There’s suicide prevention processes founded on big data and AI, and there are processes founded in clinical intuition and acumen.”

AI is only as good as the data it’s based on. If that data lacks diversity, it may miss things. And variables that apply to veterans may differ in civilians.
 

Stopping suicidal thoughts

Google is putting AI to work against suicide, too. Its MUM (Multitask Unified Model) technology seeks to understand the intent behind what we google.

MUM powers Google Search. It can often tell the difference between a search for information about suicide for someone writing a research paper on the topic and a search for information on how or where to carry out a suicide.

When Google Search detects that someone in the United States might be in crisis and at risk of suicide, the first search results that person gets are the number for the National Suicide Prevention Lifeline and other resources for people in crisis.

Google Home Assistant works in the same way. When a user makes a query that signals a suicide-related crisis, the gadget serves up resources that offer help.

MUM is working to understand the nuances of crisis language in 75 languages so that Google Search can provide people in crisis with hotlines or other resources in many countries.

“We want to find partners that are accessible to users in terms of hours of operation. We have a strong preference for finding partners that promise confidentiality and privacy to the extent that those are permitted [in that country],” says Anne Merritt, MD, a product manager at Google Search.

Other companies are working on apps that use AI to spot suicide risk in other ways, including voice technology that may notice subtle changes in the voice of someone who’s depressed and may be thinking of suicide. Those are still in development but show promise. Keep in mind that apps do not require government approval, so if you try one, be sure to let your health care provider know.
 

Changing the channel

Seeing a hotline number on your phone or computer screen can help, Dan Miller says. “If I happened to be online, searching maybe for a bridge to jump off of ... and suddenly that pops up on the screen, it’s like it changes the channel.”

It may not work for everyone, he says, but that search result could interrupt someone’s suicidal train of thought.

That’s crucial, psychologist Dr. Miller says, because most suicide attempts escalate from first thought to potentially fatal action in just 1 hour. That’s how fast it happened for Dan Miller in 2014.

“When you’re able to put time and space between the suicidal thought and the access to the method to act on that thought, you save lives,” Dr. Bernert says.
 

Making a different choice

An interruption in Mr. Miller’s thinking is what had saved his life.

Holding the gun to his head, Mr. Miller looked over at the passenger seat at a brochure from Wounded Warrior Project, which he had just learned about. Mr. Miller noticed a photo of a man in a wheelchair, a veteran like him, who had no legs. He thought that the man looked worse off than him but hadn’t given up.

Mr. Miller put down his gun and decided to get help.

Recovering from a near suicide attempt, he says, is a journey. It doesn’t happen overnight. Now, 8 years later, Mr. Miller is planning a brief break from the speaker circuit. He plans to spend 2 weeks in an outpatient counseling program for posttraumatic stress disorder and traumatic brain injury.

“Telling my story to strangers – part of it is healing me in a way, but I’m learning that repeating the story over and over again is also keeping me from letting it go. And I’m still healing.”

A version of this article first appeared on WebMD.com.

Medically reviewed by Jennifer Casarella, MD

Dan Miller has parked his Nissan Altima on the side of the road near a field outside Chicago and is holding a gun to his head. 

Haunted for years by the compounded trauma of tours of duty in the Middle East and his work as a police officer in Chicago, at that moment, Dr. Miller saw no reason to live. And there were troubles at home with his wife and children, who had grown fearful of his behavior.

“My whole world was falling apart,” he says of that dark night in 2014. “It left a hole I didn’t know how to fill.”

He chose not to pull the trigger after a brochure on the passenger seat of his car gave him an unexpected perspective – and launched him on a path to help others in his situation.

Had Mr. Miller taken his life that night, he would have joined thousands of other veterans who died by suicide. About 17 U.S. veterans lose their lives this way each day, on average, according to the Department of Veterans Affairs. In 2019, the last year for which records are available, 6,261 veterans took their own lives – and the suicide rate for veterans was 52% higher than for nonveterans, the agency’s records show. 

The problem has become so severe that the Veterans Health Administration now uses artificial intelligence (AI) to help identify veterans at the highest risk of suicide – and reach out to them before a crisis strikes.

But that wasn’t available when Dan Miller’s life was unraveling.

In the years leading up to his near-suicide, his wife had pushed him to get help. “She said, ‘You’re not the same person you were when you left. The kids are scared of you. The pets are scared of you,” he recalls.

