To the Editor: 

Palmoplantar lichen planus (LP) is an uncommon variant of LP that involves the palms and soles. The prevalence of LP is approximately 0.1% to 2% in the general population. It can affect both mucosal and cutaneous surfaces.¹ A study of 36 patients with LP showed that 25% (9/36) had palmar and/or plantar involvement.² Palmoplantar LP is more commonly found in men than women, with an average age of onset of 38 to 65 years.³ It tends to affect the soles more often than the palms, with the most common site being the plantar arch. Itching generally is the most common symptom reported. Lesions often resolve over a few months, but relapses can occur in 10% to 29% of patients.² The clinical morphology commonly is characterized as erythematous scaly plaques, hyperkeratotic plaques, or ulcerations.⁴ Due to its rare occurrence, palmoplantar LP often is misdiagnosed as psoriasis, eczematous dermatitis, tinea nigra, or secondary syphilis, making pathology extremely helpful in making the diagnosis.¹ Darker skin types can obscure defining characteristics, further impeding a timely diagnosis. We describe a novel case of palmoplantar LP that was successfully treated with methotrexate.  

A 38-year-old man with no notable medical history presented for dermatologic evaluation of a palmar and plantar rash of 4 months' duration. The rash was accompanied by intense burning pain and pruritus. Prior to presentation, he had been treated with multiple prednisone tapers starting at 40 mg daily as well as combination therapy of a 2-week course of minocycline 100 mg twice daily and clobetasol ointment twice daily for 4 months, with no notable improvement. Workup prior to presentation included a negative potassium hydroxide fungal preparation and a normal antinuclear antibody titer. A review of symptoms was negative for arthralgia, myalgia, photosensitivity, malar rash, Raynaud phenomenon, pleuritic pain, seizures, and psychosis.  

Physical examination revealed focal areas of mildly thick, hyperkeratotic scale with desquamation on the plantar and palmar surfaces of the feet and hands. The underlying skin of the feet consisted of dyspigmented patches of dark brown and hypopigmented skin with erythema, profound scaling, and sparing of the internal plantar arches (Figure 1A). On the palms, thin hyperkeratotic plaques with desquamation and erythematous maceration of the surrounding skin were observed (Figure 2A). Thin white plaques of the posterior bilateral buccal mucosa were appreciated as well as an erosion that extended to the lower lip.  

The differential diagnosis included LP, psoriasis, acquired palmoplantar keratoderma, and discoid lupus erythematosus. Tinea pedis and tinea manuum were less likely in the setting of a negative potassium hydroxide fungal preparation.  

A biopsy of the lateral aspect of the left foot showed a cell-poor interface dermatitis that could resemble partially treated LP or a lichenoid hypersensitivity reaction (Figure 3). Given the clinical and pathologic findings, a diagnosis of palmoplantar LP was favored. The patient was on no medications or over-the-counter supplements prior to the appearance of the rash, making a lichenoid hypersensitivity rash less likely. The histology findings likely were muted, as they were done at the end of the prednisone taper. 

Minocycline and clobetasol ointment were discontinued, and the prednisone taper was completed as originally prescribed. The patient was started on 25 mg daily of acitretin for 4 weeks, then increased to 35 mg daily. Notable improvement in the palmar and plantar lesions was noted after the initial 4 weeks of therapy; however, acitretin treatment was discontinued due to lack of adequate insurance coverage for the medication. The patient became symptomatic several weeks following acitretin cessation and was started on methotrexate 15 mg weekly with triamcinolone acetonide paste 0.1% for the oral lesions. Once again, improvement was seen on both the palmar and plantar surfaces after 4 weeks of therapy (Figures 1B and 2B). 

Evidence for treatment of palmoplantar LP is limited to a few case reports and case series. Documented treatments for palmoplantar LP include topical and systemic steroids, tazarotene, acitretin, and immunosuppressive medications.⁴ One case report described a patient who responded well to prednisone therapy (1 mg/kg daily for 3 weeks, then reduced to 5 mg daily).⁵ Another report described a patient who responded favorably to cyclosporine 3.5 mg/kg daily for 4 weeks, then tapered over another 4 weeks for a total of 8 weeks of treatment.⁴ Although the most common treatments described in the literature consist of acitretin as well as topical and systemic steroids, few have discussed the efficacy of methotrexate. In one study, acitretin did not result in clearance, but the patient saw profound improvement with methotrexate (titrated up to 25 mg weekly) over 2 months.¹  

In our case, treatment with methotrexate was proven successful in a patient who responded to acitretin but was unable to afford treatment. This case highlights a rare variant of a common disease and the possibility of methotrexate as a cost-effective and useful treatment option for LP.  

To the Editor: 

Palmoplantar lichen planus (LP) is an uncommon variant of LP that involves the palms and soles. The prevalence of LP is approximately 0.1% to 2% in the general population. It can affect both mucosal and cutaneous surfaces.¹ A study of 36 patients with LP showed that 25% (9/36) had palmar and/or plantar involvement.² Palmoplantar LP is more commonly found in men than women, with an average age of onset of 38 to 65 years.³ It tends to affect the soles more often than the palms, with the most common site being the plantar arch. Itching generally is the most common symptom reported. Lesions often resolve over a few months, but relapses can occur in 10% to 29% of patients.² The clinical morphology commonly is characterized as erythematous scaly plaques, hyperkeratotic plaques, or ulcerations.⁴ Due to its rare occurrence, palmoplantar LP often is misdiagnosed as psoriasis, eczematous dermatitis, tinea nigra, or secondary syphilis, making pathology extremely helpful in making the diagnosis.¹ Darker skin types can obscure defining characteristics, further impeding a timely diagnosis. We describe a novel case of palmoplantar LP that was successfully treated with methotrexate.  

A 38-year-old man with no notable medical history presented for dermatologic evaluation of a palmar and plantar rash of 4 months' duration. The rash was accompanied by intense burning pain and pruritus. Prior to presentation, he had been treated with multiple prednisone tapers starting at 40 mg daily as well as combination therapy of a 2-week course of minocycline 100 mg twice daily and clobetasol ointment twice daily for 4 months, with no notable improvement. Workup prior to presentation included a negative potassium hydroxide fungal preparation and a normal antinuclear antibody titer. A review of symptoms was negative for arthralgia, myalgia, photosensitivity, malar rash, Raynaud phenomenon, pleuritic pain, seizures, and psychosis.  

Physical examination revealed focal areas of mildly thick, hyperkeratotic scale with desquamation on the plantar and palmar surfaces of the feet and hands. The underlying skin of the feet consisted of dyspigmented patches of dark brown and hypopigmented skin with erythema, profound scaling, and sparing of the internal plantar arches (Figure 1A). On the palms, thin hyperkeratotic plaques with desquamation and erythematous maceration of the surrounding skin were observed (Figure 2A). Thin white plaques of the posterior bilateral buccal mucosa were appreciated as well as an erosion that extended to the lower lip.  

The differential diagnosis included LP, psoriasis, acquired palmoplantar keratoderma, and discoid lupus erythematosus. Tinea pedis and tinea manuum were less likely in the setting of a negative potassium hydroxide fungal preparation.  

A biopsy of the lateral aspect of the left foot showed a cell-poor interface dermatitis that could resemble partially treated LP or a lichenoid hypersensitivity reaction (Figure 3). Given the clinical and pathologic findings, a diagnosis of palmoplantar LP was favored. The patient was on no medications or over-the-counter supplements prior to the appearance of the rash, making a lichenoid hypersensitivity rash less likely. The histology findings likely were muted, as they were done at the end of the prednisone taper. 

Minocycline and clobetasol ointment were discontinued, and the prednisone taper was completed as originally prescribed. The patient was started on 25 mg daily of acitretin for 4 weeks, then increased to 35 mg daily. Notable improvement in the palmar and plantar lesions was noted after the initial 4 weeks of therapy; however, acitretin treatment was discontinued due to lack of adequate insurance coverage for the medication. The patient became symptomatic several weeks following acitretin cessation and was started on methotrexate 15 mg weekly with triamcinolone acetonide paste 0.1% for the oral lesions. Once again, improvement was seen on both the palmar and plantar surfaces after 4 weeks of therapy (Figures 1B and 2B). 

Evidence for treatment of palmoplantar LP is limited to a few case reports and case series. Documented treatments for palmoplantar LP include topical and systemic steroids, tazarotene, acitretin, and immunosuppressive medications.⁴ One case report described a patient who responded well to prednisone therapy (1 mg/kg daily for 3 weeks, then reduced to 5 mg daily).⁵ Another report described a patient who responded favorably to cyclosporine 3.5 mg/kg daily for 4 weeks, then tapered over another 4 weeks for a total of 8 weeks of treatment.⁴ Although the most common treatments described in the literature consist of acitretin as well as topical and systemic steroids, few have discussed the efficacy of methotrexate. In one study, acitretin did not result in clearance, but the patient saw profound improvement with methotrexate (titrated up to 25 mg weekly) over 2 months.¹  

In our case, treatment with methotrexate was proven successful in a patient who responded to acitretin but was unable to afford treatment. This case highlights a rare variant of a common disease and the possibility of methotrexate as a cost-effective and useful treatment option for LP.  

To the Editor: 

Palmoplantar lichen planus (LP) is an uncommon variant of LP that involves the palms and soles. The prevalence of LP is approximately 0.1% to 2% in the general population. It can affect both mucosal and cutaneous surfaces.¹ A study of 36 patients with LP showed that 25% (9/36) had palmar and/or plantar involvement.² Palmoplantar LP is more commonly found in men than women, with an average age of onset of 38 to 65 years.³ It tends to affect the soles more often than the palms, with the most common site being the plantar arch. Itching generally is the most common symptom reported. Lesions often resolve over a few months, but relapses can occur in 10% to 29% of patients.² The clinical morphology commonly is characterized as erythematous scaly plaques, hyperkeratotic plaques, or ulcerations.⁴ Due to its rare occurrence, palmoplantar LP often is misdiagnosed as psoriasis, eczematous dermatitis, tinea nigra, or secondary syphilis, making pathology extremely helpful in making the diagnosis.¹ Darker skin types can obscure defining characteristics, further impeding a timely diagnosis. We describe a novel case of palmoplantar LP that was successfully treated with methotrexate.  

A 38-year-old man with no notable medical history presented for dermatologic evaluation of a palmar and plantar rash of 4 months' duration. The rash was accompanied by intense burning pain and pruritus. Prior to presentation, he had been treated with multiple prednisone tapers starting at 40 mg daily as well as combination therapy of a 2-week course of minocycline 100 mg twice daily and clobetasol ointment twice daily for 4 months, with no notable improvement. Workup prior to presentation included a negative potassium hydroxide fungal preparation and a normal antinuclear antibody titer. A review of symptoms was negative for arthralgia, myalgia, photosensitivity, malar rash, Raynaud phenomenon, pleuritic pain, seizures, and psychosis.  

Physical examination revealed focal areas of mildly thick, hyperkeratotic scale with desquamation on the plantar and palmar surfaces of the feet and hands. The underlying skin of the feet consisted of dyspigmented patches of dark brown and hypopigmented skin with erythema, profound scaling, and sparing of the internal plantar arches (Figure 1A). On the palms, thin hyperkeratotic plaques with desquamation and erythematous maceration of the surrounding skin were observed (Figure 2A). Thin white plaques of the posterior bilateral buccal mucosa were appreciated as well as an erosion that extended to the lower lip.  

The differential diagnosis included LP, psoriasis, acquired palmoplantar keratoderma, and discoid lupus erythematosus. Tinea pedis and tinea manuum were less likely in the setting of a negative potassium hydroxide fungal preparation.  

A biopsy of the lateral aspect of the left foot showed a cell-poor interface dermatitis that could resemble partially treated LP or a lichenoid hypersensitivity reaction (Figure 3). Given the clinical and pathologic findings, a diagnosis of palmoplantar LP was favored. The patient was on no medications or over-the-counter supplements prior to the appearance of the rash, making a lichenoid hypersensitivity rash less likely. The histology findings likely were muted, as they were done at the end of the prednisone taper. 

Minocycline and clobetasol ointment were discontinued, and the prednisone taper was completed as originally prescribed. The patient was started on 25 mg daily of acitretin for 4 weeks, then increased to 35 mg daily. Notable improvement in the palmar and plantar lesions was noted after the initial 4 weeks of therapy; however, acitretin treatment was discontinued due to lack of adequate insurance coverage for the medication. The patient became symptomatic several weeks following acitretin cessation and was started on methotrexate 15 mg weekly with triamcinolone acetonide paste 0.1% for the oral lesions. Once again, improvement was seen on both the palmar and plantar surfaces after 4 weeks of therapy (Figures 1B and 2B). 

Evidence for treatment of palmoplantar LP is limited to a few case reports and case series. Documented treatments for palmoplantar LP include topical and systemic steroids, tazarotene, acitretin, and immunosuppressive medications.⁴ One case report described a patient who responded well to prednisone therapy (1 mg/kg daily for 3 weeks, then reduced to 5 mg daily).⁵ Another report described a patient who responded favorably to cyclosporine 3.5 mg/kg daily for 4 weeks, then tapered over another 4 weeks for a total of 8 weeks of treatment.⁴ Although the most common treatments described in the literature consist of acitretin as well as topical and systemic steroids, few have discussed the efficacy of methotrexate. In one study, acitretin did not result in clearance, but the patient saw profound improvement with methotrexate (titrated up to 25 mg weekly) over 2 months.¹  

In our case, treatment with methotrexate was proven successful in a patient who responded to acitretin but was unable to afford treatment. This case highlights a rare variant of a common disease and the possibility of methotrexate as a cost-effective and useful treatment option for LP.  

Case

A 45-year-old female with moderate persistent asthma is admitted for right lower extremity cellulitis. She has hyponatremia with a sodium of 129 mEq/L and reports a history of longstanding fatigue and lightheadedness on standing. An early morning serum cortisol was 10 mcg/dL, normal per the reference range for the laboratory. Has adrenal insufficiency been excluded in this patient?

Overview

Adrenal insufficiency (AI) is a clinical syndrome characterized by a deficiency of cortisol. Presentation may range from nonspecific symptoms such as fatigue, weight loss, and gastrointestinal concerns to a fulminant adrenal crisis with severe weakness and hypotension (Table 1). The diagnosis of AI is commonly delayed, negatively impacting patients’ quality of life and risking dangerous complications.^1,2

AI can occur due to diseases of the adrenal glands themselves (primary) or impairment of adrenocorticotropin (ACTH) secretion from the pituitary (secondary) or corticotropin-releasing hormone (CRH) secretion from the hypothalamus (tertiary). In the hospital setting, causes of primary AI may include autoimmune disease, infection, metastatic disease, hemorrhage, and adverse medication effects. Secondary and tertiary AI would be of particular concern for patients with traumatic brain injuries or pituitary surgery, but also are seen commonly as a result of adverse medication effects in the hospitalized patient, notably opioids and corticosteroids through suppression the hypothalamic-pituitary-adrenal (HPA) axis and immune checkpoint inhibitors via autoimmune hypophysitis.

Testing for AI in the hospitalized patient presents a host of challenges. Among these are the variability in presentation of different types of AI, high rates of exogenous corticosteroid use, the impact of critical illness on the HPA axis, medical illness altering protein binding of serum cortisol, interfering medications, the variation in assays used by laboratories, and the logistical challenges of obtaining appropriately timed phlebotomy.^2,3
 

Cortisol testing

An intact HPA axis results in ACTH-dependent cortisol release from the adrenal glands. Cortisol secretion exhibits circadian rhythm, with the highest levels in the early morning (6 a.m. to 8 a.m.) and the lowest at night (12 a.m.). It also is pulsatile, which may explain the range of “normal” morning serum cortisol observed in a study of healthy volunteers.³ Note that serum cortisol is equivalent to plasma cortisol in current immunoassays, and will henceforth be called “cortisol” in this paper.³

There are instances when morning cortisol may strongly suggest a diagnosis of AI on its own. A meta-analysis found that morning cortisol of < 5 mcg/dL predicts AI and morning cortisol of > 13 mcg/dL ruled out AI.⁴ The Endocrine Society of America favors dynamic assessment of adrenal function for most patients.²

Historically, the gold standard for assessing dynamic adrenal function has been the insulin tolerance test (ITT), whereby cortisol is measured after inducing hypoglycemia to a blood glucose < 35 mg/dL. ITT is logistically difficult and poses some risk to the patient. The corticotropin (or cosyntropin) stimulation test (CST), in which a supraphysiologic dose of a synthetic ACTH analog is administered parenterally to a patient and resultant cortisol levels are measured, has been validated against the ITT and is generally preferred.⁵ CST is used to diagnose primary AI as well as chronic secondary and tertiary AI, given that longstanding lack of ACTH stimulation causes atrophy of the adrenal glands. The sensitivity for secondary and tertiary AI is likely lower than primary AI especially in acute onset of disease.^6,7

In performance of the CST a baseline cortisol and ACTH are obtained, with subsequent cortisol testing at 30 and/or 60 minutes after administration of the ACTH analog (Figure 1). Currently, there is no consensus for which time point is preferred, but the 30-minute test is more sensitive for AI and the 60-minute test is more specific.^2,7,8

CST is typically performed using a “standard high dose” of 250 mcg of the ACTH analog. There has been interest in the use of a “low-dose” 1 mcg test, which is closer to normal physiologic stimulation of the adrenal glands and may have better sensitivity for early secondary or partial AI. However, the 250-mcg dose is easier to prepare and has fewer technical pitfalls in administration as well as a lower risk for false positive testing. At this point the data do not compellingly favor the use of low-dose CST testing in general practice.^2,3,7
 

Clinical decision making

Diagnostic evaluation should be guided by the likelihood of the disease (i.e., the pretest probability) (Figure 1). Begin with a review of the patient’s signs and symptoms, medical and family history, and medications with special consideration for opioids, exogenous steroids, and immune checkpoint inhibitors (Table 1).

For patients with low pretest probability for AI, morning cortisol and ACTH is a reasonable first test (Figure 1). A cortisol value of 18 mcg/dL or greater does not support AI and no further testing is needed.² Patients with morning cortisol of 13-18 mcg/dL could be followed clinically or could undergo further testing in the inpatient environment with CST, depending upon the clinical scenario.⁴ Patients with serum cortisol of <13 mcg/dL warrant CST.

For patients with moderate to high pretest probability for AI, we recommend initial testing with CST. While the results of high-dose CST are not necessarily impacted by time of day, if an a.m. cortisol has not yet been obtained and it is logistically feasible to do so, performing CST in the morning will provide the most useful data for clinical interpretation.

For patients presenting with possible adrenal crisis, it is essential not to delay treatment. In these patients, obtain a cortisol paired with ACTH and initiate treatment immediately. Further testing can be deferred until the time the patient is stable.²
 

Potential pitfalls

Interpreting cortisol requires awareness of multiple conditions that could directly impact the results.^2,3 (Table 2).

Currently available assays measure “total cortisol,” most of which is protein bound (cortisol-binding globulin as well as albumin). Therefore, conditions that lower serum protein (e.g., nephrotic syndrome, liver disease, inflammation) will lower the measured cortisol. Conversely, conditions that increase serum protein (e.g., estrogen excess in pregnancy and oral contraceptive use) will increase the measured cortisol.^2,3

It is also important to recognize that existing immunoassay testing techniques informed the established cut-off for exclusion of AI at 18 mcg/dL. With newer immunoassays and emerging liquid chromatography/tandem mass spectrometry, this cut-off may be lowered; thus the assay should be confirmed with the performing laboratory. There is emerging evidence that serum or plasma free cortisol and salivary cortisol testing for AI may be useful in certain cases, but these techniques are not yet widespread or included in clinical practice guidelines.^2,3,7
 

Population focus: Patients on exogenous steroids

Exogenous corticosteroids suppress the HPA axis via negative inhibition of CRH and ACTH release, often resulting in low endogenous cortisol levels which may or may not reflect true loss of adrenal function. In addition, many corticosteroids will be detected by standard serum cortisol tests that rely on immunoassays. For this reason, cortisol measurement and CST should be done at least 18-24 hours after the last dose of exogenous steroids.

Although the focus has been on higher doses and longer courses of steroids (e.g., chronic use of ≥ 5 mg prednisone daily, or ≥ 20 mg prednisone daily for > 3 weeks), there is increasing evidence that lower doses, shorter courses, and alternate routes (e.g., inhaled, intra-articular) can result in biochemical and clinical evidence of AI.⁹ Thus, a thorough history and exam should be obtained to determine all recent corticosteroid exposure and cushingoid features.
 

Application of the data to the case

To effectively assess the patient for adrenal insufficiency, we need additional information. First and foremost, is a description of the patient’s current clinical status. If she is demonstrating evidence of adrenal crisis, treatment should not be delayed for additional testing. If she is stable, a thorough history including use of corticosteroids by any route, pregnancy, oral contraceptives, recent surgery, and liver and kidney disease is essential.

Additional evaluation reveals the patient has been using her fluticasone inhaler daily. No other source of hyponatremia or lightheadedness is identified. The patient’s risk factors of corticosteroid use and unexplained hyponatremia with associated lightheadedness increase her pretest probability of AI and a single morning cortisol of 10 mcg/dL is insufficient to exclude adrenal insufficiency. The appropriate follow-up test is a standard high-dose cosyntropin stimulation test at least 18 hours after her last dose of fluticasone. A cortisol level > 18 mcg/dL at 30 minutes in the absence of other conditions that impact cortisol testing would not be suggestive of AI. A serum cortisol level of < 18 mcg/dL at 30 minutes would raise concern for abnormal adrenal reserve due to chronic corticosteroid therapy and would warrant referral to an endocrinologist.
 

