A 2-YEAR-OLD BOY presented to the emergency room with a 1-day history of a diffuse, mildly pruritic rash and swelling of his knees, ankles, and feet following treatment of acute otitis media with amoxicillin for the previous 8 days. He was mildly febrile and consolable, but he was refusing to walk. His medical history was unremarkable.

Physical examination revealed erythematous annular wheals on his chest, face, back, and extremities. Lymphadenopathy and mucous membrane involvement were not present. A complete blood count (CBC) with differential, inflammatory marker tests, and a comprehensive metabolic panel were ordered. Given the joint swelling and rash, the patient was admitted for observation.

During his second day in the hospital, his skin lesions enlarged and several formed dusky blue centers (FIGURE 1A). He also developed swelling of his hands (FIGURE 1B).

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

The patient’s lab work came back within normal range, except for an elevated white blood cell count (19,700/mm³; reference range, 4500-13,500/mm³). His mild systemic symptoms, skin lesions without blistering or necrosis, acral edema, and the absence of lymphadenopathy pointed to a diagnosis of urticaria multiforme.

Children with urticaria multiforme may have significant edema of the feet and may find walking difficult; this should not be confused with arthritis or arthralgias.

Urticaria multiforme, also called acute annular urticaria or acute urticarial hypersensitivity syndrome, is a histamine-mediated hypersensitivity reaction characterized by transient annular, polycyclic, urticarial lesions with central ecchymosis. The incidence and prevalence are not known. Urticaria multiforme is considered common, but it is frequently misdiagnosed.¹ It typically manifests in children ages 4 months to 4 years and begins with small erythematous macules, papules, and plaques that progress to large blanchable wheals with dusky blue centers.^1-3 Lesions are usually located on the face, trunk, and extremities and are often pruritic (60%-94%).^1-3 Individual lesions last less than 24 hours, but new ones may appear. The rash generally lasts 2 to 12 days.^1,3

Patients often report a preceding viral illness, otitis media, recent use of antibiotics, or recent immunizations. Dermatographism due to mast cell–mediated cutaneous hypersensitivity at sites of minor skin trauma is common (44%).¹ Patients often have associated facial or acral edema (72%).¹ Children with significant edema of the feet may find walking difficult, which should not be confused with arthritis or arthralgias. Generally, patients are nontoxic in appearance, and systemic symptoms are limited to a low-grade fever.^1-3

The diagnosis is made clinically and should not require a skin biopsy or extensive laboratory testing.When performed, laboratory studies, including CBC, erythrocyte sedimentation rate, C-reactive protein, and urinalysis are routinely normal.

Erythema multiforme and urticarial vasculitis are part of the differential

The differential diagnosis in this case includes erythema multiforme, Henoch-Schönlein purpura, serum sickness-like reaction, and urticarial vasculitis (TABLE^1,2,4).

Continue to: Erythema multiforme

Erythema multiforme is a common misdiagnosis in patients with urticaria multiforme.^1,2 The erythema multiforme rash has a “target” lesion with outer erythema and central ecchymosis, which may develop blisters or necrosis. Lesions are fixed and last 2 to 3 weeks. Unlike urticaria multiforme, patients with erythema multiforme commonly have mucous membrane erosions and occasionally ulcerations. Facial and acral edema is rare. Treatment is largely symptomatic and can include glucocorticoids. Antiviral medications may be used to treat recurrences.^1,2

Henoch-Schönlein purpura is an immunoglobulin A–mediated vasculitis that affects the skin, gastrointestinal tract, and joints.^4,5 Patients often present with arthralgias, gastrointestinal symptoms such as abdominal pain and bleeding, and a nonpruritic, erythematous rash that progresses to palpable purpura in dependent areas of the body. Treatment is generally symptomatic, but steroids may be used in severe cases.^4,5

Serum sickness-like reaction can manifest with angioedema and a similar urticarial rash (with central clearing) that lasts 1 to 6 weeks.^1,2,6,7 However, patients tend to have a high-grade fever, arthralgias, myalgias, and lymphadenopathy while dermatographism is absent. Treatment includes discontinuing the offending agent and the use of H1 and H2 antihistamines and steroids, in severe cases.