He resisted, even when his wife threatened divorce. Rising through the ranks of the Marines, Mr. Miller had become more emotionally isolated. He feared losing his job and the respect of others if he let anyone know what he was going through.

Finally, he gave the VHA a chance. He went in for an initial consultation in 2010 and didn’t find it helpful. He didn’t like being told what to do. So he stopped. He turned to obsessive exercise and excessive drinking.

That day in 2014, Mr. Miller’s wife told him she was taking the kids out for a playdate. After she left, he was served with divorce papers. Less than an hour later, he was parked in his car with his gun, ready to end his life.

But if it all had happened just a few years later, things might never have gotten to that point.
 

Scanning for suicide risk

In 2017, the VHA piloted its AI program, called REACH VET, that aims to help prevent veterans from dying by suicide.

Every month, a computer scans the electronic health records of all VHA patients who’ve had a health care visit for any reason in the last 2 years. It checks more than 140 variables and weights them to estimate someone’s overall suicide risk at that moment in time.

To build the risk algorithm, a computer combed through the medical records of 6,360 veterans confirmed to have died by suicide between 2009 and 2011. (The VHA continually updates the list of variables from the health records of VHA patients, including those who have died by suicide since then and others.)

Some variables are things you’d expect:

• A past suicide attempt.
• A diagnosis of depression or other mental illness.
• A diagnosis of a terminal illness.

Others are more surprising. For example, a diagnosis of arthritis or diabetes adds weight.

REACH VET flags the riskiest cases – the top 0.1% – for a mental health or primary care provider to review. They reach out to the patient to tell them how and why their record was flagged, discuss any recommended treatment changes, and ask them to come in for a visit.

“It’s an opportunity to talk about their risk factors, which is designed to lead to a conversation about safety planning,” says clinical psychologist Matthew Miller, PhD, national director of the U.S. Department of Veterans Affairs’ Suicide Prevention Program. He’s not related to Dan Miller.

Making a suicide safety plan

A safety plan is a document that outlines how a person can help prevent their own suicide in a crisis. 

The plan may include:

• A list of personal triggers or warning signs.
• What’s helped them in the past.
• Names of people or organizations who can support them.
• Plans to remove means of suicide, such as guns, from their environment.
• Their reasons for living.

In people at risk for suicide, research shows that having a safety plan reduces suicidal thoughts and attempts, lowers rates of depression and hopelessness, and boosts veterans’ engagement with the health care system. It may also help people manage things that trigger their suicidal thoughts.
 

Getting the call

What if REACH VET had been around when Dan Miller was in crisis – and he’d gotten a call from the VHA?

“It absolutely, positively would have helped because one of the biggest things on that day when I got served was feeling completely alone and that I had no one to turn to,” Mr. Miller says. He’s now a speaker for the Wounded Warrior Project, a nonprofit that serves veterans and active-duty service people.

Vets’ reactions to the unexpected VHA phone call, psychologist Dr. Miller says, “run the gamut from ‘Thank you for contacting me. Let’s talk,’ to ‘What are you talking about? Leave me alone!’ ”

Nothing stops all suicides. But REACH VET is having an impact. In a clinical trial, vets contacted through REACH VET had more doctor visits, were more likely to have a written suicide prevention safety plan, and had fewer hospital admissions for mental health, ER visits, and suicide attempts.
 

An assist from AI

Even simple outreach can make a big difference. And there’s research to prove it.

One study included 4,730 veterans recently discharged from psychiatric care at the VHA, a group considered at high risk for suicide. 

Half of them got 13 caring emails from hospital staff in the weeks after leaving the hospital. The emails mentioned personal things the patient had shared, like a love of hiking, and wished them well. The other veterans got routine follow-up but no emails.

Two years later, those who got the caring emails were less likely to have died by suicide than the other vets. The study was published in 2014 in Contemporary Clinical Trials.

Researchers have done studies like this many times: with handwritten notes from the primary care doctor, postcards from the ER, and so forth. The results never vary: The notes reduce suicide risk.

“If we could use AI to identify people to receive notes or phone calls, it would be a very effective and inexpensive way to guide follow-up care,” says Rebecca Bernert, PhD, director and founder of the Suicide Prevention Research Laboratory at Stanford (Calif.) University.
 

AI doesn’t replace clinical judgment.

“AI can capture data that we miss due to the limits of our humanity,” psychologist Dr. Miller says. “There’s suicide prevention processes founded on big data and AI, and there are processes founded in clinical intuition and acumen.”