Bottom line

An isolated serum cortisol is often insufficient to exclude adrenal insufficiency. Hospitalists should be aware of the many factors that impact the interpretation of this test.

Dr. Gordon is assistant professor of medicine at Tufts University, Boston, and a hospitalist at Maine Medical Center, Portland. She is the subspecialty education coordinator of inpatient medicine for the Internal Medicine Residency Program. Dr. Herrle is assistant professor of medicine at Tufts University and a hospitalist at Maine Medical Center. She is the associate director of medical student education for the department of internal medicine at MMC and a medical director for clinical informatics at MaineHealth.

References

1. Bleicken B et al. Delayed diagnosis of adrenal insufficiency is common: A cross-sectional study in 216 patients. Am J Med Sci. 2010;339(6):525-31. doi: 10.1097/MAJ.0b013e3181db6b7a.

2. Bornstein SR et al. Diagnosis and treatment of primary adrenal insufficiency: An Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2016 Feb;101(2):364-89.

3. El-Farhan N et al. Measuring cortisol in serum, urine and saliva – Are our assays good enough? Ann Clin Biochem. 2017 May;54(3):308-22. doi: 10.1177/0004563216687335.

4. Kazlauskaite R et al. Corticotropin tests for hypothalamic-pituitary-adrenal insufficiency: A metaanalysis. J Clin Endocrinol Metab. 2008;93:4245-53.

5. Wood JB et al. A rapid test of adrenocortical function. Lancet. 1965;191:243-5.

6. Singh Ospina N et al. ACTH stimulation tests for the diagnosis of adrenal insufficiency: systematic review and meta-analysis. J Clin Endocrinol Metab. 2016;101(2):427-34.

7. Burgos N et al. Pitfalls in the interpretation of the cosyntropin stimulation test for the diagnosis of adrenal insufficiency. Curr Opin Endocrinol Diabetes Obes. 2019;26(3):139-45.

8. Odom DC et al. A Single, post-ACTH cortisol measurement to screen for adrenal insufficiency in the hospitalized patient. J Hosp Med. 2018;13(8):526-30. doi: 10.12788/jhm.2928.

9. Broersen LHA et al. Adrenal insufficiency in corticosteroids use: Systematic review and meta-analysis. J Clin Endocrinol Metab. 2015;100(6): 2171-80.
 

Key points

• In general, random cortisol testing is of limited value and should be avoided.

• Serum cortisol testing in the hospitalized patient is impacted by a variety of patient and disease factors and should be interpreted carefully.

• For patients with low pretest probability of adrenal insufficiency, early morning serum cortisol testing may be sufficient to exclude the diagnosis.

• For patients with moderate to high pretest probability of adrenal insufficiency, standard high-dose (250 mcg) corticotropin stimulation testing is preferred.
 

Additional reading

Bornstein SR et al. Diagnosis and treatment of primary adrenal insufficiency: An Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2016 Feb;101(2):364-89.

Burgos N et al. Pitfalls in the interpretation of the cosyntropin stimulation test for the diagnosis of adrenal insufficiency. Curr Opin Endocrinol Diabetes Obes. 2019;26(3):139-45.
 

Quiz

An 82 y.o. woman with depression is admitted from her long-term care facility with worsening weakness and mild hypoglycemia. Her supine vital signs are stable, but she exhibits a drop in systolic blood pressure of 21 mm Hg upon standing. There is no evidence of infection by history, exam, or initial workup. She is not on chronic corticosteroids by any route.

What would be your initial workup for adrenal insufficiency?

A) Morning serum cortisol and ACTH

B) Insulin tolerance test

C) Corticotropin stimulation test

D) Would not test at this point

Answer: C. Although her symptom of weakness is nonspecific, her hypoglycemia and orthostatic hypotension are concerning enough that she would qualify as moderate to high pretest probability for AI. In this setting, one would acquire a basal serum total cortisol and ACTH then administer the standard high-dose corticotropin stimulation test (250 mcg) followed by repeat serum total cortisol at 30 or 60 minutes.

Case

A 45-year-old female with moderate persistent asthma is admitted for right lower extremity cellulitis. She has hyponatremia with a sodium of 129 mEq/L and reports a history of longstanding fatigue and lightheadedness on standing. An early morning serum cortisol was 10 mcg/dL, normal per the reference range for the laboratory. Has adrenal insufficiency been excluded in this patient?

Overview

Adrenal insufficiency (AI) is a clinical syndrome characterized by a deficiency of cortisol. Presentation may range from nonspecific symptoms such as fatigue, weight loss, and gastrointestinal concerns to a fulminant adrenal crisis with severe weakness and hypotension (Table 1). The diagnosis of AI is commonly delayed, negatively impacting patients’ quality of life and risking dangerous complications.^1,2

AI can occur due to diseases of the adrenal glands themselves (primary) or impairment of adrenocorticotropin (ACTH) secretion from the pituitary (secondary) or corticotropin-releasing hormone (CRH) secretion from the hypothalamus (tertiary). In the hospital setting, causes of primary AI may include autoimmune disease, infection, metastatic disease, hemorrhage, and adverse medication effects. Secondary and tertiary AI would be of particular concern for patients with traumatic brain injuries or pituitary surgery, but also are seen commonly as a result of adverse medication effects in the hospitalized patient, notably opioids and corticosteroids through suppression the hypothalamic-pituitary-adrenal (HPA) axis and immune checkpoint inhibitors via autoimmune hypophysitis.

Testing for AI in the hospitalized patient presents a host of challenges. Among these are the variability in presentation of different types of AI, high rates of exogenous corticosteroid use, the impact of critical illness on the HPA axis, medical illness altering protein binding of serum cortisol, interfering medications, the variation in assays used by laboratories, and the logistical challenges of obtaining appropriately timed phlebotomy.^2,3
 

Cortisol testing

An intact HPA axis results in ACTH-dependent cortisol release from the adrenal glands. Cortisol secretion exhibits circadian rhythm, with the highest levels in the early morning (6 a.m. to 8 a.m.) and the lowest at night (12 a.m.). It also is pulsatile, which may explain the range of “normal” morning serum cortisol observed in a study of healthy volunteers.³ Note that serum cortisol is equivalent to plasma cortisol in current immunoassays, and will henceforth be called “cortisol” in this paper.³

There are instances when morning cortisol may strongly suggest a diagnosis of AI on its own. A meta-analysis found that morning cortisol of < 5 mcg/dL predicts AI and morning cortisol of > 13 mcg/dL ruled out AI.⁴ The Endocrine Society of America favors dynamic assessment of adrenal function for most patients.²

Historically, the gold standard for assessing dynamic adrenal function has been the insulin tolerance test (ITT), whereby cortisol is measured after inducing hypoglycemia to a blood glucose < 35 mg/dL. ITT is logistically difficult and poses some risk to the patient. The corticotropin (or cosyntropin) stimulation test (CST), in which a supraphysiologic dose of a synthetic ACTH analog is administered parenterally to a patient and resultant cortisol levels are measured, has been validated against the ITT and is generally preferred.⁵ CST is used to diagnose primary AI as well as chronic secondary and tertiary AI, given that longstanding lack of ACTH stimulation causes atrophy of the adrenal glands. The sensitivity for secondary and tertiary AI is likely lower than primary AI especially in acute onset of disease.^6,7

In performance of the CST a baseline cortisol and ACTH are obtained, with subsequent cortisol testing at 30 and/or 60 minutes after administration of the ACTH analog (Figure 1). Currently, there is no consensus for which time point is preferred, but the 30-minute test is more sensitive for AI and the 60-minute test is more specific.^2,7,8

CST is typically performed using a “standard high dose” of 250 mcg of the ACTH analog. There has been interest in the use of a “low-dose” 1 mcg test, which is closer to normal physiologic stimulation of the adrenal glands and may have better sensitivity for early secondary or partial AI. However, the 250-mcg dose is easier to prepare and has fewer technical pitfalls in administration as well as a lower risk for false positive testing. At this point the data do not compellingly favor the use of low-dose CST testing in general practice.^2,3,7
 

Clinical decision making

Diagnostic evaluation should be guided by the likelihood of the disease (i.e., the pretest probability) (Figure 1). Begin with a review of the patient’s signs and symptoms, medical and family history, and medications with special consideration for opioids, exogenous steroids, and immune checkpoint inhibitors (Table 1).

For patients with low pretest probability for AI, morning cortisol and ACTH is a reasonable first test (Figure 1). A cortisol value of 18 mcg/dL or greater does not support AI and no further testing is needed.² Patients with morning cortisol of 13-18 mcg/dL could be followed clinically or could undergo further testing in the inpatient environment with CST, depending upon the clinical scenario.⁴ Patients with serum cortisol of <13 mcg/dL warrant CST.

For patients with moderate to high pretest probability for AI, we recommend initial testing with CST. While the results of high-dose CST are not necessarily impacted by time of day, if an a.m. cortisol has not yet been obtained and it is logistically feasible to do so, performing CST in the morning will provide the most useful data for clinical interpretation.

For patients presenting with possible adrenal crisis, it is essential not to delay treatment. In these patients, obtain a cortisol paired with ACTH and initiate treatment immediately. Further testing can be deferred until the time the patient is stable.²
 

Potential pitfalls

Interpreting cortisol requires awareness of multiple conditions that could directly impact the results.^2,3 (Table 2).

Currently available assays measure “total cortisol,” most of which is protein bound (cortisol-binding globulin as well as albumin). Therefore, conditions that lower serum protein (e.g., nephrotic syndrome, liver disease, inflammation) will lower the measured cortisol. Conversely, conditions that increase serum protein (e.g., estrogen excess in pregnancy and oral contraceptive use) will increase the measured cortisol.^2,3

It is also important to recognize that existing immunoassay testing techniques informed the established cut-off for exclusion of AI at 18 mcg/dL. With newer immunoassays and emerging liquid chromatography/tandem mass spectrometry, this cut-off may be lowered; thus the assay should be confirmed with the performing laboratory. There is emerging evidence that serum or plasma free cortisol and salivary cortisol testing for AI may be useful in certain cases, but these techniques are not yet widespread or included in clinical practice guidelines.^2,3,7
 

Population focus: Patients on exogenous steroids

Exogenous corticosteroids suppress the HPA axis via negative inhibition of CRH and ACTH release, often resulting in low endogenous cortisol levels which may or may not reflect true loss of adrenal function. In addition, many corticosteroids will be detected by standard serum cortisol tests that rely on immunoassays. For this reason, cortisol measurement and CST should be done at least 18-24 hours after the last dose of exogenous steroids.

Although the focus has been on higher doses and longer courses of steroids (e.g., chronic use of ≥ 5 mg prednisone daily, or ≥ 20 mg prednisone daily for > 3 weeks), there is increasing evidence that lower doses, shorter courses, and alternate routes (e.g., inhaled, intra-articular) can result in biochemical and clinical evidence of AI.⁹ Thus, a thorough history and exam should be obtained to determine all recent corticosteroid exposure and cushingoid features.
 

Application of the data to the case

To effectively assess the patient for adrenal insufficiency, we need additional information. First and foremost, is a description of the patient’s current clinical status. If she is demonstrating evidence of adrenal crisis, treatment should not be delayed for additional testing. If she is stable, a thorough history including use of corticosteroids by any route, pregnancy, oral contraceptives, recent surgery, and liver and kidney disease is essential.

Additional evaluation reveals the patient has been using her fluticasone inhaler daily. No other source of hyponatremia or lightheadedness is identified. The patient’s risk factors of corticosteroid use and unexplained hyponatremia with associated lightheadedness increase her pretest probability of AI and a single morning cortisol of 10 mcg/dL is insufficient to exclude adrenal insufficiency. The appropriate follow-up test is a standard high-dose cosyntropin stimulation test at least 18 hours after her last dose of fluticasone. A cortisol level > 18 mcg/dL at 30 minutes in the absence of other conditions that impact cortisol testing would not be suggestive of AI. A serum cortisol level of < 18 mcg/dL at 30 minutes would raise concern for abnormal adrenal reserve due to chronic corticosteroid therapy and would warrant referral to an endocrinologist.
 

Bottom line

An isolated serum cortisol is often insufficient to exclude adrenal insufficiency. Hospitalists should be aware of the many factors that impact the interpretation of this test.

Dr. Gordon is assistant professor of medicine at Tufts University, Boston, and a hospitalist at Maine Medical Center, Portland. She is the subspecialty education coordinator of inpatient medicine for the Internal Medicine Residency Program. Dr. Herrle is assistant professor of medicine at Tufts University and a hospitalist at Maine Medical Center. She is the associate director of medical student education for the department of internal medicine at MMC and a medical director for clinical informatics at MaineHealth.

References

1. Bleicken B et al. Delayed diagnosis of adrenal insufficiency is common: A cross-sectional study in 216 patients. Am J Med Sci. 2010;339(6):525-31. doi: 10.1097/MAJ.0b013e3181db6b7a.

2. Bornstein SR et al. Diagnosis and treatment of primary adrenal insufficiency: An Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2016 Feb;101(2):364-89.

3. El-Farhan N et al. Measuring cortisol in serum, urine and saliva – Are our assays good enough? Ann Clin Biochem. 2017 May;54(3):308-22. doi: 10.1177/0004563216687335.

4. Kazlauskaite R et al. Corticotropin tests for hypothalamic-pituitary-adrenal insufficiency: A metaanalysis. J Clin Endocrinol Metab. 2008;93:4245-53.

5. Wood JB et al. A rapid test of adrenocortical function. Lancet. 1965;191:243-5.

6. Singh Ospina N et al. ACTH stimulation tests for the diagnosis of adrenal insufficiency: systematic review and meta-analysis. J Clin Endocrinol Metab. 2016;101(2):427-34.

7. Burgos N et al. Pitfalls in the interpretation of the cosyntropin stimulation test for the diagnosis of adrenal insufficiency. Curr Opin Endocrinol Diabetes Obes. 2019;26(3):139-45.

8. Odom DC et al. A Single, post-ACTH cortisol measurement to screen for adrenal insufficiency in the hospitalized patient. J Hosp Med. 2018;13(8):526-30. doi: 10.12788/jhm.2928.

9. Broersen LHA et al. Adrenal insufficiency in corticosteroids use: Systematic review and meta-analysis. J Clin Endocrinol Metab. 2015;100(6): 2171-80.
 

Key points

• In general, random cortisol testing is of limited value and should be avoided.

• Serum cortisol testing in the hospitalized patient is impacted by a variety of patient and disease factors and should be interpreted carefully.

• For patients with low pretest probability of adrenal insufficiency, early morning serum cortisol testing may be sufficient to exclude the diagnosis.

• For patients with moderate to high pretest probability of adrenal insufficiency, standard high-dose (250 mcg) corticotropin stimulation testing is preferred.
 

Additional reading

Bornstein SR et al. Diagnosis and treatment of primary adrenal insufficiency: An Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2016 Feb;101(2):364-89.

Burgos N et al. Pitfalls in the interpretation of the cosyntropin stimulation test for the diagnosis of adrenal insufficiency. Curr Opin Endocrinol Diabetes Obes. 2019;26(3):139-45.
 

Quiz

An 82 y.o. woman with depression is admitted from her long-term care facility with worsening weakness and mild hypoglycemia. Her supine vital signs are stable, but she exhibits a drop in systolic blood pressure of 21 mm Hg upon standing. There is no evidence of infection by history, exam, or initial workup. She is not on chronic corticosteroids by any route.

What would be your initial workup for adrenal insufficiency?

A) Morning serum cortisol and ACTH

B) Insulin tolerance test

C) Corticotropin stimulation test

D) Would not test at this point

Answer: C. Although her symptom of weakness is nonspecific, her hypoglycemia and orthostatic hypotension are concerning enough that she would qualify as moderate to high pretest probability for AI. In this setting, one would acquire a basal serum total cortisol and ACTH then administer the standard high-dose corticotropin stimulation test (250 mcg) followed by repeat serum total cortisol at 30 or 60 minutes.

Case

A 45-year-old female with moderate persistent asthma is admitted for right lower extremity cellulitis. She has hyponatremia with a sodium of 129 mEq/L and reports a history of longstanding fatigue and lightheadedness on standing. An early morning serum cortisol was 10 mcg/dL, normal per the reference range for the laboratory. Has adrenal insufficiency been excluded in this patient?

Overview

Adrenal insufficiency (AI) is a clinical syndrome characterized by a deficiency of cortisol. Presentation may range from nonspecific symptoms such as fatigue, weight loss, and gastrointestinal concerns to a fulminant adrenal crisis with severe weakness and hypotension (Table 1). The diagnosis of AI is commonly delayed, negatively impacting patients’ quality of life and risking dangerous complications.^1,2

AI can occur due to diseases of the adrenal glands themselves (primary) or impairment of adrenocorticotropin (ACTH) secretion from the pituitary (secondary) or corticotropin-releasing hormone (CRH) secretion from the hypothalamus (tertiary). In the hospital setting, causes of primary AI may include autoimmune disease, infection, metastatic disease, hemorrhage, and adverse medication effects. Secondary and tertiary AI would be of particular concern for patients with traumatic brain injuries or pituitary surgery, but also are seen commonly as a result of adverse medication effects in the hospitalized patient, notably opioids and corticosteroids through suppression the hypothalamic-pituitary-adrenal (HPA) axis and immune checkpoint inhibitors via autoimmune hypophysitis.

Testing for AI in the hospitalized patient presents a host of challenges. Among these are the variability in presentation of different types of AI, high rates of exogenous corticosteroid use, the impact of critical illness on the HPA axis, medical illness altering protein binding of serum cortisol, interfering medications, the variation in assays used by laboratories, and the logistical challenges of obtaining appropriately timed phlebotomy.^2,3
 

Cortisol testing

An intact HPA axis results in ACTH-dependent cortisol release from the adrenal glands. Cortisol secretion exhibits circadian rhythm, with the highest levels in the early morning (6 a.m. to 8 a.m.) and the lowest at night (12 a.m.). It also is pulsatile, which may explain the range of “normal” morning serum cortisol observed in a study of healthy volunteers.³ Note that serum cortisol is equivalent to plasma cortisol in current immunoassays, and will henceforth be called “cortisol” in this paper.³

There are instances when morning cortisol may strongly suggest a diagnosis of AI on its own. A meta-analysis found that morning cortisol of < 5 mcg/dL predicts AI and morning cortisol of > 13 mcg/dL ruled out AI.⁴ The Endocrine Society of America favors dynamic assessment of adrenal function for most patients.²

Historically, the gold standard for assessing dynamic adrenal function has been the insulin tolerance test (ITT), whereby cortisol is measured after inducing hypoglycemia to a blood glucose < 35 mg/dL. ITT is logistically difficult and poses some risk to the patient. The corticotropin (or cosyntropin) stimulation test (CST), in which a supraphysiologic dose of a synthetic ACTH analog is administered parenterally to a patient and resultant cortisol levels are measured, has been validated against the ITT and is generally preferred.⁵ CST is used to diagnose primary AI as well as chronic secondary and tertiary AI, given that longstanding lack of ACTH stimulation causes atrophy of the adrenal glands. The sensitivity for secondary and tertiary AI is likely lower than primary AI especially in acute onset of disease.^6,7

In performance of the CST a baseline cortisol and ACTH are obtained, with subsequent cortisol testing at 30 and/or 60 minutes after administration of the ACTH analog (Figure 1). Currently, there is no consensus for which time point is preferred, but the 30-minute test is more sensitive for AI and the 60-minute test is more specific.^2,7,8

CST is typically performed using a “standard high dose” of 250 mcg of the ACTH analog. There has been interest in the use of a “low-dose” 1 mcg test, which is closer to normal physiologic stimulation of the adrenal glands and may have better sensitivity for early secondary or partial AI. However, the 250-mcg dose is easier to prepare and has fewer technical pitfalls in administration as well as a lower risk for false positive testing. At this point the data do not compellingly favor the use of low-dose CST testing in general practice.^2,3,7
 

Clinical decision making

Diagnostic evaluation should be guided by the likelihood of the disease (i.e., the pretest probability) (Figure 1). Begin with a review of the patient’s signs and symptoms, medical and family history, and medications with special consideration for opioids, exogenous steroids, and immune checkpoint inhibitors (Table 1).

For patients with low pretest probability for AI, morning cortisol and ACTH is a reasonable first test (Figure 1). A cortisol value of 18 mcg/dL or greater does not support AI and no further testing is needed.² Patients with morning cortisol of 13-18 mcg/dL could be followed clinically or could undergo further testing in the inpatient environment with CST, depending upon the clinical scenario.⁴ Patients with serum cortisol of <13 mcg/dL warrant CST.

For patients with moderate to high pretest probability for AI, we recommend initial testing with CST. While the results of high-dose CST are not necessarily impacted by time of day, if an a.m. cortisol has not yet been obtained and it is logistically feasible to do so, performing CST in the morning will provide the most useful data for clinical interpretation.

For patients presenting with possible adrenal crisis, it is essential not to delay treatment. In these patients, obtain a cortisol paired with ACTH and initiate treatment immediately. Further testing can be deferred until the time the patient is stable.²
 

Potential pitfalls

Interpreting cortisol requires awareness of multiple conditions that could directly impact the results.^2,3 (Table 2).