Urticarial vasculitis manifests as plaques or wheals lasting 1 to 7 days that may cause burning and pain but not pruritis.^2,5 Purpura or hypopigmentation may develop as the hives resolve. Angioedema and arthralgias are common, but dermatographism is not present. Triggers include infections, autoimmune disease, malignancy, and the use of certain medications. H1 and H2 blockers and nonsteroidal anti-inflammatory agents are first-line therapy.²

Step 1: Discontinue offending agents; Step 2: Recommend antihistamines

Treatment consists of discontinuing any offending agent (if suspected) and using systemic H1 or H2 antihistamines for symptom relief. Systemic steroids should only be given in refractory cases.

Continue to: Our patient's amoxicillin

Our patient’s amoxicillin was discontinued, and he was started on a 14-day course of cetirizine 5 mg bid and hydroxyzine 10 mg at bedtime. He was also started on triamcinolone 0.1% cream to be applied twice daily for 1 week. During his 3-day hospital stay, his fever resolved and his rash and edema improved.

During an outpatient follow-up visit with a pediatric dermatologist 2 weeks after discharge, the patient’s rash was still present and dermatographism was noted. In light of this, his parents were instructed to continue giving the cetirizine and hydroxyzine once daily for an additional 2 weeks and to return as needed.

A 2-YEAR-OLD BOY presented to the emergency room with a 1-day history of a diffuse, mildly pruritic rash and swelling of his knees, ankles, and feet following treatment of acute otitis media with amoxicillin for the previous 8 days. He was mildly febrile and consolable, but he was refusing to walk. His medical history was unremarkable.

Physical examination revealed erythematous annular wheals on his chest, face, back, and extremities. Lymphadenopathy and mucous membrane involvement were not present. A complete blood count (CBC) with differential, inflammatory marker tests, and a comprehensive metabolic panel were ordered. Given the joint swelling and rash, the patient was admitted for observation.

During his second day in the hospital, his skin lesions enlarged and several formed dusky blue centers (FIGURE 1A). He also developed swelling of his hands (FIGURE 1B).

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

The patient’s lab work came back within normal range, except for an elevated white blood cell count (19,700/mm³; reference range, 4500-13,500/mm³). His mild systemic symptoms, skin lesions without blistering or necrosis, acral edema, and the absence of lymphadenopathy pointed to a diagnosis of urticaria multiforme.

Children with urticaria multiforme may have significant edema of the feet and may find walking difficult; this should not be confused with arthritis or arthralgias.

Urticaria multiforme, also called acute annular urticaria or acute urticarial hypersensitivity syndrome, is a histamine-mediated hypersensitivity reaction characterized by transient annular, polycyclic, urticarial lesions with central ecchymosis. The incidence and prevalence are not known. Urticaria multiforme is considered common, but it is frequently misdiagnosed.¹ It typically manifests in children ages 4 months to 4 years and begins with small erythematous macules, papules, and plaques that progress to large blanchable wheals with dusky blue centers.^1-3 Lesions are usually located on the face, trunk, and extremities and are often pruritic (60%-94%).^1-3 Individual lesions last less than 24 hours, but new ones may appear. The rash generally lasts 2 to 12 days.^1,3

Patients often report a preceding viral illness, otitis media, recent use of antibiotics, or recent immunizations. Dermatographism due to mast cell–mediated cutaneous hypersensitivity at sites of minor skin trauma is common (44%).¹ Patients often have associated facial or acral edema (72%).¹ Children with significant edema of the feet may find walking difficult, which should not be confused with arthritis or arthralgias. Generally, patients are nontoxic in appearance, and systemic symptoms are limited to a low-grade fever.^1-3

The diagnosis is made clinically and should not require a skin biopsy or extensive laboratory testing.When performed, laboratory studies, including CBC, erythrocyte sedimentation rate, C-reactive protein, and urinalysis are routinely normal.

Erythema multiforme and urticarial vasculitis are part of the differential

The differential diagnosis in this case includes erythema multiforme, Henoch-Schönlein purpura, serum sickness-like reaction, and urticarial vasculitis (TABLE^1,2,4).