AI is only as good as the data it’s based on. If that data lacks diversity, it may miss things. And variables that apply to veterans may differ in civilians.
 

Stopping suicidal thoughts

Google is putting AI to work against suicide, too. Its MUM (Multitask Unified Model) technology seeks to understand the intent behind what we google.

MUM powers Google Search. It can often tell the difference between a search for information about suicide for someone writing a research paper on the topic and a search for information on how or where to carry out a suicide.

When Google Search detects that someone in the United States might be in crisis and at risk of suicide, the first search results that person gets are the number for the National Suicide Prevention Lifeline and other resources for people in crisis.

Google Home Assistant works in the same way. When a user makes a query that signals a suicide-related crisis, the gadget serves up resources that offer help.

MUM is working to understand the nuances of crisis language in 75 languages so that Google Search can provide people in crisis with hotlines or other resources in many countries.

“We want to find partners that are accessible to users in terms of hours of operation. We have a strong preference for finding partners that promise confidentiality and privacy to the extent that those are permitted [in that country],” says Anne Merritt, MD, a product manager at Google Search.

Other companies are working on apps that use AI to spot suicide risk in other ways, including voice technology that may notice subtle changes in the voice of someone who’s depressed and may be thinking of suicide. Those are still in development but show promise. Keep in mind that apps do not require government approval, so if you try one, be sure to let your health care provider know.
 

Changing the channel

Seeing a hotline number on your phone or computer screen can help, Dan Miller says. “If I happened to be online, searching maybe for a bridge to jump off of ... and suddenly that pops up on the screen, it’s like it changes the channel.”

It may not work for everyone, he says, but that search result could interrupt someone’s suicidal train of thought.

That’s crucial, psychologist Dr. Miller says, because most suicide attempts escalate from first thought to potentially fatal action in just 1 hour. That’s how fast it happened for Dan Miller in 2014.

“When you’re able to put time and space between the suicidal thought and the access to the method to act on that thought, you save lives,” Dr. Bernert says.
 

Making a different choice

An interruption in Mr. Miller’s thinking is what had saved his life.

Holding the gun to his head, Mr. Miller looked over at the passenger seat at a brochure from Wounded Warrior Project, which he had just learned about. Mr. Miller noticed a photo of a man in a wheelchair, a veteran like him, who had no legs. He thought that the man looked worse off than him but hadn’t given up.

Mr. Miller put down his gun and decided to get help.

Recovering from a near suicide attempt, he says, is a journey. It doesn’t happen overnight. Now, 8 years later, Mr. Miller is planning a brief break from the speaker circuit. He plans to spend 2 weeks in an outpatient counseling program for posttraumatic stress disorder and traumatic brain injury.

“Telling my story to strangers – part of it is healing me in a way, but I’m learning that repeating the story over and over again is also keeping me from letting it go. And I’m still healing.”

A version of this article first appeared on WebMD.com.

Medically reviewed by Jennifer Casarella, MD

Dan Miller has parked his Nissan Altima on the side of the road near a field outside Chicago and is holding a gun to his head. 

Haunted for years by the compounded trauma of tours of duty in the Middle East and his work as a police officer in Chicago, at that moment, Dr. Miller saw no reason to live. And there were troubles at home with his wife and children, who had grown fearful of his behavior.

“My whole world was falling apart,” he says of that dark night in 2014. “It left a hole I didn’t know how to fill.”

He chose not to pull the trigger after a brochure on the passenger seat of his car gave him an unexpected perspective – and launched him on a path to help others in his situation.

Had Mr. Miller taken his life that night, he would have joined thousands of other veterans who died by suicide. About 17 U.S. veterans lose their lives this way each day, on average, according to the Department of Veterans Affairs. In 2019, the last year for which records are available, 6,261 veterans took their own lives – and the suicide rate for veterans was 52% higher than for nonveterans, the agency’s records show. 

The problem has become so severe that the Veterans Health Administration now uses artificial intelligence (AI) to help identify veterans at the highest risk of suicide – and reach out to them before a crisis strikes.

But that wasn’t available when Dan Miller’s life was unraveling.

In the years leading up to his near-suicide, his wife had pushed him to get help. “She said, ‘You’re not the same person you were when you left. The kids are scared of you. The pets are scared of you,” he recalls.

He resisted, even when his wife threatened divorce. Rising through the ranks of the Marines, Mr. Miller had become more emotionally isolated. He feared losing his job and the respect of others if he let anyone know what he was going through.