Currently available assays measure “total cortisol,” most of which is protein bound (cortisol-binding globulin as well as albumin). Therefore, conditions that lower serum protein (e.g., nephrotic syndrome, liver disease, inflammation) will lower the measured cortisol. Conversely, conditions that increase serum protein (e.g., estrogen excess in pregnancy and oral contraceptive use) will increase the measured cortisol.^2,3

It is also important to recognize that existing immunoassay testing techniques informed the established cut-off for exclusion of AI at 18 mcg/dL. With newer immunoassays and emerging liquid chromatography/tandem mass spectrometry, this cut-off may be lowered; thus the assay should be confirmed with the performing laboratory. There is emerging evidence that serum or plasma free cortisol and salivary cortisol testing for AI may be useful in certain cases, but these techniques are not yet widespread or included in clinical practice guidelines.^2,3,7
 

Population focus: Patients on exogenous steroids

Exogenous corticosteroids suppress the HPA axis via negative inhibition of CRH and ACTH release, often resulting in low endogenous cortisol levels which may or may not reflect true loss of adrenal function. In addition, many corticosteroids will be detected by standard serum cortisol tests that rely on immunoassays. For this reason, cortisol measurement and CST should be done at least 18-24 hours after the last dose of exogenous steroids.

Although the focus has been on higher doses and longer courses of steroids (e.g., chronic use of ≥ 5 mg prednisone daily, or ≥ 20 mg prednisone daily for > 3 weeks), there is increasing evidence that lower doses, shorter courses, and alternate routes (e.g., inhaled, intra-articular) can result in biochemical and clinical evidence of AI.⁹ Thus, a thorough history and exam should be obtained to determine all recent corticosteroid exposure and cushingoid features.
 

Application of the data to the case

To effectively assess the patient for adrenal insufficiency, we need additional information. First and foremost, is a description of the patient’s current clinical status. If she is demonstrating evidence of adrenal crisis, treatment should not be delayed for additional testing. If she is stable, a thorough history including use of corticosteroids by any route, pregnancy, oral contraceptives, recent surgery, and liver and kidney disease is essential.

Additional evaluation reveals the patient has been using her fluticasone inhaler daily. No other source of hyponatremia or lightheadedness is identified. The patient’s risk factors of corticosteroid use and unexplained hyponatremia with associated lightheadedness increase her pretest probability of AI and a single morning cortisol of 10 mcg/dL is insufficient to exclude adrenal insufficiency. The appropriate follow-up test is a standard high-dose cosyntropin stimulation test at least 18 hours after her last dose of fluticasone. A cortisol level > 18 mcg/dL at 30 minutes in the absence of other conditions that impact cortisol testing would not be suggestive of AI. A serum cortisol level of < 18 mcg/dL at 30 minutes would raise concern for abnormal adrenal reserve due to chronic corticosteroid therapy and would warrant referral to an endocrinologist.
 

Bottom line

An isolated serum cortisol is often insufficient to exclude adrenal insufficiency. Hospitalists should be aware of the many factors that impact the interpretation of this test.

Dr. Gordon is assistant professor of medicine at Tufts University, Boston, and a hospitalist at Maine Medical Center, Portland. She is the subspecialty education coordinator of inpatient medicine for the Internal Medicine Residency Program. Dr. Herrle is assistant professor of medicine at Tufts University and a hospitalist at Maine Medical Center. She is the associate director of medical student education for the department of internal medicine at MMC and a medical director for clinical informatics at MaineHealth.

References

1. Bleicken B et al. Delayed diagnosis of adrenal insufficiency is common: A cross-sectional study in 216 patients. Am J Med Sci. 2010;339(6):525-31. doi: 10.1097/MAJ.0b013e3181db6b7a.

2. Bornstein SR et al. Diagnosis and treatment of primary adrenal insufficiency: An Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2016 Feb;101(2):364-89.

3. El-Farhan N et al. Measuring cortisol in serum, urine and saliva – Are our assays good enough? Ann Clin Biochem. 2017 May;54(3):308-22. doi: 10.1177/0004563216687335.

4. Kazlauskaite R et al. Corticotropin tests for hypothalamic-pituitary-adrenal insufficiency: A metaanalysis. J Clin Endocrinol Metab. 2008;93:4245-53.

5. Wood JB et al. A rapid test of adrenocortical function. Lancet. 1965;191:243-5.

6. Singh Ospina N et al. ACTH stimulation tests for the diagnosis of adrenal insufficiency: systematic review and meta-analysis. J Clin Endocrinol Metab. 2016;101(2):427-34.

7. Burgos N et al. Pitfalls in the interpretation of the cosyntropin stimulation test for the diagnosis of adrenal insufficiency. Curr Opin Endocrinol Diabetes Obes. 2019;26(3):139-45.

8. Odom DC et al. A Single, post-ACTH cortisol measurement to screen for adrenal insufficiency in the hospitalized patient. J Hosp Med. 2018;13(8):526-30. doi: 10.12788/jhm.2928.

9. Broersen LHA et al. Adrenal insufficiency in corticosteroids use: Systematic review and meta-analysis. J Clin Endocrinol Metab. 2015;100(6): 2171-80.
 

Key points

• In general, random cortisol testing is of limited value and should be avoided.

• Serum cortisol testing in the hospitalized patient is impacted by a variety of patient and disease factors and should be interpreted carefully.

• For patients with low pretest probability of adrenal insufficiency, early morning serum cortisol testing may be sufficient to exclude the diagnosis.

• For patients with moderate to high pretest probability of adrenal insufficiency, standard high-dose (250 mcg) corticotropin stimulation testing is preferred.
 

Additional reading

Bornstein SR et al. Diagnosis and treatment of primary adrenal insufficiency: An Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2016 Feb;101(2):364-89.

Burgos N et al. Pitfalls in the interpretation of the cosyntropin stimulation test for the diagnosis of adrenal insufficiency. Curr Opin Endocrinol Diabetes Obes. 2019;26(3):139-45.
 

Quiz

An 82 y.o. woman with depression is admitted from her long-term care facility with worsening weakness and mild hypoglycemia. Her supine vital signs are stable, but she exhibits a drop in systolic blood pressure of 21 mm Hg upon standing. There is no evidence of infection by history, exam, or initial workup. She is not on chronic corticosteroids by any route.

What would be your initial workup for adrenal insufficiency?

A) Morning serum cortisol and ACTH

B) Insulin tolerance test

C) Corticotropin stimulation test

D) Would not test at this point

Answer: C. Although her symptom of weakness is nonspecific, her hypoglycemia and orthostatic hypotension are concerning enough that she would qualify as moderate to high pretest probability for AI. In this setting, one would acquire a basal serum total cortisol and ACTH then administer the standard high-dose corticotropin stimulation test (250 mcg) followed by repeat serum total cortisol at 30 or 60 minutes.

Suicide by hanging results in many deaths, and half of those survivors who are admitted later die from cardiac arrest.

Although hanging is a common form of suicide, studies of the clinical outcomes of near-hanging injury are rare. To address this void, Louise de Charentenay, MD, of the Medical-Surgical Intensive Care Unit, Centre Hospitalier de Versailles (France) and colleagues examined the vital and functional outcomes of more than 800 patients with suicidal near-hanging injury over 2 decades. Despite the high in-hospital mortality rate among survivors, those who do survive have an excellent chance of a full neurocognitive recovery. The investigators published their findings in Chest.
 

New data on near-hanging injuries

Near hanging refers to strangulation or hanging that doesn’t immediately lead to death. Little data have been available on this subject, particularly on the morbidity and mortality of patients admitted to the ICU following near-hanging injuries. In a retrospective analysis spanning 23 years (1992-2014), researchers looked at outcomes and early predictors of hospital deaths in patients with this injury. The study included 886 adult patients who were admitted to 31 university or university-affiliated ICUs in France and Belgium following successful resuscitation of suicidal near-hanging injury.

Investigators used logistic multivariate regression to report vital and functional outcomes at hospital discharge as a primary objective. They also aimed to identify predictors of hospital mortality in these patients. 

Among all patients, 450 (50.8%) had hanging-induced cardiac arrest and of these, 371 (95.4%) eventually died. Although the rate of crude hospital deaths decreased over the 23-year period, hanging-induced cardiac arrest emerged as the strongest predictor of hospital mortality, followed by high blood lactate and hyperglycemia at ICU admission. “Hanging-induced cardiac arrest and worse consciousness impairment at ICU admission are directly related to the hanging, whereas higher glycemia and lactate levels at ICU admission represent biochemical markers of physiologic perturbation and injury severity that may suggest avenues for improvement in prehospital care,” wrote the investigators.

More than 56% of the patients survived to discharge, with a majority achieving favorable outcomes (a Glasgow Outcome Scale scores of 4 or 5 at discharge).
 

‘COVID-lateral’ damage and ICU management

Casey D. Bryant, MD, of the department of anesthesiology and the department of emergency medicine at Wake Forest Baptist Health, Winston-Salem, N.C., has treated these patients in the ICU and is prepared to see more of them in light of the current situation. He said in an interview, “The “COVID-lateral” damage being unleashed on the population as a result of increased isolation, lack of access to resources, higher unemployment, and increased substance abuse was detailed recently in an article by one of my colleagues, Dr. Seth Hawkins (Emerg Med News. 2020 Jun;42[6]:1,31-2). According to the Centers for Disease Control and Prevention, hanging is the second leading cause of suicide in the United States, and one can only assume that with increased mental health crises there will also be an increased number of hanging attempts.”

Dr. Bryant suggested that the first task of doctors who learn that a near-hanging patient has been admitted is to “recover from the gut-punch you feel when you learn that a fellow human has tried to take their own life.” Once one is composed, he said, the first order of business is to come up with a treatment plan, one that typically begins with the airway. “These patients are at a high risk for cervical vertebrae injury (e.g., hangman’s fracture), spinal cord injury, tracheal injury, and neck vessel injury or dissection, so care must be taken to maintain in-line stabilization and limit movement of the neck during intubation while also being prepared for all manner of airway disasters. After airway management, addressing traumatic injuries, and initial stabilization, the focus then shifts to ‘bread and butter’ critical care, including optimization of ventilator management, titration of analgosedation, providing adequate nutrition, and strict avoidance of hypoxia, hypotension, fever, and either hyper- or hypoglycemia.”

Dr. Bryant noted that targeted temperature management prescriptions remain an area of debate in those with comatose state after hanging, but fever should absolutely be avoided. He added: “As the path to recovery begins to be forged, the full gamut of mental health resources should be provided to the patients in order to give them the best chance for success once they leave the ICU, and ultimately the hospital.”

The different hospitals seemed to have varying degrees of success in saving these patients, which is surprising, Mangala Narasimhan, DO, FCCP, regional director of critical care, director of the acute lung injury/ECMO center at Northwell and a professor of medicine at the Hofstra/Northwell School of Medicine, New York, said in an interview. “Usually, the death rate for cardiac arrest is high and the death rate for hanging is high. But here, it was high in some places and low in others.” Different time frames from presenting from hanging and different treatments may explain this, said Dr. Narasimhan.
 

Patient characteristics

Consistent with previous research, near-hanging patients are predominantly male, have at least one psychiatric diagnosis and a previous suicidal attempt (rarely by hanging), and abuse substances such as an alcohol, Stéphane Legriel, MD, PhD, the study’s corresponding author, said in an interview. Overall, 67.7% of the patients had a diagnosed mental illness and 30% had previously attempted suicide. Most of the hangings took place at home (79%), while some took place in a hospital ward (6%), a correctional facility (7%), or outside (5%).

The study had several limitations: It applied only to near-hanging patients admitted to the ICU, and its long duration may have resulted in heterogeneity of the population and therapeutic interventions, and in some missing data. “However, the multivariate analysis was adjusted for the time period and we carried out a sensitivity analysis after multiple imputation for missing data by means of chained equations, which reinforces confidence in our findings,” Dr. Legriel said. Next steps are to conduct a prospective data collection.
 

Postdischarge recovery and psychiatric follow-up

Those left to treat survivors of near-hangings are psychiatrists and other mental health clinicians, Eric M. Plakun, MD, said in an interview.

“Some of these survivors will regret they survived and remain high suicide risks. Some will feel their lives are transformed or at least no longer as intensely drawn to suicide as a solution to a life filled with the impact of adversity, trauma, comorbidity, and other struggles – but even these individuals will still have to face the often complex underlying issues that led them to choose suicide as a solution,” said Dr. Plakun, medical director and CEO of the Austen Riggs Center in Stockbridge, Mass.

Patients with medically serious suicide attempts are seen a lot at Austen Riggs, he said, because acute inpatient settings are designed for brief, crisis-focused treatment of those for whom safety is an issue. After the crisis has been stabilized, patients are discharged, and then must begin to achieve recovery as outpatients, he said.

John Kruse, MD, PhD, a psychiatrist who practices in San Francisco, praised the size and the breath of the study. “One limitation was the reliance on hospital records, without an opportunity to directly evaluate or interview the patients involved.”

The authors disclosed no conflicts of interest. The study received grant support from the French public funding agency, Délégation la Recherche Clinique et de l’Innovation in Versailles, France.

SOURCE: de Charentenay L et al. 2020 Aug 3. doi: 10.1016/j.chest.2020.07.064

Suicide by hanging results in many deaths, and half of those survivors who are admitted later die from cardiac arrest.

Although hanging is a common form of suicide, studies of the clinical outcomes of near-hanging injury are rare. To address this void, Louise de Charentenay, MD, of the Medical-Surgical Intensive Care Unit, Centre Hospitalier de Versailles (France) and colleagues examined the vital and functional outcomes of more than 800 patients with suicidal near-hanging injury over 2 decades. Despite the high in-hospital mortality rate among survivors, those who do survive have an excellent chance of a full neurocognitive recovery. The investigators published their findings in Chest.
 

New data on near-hanging injuries

Near hanging refers to strangulation or hanging that doesn’t immediately lead to death. Little data have been available on this subject, particularly on the morbidity and mortality of patients admitted to the ICU following near-hanging injuries. In a retrospective analysis spanning 23 years (1992-2014), researchers looked at outcomes and early predictors of hospital deaths in patients with this injury. The study included 886 adult patients who were admitted to 31 university or university-affiliated ICUs in France and Belgium following successful resuscitation of suicidal near-hanging injury.

Investigators used logistic multivariate regression to report vital and functional outcomes at hospital discharge as a primary objective. They also aimed to identify predictors of hospital mortality in these patients. 

Among all patients, 450 (50.8%) had hanging-induced cardiac arrest and of these, 371 (95.4%) eventually died. Although the rate of crude hospital deaths decreased over the 23-year period, hanging-induced cardiac arrest emerged as the strongest predictor of hospital mortality, followed by high blood lactate and hyperglycemia at ICU admission. “Hanging-induced cardiac arrest and worse consciousness impairment at ICU admission are directly related to the hanging, whereas higher glycemia and lactate levels at ICU admission represent biochemical markers of physiologic perturbation and injury severity that may suggest avenues for improvement in prehospital care,” wrote the investigators.

More than 56% of the patients survived to discharge, with a majority achieving favorable outcomes (a Glasgow Outcome Scale scores of 4 or 5 at discharge).
 

‘COVID-lateral’ damage and ICU management

Casey D. Bryant, MD, of the department of anesthesiology and the department of emergency medicine at Wake Forest Baptist Health, Winston-Salem, N.C., has treated these patients in the ICU and is prepared to see more of them in light of the current situation. He said in an interview, “The “COVID-lateral” damage being unleashed on the population as a result of increased isolation, lack of access to resources, higher unemployment, and increased substance abuse was detailed recently in an article by one of my colleagues, Dr. Seth Hawkins (Emerg Med News. 2020 Jun;42[6]:1,31-2). According to the Centers for Disease Control and Prevention, hanging is the second leading cause of suicide in the United States, and one can only assume that with increased mental health crises there will also be an increased number of hanging attempts.”

Dr. Bryant suggested that the first task of doctors who learn that a near-hanging patient has been admitted is to “recover from the gut-punch you feel when you learn that a fellow human has tried to take their own life.” Once one is composed, he said, the first order of business is to come up with a treatment plan, one that typically begins with the airway. “These patients are at a high risk for cervical vertebrae injury (e.g., hangman’s fracture), spinal cord injury, tracheal injury, and neck vessel injury or dissection, so care must be taken to maintain in-line stabilization and limit movement of the neck during intubation while also being prepared for all manner of airway disasters. After airway management, addressing traumatic injuries, and initial stabilization, the focus then shifts to ‘bread and butter’ critical care, including optimization of ventilator management, titration of analgosedation, providing adequate nutrition, and strict avoidance of hypoxia, hypotension, fever, and either hyper- or hypoglycemia.”

Dr. Bryant noted that targeted temperature management prescriptions remain an area of debate in those with comatose state after hanging, but fever should absolutely be avoided. He added: “As the path to recovery begins to be forged, the full gamut of mental health resources should be provided to the patients in order to give them the best chance for success once they leave the ICU, and ultimately the hospital.”

The different hospitals seemed to have varying degrees of success in saving these patients, which is surprising, Mangala Narasimhan, DO, FCCP, regional director of critical care, director of the acute lung injury/ECMO center at Northwell and a professor of medicine at the Hofstra/Northwell School of Medicine, New York, said in an interview. “Usually, the death rate for cardiac arrest is high and the death rate for hanging is high. But here, it was high in some places and low in others.” Different time frames from presenting from hanging and different treatments may explain this, said Dr. Narasimhan.
 

Patient characteristics

Consistent with previous research, near-hanging patients are predominantly male, have at least one psychiatric diagnosis and a previous suicidal attempt (rarely by hanging), and abuse substances such as an alcohol, Stéphane Legriel, MD, PhD, the study’s corresponding author, said in an interview. Overall, 67.7% of the patients had a diagnosed mental illness and 30% had previously attempted suicide. Most of the hangings took place at home (79%), while some took place in a hospital ward (6%), a correctional facility (7%), or outside (5%).

The study had several limitations: It applied only to near-hanging patients admitted to the ICU, and its long duration may have resulted in heterogeneity of the population and therapeutic interventions, and in some missing data. “However, the multivariate analysis was adjusted for the time period and we carried out a sensitivity analysis after multiple imputation for missing data by means of chained equations, which reinforces confidence in our findings,” Dr. Legriel said. Next steps are to conduct a prospective data collection.
 

Postdischarge recovery and psychiatric follow-up

Those left to treat survivors of near-hangings are psychiatrists and other mental health clinicians, Eric M. Plakun, MD, said in an interview.

“Some of these survivors will regret they survived and remain high suicide risks. Some will feel their lives are transformed or at least no longer as intensely drawn to suicide as a solution to a life filled with the impact of adversity, trauma, comorbidity, and other struggles – but even these individuals will still have to face the often complex underlying issues that led them to choose suicide as a solution,” said Dr. Plakun, medical director and CEO of the Austen Riggs Center in Stockbridge, Mass.

Patients with medically serious suicide attempts are seen a lot at Austen Riggs, he said, because acute inpatient settings are designed for brief, crisis-focused treatment of those for whom safety is an issue. After the crisis has been stabilized, patients are discharged, and then must begin to achieve recovery as outpatients, he said.

John Kruse, MD, PhD, a psychiatrist who practices in San Francisco, praised the size and the breath of the study. “One limitation was the reliance on hospital records, without an opportunity to directly evaluate or interview the patients involved.”

The authors disclosed no conflicts of interest. The study received grant support from the French public funding agency, Délégation la Recherche Clinique et de l’Innovation in Versailles, France.

SOURCE: de Charentenay L et al. 2020 Aug 3. doi: 10.1016/j.chest.2020.07.064

Suicide by hanging results in many deaths, and half of those survivors who are admitted later die from cardiac arrest.

Although hanging is a common form of suicide, studies of the clinical outcomes of near-hanging injury are rare. To address this void, Louise de Charentenay, MD, of the Medical-Surgical Intensive Care Unit, Centre Hospitalier de Versailles (France) and colleagues examined the vital and functional outcomes of more than 800 patients with suicidal near-hanging injury over 2 decades. Despite the high in-hospital mortality rate among survivors, those who do survive have an excellent chance of a full neurocognitive recovery. The investigators published their findings in Chest.
 

New data on near-hanging injuries

Near hanging refers to strangulation or hanging that doesn’t immediately lead to death. Little data have been available on this subject, particularly on the morbidity and mortality of patients admitted to the ICU following near-hanging injuries. In a retrospective analysis spanning 23 years (1992-2014), researchers looked at outcomes and early predictors of hospital deaths in patients with this injury. The study included 886 adult patients who were admitted to 31 university or university-affiliated ICUs in France and Belgium following successful resuscitation of suicidal near-hanging injury.

Investigators used logistic multivariate regression to report vital and functional outcomes at hospital discharge as a primary objective. They also aimed to identify predictors of hospital mortality in these patients. 

Among all patients, 450 (50.8%) had hanging-induced cardiac arrest and of these, 371 (95.4%) eventually died. Although the rate of crude hospital deaths decreased over the 23-year period, hanging-induced cardiac arrest emerged as the strongest predictor of hospital mortality, followed by high blood lactate and hyperglycemia at ICU admission. “Hanging-induced cardiac arrest and worse consciousness impairment at ICU admission are directly related to the hanging, whereas higher glycemia and lactate levels at ICU admission represent biochemical markers of physiologic perturbation and injury severity that may suggest avenues for improvement in prehospital care,” wrote the investigators.

More than 56% of the patients survived to discharge, with a majority achieving favorable outcomes (a Glasgow Outcome Scale scores of 4 or 5 at discharge).
 