Continue to: Erythema multiforme

Erythema multiforme is a common misdiagnosis in patients with urticaria multiforme.^1,2 The erythema multiforme rash has a “target” lesion with outer erythema and central ecchymosis, which may develop blisters or necrosis. Lesions are fixed and last 2 to 3 weeks. Unlike urticaria multiforme, patients with erythema multiforme commonly have mucous membrane erosions and occasionally ulcerations. Facial and acral edema is rare. Treatment is largely symptomatic and can include glucocorticoids. Antiviral medications may be used to treat recurrences.^1,2

Henoch-Schönlein purpura is an immunoglobulin A–mediated vasculitis that affects the skin, gastrointestinal tract, and joints.^4,5 Patients often present with arthralgias, gastrointestinal symptoms such as abdominal pain and bleeding, and a nonpruritic, erythematous rash that progresses to palpable purpura in dependent areas of the body. Treatment is generally symptomatic, but steroids may be used in severe cases.^4,5

Serum sickness-like reaction can manifest with angioedema and a similar urticarial rash (with central clearing) that lasts 1 to 6 weeks.^1,2,6,7 However, patients tend to have a high-grade fever, arthralgias, myalgias, and lymphadenopathy while dermatographism is absent. Treatment includes discontinuing the offending agent and the use of H1 and H2 antihistamines and steroids, in severe cases.

Urticarial vasculitis manifests as plaques or wheals lasting 1 to 7 days that may cause burning and pain but not pruritis.^2,5 Purpura or hypopigmentation may develop as the hives resolve. Angioedema and arthralgias are common, but dermatographism is not present. Triggers include infections, autoimmune disease, malignancy, and the use of certain medications. H1 and H2 blockers and nonsteroidal anti-inflammatory agents are first-line therapy.²

Step 1: Discontinue offending agents; Step 2: Recommend antihistamines

Treatment consists of discontinuing any offending agent (if suspected) and using systemic H1 or H2 antihistamines for symptom relief. Systemic steroids should only be given in refractory cases.

Continue to: Our patient's amoxicillin

Our patient’s amoxicillin was discontinued, and he was started on a 14-day course of cetirizine 5 mg bid and hydroxyzine 10 mg at bedtime. He was also started on triamcinolone 0.1% cream to be applied twice daily for 1 week. During his 3-day hospital stay, his fever resolved and his rash and edema improved.

During an outpatient follow-up visit with a pediatric dermatologist 2 weeks after discharge, the patient’s rash was still present and dermatographism was noted. In light of this, his parents were instructed to continue giving the cetirizine and hydroxyzine once daily for an additional 2 weeks and to return as needed.

A 2-YEAR-OLD BOY presented to the emergency room with a 1-day history of a diffuse, mildly pruritic rash and swelling of his knees, ankles, and feet following treatment of acute otitis media with amoxicillin for the previous 8 days. He was mildly febrile and consolable, but he was refusing to walk. His medical history was unremarkable.

Physical examination revealed erythematous annular wheals on his chest, face, back, and extremities. Lymphadenopathy and mucous membrane involvement were not present. A complete blood count (CBC) with differential, inflammatory marker tests, and a comprehensive metabolic panel were ordered. Given the joint swelling and rash, the patient was admitted for observation.

During his second day in the hospital, his skin lesions enlarged and several formed dusky blue centers (FIGURE 1A). He also developed swelling of his hands (FIGURE 1B).

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

The patient’s lab work came back within normal range, except for an elevated white blood cell count (19,700/mm³; reference range, 4500-13,500/mm³). His mild systemic symptoms, skin lesions without blistering or necrosis, acral edema, and the absence of lymphadenopathy pointed to a diagnosis of urticaria multiforme.

Children with urticaria multiforme may have significant edema of the feet and may find walking difficult; this should not be confused with arthritis or arthralgias.

Urticaria multiforme, also called acute annular urticaria or acute urticarial hypersensitivity syndrome, is a histamine-mediated hypersensitivity reaction characterized by transient annular, polycyclic, urticarial lesions with central ecchymosis. The incidence and prevalence are not known. Urticaria multiforme is considered common, but it is frequently misdiagnosed.¹ It typically manifests in children ages 4 months to 4 years and begins with small erythematous macules, papules, and plaques that progress to large blanchable wheals with dusky blue centers.^1-3 Lesions are usually located on the face, trunk, and extremities and are often pruritic (60%-94%).^1-3 Individual lesions last less than 24 hours, but new ones may appear. The rash generally lasts 2 to 12 days.^1,3

Patients often report a preceding viral illness, otitis media, recent use of antibiotics, or recent immunizations. Dermatographism due to mast cell–mediated cutaneous hypersensitivity at sites of minor skin trauma is common (44%).¹ Patients often have associated facial or acral edema (72%).¹ Children with significant edema of the feet may find walking difficult, which should not be confused with arthritis or arthralgias. Generally, patients are nontoxic in appearance, and systemic symptoms are limited to a low-grade fever.^1-3

The diagnosis is made clinically and should not require a skin biopsy or extensive laboratory testing.When performed, laboratory studies, including CBC, erythrocyte sedimentation rate, C-reactive protein, and urinalysis are routinely normal.