Finally, he gave the VHA a chance. He went in for an initial consultation in 2010 and didn’t find it helpful. He didn’t like being told what to do. So he stopped. He turned to obsessive exercise and excessive drinking.

That day in 2014, Mr. Miller’s wife told him she was taking the kids out for a playdate. After she left, he was served with divorce papers. Less than an hour later, he was parked in his car with his gun, ready to end his life.

But if it all had happened just a few years later, things might never have gotten to that point.
 

Scanning for suicide risk

In 2017, the VHA piloted its AI program, called REACH VET, that aims to help prevent veterans from dying by suicide.

Every month, a computer scans the electronic health records of all VHA patients who’ve had a health care visit for any reason in the last 2 years. It checks more than 140 variables and weights them to estimate someone’s overall suicide risk at that moment in time.

To build the risk algorithm, a computer combed through the medical records of 6,360 veterans confirmed to have died by suicide between 2009 and 2011. (The VHA continually updates the list of variables from the health records of VHA patients, including those who have died by suicide since then and others.)

Some variables are things you’d expect:

• A past suicide attempt.
• A diagnosis of depression or other mental illness.
• A diagnosis of a terminal illness.

Others are more surprising. For example, a diagnosis of arthritis or diabetes adds weight.

REACH VET flags the riskiest cases – the top 0.1% – for a mental health or primary care provider to review. They reach out to the patient to tell them how and why their record was flagged, discuss any recommended treatment changes, and ask them to come in for a visit.

“It’s an opportunity to talk about their risk factors, which is designed to lead to a conversation about safety planning,” says clinical psychologist Matthew Miller, PhD, national director of the U.S. Department of Veterans Affairs’ Suicide Prevention Program. He’s not related to Dan Miller.

Making a suicide safety plan

A safety plan is a document that outlines how a person can help prevent their own suicide in a crisis. 

The plan may include:

• A list of personal triggers or warning signs.
• What’s helped them in the past.
• Names of people or organizations who can support them.
• Plans to remove means of suicide, such as guns, from their environment.
• Their reasons for living.

In people at risk for suicide, research shows that having a safety plan reduces suicidal thoughts and attempts, lowers rates of depression and hopelessness, and boosts veterans’ engagement with the health care system. It may also help people manage things that trigger their suicidal thoughts.
 

Getting the call

What if REACH VET had been around when Dan Miller was in crisis – and he’d gotten a call from the VHA?

“It absolutely, positively would have helped because one of the biggest things on that day when I got served was feeling completely alone and that I had no one to turn to,” Mr. Miller says. He’s now a speaker for the Wounded Warrior Project, a nonprofit that serves veterans and active-duty service people.

Vets’ reactions to the unexpected VHA phone call, psychologist Dr. Miller says, “run the gamut from ‘Thank you for contacting me. Let’s talk,’ to ‘What are you talking about? Leave me alone!’ ”

Nothing stops all suicides. But REACH VET is having an impact. In a clinical trial, vets contacted through REACH VET had more doctor visits, were more likely to have a written suicide prevention safety plan, and had fewer hospital admissions for mental health, ER visits, and suicide attempts.
 

An assist from AI

Even simple outreach can make a big difference. And there’s research to prove it.

One study included 4,730 veterans recently discharged from psychiatric care at the VHA, a group considered at high risk for suicide. 

Half of them got 13 caring emails from hospital staff in the weeks after leaving the hospital. The emails mentioned personal things the patient had shared, like a love of hiking, and wished them well. The other veterans got routine follow-up but no emails.

Two years later, those who got the caring emails were less likely to have died by suicide than the other vets. The study was published in 2014 in Contemporary Clinical Trials.

Researchers have done studies like this many times: with handwritten notes from the primary care doctor, postcards from the ER, and so forth. The results never vary: The notes reduce suicide risk.

“If we could use AI to identify people to receive notes or phone calls, it would be a very effective and inexpensive way to guide follow-up care,” says Rebecca Bernert, PhD, director and founder of the Suicide Prevention Research Laboratory at Stanford (Calif.) University.
 

AI doesn’t replace clinical judgment.

“AI can capture data that we miss due to the limits of our humanity,” psychologist Dr. Miller says. “There’s suicide prevention processes founded on big data and AI, and there are processes founded in clinical intuition and acumen.”

AI is only as good as the data it’s based on. If that data lacks diversity, it may miss things. And variables that apply to veterans may differ in civilians.
 