‘COVID-lateral’ damage and ICU management

Casey D. Bryant, MD, of the department of anesthesiology and the department of emergency medicine at Wake Forest Baptist Health, Winston-Salem, N.C., has treated these patients in the ICU and is prepared to see more of them in light of the current situation. He said in an interview, “The “COVID-lateral” damage being unleashed on the population as a result of increased isolation, lack of access to resources, higher unemployment, and increased substance abuse was detailed recently in an article by one of my colleagues, Dr. Seth Hawkins (Emerg Med News. 2020 Jun;42[6]:1,31-2). According to the Centers for Disease Control and Prevention, hanging is the second leading cause of suicide in the United States, and one can only assume that with increased mental health crises there will also be an increased number of hanging attempts.”

Dr. Bryant suggested that the first task of doctors who learn that a near-hanging patient has been admitted is to “recover from the gut-punch you feel when you learn that a fellow human has tried to take their own life.” Once one is composed, he said, the first order of business is to come up with a treatment plan, one that typically begins with the airway. “These patients are at a high risk for cervical vertebrae injury (e.g., hangman’s fracture), spinal cord injury, tracheal injury, and neck vessel injury or dissection, so care must be taken to maintain in-line stabilization and limit movement of the neck during intubation while also being prepared for all manner of airway disasters. After airway management, addressing traumatic injuries, and initial stabilization, the focus then shifts to ‘bread and butter’ critical care, including optimization of ventilator management, titration of analgosedation, providing adequate nutrition, and strict avoidance of hypoxia, hypotension, fever, and either hyper- or hypoglycemia.”

Dr. Bryant noted that targeted temperature management prescriptions remain an area of debate in those with comatose state after hanging, but fever should absolutely be avoided. He added: “As the path to recovery begins to be forged, the full gamut of mental health resources should be provided to the patients in order to give them the best chance for success once they leave the ICU, and ultimately the hospital.”

The different hospitals seemed to have varying degrees of success in saving these patients, which is surprising, Mangala Narasimhan, DO, FCCP, regional director of critical care, director of the acute lung injury/ECMO center at Northwell and a professor of medicine at the Hofstra/Northwell School of Medicine, New York, said in an interview. “Usually, the death rate for cardiac arrest is high and the death rate for hanging is high. But here, it was high in some places and low in others.” Different time frames from presenting from hanging and different treatments may explain this, said Dr. Narasimhan.
 

Patient characteristics

Consistent with previous research, near-hanging patients are predominantly male, have at least one psychiatric diagnosis and a previous suicidal attempt (rarely by hanging), and abuse substances such as an alcohol, Stéphane Legriel, MD, PhD, the study’s corresponding author, said in an interview. Overall, 67.7% of the patients had a diagnosed mental illness and 30% had previously attempted suicide. Most of the hangings took place at home (79%), while some took place in a hospital ward (6%), a correctional facility (7%), or outside (5%).

The study had several limitations: It applied only to near-hanging patients admitted to the ICU, and its long duration may have resulted in heterogeneity of the population and therapeutic interventions, and in some missing data. “However, the multivariate analysis was adjusted for the time period and we carried out a sensitivity analysis after multiple imputation for missing data by means of chained equations, which reinforces confidence in our findings,” Dr. Legriel said. Next steps are to conduct a prospective data collection.
 

Postdischarge recovery and psychiatric follow-up

Those left to treat survivors of near-hangings are psychiatrists and other mental health clinicians, Eric M. Plakun, MD, said in an interview.

“Some of these survivors will regret they survived and remain high suicide risks. Some will feel their lives are transformed or at least no longer as intensely drawn to suicide as a solution to a life filled with the impact of adversity, trauma, comorbidity, and other struggles – but even these individuals will still have to face the often complex underlying issues that led them to choose suicide as a solution,” said Dr. Plakun, medical director and CEO of the Austen Riggs Center in Stockbridge, Mass.

Patients with medically serious suicide attempts are seen a lot at Austen Riggs, he said, because acute inpatient settings are designed for brief, crisis-focused treatment of those for whom safety is an issue. After the crisis has been stabilized, patients are discharged, and then must begin to achieve recovery as outpatients, he said.

John Kruse, MD, PhD, a psychiatrist who practices in San Francisco, praised the size and the breath of the study. “One limitation was the reliance on hospital records, without an opportunity to directly evaluate or interview the patients involved.”

The authors disclosed no conflicts of interest. The study received grant support from the French public funding agency, Délégation la Recherche Clinique et de l’Innovation in Versailles, France.

SOURCE: de Charentenay L et al. 2020 Aug 3. doi: 10.1016/j.chest.2020.07.064

Dersimelagon, a novel once-daily oral selective melanocortin-1 receptor agonist, significantly boosted sunlight tolerance in patients with erythropoietic protoporphyria in a multicenter, phase 2, randomized trial, Kirstine Belongie, PhD, reported at the virtual annual meeting of the American Academy of Dermatology.

Based upon these favorable phase 2 results, a pivotal phase 3 clinical trial is now underway, added Dr. Belongie of Mitsubishi Tanabe Pharma Development America, in Jersey City, N.J., the study sponsor.

Erythropoietic protoporphyria (EPP) is the most common cutaneous porphyria as well as the most common porphyria of any type in children. It’s a rare but devastating disorder, with an incidence estimated at 1 in 75,000-200,000. It involves acute cutaneous photosensitivity to sunlight, which takes the form of incapacitating burning pain that lasts 3-7 days and is then followed by erythema and edema.

“These phototoxic reactions are extremely painful and cause the patients to have extreme fear of the sun. They do everything they can to avoid the sun. It leads to a highly impaired quality of life that’s restricted to the indoors,” she explained.

Current first-line therapy is sun avoidance, the use of zinc oxide sunblock, and protective clothing. It’s inadequate for most patients. “There is a tremendously high unmet medical need for treatment options, especially in the pediatric population,” Dr. Belongie observed.

Patients with EPP experience prodromal symptoms – tingling, itching, and burning – which serve as a signal to get out of the sun immediately. As demonstrated in the phase 2 trial, dersimelagon prolongs the time to onset of these prodromal symptoms by increasing melanin density in the skin in a dose-dependent fashion.

The phase 2 study included 102 EPP patients, with an average age 40 years, at 9 sites, who were randomized double blind to 16 weeks of dersimelagon at 100 mg or 300 mg once daily or placebo. The goal was to increase their pain-free sunlight exposure time.

The primary endpoint was change from baseline to week 16 in the average daily time to first prodromal symptoms. There was a 20-minute increase with placebo, a 74-minute gain with dersimelagon at 100 mg, and an 83-minute gain with dersimelagon at 300 mg. The difference between active medication and placebo became significant at week 6.

Treatment-emergent adverse events leading to study discontinuation occurred in one patient on dersimelagon at 100 mg/day, five patients on the higher dose, and none on placebo. Dr. Belangie said that the drug was well tolerated, with roughly 90% of adverse events being mild or moderate in severity. The frequency of adverse events was dose-related. The most common were headache, nausea, and diarrhea, occurring in 29%, 46%, and 23%, respectively, of patients on dersimelagon at 300 mg/day, compared with 18%, 12% and 12% of those on placebo.

Consistent with the drug’s mechanism of action, there was also a dose-related increase in hyperpigmentation side effects. New freckles were documented in 15% and 31% of patients on low- and high-dose dersimelagon, skin hyperpigmentation in 9% and 31%, and melanocytic nevi in 12% and 20%.

The ongoing double-blind, international, phase 3 trial includes not only patients with EPP, but also individuals with X-linked porphyria, which has similar clinical symptoms. The trial is double blind for the first 26 weeks, followed by another 26 weeks of open-label treatment.

EPP is an inherited metabolic disorder caused by a genetic mutation resulting in deficient activity of the enzyme ferrochelatase. This leads to accumulation of protoporphyrin IX in erythrocytes, skin, and the liver. The excess protoporphyrin is excreted in bile and can cause hepatobiliary disease. Indeed, up to 5% of patients with EPP develop liver failure.

In October 2019, the Food and Drug Administration approved afamelanotide (Scenesse), also a melanocortin-1 receptor agonist, to increase pain-free light exposure in adults with a history of phototoxic reactions EPP; this was the first FDA-approved treatment for helping EPP patients increase their exposure to light, according to the agency. It is administered as an implant every 2 months.

Dr. Belangie is employed by the study sponsor.

[email protected]

Dersimelagon, a novel once-daily oral selective melanocortin-1 receptor agonist, significantly boosted sunlight tolerance in patients with erythropoietic protoporphyria in a multicenter, phase 2, randomized trial, Kirstine Belongie, PhD, reported at the virtual annual meeting of the American Academy of Dermatology.

Based upon these favorable phase 2 results, a pivotal phase 3 clinical trial is now underway, added Dr. Belongie of Mitsubishi Tanabe Pharma Development America, in Jersey City, N.J., the study sponsor.

Erythropoietic protoporphyria (EPP) is the most common cutaneous porphyria as well as the most common porphyria of any type in children. It’s a rare but devastating disorder, with an incidence estimated at 1 in 75,000-200,000. It involves acute cutaneous photosensitivity to sunlight, which takes the form of incapacitating burning pain that lasts 3-7 days and is then followed by erythema and edema.

“These phototoxic reactions are extremely painful and cause the patients to have extreme fear of the sun. They do everything they can to avoid the sun. It leads to a highly impaired quality of life that’s restricted to the indoors,” she explained.

Current first-line therapy is sun avoidance, the use of zinc oxide sunblock, and protective clothing. It’s inadequate for most patients. “There is a tremendously high unmet medical need for treatment options, especially in the pediatric population,” Dr. Belongie observed.

Patients with EPP experience prodromal symptoms – tingling, itching, and burning – which serve as a signal to get out of the sun immediately. As demonstrated in the phase 2 trial, dersimelagon prolongs the time to onset of these prodromal symptoms by increasing melanin density in the skin in a dose-dependent fashion.

The phase 2 study included 102 EPP patients, with an average age 40 years, at 9 sites, who were randomized double blind to 16 weeks of dersimelagon at 100 mg or 300 mg once daily or placebo. The goal was to increase their pain-free sunlight exposure time.

The primary endpoint was change from baseline to week 16 in the average daily time to first prodromal symptoms. There was a 20-minute increase with placebo, a 74-minute gain with dersimelagon at 100 mg, and an 83-minute gain with dersimelagon at 300 mg. The difference between active medication and placebo became significant at week 6.

Treatment-emergent adverse events leading to study discontinuation occurred in one patient on dersimelagon at 100 mg/day, five patients on the higher dose, and none on placebo. Dr. Belangie said that the drug was well tolerated, with roughly 90% of adverse events being mild or moderate in severity. The frequency of adverse events was dose-related. The most common were headache, nausea, and diarrhea, occurring in 29%, 46%, and 23%, respectively, of patients on dersimelagon at 300 mg/day, compared with 18%, 12% and 12% of those on placebo.

Consistent with the drug’s mechanism of action, there was also a dose-related increase in hyperpigmentation side effects. New freckles were documented in 15% and 31% of patients on low- and high-dose dersimelagon, skin hyperpigmentation in 9% and 31%, and melanocytic nevi in 12% and 20%.

The ongoing double-blind, international, phase 3 trial includes not only patients with EPP, but also individuals with X-linked porphyria, which has similar clinical symptoms. The trial is double blind for the first 26 weeks, followed by another 26 weeks of open-label treatment.

EPP is an inherited metabolic disorder caused by a genetic mutation resulting in deficient activity of the enzyme ferrochelatase. This leads to accumulation of protoporphyrin IX in erythrocytes, skin, and the liver. The excess protoporphyrin is excreted in bile and can cause hepatobiliary disease. Indeed, up to 5% of patients with EPP develop liver failure.

In October 2019, the Food and Drug Administration approved afamelanotide (Scenesse), also a melanocortin-1 receptor agonist, to increase pain-free light exposure in adults with a history of phototoxic reactions EPP; this was the first FDA-approved treatment for helping EPP patients increase their exposure to light, according to the agency. It is administered as an implant every 2 months.

Dr. Belangie is employed by the study sponsor.

[email protected]

Dersimelagon, a novel once-daily oral selective melanocortin-1 receptor agonist, significantly boosted sunlight tolerance in patients with erythropoietic protoporphyria in a multicenter, phase 2, randomized trial, Kirstine Belongie, PhD, reported at the virtual annual meeting of the American Academy of Dermatology.

Based upon these favorable phase 2 results, a pivotal phase 3 clinical trial is now underway, added Dr. Belongie of Mitsubishi Tanabe Pharma Development America, in Jersey City, N.J., the study sponsor.

Erythropoietic protoporphyria (EPP) is the most common cutaneous porphyria as well as the most common porphyria of any type in children. It’s a rare but devastating disorder, with an incidence estimated at 1 in 75,000-200,000. It involves acute cutaneous photosensitivity to sunlight, which takes the form of incapacitating burning pain that lasts 3-7 days and is then followed by erythema and edema.

“These phototoxic reactions are extremely painful and cause the patients to have extreme fear of the sun. They do everything they can to avoid the sun. It leads to a highly impaired quality of life that’s restricted to the indoors,” she explained.

Current first-line therapy is sun avoidance, the use of zinc oxide sunblock, and protective clothing. It’s inadequate for most patients. “There is a tremendously high unmet medical need for treatment options, especially in the pediatric population,” Dr. Belongie observed.

Patients with EPP experience prodromal symptoms – tingling, itching, and burning – which serve as a signal to get out of the sun immediately. As demonstrated in the phase 2 trial, dersimelagon prolongs the time to onset of these prodromal symptoms by increasing melanin density in the skin in a dose-dependent fashion.

The phase 2 study included 102 EPP patients, with an average age 40 years, at 9 sites, who were randomized double blind to 16 weeks of dersimelagon at 100 mg or 300 mg once daily or placebo. The goal was to increase their pain-free sunlight exposure time.

The primary endpoint was change from baseline to week 16 in the average daily time to first prodromal symptoms. There was a 20-minute increase with placebo, a 74-minute gain with dersimelagon at 100 mg, and an 83-minute gain with dersimelagon at 300 mg. The difference between active medication and placebo became significant at week 6.

Treatment-emergent adverse events leading to study discontinuation occurred in one patient on dersimelagon at 100 mg/day, five patients on the higher dose, and none on placebo. Dr. Belangie said that the drug was well tolerated, with roughly 90% of adverse events being mild or moderate in severity. The frequency of adverse events was dose-related. The most common were headache, nausea, and diarrhea, occurring in 29%, 46%, and 23%, respectively, of patients on dersimelagon at 300 mg/day, compared with 18%, 12% and 12% of those on placebo.

Consistent with the drug’s mechanism of action, there was also a dose-related increase in hyperpigmentation side effects. New freckles were documented in 15% and 31% of patients on low- and high-dose dersimelagon, skin hyperpigmentation in 9% and 31%, and melanocytic nevi in 12% and 20%.

The ongoing double-blind, international, phase 3 trial includes not only patients with EPP, but also individuals with X-linked porphyria, which has similar clinical symptoms. The trial is double blind for the first 26 weeks, followed by another 26 weeks of open-label treatment.

EPP is an inherited metabolic disorder caused by a genetic mutation resulting in deficient activity of the enzyme ferrochelatase. This leads to accumulation of protoporphyrin IX in erythrocytes, skin, and the liver. The excess protoporphyrin is excreted in bile and can cause hepatobiliary disease. Indeed, up to 5% of patients with EPP develop liver failure.

In October 2019, the Food and Drug Administration approved afamelanotide (Scenesse), also a melanocortin-1 receptor agonist, to increase pain-free light exposure in adults with a history of phototoxic reactions EPP; this was the first FDA-approved treatment for helping EPP patients increase their exposure to light, according to the agency. It is administered as an implant every 2 months.

Dr. Belangie is employed by the study sponsor.

[email protected]

In late June, Lisa Richardson, MD, emerged from Atlanta, Georgia’s initial COVID-19 lockdown, and “got back out there” for some overdue doctor’s appointments, including a mammogram.

The mammogram was a particular priority for her, since she is director of the CDC’s Division of Cancer Prevention and Control. But she knows that cancer screening is going to be a much tougher sell for the average person going forward in the pandemic era.

“It really is a challenge trying to get people to feel comfortable coming back in to be screened,” she said. Richardson was speaking recently at the AACR virtual meeting: COVID-19 and Cancer, a virtual symposium on cancer prevention and early detection in the COVID-19 pandemic organized by the American Association for Cancer Research.

While health service shutdowns and stay-at-home orders forced the country’s initial precipitous decline in cancer screening, fear of contracting COVID-19 is a big part of what is preventing patients from returning.

“We’ve known even pre-pandemic that people were hesitant to do cancer screening and in some ways this has really given them an out to say, ‘Well, I’m going to hold off on that colonoscopy,’ ” Amy Leader, MD, from Thomas Jefferson University’s Kimmel Cancer Center in Philadelphia, Pennsylvania, said during the symposium.
 

Estimating the pandemic’s impact on cancer care

While the impact of the pandemic on cancer can only be estimated at the moment, the prospects are already daunting, said Richardson, speculating that the hard-won 26% drop in cancer mortality over the past two decades “may be put on hold or reversed” by COVID-19.

There could be as many as 10,000 excess deaths in the US from colorectal and breast cancer alone because of COVID-19 delays, predicted Norman E. Sharpless, director of the US National Cancer Institute in Bethesda, Maryland.

But even Sharpless acknowledges that his modeling gives a conservative estimate, “as it does not consider other cancer types, it does not account for the additional nonlethal morbidity from upstaging, and it assumes a moderate disruption in care that completely resolves after 6 months.”

With still no end to the pandemic in sight, the true scope of cancer screening and treatment disruptions will take a long time to assess, but several studies presented during the symposium revealed some early indications.

A national survey launched in mid-May, which involved 534 women either diagnosed with breast cancer or undergoing screening or diagnostic evaluation for it, found that delays in screening were reported by 31.7% of those with breast cancer, and 26.7% of those without. Additionally, 21% of those on active treatment for breast cancer reported treatment delays.

“It’s going to be really important to implement strategies to help patients return to care ... creating a culture and a feeling of safety among patients and communicating through the uncertainty that exists in the pandemic,” said study investigator Erica T. Warner, ScD MPH, from Massachusetts General Hospital, Boston.

Screening for prostate cancer (via prostate-specific antigen testing) also declined, though not as dramatically as that for breast cancer, noted Mara Epstein, ScD, from The Meyers Primary Care Institute, University of Massachusetts Medical School, Worcester. Her study at a large healthcare provider group compared rates of both screening and diagnostic mammographies, and also PSA testing, as well as breast and prostate biopsies in the first five months of 2020 vs the same months in 2019.

While a decrease from 2019 to 2020 was seen in all procedures over the entire study period, the greatest decline was seen in April for screening mammography (down 98%), and tomosynthesis (down 96%), as well as PSA testing (down 83%), she said.

More recent figures are hard to come by, but a recent weekly survey from the Primary Care Collaborative shows 46% of practices are offering preventive and chronic care management visits, but patients are not scheduling them, and 44% report that in-person visit volume is between 30%-50% below normal over the last 4 weeks. 
 

Will COVID-19 exacerbate racial disparities in cancer?

Neither of the studies presented at the symposium analyzed cancer care disruptions by race, but there was concern among some panelists that cancer care disparities that existed before the pandemic will be magnified further.

“Over the next several months and into the next year there’s going to be some catch-up in screening and treatment, and one of my concerns is minority and underserved populations will not partake in that catch-up the way many middle-class Americans will,” said Otis Brawley, MD, from Johns Hopkins University, Baltimore, Maryland.

There is ample evidence that minority populations have been disproportionately hit by COVID-19, job losses, and lost health insurance, said the CDC’s Richardson, and all these factors could widen the cancer gap.

“It’s not a race thing, it’s a ‘what do you do thing,’ and an access to care thing, and what your socioeconomic status is,” Richardson said in an interview. “People who didn’t have sick leave before the pandemic still don’t have sick leave; if they didn’t have time to get their mammogram they still don’t have time.”

But she acknowledges that evidence is still lacking. Could some minority populations actually be less fearful of medical encounters because their work has already prevented them from sheltering in place? “It could go either way,” she said. “They might be less wary of venturing out into the clinic, but they also might reason that they’ve exposed themselves enough already at work and don’t want any additional exposure.”

In that regard, Richardson suggests population-specific messaging will be an important way of communicating with under-served populations to restart screening.

“We’re struggling at CDC with how to develop messages that resonate within different communities, because we’re missing the point of actually speaking to people within their culture and within the places that they live,” she said. “Just saying the same thing and putting a black face on it is not going to make a difference; you actually have to speak the language of the people you’re trying to reach — the same message in different packages.”

To that end, even before the pandemic, the CDC supported the development of Make It Your Own, a website that uses “evidence-based strategies” to assist healthcare organizations in customizing health information “by race, ethnicity, age, gender and location”, and target messages  to “specific populations, cultural groups and languages”.

But Mass General’s Warner says she’s not sure she would argue for messages to be tailored by race, “at least not without evidence that values and priorities regarding returning to care differ between racial/ethnic groups.”

“Tailoring in the absence of data requires assumptions that may or may not be correct and ignores within-group heterogeneity,” Warner told Medscape Medical News. “However, I do believe that messaging about return to cancer screening and care should be multifaceted and use diverse imagery. This recognizes that some messages will resonate more or less with individuals based on their own characteristics, of which race may be one.”