Erythema multiforme and urticarial vasculitis are part of the differential

The differential diagnosis in this case includes erythema multiforme, Henoch-Schönlein purpura, serum sickness-like reaction, and urticarial vasculitis (TABLE^1,2,4).

Continue to: Erythema multiforme

Erythema multiforme is a common misdiagnosis in patients with urticaria multiforme.^1,2 The erythema multiforme rash has a “target” lesion with outer erythema and central ecchymosis, which may develop blisters or necrosis. Lesions are fixed and last 2 to 3 weeks. Unlike urticaria multiforme, patients with erythema multiforme commonly have mucous membrane erosions and occasionally ulcerations. Facial and acral edema is rare. Treatment is largely symptomatic and can include glucocorticoids. Antiviral medications may be used to treat recurrences.^1,2

Henoch-Schönlein purpura is an immunoglobulin A–mediated vasculitis that affects the skin, gastrointestinal tract, and joints.^4,5 Patients often present with arthralgias, gastrointestinal symptoms such as abdominal pain and bleeding, and a nonpruritic, erythematous rash that progresses to palpable purpura in dependent areas of the body. Treatment is generally symptomatic, but steroids may be used in severe cases.^4,5

Serum sickness-like reaction can manifest with angioedema and a similar urticarial rash (with central clearing) that lasts 1 to 6 weeks.^1,2,6,7 However, patients tend to have a high-grade fever, arthralgias, myalgias, and lymphadenopathy while dermatographism is absent. Treatment includes discontinuing the offending agent and the use of H1 and H2 antihistamines and steroids, in severe cases.

Urticarial vasculitis manifests as plaques or wheals lasting 1 to 7 days that may cause burning and pain but not pruritis.^2,5 Purpura or hypopigmentation may develop as the hives resolve. Angioedema and arthralgias are common, but dermatographism is not present. Triggers include infections, autoimmune disease, malignancy, and the use of certain medications. H1 and H2 blockers and nonsteroidal anti-inflammatory agents are first-line therapy.²

Step 1: Discontinue offending agents; Step 2: Recommend antihistamines

Treatment consists of discontinuing any offending agent (if suspected) and using systemic H1 or H2 antihistamines for symptom relief. Systemic steroids should only be given in refractory cases.

Continue to: Our patient's amoxicillin

Our patient’s amoxicillin was discontinued, and he was started on a 14-day course of cetirizine 5 mg bid and hydroxyzine 10 mg at bedtime. He was also started on triamcinolone 0.1% cream to be applied twice daily for 1 week. During his 3-day hospital stay, his fever resolved and his rash and edema improved.

During an outpatient follow-up visit with a pediatric dermatologist 2 weeks after discharge, the patient’s rash was still present and dermatographism was noted. In light of this, his parents were instructed to continue giving the cetirizine and hydroxyzine once daily for an additional 2 weeks and to return as needed.

Primary care clinicians care for the vast majority of the 34 million individuals in the United States with type 2 diabetes; these patients make up about 11% of visits in most practices.^1,2 Maximizing their health requires that we make the most of the ever-growing number of medications and devices that can be used to manage diabetes, while being sensitive to the health care inequities that limit patient access to the best care we have to offer.

A growing number of effective Tx options. In the past few years, we have seen the number of new drug classes for treating type 2 diabetes climb steadily. Within-class effects and adverse effects vary widely, demanding familiarity with the proven benefits of each individual drug. The advent of oral and injectable agents that include glucagon-like peptide 1 (GLP-1) receptor agonists and sodium glucose cotransporter 2 (SGLT2) inhibitors now supplement an expanding list of reliable basal insulins. Never before have we had such effective drugs with fewer adverse effects to manage glycemic control. New evidence supports adding selected medicines from these categories to reduce the risk of cardiovascular disease, heart failure, or chronic kidney dis­ease in patients at risk—regardless of the level of glucose control.