Stopping suicidal thoughts

Google is putting AI to work against suicide, too. Its MUM (Multitask Unified Model) technology seeks to understand the intent behind what we google.

MUM powers Google Search. It can often tell the difference between a search for information about suicide for someone writing a research paper on the topic and a search for information on how or where to carry out a suicide.

When Google Search detects that someone in the United States might be in crisis and at risk of suicide, the first search results that person gets are the number for the National Suicide Prevention Lifeline and other resources for people in crisis.

Google Home Assistant works in the same way. When a user makes a query that signals a suicide-related crisis, the gadget serves up resources that offer help.

MUM is working to understand the nuances of crisis language in 75 languages so that Google Search can provide people in crisis with hotlines or other resources in many countries.

“We want to find partners that are accessible to users in terms of hours of operation. We have a strong preference for finding partners that promise confidentiality and privacy to the extent that those are permitted [in that country],” says Anne Merritt, MD, a product manager at Google Search.

Other companies are working on apps that use AI to spot suicide risk in other ways, including voice technology that may notice subtle changes in the voice of someone who’s depressed and may be thinking of suicide. Those are still in development but show promise. Keep in mind that apps do not require government approval, so if you try one, be sure to let your health care provider know.
 

Changing the channel

Seeing a hotline number on your phone or computer screen can help, Dan Miller says. “If I happened to be online, searching maybe for a bridge to jump off of ... and suddenly that pops up on the screen, it’s like it changes the channel.”

It may not work for everyone, he says, but that search result could interrupt someone’s suicidal train of thought.

That’s crucial, psychologist Dr. Miller says, because most suicide attempts escalate from first thought to potentially fatal action in just 1 hour. That’s how fast it happened for Dan Miller in 2014.

“When you’re able to put time and space between the suicidal thought and the access to the method to act on that thought, you save lives,” Dr. Bernert says.
 

Making a different choice

An interruption in Mr. Miller’s thinking is what had saved his life.

Holding the gun to his head, Mr. Miller looked over at the passenger seat at a brochure from Wounded Warrior Project, which he had just learned about. Mr. Miller noticed a photo of a man in a wheelchair, a veteran like him, who had no legs. He thought that the man looked worse off than him but hadn’t given up.

Mr. Miller put down his gun and decided to get help.

Recovering from a near suicide attempt, he says, is a journey. It doesn’t happen overnight. Now, 8 years later, Mr. Miller is planning a brief break from the speaker circuit. He plans to spend 2 weeks in an outpatient counseling program for posttraumatic stress disorder and traumatic brain injury.

“Telling my story to strangers – part of it is healing me in a way, but I’m learning that repeating the story over and over again is also keeping me from letting it go. And I’m still healing.”

A version of this article first appeared on WebMD.com.

Iron accumulation in the brain as a result of alcohol consumption may explain why even moderate drinking is linked to compromised cognitive function.

Results of a large observational study suggest brain iron accumulation is a “plausible pathway” through which alcohol negatively affects cognition, study Anya Topiwala, MD, PhD, senior clinical researcher, Nuffield Department of Population Health, University of Oxford, England, said in an interview.

Study participants who drank 56 grams of alcohol a week had higher brain iron levels. The U.K. guideline for “low risk” alcohol consumption is less than 14 units weekly, or 112 grams.

“We are finding harmful associations with iron within those low-risk alcohol intake guidelines,” said Dr. Topiwala.

The study was published online  in PLOS Medicine.
 

Early intervention opportunity?

Previous research suggests higher brain iron may be involved in the pathophysiology of Alzheimer’s and Parkinson’s diseases. However, it’s unclear whether deposition plays a role in alcohol’s effect on the brain and if it does, whether this could present an opportunity for early intervention with, for example, chelating agents.

The study included 20,729 participants in the UK Biobank study, which recruited volunteers from 2006 to 2010. Participants had a mean age of 54.8 years, and 48.6% were female.

Participants self-identified as current, never, or previous alcohol consumers. For current drinkers, researchers calculated the total weekly number of U.K. units of alcohol consumed. One unit is 8 grams. A standard drink in the United States is 14 grams. They categorized weekly consumption into quintiles and used the lowest quintile as the reference category.

Participants underwent MRI to determine brain iron levels. Areas of interest were deep brain structures in the basal ganglia.

Mean weekly alcohol consumption was 17.7 units, which is higher than U.K. guidelines for low-risk consumption. “Half of the sample were drinking above what is recommended,” said Dr. Topiwala.