Warner does believe in the power of tailored messaging though. “Part of the onus for healthcare institutions and providers is to make some decisions about who it is really important to bring back in soonest,” she said.

“Those are the ones we want to prioritize, as opposed to those who we want to get back into care but we don’t need to get them in right now,” Warner emphasized. “As they are balancing all the needs of their family and their community and their other needs, messaging that adds additional stress, worry, anxiety and shame is not what we want to do. So really we need to distinguish between these populations, identify the priorities, hit the hard message to people who really need it now, and encourage others to come back in as they can.”
 

Building trust

All the panelists agreed that building trust with the public will be key to getting cancer care back on track.  

“I don’t think anyone trusts the healthcare community right now, but we already had this baseline distrust of healthcare among many minority communities, and now with COVID-19, the African American community in particular is seeing people go into the hospital and never come back,” said Richardson.

For Warner, the onus really falls on healthcare institutions. “We have to be proactive and not leave the burden of deciding when and how to return to care up to patients,” she said.

“What we need to focus on as much as possible is to get people to realize it is safe to come see the doctor,” said Johns Hopkins oncologist Brawley. “We have to make it safe for them to come see us, and then we have to convince them it is safe to come see us.”

Venturing out to her mammography appointment in early June, Richardson said she felt safe. “Everything was just the way it was supposed to be, everyone was masked, everyone was washing their hands,” she said.

Yet, by mid-June she had contracted COVID-19. “I don’t know where I got it,” she said. “No matter how careful you are, understand that if you’re in a total red spot, as I am, you can just get it.”

This article first appeared on Medscape.com.

In late June, Lisa Richardson, MD, emerged from Atlanta, Georgia’s initial COVID-19 lockdown, and “got back out there” for some overdue doctor’s appointments, including a mammogram.

The mammogram was a particular priority for her, since she is director of the CDC’s Division of Cancer Prevention and Control. But she knows that cancer screening is going to be a much tougher sell for the average person going forward in the pandemic era.

“It really is a challenge trying to get people to feel comfortable coming back in to be screened,” she said. Richardson was speaking recently at the AACR virtual meeting: COVID-19 and Cancer, a virtual symposium on cancer prevention and early detection in the COVID-19 pandemic organized by the American Association for Cancer Research.

While health service shutdowns and stay-at-home orders forced the country’s initial precipitous decline in cancer screening, fear of contracting COVID-19 is a big part of what is preventing patients from returning.

“We’ve known even pre-pandemic that people were hesitant to do cancer screening and in some ways this has really given them an out to say, ‘Well, I’m going to hold off on that colonoscopy,’ ” Amy Leader, MD, from Thomas Jefferson University’s Kimmel Cancer Center in Philadelphia, Pennsylvania, said during the symposium.
 

Estimating the pandemic’s impact on cancer care

While the impact of the pandemic on cancer can only be estimated at the moment, the prospects are already daunting, said Richardson, speculating that the hard-won 26% drop in cancer mortality over the past two decades “may be put on hold or reversed” by COVID-19.

There could be as many as 10,000 excess deaths in the US from colorectal and breast cancer alone because of COVID-19 delays, predicted Norman E. Sharpless, director of the US National Cancer Institute in Bethesda, Maryland.

But even Sharpless acknowledges that his modeling gives a conservative estimate, “as it does not consider other cancer types, it does not account for the additional nonlethal morbidity from upstaging, and it assumes a moderate disruption in care that completely resolves after 6 months.”

With still no end to the pandemic in sight, the true scope of cancer screening and treatment disruptions will take a long time to assess, but several studies presented during the symposium revealed some early indications.

A national survey launched in mid-May, which involved 534 women either diagnosed with breast cancer or undergoing screening or diagnostic evaluation for it, found that delays in screening were reported by 31.7% of those with breast cancer, and 26.7% of those without. Additionally, 21% of those on active treatment for breast cancer reported treatment delays.

“It’s going to be really important to implement strategies to help patients return to care ... creating a culture and a feeling of safety among patients and communicating through the uncertainty that exists in the pandemic,” said study investigator Erica T. Warner, ScD MPH, from Massachusetts General Hospital, Boston.

Screening for prostate cancer (via prostate-specific antigen testing) also declined, though not as dramatically as that for breast cancer, noted Mara Epstein, ScD, from The Meyers Primary Care Institute, University of Massachusetts Medical School, Worcester. Her study at a large healthcare provider group compared rates of both screening and diagnostic mammographies, and also PSA testing, as well as breast and prostate biopsies in the first five months of 2020 vs the same months in 2019.

While a decrease from 2019 to 2020 was seen in all procedures over the entire study period, the greatest decline was seen in April for screening mammography (down 98%), and tomosynthesis (down 96%), as well as PSA testing (down 83%), she said.

More recent figures are hard to come by, but a recent weekly survey from the Primary Care Collaborative shows 46% of practices are offering preventive and chronic care management visits, but patients are not scheduling them, and 44% report that in-person visit volume is between 30%-50% below normal over the last 4 weeks. 
 

Will COVID-19 exacerbate racial disparities in cancer?

Neither of the studies presented at the symposium analyzed cancer care disruptions by race, but there was concern among some panelists that cancer care disparities that existed before the pandemic will be magnified further.

“Over the next several months and into the next year there’s going to be some catch-up in screening and treatment, and one of my concerns is minority and underserved populations will not partake in that catch-up the way many middle-class Americans will,” said Otis Brawley, MD, from Johns Hopkins University, Baltimore, Maryland.

There is ample evidence that minority populations have been disproportionately hit by COVID-19, job losses, and lost health insurance, said the CDC’s Richardson, and all these factors could widen the cancer gap.

“It’s not a race thing, it’s a ‘what do you do thing,’ and an access to care thing, and what your socioeconomic status is,” Richardson said in an interview. “People who didn’t have sick leave before the pandemic still don’t have sick leave; if they didn’t have time to get their mammogram they still don’t have time.”

But she acknowledges that evidence is still lacking. Could some minority populations actually be less fearful of medical encounters because their work has already prevented them from sheltering in place? “It could go either way,” she said. “They might be less wary of venturing out into the clinic, but they also might reason that they’ve exposed themselves enough already at work and don’t want any additional exposure.”

In that regard, Richardson suggests population-specific messaging will be an important way of communicating with under-served populations to restart screening.

“We’re struggling at CDC with how to develop messages that resonate within different communities, because we’re missing the point of actually speaking to people within their culture and within the places that they live,” she said. “Just saying the same thing and putting a black face on it is not going to make a difference; you actually have to speak the language of the people you’re trying to reach — the same message in different packages.”

To that end, even before the pandemic, the CDC supported the development of Make It Your Own, a website that uses “evidence-based strategies” to assist healthcare organizations in customizing health information “by race, ethnicity, age, gender and location”, and target messages  to “specific populations, cultural groups and languages”.

But Mass General’s Warner says she’s not sure she would argue for messages to be tailored by race, “at least not without evidence that values and priorities regarding returning to care differ between racial/ethnic groups.”

“Tailoring in the absence of data requires assumptions that may or may not be correct and ignores within-group heterogeneity,” Warner told Medscape Medical News. “However, I do believe that messaging about return to cancer screening and care should be multifaceted and use diverse imagery. This recognizes that some messages will resonate more or less with individuals based on their own characteristics, of which race may be one.”

Warner does believe in the power of tailored messaging though. “Part of the onus for healthcare institutions and providers is to make some decisions about who it is really important to bring back in soonest,” she said.

“Those are the ones we want to prioritize, as opposed to those who we want to get back into care but we don’t need to get them in right now,” Warner emphasized. “As they are balancing all the needs of their family and their community and their other needs, messaging that adds additional stress, worry, anxiety and shame is not what we want to do. So really we need to distinguish between these populations, identify the priorities, hit the hard message to people who really need it now, and encourage others to come back in as they can.”
 

Building trust

All the panelists agreed that building trust with the public will be key to getting cancer care back on track.  

“I don’t think anyone trusts the healthcare community right now, but we already had this baseline distrust of healthcare among many minority communities, and now with COVID-19, the African American community in particular is seeing people go into the hospital and never come back,” said Richardson.

For Warner, the onus really falls on healthcare institutions. “We have to be proactive and not leave the burden of deciding when and how to return to care up to patients,” she said.

“What we need to focus on as much as possible is to get people to realize it is safe to come see the doctor,” said Johns Hopkins oncologist Brawley. “We have to make it safe for them to come see us, and then we have to convince them it is safe to come see us.”

Venturing out to her mammography appointment in early June, Richardson said she felt safe. “Everything was just the way it was supposed to be, everyone was masked, everyone was washing their hands,” she said.

Yet, by mid-June she had contracted COVID-19. “I don’t know where I got it,” she said. “No matter how careful you are, understand that if you’re in a total red spot, as I am, you can just get it.”

This article first appeared on Medscape.com.

In late June, Lisa Richardson, MD, emerged from Atlanta, Georgia’s initial COVID-19 lockdown, and “got back out there” for some overdue doctor’s appointments, including a mammogram.

The mammogram was a particular priority for her, since she is director of the CDC’s Division of Cancer Prevention and Control. But she knows that cancer screening is going to be a much tougher sell for the average person going forward in the pandemic era.

“It really is a challenge trying to get people to feel comfortable coming back in to be screened,” she said. Richardson was speaking recently at the AACR virtual meeting: COVID-19 and Cancer, a virtual symposium on cancer prevention and early detection in the COVID-19 pandemic organized by the American Association for Cancer Research.

While health service shutdowns and stay-at-home orders forced the country’s initial precipitous decline in cancer screening, fear of contracting COVID-19 is a big part of what is preventing patients from returning.

“We’ve known even pre-pandemic that people were hesitant to do cancer screening and in some ways this has really given them an out to say, ‘Well, I’m going to hold off on that colonoscopy,’ ” Amy Leader, MD, from Thomas Jefferson University’s Kimmel Cancer Center in Philadelphia, Pennsylvania, said during the symposium.
 

Estimating the pandemic’s impact on cancer care

While the impact of the pandemic on cancer can only be estimated at the moment, the prospects are already daunting, said Richardson, speculating that the hard-won 26% drop in cancer mortality over the past two decades “may be put on hold or reversed” by COVID-19.

There could be as many as 10,000 excess deaths in the US from colorectal and breast cancer alone because of COVID-19 delays, predicted Norman E. Sharpless, director of the US National Cancer Institute in Bethesda, Maryland.

But even Sharpless acknowledges that his modeling gives a conservative estimate, “as it does not consider other cancer types, it does not account for the additional nonlethal morbidity from upstaging, and it assumes a moderate disruption in care that completely resolves after 6 months.”

With still no end to the pandemic in sight, the true scope of cancer screening and treatment disruptions will take a long time to assess, but several studies presented during the symposium revealed some early indications.

A national survey launched in mid-May, which involved 534 women either diagnosed with breast cancer or undergoing screening or diagnostic evaluation for it, found that delays in screening were reported by 31.7% of those with breast cancer, and 26.7% of those without. Additionally, 21% of those on active treatment for breast cancer reported treatment delays.

“It’s going to be really important to implement strategies to help patients return to care ... creating a culture and a feeling of safety among patients and communicating through the uncertainty that exists in the pandemic,” said study investigator Erica T. Warner, ScD MPH, from Massachusetts General Hospital, Boston.

Screening for prostate cancer (via prostate-specific antigen testing) also declined, though not as dramatically as that for breast cancer, noted Mara Epstein, ScD, from The Meyers Primary Care Institute, University of Massachusetts Medical School, Worcester. Her study at a large healthcare provider group compared rates of both screening and diagnostic mammographies, and also PSA testing, as well as breast and prostate biopsies in the first five months of 2020 vs the same months in 2019.

While a decrease from 2019 to 2020 was seen in all procedures over the entire study period, the greatest decline was seen in April for screening mammography (down 98%), and tomosynthesis (down 96%), as well as PSA testing (down 83%), she said.

More recent figures are hard to come by, but a recent weekly survey from the Primary Care Collaborative shows 46% of practices are offering preventive and chronic care management visits, but patients are not scheduling them, and 44% report that in-person visit volume is between 30%-50% below normal over the last 4 weeks. 
 

Will COVID-19 exacerbate racial disparities in cancer?

Neither of the studies presented at the symposium analyzed cancer care disruptions by race, but there was concern among some panelists that cancer care disparities that existed before the pandemic will be magnified further.

“Over the next several months and into the next year there’s going to be some catch-up in screening and treatment, and one of my concerns is minority and underserved populations will not partake in that catch-up the way many middle-class Americans will,” said Otis Brawley, MD, from Johns Hopkins University, Baltimore, Maryland.

There is ample evidence that minority populations have been disproportionately hit by COVID-19, job losses, and lost health insurance, said the CDC’s Richardson, and all these factors could widen the cancer gap.

“It’s not a race thing, it’s a ‘what do you do thing,’ and an access to care thing, and what your socioeconomic status is,” Richardson said in an interview. “People who didn’t have sick leave before the pandemic still don’t have sick leave; if they didn’t have time to get their mammogram they still don’t have time.”

But she acknowledges that evidence is still lacking. Could some minority populations actually be less fearful of medical encounters because their work has already prevented them from sheltering in place? “It could go either way,” she said. “They might be less wary of venturing out into the clinic, but they also might reason that they’ve exposed themselves enough already at work and don’t want any additional exposure.”

In that regard, Richardson suggests population-specific messaging will be an important way of communicating with under-served populations to restart screening.

“We’re struggling at CDC with how to develop messages that resonate within different communities, because we’re missing the point of actually speaking to people within their culture and within the places that they live,” she said. “Just saying the same thing and putting a black face on it is not going to make a difference; you actually have to speak the language of the people you’re trying to reach — the same message in different packages.”

To that end, even before the pandemic, the CDC supported the development of Make It Your Own, a website that uses “evidence-based strategies” to assist healthcare organizations in customizing health information “by race, ethnicity, age, gender and location”, and target messages  to “specific populations, cultural groups and languages”.

But Mass General’s Warner says she’s not sure she would argue for messages to be tailored by race, “at least not without evidence that values and priorities regarding returning to care differ between racial/ethnic groups.”

“Tailoring in the absence of data requires assumptions that may or may not be correct and ignores within-group heterogeneity,” Warner told Medscape Medical News. “However, I do believe that messaging about return to cancer screening and care should be multifaceted and use diverse imagery. This recognizes that some messages will resonate more or less with individuals based on their own characteristics, of which race may be one.”

Warner does believe in the power of tailored messaging though. “Part of the onus for healthcare institutions and providers is to make some decisions about who it is really important to bring back in soonest,” she said.

“Those are the ones we want to prioritize, as opposed to those who we want to get back into care but we don’t need to get them in right now,” Warner emphasized. “As they are balancing all the needs of their family and their community and their other needs, messaging that adds additional stress, worry, anxiety and shame is not what we want to do. So really we need to distinguish between these populations, identify the priorities, hit the hard message to people who really need it now, and encourage others to come back in as they can.”
 

Building trust

All the panelists agreed that building trust with the public will be key to getting cancer care back on track.  

“I don’t think anyone trusts the healthcare community right now, but we already had this baseline distrust of healthcare among many minority communities, and now with COVID-19, the African American community in particular is seeing people go into the hospital and never come back,” said Richardson.

For Warner, the onus really falls on healthcare institutions. “We have to be proactive and not leave the burden of deciding when and how to return to care up to patients,” she said.

“What we need to focus on as much as possible is to get people to realize it is safe to come see the doctor,” said Johns Hopkins oncologist Brawley. “We have to make it safe for them to come see us, and then we have to convince them it is safe to come see us.”

Venturing out to her mammography appointment in early June, Richardson said she felt safe. “Everything was just the way it was supposed to be, everyone was masked, everyone was washing their hands,” she said.

Yet, by mid-June she had contracted COVID-19. “I don’t know where I got it,” she said. “No matter how careful you are, understand that if you’re in a total red spot, as I am, you can just get it.”

This article first appeared on Medscape.com.

A new Canadian clinical practice guideline for treating adults with obesity emphasizes improving health rather than simply losing weight, among other things.

A summary of the guideline, which was developed by Obesity Canada and the Canadian Association of Bariatric Physicians and Surgeons, was published online August 4 in the Canadian Medical Association Journal.

This patient-centered update to the 2006 guidelines is “provocative,” starting with its definition of obesity, co–lead author Sean Wharton, MD, adjunct professor at McMaster University, Hamilton, Ont., said in an interview.

The guideline was authored by more than 60 health care professionals and researchers who assessed more than 500,000 peer-reviewed articles and made 80 key recommendations.

These reflect substantial recent advances in the understanding of obesity. Individuals with obesity (from a patient committee of the Obesity Society) helped to shape the key messages.

“People who live with obesity have been shut out of receiving quality health care because of the biased, deeply flawed misconceptions about what drives obesity and how we can improve health,” Lisa Schaffer, chair of Obesity Canada’s Public Engagement Committee, said in a press release.

“Obesity is widely seen as the result of poor personal decisions, but research tells us it is far more complicated than that. Our hope with the [new] clinical practice guideline is that more health care professionals, health policy makers, benefits providers and people living with obesity will have a better understanding of it, so we can help more of those who need it.”

“Obesity management should be about compassion and empathy, and then everything falls into place,” Dr. Wharton said. “Think of obesity like breast cancer.”

Address the root causes of obesity

The guideline defines obesity as “a prevalent, complex, progressive and relapsing chronic disease, characterized by abnormal or excessive body fat (adiposity) that impairs health.”

Aimed at primary care providers, the document stresses that clinicians need to “move beyond simplistic approaches of ‘eat less, move more,’ and address the root drivers of obesity.”

As a first step, doctors should ask a patient for permission to discuss weight (e.g., they can ask: “Would it be all right if we discussed your weight?”) – which demonstrates empathy and can help build patient-provider trust.

Clinicians can still measure body mass index as part of a routine physical examination, but they should also obtain a comprehensive patient history to identify the root causes of any weight gain (which could include genetics or psychological factors such as depression and anxiety), as well as any barriers to managing obesity.

‘Eat less, move more’ is too simple: Employ three pillars

Advice to “eat less and move more is dangerously simplistic,” coauthor Arya M. Sharma, MD, from the University of Alberta, Edmonton, and scientific director of Obesity Canada, said in an interview that “the body fights to put back any lost weight.”

Patients with obesity need “medical nutrition therapy.” For patients at risk for heart disease, that may mean following a Mediterranean diet, Dr. Wharton said.

“Physical activity and medical nutrition therapy are absolutely necessary” to manage obesity, he clarified. As a person loses weight, their body “releases a cascade of neurochemicals and hormones that try to push the weight back up” to the original weight or even higher.

Therefore, to maintain weight loss, people need support from one or more of what he calls the “three pillars” of effective long-term weight loss – pharmacotherapy, bariatric surgery, and cognitive-behavioral therapy – which tempers this cascade of neurochemicals.

Cognitive-behavioral therapy could be given by various health care professionals, he noted. A behavioral strategy to stop snacking, for example, is to wait 5 minutes before eating a desired snack to make sure you still want it.

Similarly, Dr. Sharma noted, “the reason obesity is a chronic disease is that once you’ve gained the weight, your body is not going to want to lose it. That is what I tell all my patients: ‘Your body doesn’t care why you put on the weight, but it does care about keeping it there, and it’s going to fight you’ when you try to maintain weight loss.”

“Clinicians should feel very comfortable” treating obesity as a chronic disease, he added, because they are already treating chronic diseases such as heart, lung, and kidney disease.

Don’t play the blame game: ‘Think of obesity like breast cancer’

Clinicians also need to avoid “shaming and blaming patients with obesity,” said Dr. Sharma.

He noted that many patients have internalized weight bias and blame their excess weight on their lack of willpower. They may not want to talk about weight-loss medications or bariatric surgery because they feel that’s “cheating.”

By thinking of obesity in a similar way to cancer, doctors can help themselves respond to patients in a kinder way. “What would we do with somebody who has breast cancer? We would have compassion. We would talk about surgery to get the lump out and medication to keep the cancer from coming back, and we would engage them in psychological treatment or counseling for some of the challenges they have to face,” Dr. Wharton said.

“The right answer is to treat [obesity] like a disease – with surgery, medication, and psychological intervention,” depending on the individual patient, he added.

The complete guideline is available on the Obesity Canada website.

The study was funded by Obesity Canada, the Canadian Association of Bariatric Physicians and Surgeons, and the Canadian Institutes of Health Research. Dr. Wharton has received honoraria and travel expenses and has participated in academic advisory boards for Novo Nordisk, Bausch Health, Eli Lilly, and Janssen. He is the medical director of a medical clinic specializing in weight management and diabetes. Dr. Sharma has received speaker’s bureau and consulting fees from Novo Nordisk, Bausch Pharmaceuticals, and AstraZeneca.

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

A new Canadian clinical practice guideline for treating adults with obesity emphasizes improving health rather than simply losing weight, among other things.

A summary of the guideline, which was developed by Obesity Canada and the Canadian Association of Bariatric Physicians and Surgeons, was published online August 4 in the Canadian Medical Association Journal.

This patient-centered update to the 2006 guidelines is “provocative,” starting with its definition of obesity, co–lead author Sean Wharton, MD, adjunct professor at McMaster University, Hamilton, Ont., said in an interview.

The guideline was authored by more than 60 health care professionals and researchers who assessed more than 500,000 peer-reviewed articles and made 80 key recommendations.

These reflect substantial recent advances in the understanding of obesity. Individuals with obesity (from a patient committee of the Obesity Society) helped to shape the key messages.