Alcohol consumption was associated with markers of higher iron in the bilateral putamen (beta, 0.08 standard deviation; 95% confidence interval, 0.06-0.09; P < .001), caudate (beta, 0.05; 95% CI, 0.04-0.07; P < .001), and substantia nigra (beta, 0.03; 95% CI; 0.02-0.05; P < .001).
 

Poorer performance

Drinking more than 7 units (56 grams) weekly was associated with higher susceptibility for all brain regions, except the thalamus.

Controlling for menopause status did not alter associations between alcohol and susceptibility for any brain region. This was also the case when excluding blood pressure and cholesterol as covariates.

There were significant interactions with age in the bilateral putamen and caudate but not with sex, smoking, or Townsend Deprivation Index, which includes such factors as unemployment and living conditions.

To gather data on liver iron levels, participants underwent abdominal imaging at the same time as brain imaging. Dr. Topiwala explained that the liver is a primary storage center for iron, so it was used as “a kind of surrogate marker” of iron in the body.

The researchers showed an indirect effect of alcohol through systemic iron. A 1 SD increase in weekly alcohol consumption was associated with a 0.05 mg/g (95% CI, 0.02-0.07; P < .001) increase in liver iron. In addition, a 1 mg/g increase in liver iron was associated with a 0.44 (95% CI, 0.35-0.52; P < .001) SD increase in left putamen susceptibility.

In this sample, 32% (95% CI, 22-49; P < .001) of alcohol’s total effect on left putamen susceptibility was mediated via higher systemic iron levels.

To minimize the impact of other factors influencing the association between alcohol consumption and brain iron – and the possibility that people with more brain iron drink more – researchers used Mendelian randomization that considers genetically predicted alcohol intake. This analysis supported findings of associations between alcohol consumption and brain iron.

Participants completed a cognitive battery, which included trail-making tests that reflect executive function, puzzle tests that assess fluid intelligence or logic and reasoning, and task-based tests using the “Snap” card game to measure reaction time.

Investigators found the more iron that was present in certain brain regions, the poorer participants’ cognitive performance.

Patients should know about the risks of moderate alcohol intake so they can make decisions about drinking, said Dr. Topiwala. “They should be aware that 14 units of alcohol per week is not a zero risk.”
 

Novel research

Commenting for this news organization, Heather Snyder, PhD, vice president of medical and scientific relations, Alzheimer’s Association, noted the study’s large size as a strength of the research.

She noted previous research has shown an association between higher iron levels and alcohol dependence and worse cognitive function, but the potential connection of brain iron levels, moderate alcohol consumption, and cognition has not been studied to date.

“This paper aims to look at whether there is a potential biological link between moderate alcohol consumption and cognition through iron-related pathways.”

The authors suggest more work is needed to understand whether alcohol consumption impacts iron-related biologies to affect downstream cognition, said Dr. Snyder. “Although this study does not answer that question, it does highlight some important questions.”

Study authors received funding from Wellcome Trust, UK Medical Research Council, National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, BHF Centre of Research Excellence, British Heart Foundation, NIHR Cambridge Biomedical Research Centre, U.S. Department of Veterans Affairs, China Scholarship Council, and Li Ka Shing Centre for Health Information and Discovery. Dr. Topiwala has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Iron accumulation in the brain as a result of alcohol consumption may explain why even moderate drinking is linked to compromised cognitive function.

Results of a large observational study suggest brain iron accumulation is a “plausible pathway” through which alcohol negatively affects cognition, study Anya Topiwala, MD, PhD, senior clinical researcher, Nuffield Department of Population Health, University of Oxford, England, said in an interview.

Study participants who drank 56 grams of alcohol a week had higher brain iron levels. The U.K. guideline for “low risk” alcohol consumption is less than 14 units weekly, or 112 grams.

“We are finding harmful associations with iron within those low-risk alcohol intake guidelines,” said Dr. Topiwala.

The study was published online  in PLOS Medicine.
 

Early intervention opportunity?

Previous research suggests higher brain iron may be involved in the pathophysiology of Alzheimer’s and Parkinson’s diseases. However, it’s unclear whether deposition plays a role in alcohol’s effect on the brain and if it does, whether this could present an opportunity for early intervention with, for example, chelating agents.

The study included 20,729 participants in the UK Biobank study, which recruited volunteers from 2006 to 2010. Participants had a mean age of 54.8 years, and 48.6% were female.