“People who live with obesity have been shut out of receiving quality health care because of the biased, deeply flawed misconceptions about what drives obesity and how we can improve health,” Lisa Schaffer, chair of Obesity Canada’s Public Engagement Committee, said in a press release.

“Obesity is widely seen as the result of poor personal decisions, but research tells us it is far more complicated than that. Our hope with the [new] clinical practice guideline is that more health care professionals, health policy makers, benefits providers and people living with obesity will have a better understanding of it, so we can help more of those who need it.”

“Obesity management should be about compassion and empathy, and then everything falls into place,” Dr. Wharton said. “Think of obesity like breast cancer.”

Address the root causes of obesity

The guideline defines obesity as “a prevalent, complex, progressive and relapsing chronic disease, characterized by abnormal or excessive body fat (adiposity) that impairs health.”

Aimed at primary care providers, the document stresses that clinicians need to “move beyond simplistic approaches of ‘eat less, move more,’ and address the root drivers of obesity.”

As a first step, doctors should ask a patient for permission to discuss weight (e.g., they can ask: “Would it be all right if we discussed your weight?”) – which demonstrates empathy and can help build patient-provider trust.

Clinicians can still measure body mass index as part of a routine physical examination, but they should also obtain a comprehensive patient history to identify the root causes of any weight gain (which could include genetics or psychological factors such as depression and anxiety), as well as any barriers to managing obesity.

‘Eat less, move more’ is too simple: Employ three pillars

Advice to “eat less and move more is dangerously simplistic,” coauthor Arya M. Sharma, MD, from the University of Alberta, Edmonton, and scientific director of Obesity Canada, said in an interview that “the body fights to put back any lost weight.”

Patients with obesity need “medical nutrition therapy.” For patients at risk for heart disease, that may mean following a Mediterranean diet, Dr. Wharton said.

“Physical activity and medical nutrition therapy are absolutely necessary” to manage obesity, he clarified. As a person loses weight, their body “releases a cascade of neurochemicals and hormones that try to push the weight back up” to the original weight or even higher.

Therefore, to maintain weight loss, people need support from one or more of what he calls the “three pillars” of effective long-term weight loss – pharmacotherapy, bariatric surgery, and cognitive-behavioral therapy – which tempers this cascade of neurochemicals.

Cognitive-behavioral therapy could be given by various health care professionals, he noted. A behavioral strategy to stop snacking, for example, is to wait 5 minutes before eating a desired snack to make sure you still want it.

Similarly, Dr. Sharma noted, “the reason obesity is a chronic disease is that once you’ve gained the weight, your body is not going to want to lose it. That is what I tell all my patients: ‘Your body doesn’t care why you put on the weight, but it does care about keeping it there, and it’s going to fight you’ when you try to maintain weight loss.”

“Clinicians should feel very comfortable” treating obesity as a chronic disease, he added, because they are already treating chronic diseases such as heart, lung, and kidney disease.

Don’t play the blame game: ‘Think of obesity like breast cancer’

Clinicians also need to avoid “shaming and blaming patients with obesity,” said Dr. Sharma.

He noted that many patients have internalized weight bias and blame their excess weight on their lack of willpower. They may not want to talk about weight-loss medications or bariatric surgery because they feel that’s “cheating.”

By thinking of obesity in a similar way to cancer, doctors can help themselves respond to patients in a kinder way. “What would we do with somebody who has breast cancer? We would have compassion. We would talk about surgery to get the lump out and medication to keep the cancer from coming back, and we would engage them in psychological treatment or counseling for some of the challenges they have to face,” Dr. Wharton said.

“The right answer is to treat [obesity] like a disease – with surgery, medication, and psychological intervention,” depending on the individual patient, he added.

The complete guideline is available on the Obesity Canada website.

The study was funded by Obesity Canada, the Canadian Association of Bariatric Physicians and Surgeons, and the Canadian Institutes of Health Research. Dr. Wharton has received honoraria and travel expenses and has participated in academic advisory boards for Novo Nordisk, Bausch Health, Eli Lilly, and Janssen. He is the medical director of a medical clinic specializing in weight management and diabetes. Dr. Sharma has received speaker’s bureau and consulting fees from Novo Nordisk, Bausch Pharmaceuticals, and AstraZeneca.

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

A new Canadian clinical practice guideline for treating adults with obesity emphasizes improving health rather than simply losing weight, among other things.

A summary of the guideline, which was developed by Obesity Canada and the Canadian Association of Bariatric Physicians and Surgeons, was published online August 4 in the Canadian Medical Association Journal.

This patient-centered update to the 2006 guidelines is “provocative,” starting with its definition of obesity, co–lead author Sean Wharton, MD, adjunct professor at McMaster University, Hamilton, Ont., said in an interview.

The guideline was authored by more than 60 health care professionals and researchers who assessed more than 500,000 peer-reviewed articles and made 80 key recommendations.

These reflect substantial recent advances in the understanding of obesity. Individuals with obesity (from a patient committee of the Obesity Society) helped to shape the key messages.

“People who live with obesity have been shut out of receiving quality health care because of the biased, deeply flawed misconceptions about what drives obesity and how we can improve health,” Lisa Schaffer, chair of Obesity Canada’s Public Engagement Committee, said in a press release.

“Obesity is widely seen as the result of poor personal decisions, but research tells us it is far more complicated than that. Our hope with the [new] clinical practice guideline is that more health care professionals, health policy makers, benefits providers and people living with obesity will have a better understanding of it, so we can help more of those who need it.”

“Obesity management should be about compassion and empathy, and then everything falls into place,” Dr. Wharton said. “Think of obesity like breast cancer.”

Address the root causes of obesity

The guideline defines obesity as “a prevalent, complex, progressive and relapsing chronic disease, characterized by abnormal or excessive body fat (adiposity) that impairs health.”

Aimed at primary care providers, the document stresses that clinicians need to “move beyond simplistic approaches of ‘eat less, move more,’ and address the root drivers of obesity.”

As a first step, doctors should ask a patient for permission to discuss weight (e.g., they can ask: “Would it be all right if we discussed your weight?”) – which demonstrates empathy and can help build patient-provider trust.

Clinicians can still measure body mass index as part of a routine physical examination, but they should also obtain a comprehensive patient history to identify the root causes of any weight gain (which could include genetics or psychological factors such as depression and anxiety), as well as any barriers to managing obesity.

‘Eat less, move more’ is too simple: Employ three pillars

Advice to “eat less and move more is dangerously simplistic,” coauthor Arya M. Sharma, MD, from the University of Alberta, Edmonton, and scientific director of Obesity Canada, said in an interview that “the body fights to put back any lost weight.”

Patients with obesity need “medical nutrition therapy.” For patients at risk for heart disease, that may mean following a Mediterranean diet, Dr. Wharton said.

“Physical activity and medical nutrition therapy are absolutely necessary” to manage obesity, he clarified. As a person loses weight, their body “releases a cascade of neurochemicals and hormones that try to push the weight back up” to the original weight or even higher.

Therefore, to maintain weight loss, people need support from one or more of what he calls the “three pillars” of effective long-term weight loss – pharmacotherapy, bariatric surgery, and cognitive-behavioral therapy – which tempers this cascade of neurochemicals.

Cognitive-behavioral therapy could be given by various health care professionals, he noted. A behavioral strategy to stop snacking, for example, is to wait 5 minutes before eating a desired snack to make sure you still want it.

Similarly, Dr. Sharma noted, “the reason obesity is a chronic disease is that once you’ve gained the weight, your body is not going to want to lose it. That is what I tell all my patients: ‘Your body doesn’t care why you put on the weight, but it does care about keeping it there, and it’s going to fight you’ when you try to maintain weight loss.”

“Clinicians should feel very comfortable” treating obesity as a chronic disease, he added, because they are already treating chronic diseases such as heart, lung, and kidney disease.

Don’t play the blame game: ‘Think of obesity like breast cancer’

Clinicians also need to avoid “shaming and blaming patients with obesity,” said Dr. Sharma.

He noted that many patients have internalized weight bias and blame their excess weight on their lack of willpower. They may not want to talk about weight-loss medications or bariatric surgery because they feel that’s “cheating.”

By thinking of obesity in a similar way to cancer, doctors can help themselves respond to patients in a kinder way. “What would we do with somebody who has breast cancer? We would have compassion. We would talk about surgery to get the lump out and medication to keep the cancer from coming back, and we would engage them in psychological treatment or counseling for some of the challenges they have to face,” Dr. Wharton said.

“The right answer is to treat [obesity] like a disease – with surgery, medication, and psychological intervention,” depending on the individual patient, he added.

The complete guideline is available on the Obesity Canada website.

The study was funded by Obesity Canada, the Canadian Association of Bariatric Physicians and Surgeons, and the Canadian Institutes of Health Research. Dr. Wharton has received honoraria and travel expenses and has participated in academic advisory boards for Novo Nordisk, Bausch Health, Eli Lilly, and Janssen. He is the medical director of a medical clinic specializing in weight management and diabetes. Dr. Sharma has received speaker’s bureau and consulting fees from Novo Nordisk, Bausch Pharmaceuticals, and AstraZeneca.

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

The historically higher incidence rates of lung cancer among Black men, compared with White men, in the United States have all but been eliminated, at least among most men in the younger age groups, a new analysis from the American Cancer Society (ACS) indicates.

Among women, the trend is even more impressive, as the Black/White gap in lung cancer incidence rates has actually reversed in younger women. Black women in certain age groups are now less likely to develop lung cancer than White women, the same study indicates.

These trends reflect the steeper declines in smoking rates among Blacks in the US, compared with comparably-aged Whites, say the authors.

“This is the only cancer where this has happened,” lead author Ahmedin Jemal, DVM, PhD, senior vice president for Data Science at the American Cancer Society, told Medscape Medical News.

“If you look at cancers that are affected by access to screening and treatment, the disparity between the Blacks and the Whites has been increasing over the years because tests and treatment require access to insurance, so the Whites are getting more of them than the Blacks,” Jemal explained.

“But for smoking, all you have to do for prevention is just don’t smoke, so this is a success story that really should be highlighted,” he emphasized.

The study was published online Aug. 20 in JNCI Cancer: Spectrum.

Nationwide Incidence Data

For this study, Jemal and colleagues collected nationwide incidence data on individuals between ages 30 and 54 who had been diagnosed with lung cancer between 1997 and 2016.

“We categorized age at diagnosis by 5-year age intervals (from 30-34 to 50-54 years) and year of diagnosis by 5-year calendar period (from 1997-2001 to 2012-2016),” the investigators explain.

Analyses showed that lung cancer incidence rates generally decreased among both Black and White men during the study interval but the decline in incidence rates was steeper in Black men than in White men. As a consequence, the Black-to-White incidence rate ratios (IRRs) became similar in men born between 1967 and 1972 and reversed in women born since about 1967. For example, the Black-to-White IRRs in men between the ages of 40 and 44 who were born between 1957 and 1972 declined from 1.92 to 1.03.

Similarly, lung cancer incidence rates during the study interval declined among both Black and White women between the ages of 30 and 49 but, again, the decline was “considerably larger” among Black women. As a consequence, the Black-to-White IRR in women age 45 to 49 dropped from 1.25 during the period 1997-2001 down to 0.83 during the period 2012-2016.

This is in stark contrast to historical trends in lung cancer incidence rates, which were over 30% higher among similarly aged Black women born in the late 1950s. Now, lung cancer incidence rates are about 30% lower for similarly aged Black women born in 1972, compared with White women.

For Black and White women between age 50 and 54, lung cancer incidence rates either declined only slightly or remained stable during the study interval, the investigators reported.

The one exception to the diminishing gap in lung cancer incidence rates between Black and White men was an observed increase in IRRs in men born around the period 1977-1982

Among this group of men, who were between age 30 and 39 in the years 2012-2016, lung cancer incidence rates were higher in Black men than in White men.

As the authors point out, this increase in lung cancer rates among young Black men likely reflects a rapid rise in smoking seen among Black youth in the 1990s.

This trend coincided with an R.J. Reynolds tobacco ad campaign in which African Americans were targeted; between 1991 and 1997, the prevalence of smoking among Black high school students doubled from 14.1% to 28.2%, the investigators point out, citing a 2008 Centers for Disease Control and Prevention report on cigarette use among US high school students.

Smoking Prevalence Rates

Smoking prevalence rates were derived from National Health Interview Survey data from 1970 to 2016.

Mirroring findings in the racial patterns of lung cancer incidence rates, smoking prevalence rates declined in successive birth cohorts in both Black and White males and females, but the decline was again steeper in Black men and women than it was in White men and women.

As a result, the historically higher sex-specific smoking prevalence rates seen historically in Blacks disappeared in men born around 1960, and reversed in women born at the same time, Jemal and colleagues point out.

As the authors explain, the more rapid decline in smoking prevalence after 1960 is likely a reflection of the “precipitous” drop in smoking initiation rates among Black teenagers starting about the late 1970s through to the early 1990s.

For example, among 12th graders, smoking prevalence rates between 1977 and 1992 dropped from 36.7% to 8.1% among Black teens. In stark contrast, they hardly changed at all among White teens, dropping only from 38.3% in 1977 to 31.8% in 1992.

Jemal suggested that steeper decline in smoking initiation rates seen between the late 1970s and early 90s reflects the fact that Black teenagers were deterred from smoking because the cost of cigarettes kept going up.

He also suggested that smoking is less acceptable in the Black community than it is in the White community, especially among churchgoers, where smoking is severely frowned upon and nonsmoking is the community “norm.”

Additionally, Black youth may simply be heeding government antismoking messages to a greater extent than White youth, Jemal suggested.  

He wondered if there are parallels now in the current pandemic. “When I go to a store here in Georgia, I would say almost all Blacks are wearing a mask [even though masks are not mandatory in Georgia] whereas it’s amazing the number of Whites who don’t wear a mask,” he recounts.

“So it would seem that Whites feel that government is simply interfering with their lives, while Blacks have a better perspective of the harms of smoking, so they are listening to the government’s antismoking campaigns,” he speculated.

Some Isolated Areas

Asked to comment on the study’s findings, Otis Brawley, MD, Bloomberg, distinguished professor of oncology and epidemiology at Johns Hopkins University in Baltimore, said that, while overall Black smoking rates are declining, there are some isolated areas where they are still very high.

For example, in his hometown of Baltimore, recent prevalence rates indicate that over 30% of Blacks are still smoking, “so these areas with high usage are still areas to focus on,” he told Medscape Medical News.

On the other hand, the study also supports the benefits of local, state, and federal government efforts to promote antismoking messages and tobacco-control activities over the past number of years.

“It proves that tactics used to control tobacco use have had some effect [even though] the study also shows that the tobacco industry’s advertising tactics such as the R.J. Reynolds targeted ads in the 90s can have deleterious effects,” Brawley noted.

Lung cancer has traditionally been one of the biggest drivers in the Black/White cancer mortality gap, Brawley said, adding that steeper declines in smoking initiation rates among Blacks compared with Whites are the main reason why this disparity is decreasing.

The study was supported by the Intramural Research Department of the American Cancer Society. The study authors have disclosed no relevant financial relationships. Brawley declares he does some consulting work for pharmaceutical company Genentech.
 

This article first appeared on Medscape.com.

The historically higher incidence rates of lung cancer among Black men, compared with White men, in the United States have all but been eliminated, at least among most men in the younger age groups, a new analysis from the American Cancer Society (ACS) indicates.

Among women, the trend is even more impressive, as the Black/White gap in lung cancer incidence rates has actually reversed in younger women. Black women in certain age groups are now less likely to develop lung cancer than White women, the same study indicates.

These trends reflect the steeper declines in smoking rates among Blacks in the US, compared with comparably-aged Whites, say the authors.

“This is the only cancer where this has happened,” lead author Ahmedin Jemal, DVM, PhD, senior vice president for Data Science at the American Cancer Society, told Medscape Medical News.

“If you look at cancers that are affected by access to screening and treatment, the disparity between the Blacks and the Whites has been increasing over the years because tests and treatment require access to insurance, so the Whites are getting more of them than the Blacks,” Jemal explained.

“But for smoking, all you have to do for prevention is just don’t smoke, so this is a success story that really should be highlighted,” he emphasized.

The study was published online Aug. 20 in JNCI Cancer: Spectrum.

Nationwide Incidence Data

For this study, Jemal and colleagues collected nationwide incidence data on individuals between ages 30 and 54 who had been diagnosed with lung cancer between 1997 and 2016.

“We categorized age at diagnosis by 5-year age intervals (from 30-34 to 50-54 years) and year of diagnosis by 5-year calendar period (from 1997-2001 to 2012-2016),” the investigators explain.

Analyses showed that lung cancer incidence rates generally decreased among both Black and White men during the study interval but the decline in incidence rates was steeper in Black men than in White men. As a consequence, the Black-to-White incidence rate ratios (IRRs) became similar in men born between 1967 and 1972 and reversed in women born since about 1967. For example, the Black-to-White IRRs in men between the ages of 40 and 44 who were born between 1957 and 1972 declined from 1.92 to 1.03.

Similarly, lung cancer incidence rates during the study interval declined among both Black and White women between the ages of 30 and 49 but, again, the decline was “considerably larger” among Black women. As a consequence, the Black-to-White IRR in women age 45 to 49 dropped from 1.25 during the period 1997-2001 down to 0.83 during the period 2012-2016.

This is in stark contrast to historical trends in lung cancer incidence rates, which were over 30% higher among similarly aged Black women born in the late 1950s. Now, lung cancer incidence rates are about 30% lower for similarly aged Black women born in 1972, compared with White women.

For Black and White women between age 50 and 54, lung cancer incidence rates either declined only slightly or remained stable during the study interval, the investigators reported.

The one exception to the diminishing gap in lung cancer incidence rates between Black and White men was an observed increase in IRRs in men born around the period 1977-1982

Among this group of men, who were between age 30 and 39 in the years 2012-2016, lung cancer incidence rates were higher in Black men than in White men.

As the authors point out, this increase in lung cancer rates among young Black men likely reflects a rapid rise in smoking seen among Black youth in the 1990s.

This trend coincided with an R.J. Reynolds tobacco ad campaign in which African Americans were targeted; between 1991 and 1997, the prevalence of smoking among Black high school students doubled from 14.1% to 28.2%, the investigators point out, citing a 2008 Centers for Disease Control and Prevention report on cigarette use among US high school students.

Smoking Prevalence Rates

Smoking prevalence rates were derived from National Health Interview Survey data from 1970 to 2016.

Mirroring findings in the racial patterns of lung cancer incidence rates, smoking prevalence rates declined in successive birth cohorts in both Black and White males and females, but the decline was again steeper in Black men and women than it was in White men and women.

As a result, the historically higher sex-specific smoking prevalence rates seen historically in Blacks disappeared in men born around 1960, and reversed in women born at the same time, Jemal and colleagues point out.

As the authors explain, the more rapid decline in smoking prevalence after 1960 is likely a reflection of the “precipitous” drop in smoking initiation rates among Black teenagers starting about the late 1970s through to the early 1990s.

For example, among 12th graders, smoking prevalence rates between 1977 and 1992 dropped from 36.7% to 8.1% among Black teens. In stark contrast, they hardly changed at all among White teens, dropping only from 38.3% in 1977 to 31.8% in 1992.

Jemal suggested that steeper decline in smoking initiation rates seen between the late 1970s and early 90s reflects the fact that Black teenagers were deterred from smoking because the cost of cigarettes kept going up.

He also suggested that smoking is less acceptable in the Black community than it is in the White community, especially among churchgoers, where smoking is severely frowned upon and nonsmoking is the community “norm.”

Additionally, Black youth may simply be heeding government antismoking messages to a greater extent than White youth, Jemal suggested.  

He wondered if there are parallels now in the current pandemic. “When I go to a store here in Georgia, I would say almost all Blacks are wearing a mask [even though masks are not mandatory in Georgia] whereas it’s amazing the number of Whites who don’t wear a mask,” he recounts.

“So it would seem that Whites feel that government is simply interfering with their lives, while Blacks have a better perspective of the harms of smoking, so they are listening to the government’s antismoking campaigns,” he speculated.

Some Isolated Areas

Asked to comment on the study’s findings, Otis Brawley, MD, Bloomberg, distinguished professor of oncology and epidemiology at Johns Hopkins University in Baltimore, said that, while overall Black smoking rates are declining, there are some isolated areas where they are still very high.

For example, in his hometown of Baltimore, recent prevalence rates indicate that over 30% of Blacks are still smoking, “so these areas with high usage are still areas to focus on,” he told Medscape Medical News.

On the other hand, the study also supports the benefits of local, state, and federal government efforts to promote antismoking messages and tobacco-control activities over the past number of years.

“It proves that tactics used to control tobacco use have had some effect [even though] the study also shows that the tobacco industry’s advertising tactics such as the R.J. Reynolds targeted ads in the 90s can have deleterious effects,” Brawley noted.

Lung cancer has traditionally been one of the biggest drivers in the Black/White cancer mortality gap, Brawley said, adding that steeper declines in smoking initiation rates among Blacks compared with Whites are the main reason why this disparity is decreasing.

The study was supported by the Intramural Research Department of the American Cancer Society. The study authors have disclosed no relevant financial relationships. Brawley declares he does some consulting work for pharmaceutical company Genentech.
 

This article first appeared on Medscape.com.

The historically higher incidence rates of lung cancer among Black men, compared with White men, in the United States have all but been eliminated, at least among most men in the younger age groups, a new analysis from the American Cancer Society (ACS) indicates.

Among women, the trend is even more impressive, as the Black/White gap in lung cancer incidence rates has actually reversed in younger women. Black women in certain age groups are now less likely to develop lung cancer than White women, the same study indicates.

These trends reflect the steeper declines in smoking rates among Blacks in the US, compared with comparably-aged Whites, say the authors.

“This is the only cancer where this has happened,” lead author Ahmedin Jemal, DVM, PhD, senior vice president for Data Science at the American Cancer Society, told Medscape Medical News.

“If you look at cancers that are affected by access to screening and treatment, the disparity between the Blacks and the Whites has been increasing over the years because tests and treatment require access to insurance, so the Whites are getting more of them than the Blacks,” Jemal explained.

“But for smoking, all you have to do for prevention is just don’t smoke, so this is a success story that really should be highlighted,” he emphasized.

The study was published online Aug. 20 in JNCI Cancer: Spectrum.

Nationwide Incidence Data

For this study, Jemal and colleagues collected nationwide incidence data on individuals between ages 30 and 54 who had been diagnosed with lung cancer between 1997 and 2016.

“We categorized age at diagnosis by 5-year age intervals (from 30-34 to 50-54 years) and year of diagnosis by 5-year calendar period (from 1997-2001 to 2012-2016),” the investigators explain.

Analyses showed that lung cancer incidence rates generally decreased among both Black and White men during the study interval but the decline in incidence rates was steeper in Black men than in White men. As a consequence, the Black-to-White incidence rate ratios (IRRs) became similar in men born between 1967 and 1972 and reversed in women born since about 1967. For example, the Black-to-White IRRs in men between the ages of 40 and 44 who were born between 1957 and 1972 declined from 1.92 to 1.03.

Similarly, lung cancer incidence rates during the study interval declined among both Black and White women between the ages of 30 and 49 but, again, the decline was “considerably larger” among Black women. As a consequence, the Black-to-White IRR in women age 45 to 49 dropped from 1.25 during the period 1997-2001 down to 0.83 during the period 2012-2016.

This is in stark contrast to historical trends in lung cancer incidence rates, which were over 30% higher among similarly aged Black women born in the late 1950s. Now, lung cancer incidence rates are about 30% lower for similarly aged Black women born in 1972, compared with White women.

For Black and White women between age 50 and 54, lung cancer incidence rates either declined only slightly or remained stable during the study interval, the investigators reported.

The one exception to the diminishing gap in lung cancer incidence rates between Black and White men was an observed increase in IRRs in men born around the period 1977-1982

Among this group of men, who were between age 30 and 39 in the years 2012-2016, lung cancer incidence rates were higher in Black men than in White men.

As the authors point out, this increase in lung cancer rates among young Black men likely reflects a rapid rise in smoking seen among Black youth in the 1990s.

This trend coincided with an R.J. Reynolds tobacco ad campaign in which African Americans were targeted; between 1991 and 1997, the prevalence of smoking among Black high school students doubled from 14.1% to 28.2%, the investigators point out, citing a 2008 Centers for Disease Control and Prevention report on cigarette use among US high school students.

Smoking Prevalence Rates

Smoking prevalence rates were derived from National Health Interview Survey data from 1970 to 2016.

Mirroring findings in the racial patterns of lung cancer incidence rates, smoking prevalence rates declined in successive birth cohorts in both Black and White males and females, but the decline was again steeper in Black men and women than it was in White men and women.

As a result, the historically higher sex-specific smoking prevalence rates seen historically in Blacks disappeared in men born around 1960, and reversed in women born at the same time, Jemal and colleagues point out.

As the authors explain, the more rapid decline in smoking prevalence after 1960 is likely a reflection of the “precipitous” drop in smoking initiation rates among Black teenagers starting about the late 1970s through to the early 1990s.

For example, among 12th graders, smoking prevalence rates between 1977 and 1992 dropped from 36.7% to 8.1% among Black teens. In stark contrast, they hardly changed at all among White teens, dropping only from 38.3% in 1977 to 31.8% in 1992.

Jemal suggested that steeper decline in smoking initiation rates seen between the late 1970s and early 90s reflects the fact that Black teenagers were deterred from smoking because the cost of cigarettes kept going up.

He also suggested that smoking is less acceptable in the Black community than it is in the White community, especially among churchgoers, where smoking is severely frowned upon and nonsmoking is the community “norm.”

Additionally, Black youth may simply be heeding government antismoking messages to a greater extent than White youth, Jemal suggested.  

He wondered if there are parallels now in the current pandemic. “When I go to a store here in Georgia, I would say almost all Blacks are wearing a mask [even though masks are not mandatory in Georgia] whereas it’s amazing the number of Whites who don’t wear a mask,” he recounts.

“So it would seem that Whites feel that government is simply interfering with their lives, while Blacks have a better perspective of the harms of smoking, so they are listening to the government’s antismoking campaigns,” he speculated.

Some Isolated Areas

Asked to comment on the study’s findings, Otis Brawley, MD, Bloomberg, distinguished professor of oncology and epidemiology at Johns Hopkins University in Baltimore, said that, while overall Black smoking rates are declining, there are some isolated areas where they are still very high.

For example, in his hometown of Baltimore, recent prevalence rates indicate that over 30% of Blacks are still smoking, “so these areas with high usage are still areas to focus on,” he told Medscape Medical News.

On the other hand, the study also supports the benefits of local, state, and federal government efforts to promote antismoking messages and tobacco-control activities over the past number of years.

“It proves that tactics used to control tobacco use have had some effect [even though] the study also shows that the tobacco industry’s advertising tactics such as the R.J. Reynolds targeted ads in the 90s can have deleterious effects,” Brawley noted.

Lung cancer has traditionally been one of the biggest drivers in the Black/White cancer mortality gap, Brawley said, adding that steeper declines in smoking initiation rates among Blacks compared with Whites are the main reason why this disparity is decreasing.

The study was supported by the Intramural Research Department of the American Cancer Society. The study authors have disclosed no relevant financial relationships. Brawley declares he does some consulting work for pharmaceutical company Genentech.
 

This article first appeared on Medscape.com.

Spirituality and religion remain central to the worldview of millions of Americans. According to the Pew Research Center, almost 75% of Americans identify as Christian, Jewish, Muslim, Buddhist, or Hindu.¹ As is the case with many Americans,² the lens of spirituality³ and religion shaped my own worldview since childhood.

j-wildman/Getty Images

Growing up in a Christian household, many of my family’s discussions centered on bolstering our spiritual health. I grew to internalize the notion that spiritual health relates to a sense of self, a sense of purpose, and a connection to God, nature, and others. Religious texts such as the Bible, Quran, and Torah share principles aimed at developing believers’ spiritual health. However, the intricacies of mental health remain entirely foreign within many faith communities. In these communities, unfamiliarity with mental health topics seemingly leads to the conflation of spiritual health and mental health.⁴

Within faith communities, I often hear the phrase, “You can’t worry and pray at the same time.” This commonly used expression encourages people of faith to lean on their spiritual health in times of uncertainty. The perceived dichotomy between worry and prayer represents the theology of sole reliance on spiritual coping skills, such as prayer, when feelings of anxiety and other psychological stressors arise. Because of “pray it away” doctrines and ongoing stigma related to mental health, many of our spiritually minded patients are more likely to seek counsel from religious leaders than they are from mental health clinicians in times of psychological distress.^5,6

About 54% of U.S. adults identify as religious, and 75% think of themselves as spiritual.⁷ This intrapersonal conflict between religious/spiritual health and mental health raises an important question: How can psychiatrists more actively collaborate with religious communities to ease the perceived tensions between spiritual health and mental health for our patients?
 

Engaging with the community

In a recent virtual talk titled, “Dealing with Depression: Faith, Meds, and Therapy,” I openly discussed varying aspects of mental health and mental illness with approximately 70 women at my church in Philadelphia. Before this presentation, there had never been a leadership-sponsored conversation within the church to discuss spiritual health and mental health as separate but highly interconnected entities.

Throughout the nearly 2-hour session, I used biblical and biological principles to explain the differences between spiritual health and mental health, strategies to recognize signs and symptoms of depression, and treatment options for depression. After the formal presentation, a 45-minute question-and-answer session followed in which some members shared their own experiences with mental illness.

Two major themes emerged as central points of discussion during our time of open dialogue. First, several women shared the spiritual and clinical avenues they used to access support in times of psychological distress. There was a general tone of agreement among attendees that spiritual health and mental health are, in fact, different. Second, the presentation opened the door for attendees, previously unfamiliar with mental health services, to ask questions about connecting with the appropriate resources to receive mental health treatment. The subject of seeking psychiatric care for mental health challenges was, at least in part, demystified and brought to the forefront of the attendees’ minds.

Studies show that many faith-based communities are more likely to seek counsel for psychological distress from religious leaders than from mental health professionals. In this vein, my recent community engagement highlighted to me ways that we can readily reach spiritually and religiously minded patients who otherwise would not receive the psychiatric care that they need. Psychiatrists can play an integral role in bridging the gap in psychiatric care for faith-based persons through outreach to and collaboration with religious communities.
 

Opportunities for collaboration

In collaboration with religious leaders, psychiatrists can actively support the mental health of spiritually and religiously minded patients through several low-effort, but potentially high-yield, initiatives. Notably, many of my suggested interventions do not require significant, if any, infrastructural changes to the health care system or worship communities. As psychiatrists, we can collaborate with faith leaders as follows:

1. More regularly assess the role of religion and spirituality in our patients’ daily lives to better meet their spiritual and mental health needs.

2. Better use existing chaplain services to provide spiritual support for hospitalized patients.

3. Present information about mental health – in-person, virtually, or in written form – to religious communities through talks, discussions, popular religious publications, social media platforms, and webinars.

4. Amplify existing mental health guides for faith leaders (i.e., the American Psychiatric Association’s guidebook Mental Health: A Guide for Faith Leaders),⁸ thereby encouraging church leaders and staff to become better informed about common mental health conditions.

5. Collaborate with places of worship to offer psychiatric and psychological services to their members.

This sort of engagement with religious communities is the collective role of community-oriented psychiatrists, not just psychiatrists who ascribe to religious or spiritual beliefs. We ought to remain mindful of the spiritual distress that many spiritual and religious patients feel when they experience mental illness,⁹ particularly in light of the distress caused by the coronavirus pandemic.¹⁰ But first, we must become comfortable with asking our patients about their religious or spiritual affiliations using tools such as the Cultural Formulation Interview.¹¹ The more we recognize the role of spirituality in our patients’ lives, the better equipped we become to help patients identify and seek treatment for mental illness without the distress of their feeling spiritually deficient.
 

Dr. Jordan is a psychiatry resident physician in Philadelphia. She has no conflicts of interest.

References

1. Religious Landscape Study. pewforum.org.

2. U.S. Religion Census Census: Religious Congregations and Membership Study. Association of Religion Data Archives. 2010. doi: 10.17605/OSF.IO/9AMDJ.

3. J Med Ethics Hist Med. 2018 Apr 9;11:3.

4. The Dimensions of Health: Conceptual Models. Sudbury, Mass.: Jones & Bartlett, 2010.

5. J Res Christ Educ. 2014;23(2):176-86.

6. Health Serv Res. 2003 Apr;38(2):647-73.

7. “More Americans say they’re spiritual but not religious.” pewresearch.org. 2017 Sep 6.

8. Mental Health: A Guide for Faith Leaders. Washington: American Psychiatric Association Foundation, 2018.

9. Mental Health by the Numbers. NAMI: National Alliance on Mental Illness. 2019.

10. “Most Americans say coronavirus outbreak has impacted their lives. Pew Research Center. pewsocialtrends.org. 2020 Mar 30.

11. DSM-5 Handbook on the Cultural Formulation Interview. Washington: American Psychiatric Association Publishing, 2016.

Spirituality and religion remain central to the worldview of millions of Americans. According to the Pew Research Center, almost 75% of Americans identify as Christian, Jewish, Muslim, Buddhist, or Hindu.¹ As is the case with many Americans,² the lens of spirituality³ and religion shaped my own worldview since childhood.

j-wildman/Getty Images

Growing up in a Christian household, many of my family’s discussions centered on bolstering our spiritual health. I grew to internalize the notion that spiritual health relates to a sense of self, a sense of purpose, and a connection to God, nature, and others. Religious texts such as the Bible, Quran, and Torah share principles aimed at developing believers’ spiritual health. However, the intricacies of mental health remain entirely foreign within many faith communities. In these communities, unfamiliarity with mental health topics seemingly leads to the conflation of spiritual health and mental health.⁴

Within faith communities, I often hear the phrase, “You can’t worry and pray at the same time.” This commonly used expression encourages people of faith to lean on their spiritual health in times of uncertainty. The perceived dichotomy between worry and prayer represents the theology of sole reliance on spiritual coping skills, such as prayer, when feelings of anxiety and other psychological stressors arise. Because of “pray it away” doctrines and ongoing stigma related to mental health, many of our spiritually minded patients are more likely to seek counsel from religious leaders than they are from mental health clinicians in times of psychological distress.^5,6

About 54% of U.S. adults identify as religious, and 75% think of themselves as spiritual.⁷ This intrapersonal conflict between religious/spiritual health and mental health raises an important question: How can psychiatrists more actively collaborate with religious communities to ease the perceived tensions between spiritual health and mental health for our patients?
 

Engaging with the community

In a recent virtual talk titled, “Dealing with Depression: Faith, Meds, and Therapy,” I openly discussed varying aspects of mental health and mental illness with approximately 70 women at my church in Philadelphia. Before this presentation, there had never been a leadership-sponsored conversation within the church to discuss spiritual health and mental health as separate but highly interconnected entities.

Throughout the nearly 2-hour session, I used biblical and biological principles to explain the differences between spiritual health and mental health, strategies to recognize signs and symptoms of depression, and treatment options for depression. After the formal presentation, a 45-minute question-and-answer session followed in which some members shared their own experiences with mental illness.

Two major themes emerged as central points of discussion during our time of open dialogue. First, several women shared the spiritual and clinical avenues they used to access support in times of psychological distress. There was a general tone of agreement among attendees that spiritual health and mental health are, in fact, different. Second, the presentation opened the door for attendees, previously unfamiliar with mental health services, to ask questions about connecting with the appropriate resources to receive mental health treatment. The subject of seeking psychiatric care for mental health challenges was, at least in part, demystified and brought to the forefront of the attendees’ minds.

Studies show that many faith-based communities are more likely to seek counsel for psychological distress from religious leaders than from mental health professionals. In this vein, my recent community engagement highlighted to me ways that we can readily reach spiritually and religiously minded patients who otherwise would not receive the psychiatric care that they need. Psychiatrists can play an integral role in bridging the gap in psychiatric care for faith-based persons through outreach to and collaboration with religious communities.
 

Opportunities for collaboration

In collaboration with religious leaders, psychiatrists can actively support the mental health of spiritually and religiously minded patients through several low-effort, but potentially high-yield, initiatives. Notably, many of my suggested interventions do not require significant, if any, infrastructural changes to the health care system or worship communities. As psychiatrists, we can collaborate with faith leaders as follows:

1. More regularly assess the role of religion and spirituality in our patients’ daily lives to better meet their spiritual and mental health needs.

2. Better use existing chaplain services to provide spiritual support for hospitalized patients.

3. Present information about mental health – in-person, virtually, or in written form – to religious communities through talks, discussions, popular religious publications, social media platforms, and webinars.

4. Amplify existing mental health guides for faith leaders (i.e., the American Psychiatric Association’s guidebook Mental Health: A Guide for Faith Leaders),⁸ thereby encouraging church leaders and staff to become better informed about common mental health conditions.

5. Collaborate with places of worship to offer psychiatric and psychological services to their members.

This sort of engagement with religious communities is the collective role of community-oriented psychiatrists, not just psychiatrists who ascribe to religious or spiritual beliefs. We ought to remain mindful of the spiritual distress that many spiritual and religious patients feel when they experience mental illness,⁹ particularly in light of the distress caused by the coronavirus pandemic.¹⁰ But first, we must become comfortable with asking our patients about their religious or spiritual affiliations using tools such as the Cultural Formulation Interview.¹¹ The more we recognize the role of spirituality in our patients’ lives, the better equipped we become to help patients identify and seek treatment for mental illness without the distress of their feeling spiritually deficient.
 

Dr. Jordan is a psychiatry resident physician in Philadelphia. She has no conflicts of interest.

References

1. Religious Landscape Study. pewforum.org.

2. U.S. Religion Census Census: Religious Congregations and Membership Study. Association of Religion Data Archives. 2010. doi: 10.17605/OSF.IO/9AMDJ.

3. J Med Ethics Hist Med. 2018 Apr 9;11:3.

4. The Dimensions of Health: Conceptual Models. Sudbury, Mass.: Jones & Bartlett, 2010.

5. J Res Christ Educ. 2014;23(2):176-86.

6. Health Serv Res. 2003 Apr;38(2):647-73.

7. “More Americans say they’re spiritual but not religious.” pewresearch.org. 2017 Sep 6.

8. Mental Health: A Guide for Faith Leaders. Washington: American Psychiatric Association Foundation, 2018.

9. Mental Health by the Numbers. NAMI: National Alliance on Mental Illness. 2019.

10. “Most Americans say coronavirus outbreak has impacted their lives. Pew Research Center. pewsocialtrends.org. 2020 Mar 30.

11. DSM-5 Handbook on the Cultural Formulation Interview. Washington: American Psychiatric Association Publishing, 2016.

Spirituality and religion remain central to the worldview of millions of Americans. According to the Pew Research Center, almost 75% of Americans identify as Christian, Jewish, Muslim, Buddhist, or Hindu.¹ As is the case with many Americans,² the lens of spirituality³ and religion shaped my own worldview since childhood.

j-wildman/Getty Images

Growing up in a Christian household, many of my family’s discussions centered on bolstering our spiritual health. I grew to internalize the notion that spiritual health relates to a sense of self, a sense of purpose, and a connection to God, nature, and others. Religious texts such as the Bible, Quran, and Torah share principles aimed at developing believers’ spiritual health. However, the intricacies of mental health remain entirely foreign within many faith communities. In these communities, unfamiliarity with mental health topics seemingly leads to the conflation of spiritual health and mental health.⁴

Within faith communities, I often hear the phrase, “You can’t worry and pray at the same time.” This commonly used expression encourages people of faith to lean on their spiritual health in times of uncertainty. The perceived dichotomy between worry and prayer represents the theology of sole reliance on spiritual coping skills, such as prayer, when feelings of anxiety and other psychological stressors arise. Because of “pray it away” doctrines and ongoing stigma related to mental health, many of our spiritually minded patients are more likely to seek counsel from religious leaders than they are from mental health clinicians in times of psychological distress.^5,6

About 54% of U.S. adults identify as religious, and 75% think of themselves as spiritual.⁷ This intrapersonal conflict between religious/spiritual health and mental health raises an important question: How can psychiatrists more actively collaborate with religious communities to ease the perceived tensions between spiritual health and mental health for our patients?
 

Engaging with the community

In a recent virtual talk titled, “Dealing with Depression: Faith, Meds, and Therapy,” I openly discussed varying aspects of mental health and mental illness with approximately 70 women at my church in Philadelphia. Before this presentation, there had never been a leadership-sponsored conversation within the church to discuss spiritual health and mental health as separate but highly interconnected entities.

Throughout the nearly 2-hour session, I used biblical and biological principles to explain the differences between spiritual health and mental health, strategies to recognize signs and symptoms of depression, and treatment options for depression. After the formal presentation, a 45-minute question-and-answer session followed in which some members shared their own experiences with mental illness.

Two major themes emerged as central points of discussion during our time of open dialogue. First, several women shared the spiritual and clinical avenues they used to access support in times of psychological distress. There was a general tone of agreement among attendees that spiritual health and mental health are, in fact, different. Second, the presentation opened the door for attendees, previously unfamiliar with mental health services, to ask questions about connecting with the appropriate resources to receive mental health treatment. The subject of seeking psychiatric care for mental health challenges was, at least in part, demystified and brought to the forefront of the attendees’ minds.

Studies show that many faith-based communities are more likely to seek counsel for psychological distress from religious leaders than from mental health professionals. In this vein, my recent community engagement highlighted to me ways that we can readily reach spiritually and religiously minded patients who otherwise would not receive the psychiatric care that they need. Psychiatrists can play an integral role in bridging the gap in psychiatric care for faith-based persons through outreach to and collaboration with religious communities.
 

Opportunities for collaboration

In collaboration with religious leaders, psychiatrists can actively support the mental health of spiritually and religiously minded patients through several low-effort, but potentially high-yield, initiatives. Notably, many of my suggested interventions do not require significant, if any, infrastructural changes to the health care system or worship communities. As psychiatrists, we can collaborate with faith leaders as follows:

1. More regularly assess the role of religion and spirituality in our patients’ daily lives to better meet their spiritual and mental health needs.

2. Better use existing chaplain services to provide spiritual support for hospitalized patients.

3. Present information about mental health – in-person, virtually, or in written form – to religious communities through talks, discussions, popular religious publications, social media platforms, and webinars.

4. Amplify existing mental health guides for faith leaders (i.e., the American Psychiatric Association’s guidebook Mental Health: A Guide for Faith Leaders),⁸ thereby encouraging church leaders and staff to become better informed about common mental health conditions.