Participants self-identified as current, never, or previous alcohol consumers. For current drinkers, researchers calculated the total weekly number of U.K. units of alcohol consumed. One unit is 8 grams. A standard drink in the United States is 14 grams. They categorized weekly consumption into quintiles and used the lowest quintile as the reference category.

Participants underwent MRI to determine brain iron levels. Areas of interest were deep brain structures in the basal ganglia.

Mean weekly alcohol consumption was 17.7 units, which is higher than U.K. guidelines for low-risk consumption. “Half of the sample were drinking above what is recommended,” said Dr. Topiwala.

Alcohol consumption was associated with markers of higher iron in the bilateral putamen (beta, 0.08 standard deviation; 95% confidence interval, 0.06-0.09; P < .001), caudate (beta, 0.05; 95% CI, 0.04-0.07; P < .001), and substantia nigra (beta, 0.03; 95% CI; 0.02-0.05; P < .001).
 

Poorer performance

Drinking more than 7 units (56 grams) weekly was associated with higher susceptibility for all brain regions, except the thalamus.

Controlling for menopause status did not alter associations between alcohol and susceptibility for any brain region. This was also the case when excluding blood pressure and cholesterol as covariates.

There were significant interactions with age in the bilateral putamen and caudate but not with sex, smoking, or Townsend Deprivation Index, which includes such factors as unemployment and living conditions.

To gather data on liver iron levels, participants underwent abdominal imaging at the same time as brain imaging. Dr. Topiwala explained that the liver is a primary storage center for iron, so it was used as “a kind of surrogate marker” of iron in the body.

The researchers showed an indirect effect of alcohol through systemic iron. A 1 SD increase in weekly alcohol consumption was associated with a 0.05 mg/g (95% CI, 0.02-0.07; P < .001) increase in liver iron. In addition, a 1 mg/g increase in liver iron was associated with a 0.44 (95% CI, 0.35-0.52; P < .001) SD increase in left putamen susceptibility.

In this sample, 32% (95% CI, 22-49; P < .001) of alcohol’s total effect on left putamen susceptibility was mediated via higher systemic iron levels.

To minimize the impact of other factors influencing the association between alcohol consumption and brain iron – and the possibility that people with more brain iron drink more – researchers used Mendelian randomization that considers genetically predicted alcohol intake. This analysis supported findings of associations between alcohol consumption and brain iron.

Participants completed a cognitive battery, which included trail-making tests that reflect executive function, puzzle tests that assess fluid intelligence or logic and reasoning, and task-based tests using the “Snap” card game to measure reaction time.

Investigators found the more iron that was present in certain brain regions, the poorer participants’ cognitive performance.

Patients should know about the risks of moderate alcohol intake so they can make decisions about drinking, said Dr. Topiwala. “They should be aware that 14 units of alcohol per week is not a zero risk.”
 

Novel research

Commenting for this news organization, Heather Snyder, PhD, vice president of medical and scientific relations, Alzheimer’s Association, noted the study’s large size as a strength of the research.

She noted previous research has shown an association between higher iron levels and alcohol dependence and worse cognitive function, but the potential connection of brain iron levels, moderate alcohol consumption, and cognition has not been studied to date.

“This paper aims to look at whether there is a potential biological link between moderate alcohol consumption and cognition through iron-related pathways.”

The authors suggest more work is needed to understand whether alcohol consumption impacts iron-related biologies to affect downstream cognition, said Dr. Snyder. “Although this study does not answer that question, it does highlight some important questions.”

Study authors received funding from Wellcome Trust, UK Medical Research Council, National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, BHF Centre of Research Excellence, British Heart Foundation, NIHR Cambridge Biomedical Research Centre, U.S. Department of Veterans Affairs, China Scholarship Council, and Li Ka Shing Centre for Health Information and Discovery. Dr. Topiwala has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Iron accumulation in the brain as a result of alcohol consumption may explain why even moderate drinking is linked to compromised cognitive function.

Results of a large observational study suggest brain iron accumulation is a “plausible pathway” through which alcohol negatively affects cognition, study Anya Topiwala, MD, PhD, senior clinical researcher, Nuffield Department of Population Health, University of Oxford, England, said in an interview.

Study participants who drank 56 grams of alcohol a week had higher brain iron levels. The U.K. guideline for “low risk” alcohol consumption is less than 14 units weekly, or 112 grams.