5. Collaborate with places of worship to offer psychiatric and psychological services to their members.

This sort of engagement with religious communities is the collective role of community-oriented psychiatrists, not just psychiatrists who ascribe to religious or spiritual beliefs. We ought to remain mindful of the spiritual distress that many spiritual and religious patients feel when they experience mental illness,⁹ particularly in light of the distress caused by the coronavirus pandemic.¹⁰ But first, we must become comfortable with asking our patients about their religious or spiritual affiliations using tools such as the Cultural Formulation Interview.¹¹ The more we recognize the role of spirituality in our patients’ lives, the better equipped we become to help patients identify and seek treatment for mental illness without the distress of their feeling spiritually deficient.
 

Dr. Jordan is a psychiatry resident physician in Philadelphia. She has no conflicts of interest.

References

1. Religious Landscape Study. pewforum.org.

2. U.S. Religion Census Census: Religious Congregations and Membership Study. Association of Religion Data Archives. 2010. doi: 10.17605/OSF.IO/9AMDJ.

3. J Med Ethics Hist Med. 2018 Apr 9;11:3.

4. The Dimensions of Health: Conceptual Models. Sudbury, Mass.: Jones & Bartlett, 2010.

5. J Res Christ Educ. 2014;23(2):176-86.

6. Health Serv Res. 2003 Apr;38(2):647-73.

7. “More Americans say they’re spiritual but not religious.” pewresearch.org. 2017 Sep 6.

8. Mental Health: A Guide for Faith Leaders. Washington: American Psychiatric Association Foundation, 2018.

9. Mental Health by the Numbers. NAMI: National Alliance on Mental Illness. 2019.

10. “Most Americans say coronavirus outbreak has impacted their lives. Pew Research Center. pewsocialtrends.org. 2020 Mar 30.

11. DSM-5 Handbook on the Cultural Formulation Interview. Washington: American Psychiatric Association Publishing, 2016.

The beneficial effect on all-cause mortality of coronary artery bypass grafting surgery observed at 4 and 5 years in women with complex coronary disease seen in the SYNTAX trial is gone at 10 years.

If anything, the results suggest a mortality benefit for coronary artery bypass grafting (CABG) over percutaneous coronary intervention (PCI) mainly for men (adjusted hazard ratio, 0.76; 95% confidence interval, 0.56-1.02) and not for women (adjusted HR, 0.90; 95% CI, 0.54-1.51) in the SYNTAX Extended Survival (SYNTAXES) study.

The sex-treatment interaction for all-cause mortality was significant at 5 years (P = .025) but not at 10 years (P = .952).

“I’m becoming very humble with trials because I’m not expecting the convergence of the curve. I was expecting like a surge, a further divergence,” senior author Patrick Serruys, MD, PhD, National University of Ireland, Galway, said in an interview. “You could say, at the end of the day, everybody dies. And that’s the life expectancy factor.”

Although female patients had slightly lower anatomic SYNTAX scores at randomization (27.0 vs. 29.2), they were on average 4 years older than men (mean age, 68 years) and had higher prevalence rates of diabetes, hypertension, and chronic kidney disease, he noted. “The other explanation is that we know that the bypass graft, the saphenous bypass graft, became vulnerable around 7 years; that’s probably the half-life.”

Overall, mortality in both men and women tended to be lower after CABG than after PCI, although the differences were not statistically significant, the authors reported August 17 in the Journal of the American College of Cardiology.

The 1,800-patient SYNTAX trial showed no difference in all-cause mortality at 5 years between CABG and PCI, although CABG was associated with fewer major adverse cardiac and cerebrovascular events (MACCE) and more favorable results among those with complex, three-vessel disease.

The findings were confirmed in 10-year follow-up reported last year from SYNTAXES, which analyzed only all-cause mortality.

Female sex, however, was an independent predictor of mortality with PCI at 4-years follow-up (HR, 2.87) in SYNTAX and led to sex being incorporated into the SYNTAX II score to help guide revascularization decisions. Notably, this interaction for all-cause mortality has not been seen in other studies.

Treatment effect by sex

In the new prespecified subgroup analysis, women had a higher crude rate of all-cause mortality at 10 years than men (32.8% vs. 24.7%; log-rank P = .002). This held true whether women were in the PCI group (33.0% vs. 27.0%; log-rank P = .053) or the CABG group (32.5% vs. 22.5%; log-rank P = .017).

In women, the mortality rate was significantly higher with PCI than with CABG at 5 years, but was no longer different at 10 years (33.0% vs. 32.5%; log-rank P = .601). This was largely caused by an uptick in deaths between 5 and 10 years in those treated with CABG, compared with PCI.

In men, the mortality rate was similar between PCI and CABG at 5 years, but tended to be higher with PCI at 10 years (27.0% vs. 22.5%; log-rank P = .082).

Asked about the possible late benefit for CABG in men, Dr. Serruys replied: “Of course, everyone had made a hypothesis – ‘let’s look at the use of internal mammary arteries in these patients, etc.’ – but I must be honest, we don’t have an explanation so far.”

Roxana Mehran, MD, Mount Sinai School of Medicine, New York City, said with just 402 women and using a no-longer-available, first-generation (Taxus) stent, the findings are, unfortunately, not informative.

“For me, it would be important for these investigators to share their data for women so we can do a patient-based analysis to better figure out the differential between first-generation stents and how well we’re doing,” Dr. Mehran said.

“What’s really important is to have a study where you actually collect female-specific risk factors that are never, ever looked at, [such as] age at menopause or having had pregnancy-related complications, that predispose these women to more of an atherosclerotic risk. And, even so, to better understand their anatomy and what suits them better,” she said. “I just don’t think we know enough or have put enough effort into understanding the biology that is sex specific and different for men and women.”
 

Revising SYNTAX II score

Given the lack of a sex-treatment interaction in the analysis, Dr. Serruys and colleagues suggest that the SYNTAX II score “should be reevaluated for the prediction of all-cause mortality at 10 years.”

Lending further support to this is the fact that SYNTAX II score was similar between women who died at 5-10 years and those who died in the first 5 years after CABG (31.8 vs. 31.6).

“The authors rightfully ask whether the SYNTAX II score should be revised to remove female sex, and given the current study result this appears warranted,” Arnold H. Seto, MD, MPA, Long Beach (Calif.) Veterans Administration Hospital, said in a related editorial.

He pointed out that women in SYNTAXES treated with CABG tended to have a survival time 0.51 years longer than women treated with PCI (P = .07). Nonetheless, the lack of confirmation for a sex-specific treatment interaction in any other study – EXCEL, FREEDOM, BEST, PRECOMBAT, BARI, or MASS – strongly suggests that the interaction seen in SYNTAX is likely a “type 1 error.”

Rather than focusing on early mortality, which may represent relatively rare events that are susceptible to chance, Dr. Seto suggested “other endpoints such years of life saved, quality adjusted life-years, and MACE may better capture the benefits of different revascularization decisions, even if they have a higher risk for bias.”

A new risk model, SYNTAX score 2020, has been developed and will be published imminently, Dr. Serruys said in an interview.

The SYNTAX Extended Survival study was supported by the German Foundation of Heart Research. The SYNTAX trial, during 0- to 5-years of follow-up, was funded by Boston Scientific. Both sponsors had no role in study design or data collection, analyses, and interpretation, nor were they involved in the decision to publish the final manuscript. Dr. Serruys has received personal fees from Biosensors, Micel Technologies, Sinomedical Sciences Technology, Philips/Volcano, Xeltis, and HeartFlow, outside the submitted work. Dr. Seto reported research grants from Philips and Acist, and honoraria from Terumo, Getinge, Boston Scientific, General Electric, and Janssen.

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

The beneficial effect on all-cause mortality of coronary artery bypass grafting surgery observed at 4 and 5 years in women with complex coronary disease seen in the SYNTAX trial is gone at 10 years.

If anything, the results suggest a mortality benefit for coronary artery bypass grafting (CABG) over percutaneous coronary intervention (PCI) mainly for men (adjusted hazard ratio, 0.76; 95% confidence interval, 0.56-1.02) and not for women (adjusted HR, 0.90; 95% CI, 0.54-1.51) in the SYNTAX Extended Survival (SYNTAXES) study.

The sex-treatment interaction for all-cause mortality was significant at 5 years (P = .025) but not at 10 years (P = .952).

“I’m becoming very humble with trials because I’m not expecting the convergence of the curve. I was expecting like a surge, a further divergence,” senior author Patrick Serruys, MD, PhD, National University of Ireland, Galway, said in an interview. “You could say, at the end of the day, everybody dies. And that’s the life expectancy factor.”

Although female patients had slightly lower anatomic SYNTAX scores at randomization (27.0 vs. 29.2), they were on average 4 years older than men (mean age, 68 years) and had higher prevalence rates of diabetes, hypertension, and chronic kidney disease, he noted. “The other explanation is that we know that the bypass graft, the saphenous bypass graft, became vulnerable around 7 years; that’s probably the half-life.”

Overall, mortality in both men and women tended to be lower after CABG than after PCI, although the differences were not statistically significant, the authors reported August 17 in the Journal of the American College of Cardiology.

The 1,800-patient SYNTAX trial showed no difference in all-cause mortality at 5 years between CABG and PCI, although CABG was associated with fewer major adverse cardiac and cerebrovascular events (MACCE) and more favorable results among those with complex, three-vessel disease.

The findings were confirmed in 10-year follow-up reported last year from SYNTAXES, which analyzed only all-cause mortality.

Female sex, however, was an independent predictor of mortality with PCI at 4-years follow-up (HR, 2.87) in SYNTAX and led to sex being incorporated into the SYNTAX II score to help guide revascularization decisions. Notably, this interaction for all-cause mortality has not been seen in other studies.

Treatment effect by sex

In the new prespecified subgroup analysis, women had a higher crude rate of all-cause mortality at 10 years than men (32.8% vs. 24.7%; log-rank P = .002). This held true whether women were in the PCI group (33.0% vs. 27.0%; log-rank P = .053) or the CABG group (32.5% vs. 22.5%; log-rank P = .017).

In women, the mortality rate was significantly higher with PCI than with CABG at 5 years, but was no longer different at 10 years (33.0% vs. 32.5%; log-rank P = .601). This was largely caused by an uptick in deaths between 5 and 10 years in those treated with CABG, compared with PCI.

In men, the mortality rate was similar between PCI and CABG at 5 years, but tended to be higher with PCI at 10 years (27.0% vs. 22.5%; log-rank P = .082).

Asked about the possible late benefit for CABG in men, Dr. Serruys replied: “Of course, everyone had made a hypothesis – ‘let’s look at the use of internal mammary arteries in these patients, etc.’ – but I must be honest, we don’t have an explanation so far.”

Roxana Mehran, MD, Mount Sinai School of Medicine, New York City, said with just 402 women and using a no-longer-available, first-generation (Taxus) stent, the findings are, unfortunately, not informative.

“For me, it would be important for these investigators to share their data for women so we can do a patient-based analysis to better figure out the differential between first-generation stents and how well we’re doing,” Dr. Mehran said.

“What’s really important is to have a study where you actually collect female-specific risk factors that are never, ever looked at, [such as] age at menopause or having had pregnancy-related complications, that predispose these women to more of an atherosclerotic risk. And, even so, to better understand their anatomy and what suits them better,” she said. “I just don’t think we know enough or have put enough effort into understanding the biology that is sex specific and different for men and women.”
 

Revising SYNTAX II score

Given the lack of a sex-treatment interaction in the analysis, Dr. Serruys and colleagues suggest that the SYNTAX II score “should be reevaluated for the prediction of all-cause mortality at 10 years.”

Lending further support to this is the fact that SYNTAX II score was similar between women who died at 5-10 years and those who died in the first 5 years after CABG (31.8 vs. 31.6).

“The authors rightfully ask whether the SYNTAX II score should be revised to remove female sex, and given the current study result this appears warranted,” Arnold H. Seto, MD, MPA, Long Beach (Calif.) Veterans Administration Hospital, said in a related editorial.

He pointed out that women in SYNTAXES treated with CABG tended to have a survival time 0.51 years longer than women treated with PCI (P = .07). Nonetheless, the lack of confirmation for a sex-specific treatment interaction in any other study – EXCEL, FREEDOM, BEST, PRECOMBAT, BARI, or MASS – strongly suggests that the interaction seen in SYNTAX is likely a “type 1 error.”

Rather than focusing on early mortality, which may represent relatively rare events that are susceptible to chance, Dr. Seto suggested “other endpoints such years of life saved, quality adjusted life-years, and MACE may better capture the benefits of different revascularization decisions, even if they have a higher risk for bias.”

A new risk model, SYNTAX score 2020, has been developed and will be published imminently, Dr. Serruys said in an interview.

The SYNTAX Extended Survival study was supported by the German Foundation of Heart Research. The SYNTAX trial, during 0- to 5-years of follow-up, was funded by Boston Scientific. Both sponsors had no role in study design or data collection, analyses, and interpretation, nor were they involved in the decision to publish the final manuscript. Dr. Serruys has received personal fees from Biosensors, Micel Technologies, Sinomedical Sciences Technology, Philips/Volcano, Xeltis, and HeartFlow, outside the submitted work. Dr. Seto reported research grants from Philips and Acist, and honoraria from Terumo, Getinge, Boston Scientific, General Electric, and Janssen.

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

The beneficial effect on all-cause mortality of coronary artery bypass grafting surgery observed at 4 and 5 years in women with complex coronary disease seen in the SYNTAX trial is gone at 10 years.

If anything, the results suggest a mortality benefit for coronary artery bypass grafting (CABG) over percutaneous coronary intervention (PCI) mainly for men (adjusted hazard ratio, 0.76; 95% confidence interval, 0.56-1.02) and not for women (adjusted HR, 0.90; 95% CI, 0.54-1.51) in the SYNTAX Extended Survival (SYNTAXES) study.

The sex-treatment interaction for all-cause mortality was significant at 5 years (P = .025) but not at 10 years (P = .952).

“I’m becoming very humble with trials because I’m not expecting the convergence of the curve. I was expecting like a surge, a further divergence,” senior author Patrick Serruys, MD, PhD, National University of Ireland, Galway, said in an interview. “You could say, at the end of the day, everybody dies. And that’s the life expectancy factor.”

Although female patients had slightly lower anatomic SYNTAX scores at randomization (27.0 vs. 29.2), they were on average 4 years older than men (mean age, 68 years) and had higher prevalence rates of diabetes, hypertension, and chronic kidney disease, he noted. “The other explanation is that we know that the bypass graft, the saphenous bypass graft, became vulnerable around 7 years; that’s probably the half-life.”

Overall, mortality in both men and women tended to be lower after CABG than after PCI, although the differences were not statistically significant, the authors reported August 17 in the Journal of the American College of Cardiology.

The 1,800-patient SYNTAX trial showed no difference in all-cause mortality at 5 years between CABG and PCI, although CABG was associated with fewer major adverse cardiac and cerebrovascular events (MACCE) and more favorable results among those with complex, three-vessel disease.

The findings were confirmed in 10-year follow-up reported last year from SYNTAXES, which analyzed only all-cause mortality.

Female sex, however, was an independent predictor of mortality with PCI at 4-years follow-up (HR, 2.87) in SYNTAX and led to sex being incorporated into the SYNTAX II score to help guide revascularization decisions. Notably, this interaction for all-cause mortality has not been seen in other studies.

Treatment effect by sex

In the new prespecified subgroup analysis, women had a higher crude rate of all-cause mortality at 10 years than men (32.8% vs. 24.7%; log-rank P = .002). This held true whether women were in the PCI group (33.0% vs. 27.0%; log-rank P = .053) or the CABG group (32.5% vs. 22.5%; log-rank P = .017).

In women, the mortality rate was significantly higher with PCI than with CABG at 5 years, but was no longer different at 10 years (33.0% vs. 32.5%; log-rank P = .601). This was largely caused by an uptick in deaths between 5 and 10 years in those treated with CABG, compared with PCI.

In men, the mortality rate was similar between PCI and CABG at 5 years, but tended to be higher with PCI at 10 years (27.0% vs. 22.5%; log-rank P = .082).

Asked about the possible late benefit for CABG in men, Dr. Serruys replied: “Of course, everyone had made a hypothesis – ‘let’s look at the use of internal mammary arteries in these patients, etc.’ – but I must be honest, we don’t have an explanation so far.”

Roxana Mehran, MD, Mount Sinai School of Medicine, New York City, said with just 402 women and using a no-longer-available, first-generation (Taxus) stent, the findings are, unfortunately, not informative.

“For me, it would be important for these investigators to share their data for women so we can do a patient-based analysis to better figure out the differential between first-generation stents and how well we’re doing,” Dr. Mehran said.

“What’s really important is to have a study where you actually collect female-specific risk factors that are never, ever looked at, [such as] age at menopause or having had pregnancy-related complications, that predispose these women to more of an atherosclerotic risk. And, even so, to better understand their anatomy and what suits them better,” she said. “I just don’t think we know enough or have put enough effort into understanding the biology that is sex specific and different for men and women.”
 

Revising SYNTAX II score

Given the lack of a sex-treatment interaction in the analysis, Dr. Serruys and colleagues suggest that the SYNTAX II score “should be reevaluated for the prediction of all-cause mortality at 10 years.”

Lending further support to this is the fact that SYNTAX II score was similar between women who died at 5-10 years and those who died in the first 5 years after CABG (31.8 vs. 31.6).

“The authors rightfully ask whether the SYNTAX II score should be revised to remove female sex, and given the current study result this appears warranted,” Arnold H. Seto, MD, MPA, Long Beach (Calif.) Veterans Administration Hospital, said in a related editorial.

He pointed out that women in SYNTAXES treated with CABG tended to have a survival time 0.51 years longer than women treated with PCI (P = .07). Nonetheless, the lack of confirmation for a sex-specific treatment interaction in any other study – EXCEL, FREEDOM, BEST, PRECOMBAT, BARI, or MASS – strongly suggests that the interaction seen in SYNTAX is likely a “type 1 error.”

Rather than focusing on early mortality, which may represent relatively rare events that are susceptible to chance, Dr. Seto suggested “other endpoints such years of life saved, quality adjusted life-years, and MACE may better capture the benefits of different revascularization decisions, even if they have a higher risk for bias.”

A new risk model, SYNTAX score 2020, has been developed and will be published imminently, Dr. Serruys said in an interview.

The SYNTAX Extended Survival study was supported by the German Foundation of Heart Research. The SYNTAX trial, during 0- to 5-years of follow-up, was funded by Boston Scientific. Both sponsors had no role in study design or data collection, analyses, and interpretation, nor were they involved in the decision to publish the final manuscript. Dr. Serruys has received personal fees from Biosensors, Micel Technologies, Sinomedical Sciences Technology, Philips/Volcano, Xeltis, and HeartFlow, outside the submitted work. Dr. Seto reported research grants from Philips and Acist, and honoraria from Terumo, Getinge, Boston Scientific, General Electric, and Janssen.

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

Key clinical point: The follow-up of patients with progressive multiple sclerosis (PMS) starting high-dose biotin (HDB) should include careful assessment of clinical and radiological activity to monitor the potential pro-inflammatory effect of biotin.

Major finding: In the crossover analysis among patients who received HDB (n=42), the number of relapses was statistically and clinically significantly higher after vs. before biotin initiation (incident rate ratio, 7.4; P less than .0001). With the propensity score matching method, relapse risk was significantly higher in the biotin vs. control group (hazard ratio [HR], 4.3; P = .01). The inverse probability of treatment weighting method with 440 control participants showed consistent results with higher risk in the biotin group (HR, 5.1; P less than .0001).

Study details: This study evaluated the association between exposure to HDB and the risk of relapse among 482 patients with PMS.

Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.

Citation: Branger P et al. Neurotherapeutics. 2020 Jun 15. doi: 10.1007/s13311-020-00880-z.

Key clinical point: The follow-up of patients with progressive multiple sclerosis (PMS) starting high-dose biotin (HDB) should include careful assessment of clinical and radiological activity to monitor the potential pro-inflammatory effect of biotin.

Major finding: In the crossover analysis among patients who received HDB (n=42), the number of relapses was statistically and clinically significantly higher after vs. before biotin initiation (incident rate ratio, 7.4; P less than .0001). With the propensity score matching method, relapse risk was significantly higher in the biotin vs. control group (hazard ratio [HR], 4.3; P = .01). The inverse probability of treatment weighting method with 440 control participants showed consistent results with higher risk in the biotin group (HR, 5.1; P less than .0001).

Study details: This study evaluated the association between exposure to HDB and the risk of relapse among 482 patients with PMS.

Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.

Citation: Branger P et al. Neurotherapeutics. 2020 Jun 15. doi: 10.1007/s13311-020-00880-z.

Key clinical point: The follow-up of patients with progressive multiple sclerosis (PMS) starting high-dose biotin (HDB) should include careful assessment of clinical and radiological activity to monitor the potential pro-inflammatory effect of biotin.

Major finding: In the crossover analysis among patients who received HDB (n=42), the number of relapses was statistically and clinically significantly higher after vs. before biotin initiation (incident rate ratio, 7.4; P less than .0001). With the propensity score matching method, relapse risk was significantly higher in the biotin vs. control group (hazard ratio [HR], 4.3; P = .01). The inverse probability of treatment weighting method with 440 control participants showed consistent results with higher risk in the biotin group (HR, 5.1; P less than .0001).

Study details: This study evaluated the association between exposure to HDB and the risk of relapse among 482 patients with PMS.

Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.

Citation: Branger P et al. Neurotherapeutics. 2020 Jun 15. doi: 10.1007/s13311-020-00880-z.