“We are finding harmful associations with iron within those low-risk alcohol intake guidelines,” said Dr. Topiwala.

The study was published online  in PLOS Medicine.
 

Early intervention opportunity?

Previous research suggests higher brain iron may be involved in the pathophysiology of Alzheimer’s and Parkinson’s diseases. However, it’s unclear whether deposition plays a role in alcohol’s effect on the brain and if it does, whether this could present an opportunity for early intervention with, for example, chelating agents.

The study included 20,729 participants in the UK Biobank study, which recruited volunteers from 2006 to 2010. Participants had a mean age of 54.8 years, and 48.6% were female.

Participants self-identified as current, never, or previous alcohol consumers. For current drinkers, researchers calculated the total weekly number of U.K. units of alcohol consumed. One unit is 8 grams. A standard drink in the United States is 14 grams. They categorized weekly consumption into quintiles and used the lowest quintile as the reference category.

Participants underwent MRI to determine brain iron levels. Areas of interest were deep brain structures in the basal ganglia.

Mean weekly alcohol consumption was 17.7 units, which is higher than U.K. guidelines for low-risk consumption. “Half of the sample were drinking above what is recommended,” said Dr. Topiwala.

Alcohol consumption was associated with markers of higher iron in the bilateral putamen (beta, 0.08 standard deviation; 95% confidence interval, 0.06-0.09; P < .001), caudate (beta, 0.05; 95% CI, 0.04-0.07; P < .001), and substantia nigra (beta, 0.03; 95% CI; 0.02-0.05; P < .001).
 

Poorer performance

Drinking more than 7 units (56 grams) weekly was associated with higher susceptibility for all brain regions, except the thalamus.

Controlling for menopause status did not alter associations between alcohol and susceptibility for any brain region. This was also the case when excluding blood pressure and cholesterol as covariates.

There were significant interactions with age in the bilateral putamen and caudate but not with sex, smoking, or Townsend Deprivation Index, which includes such factors as unemployment and living conditions.

To gather data on liver iron levels, participants underwent abdominal imaging at the same time as brain imaging. Dr. Topiwala explained that the liver is a primary storage center for iron, so it was used as “a kind of surrogate marker” of iron in the body.

The researchers showed an indirect effect of alcohol through systemic iron. A 1 SD increase in weekly alcohol consumption was associated with a 0.05 mg/g (95% CI, 0.02-0.07; P < .001) increase in liver iron. In addition, a 1 mg/g increase in liver iron was associated with a 0.44 (95% CI, 0.35-0.52; P < .001) SD increase in left putamen susceptibility.

In this sample, 32% (95% CI, 22-49; P < .001) of alcohol’s total effect on left putamen susceptibility was mediated via higher systemic iron levels.

To minimize the impact of other factors influencing the association between alcohol consumption and brain iron – and the possibility that people with more brain iron drink more – researchers used Mendelian randomization that considers genetically predicted alcohol intake. This analysis supported findings of associations between alcohol consumption and brain iron.

Participants completed a cognitive battery, which included trail-making tests that reflect executive function, puzzle tests that assess fluid intelligence or logic and reasoning, and task-based tests using the “Snap” card game to measure reaction time.

Investigators found the more iron that was present in certain brain regions, the poorer participants’ cognitive performance.

Patients should know about the risks of moderate alcohol intake so they can make decisions about drinking, said Dr. Topiwala. “They should be aware that 14 units of alcohol per week is not a zero risk.”
 

Novel research

Commenting for this news organization, Heather Snyder, PhD, vice president of medical and scientific relations, Alzheimer’s Association, noted the study’s large size as a strength of the research.

She noted previous research has shown an association between higher iron levels and alcohol dependence and worse cognitive function, but the potential connection of brain iron levels, moderate alcohol consumption, and cognition has not been studied to date.

“This paper aims to look at whether there is a potential biological link between moderate alcohol consumption and cognition through iron-related pathways.”

The authors suggest more work is needed to understand whether alcohol consumption impacts iron-related biologies to affect downstream cognition, said Dr. Snyder. “Although this study does not answer that question, it does highlight some important questions.”

Study authors received funding from Wellcome Trust, UK Medical Research Council, National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, BHF Centre of Research Excellence, British Heart Foundation, NIHR Cambridge Biomedical Research Centre, U.S. Department of Veterans Affairs, China Scholarship Council, and Li Ka Shing Centre for Health Information and Discovery. Dr. Topiwala has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.