The benefit of more achievable goals. When the ACCORD (Action to Control Cardiovascular Risk in Diabetes) trial began in 1999, the UKPDS (United Kingdom Prospective Diabetes Study) had just demonstrated that lower blood sugars resulted in lower morbidity in patients with type 2 diabetes. Colleagues insisted that an extrapolation of UKPDS results suggested that low blood sugars were better, and that it would be unethical to allow a patient to maintain an A1C of 7.5% if less than 6.0% was possible.

We can expect amplified inequities in diabetes clinical outcomes to continue unless we develop a better system of distributing these life-changing medicines to Americans who need them.

By 2008, the ACCORD trial demonstrated that more lives were saved with a less aggressive approach, and family physicians could breathe a sigh of relief as they addressed other important comorbidities of diabetes. However, the tools we used in ACCORD were rudimentary compared to today’s approaches. As glycemic control becomes safer and more effective, demands for further normalizing glycemic control to minimize complications are inevitable.

Devices have transformed care, too. A wide variety of new continuous monitoring devices, delivery systems, and self-management tools provide more options for ensuring that treatment is less disruptive and more effective than ever before. Inevitably, the advent of these major advances also brings new and serious challenges. Practices will need to transform to support the demands and the needs of our patients.

Practice transformation is necessary if primary care is to continue the delivery of high-quality diabetes care. The link between practice diabetes performance measures and the introduction of enhanced patient-centered care teams providing proactive outreach is clear.³

Our biggest challenge. Despite advances in the science, perhaps the biggest challenge in diabetes care is the inevitable inequity in access to new medications. The average wholesale price of glargine has soared to $340 per month, while the most effective new GLP-1 receptor agonists are close to $1000 per month.⁴

Continue to: Although primary care doctors...

Although primary care doctors have always tried to accommodate the uninsured, the stark differences between new and old medicines now resembles a 2-tiered system. We can all celebrate advances in diabetes care and work hard to learn when and how to best use them, but those advances are accompanied by an uncomfortable awareness of the enormous inequity of prescribing regimens that haven't been considered best practice since the 1990s to patients who simply can’t afford better medicine.

We can expect amplified inequities in diabetes clinical outcomes to continue unless we develop a better system of distributing these life-changing medicines to those Americans who need them. Some state legislatures have made progress by supporting limited access to affordable insulin. However, ensuring that all patients with diabetes have access to modern insulin and effective medications is a national responsibility that needs a national response. Universal access to the modern tools of basic health care is a long-overdue treatment for an expanding epidemic of inequity.

Primary care clinicians care for the vast majority of the 34 million individuals in the United States with type 2 diabetes; these patients make up about 11% of visits in most practices.^1,2 Maximizing their health requires that we make the most of the ever-growing number of medications and devices that can be used to manage diabetes, while being sensitive to the health care inequities that limit patient access to the best care we have to offer.

A growing number of effective Tx options. In the past few years, we have seen the number of new drug classes for treating type 2 diabetes climb steadily. Within-class effects and adverse effects vary widely, demanding familiarity with the proven benefits of each individual drug. The advent of oral and injectable agents that include glucagon-like peptide 1 (GLP-1) receptor agonists and sodium glucose cotransporter 2 (SGLT2) inhibitors now supplement an expanding list of reliable basal insulins. Never before have we had such effective drugs with fewer adverse effects to manage glycemic control. New evidence supports adding selected medicines from these categories to reduce the risk of cardiovascular disease, heart failure, or chronic kidney dis­ease in patients at risk—regardless of the level of glucose control.

The benefit of more achievable goals. When the ACCORD (Action to Control Cardiovascular Risk in Diabetes) trial began in 1999, the UKPDS (United Kingdom Prospective Diabetes Study) had just demonstrated that lower blood sugars resulted in lower morbidity in patients with type 2 diabetes. Colleagues insisted that an extrapolation of UKPDS results suggested that low blood sugars were better, and that it would be unethical to allow a patient to maintain an A1C of 7.5% if less than 6.0% was possible.

We can expect amplified inequities in diabetes clinical outcomes to continue unless we develop a better system of distributing these life-changing medicines to Americans who need them.

By 2008, the ACCORD trial demonstrated that more lives were saved with a less aggressive approach, and family physicians could breathe a sigh of relief as they addressed other important comorbidities of diabetes. However, the tools we used in ACCORD were rudimentary compared to today’s approaches. As glycemic control becomes safer and more effective, demands for further normalizing glycemic control to minimize complications are inevitable.

Devices have transformed care, too. A wide variety of new continuous monitoring devices, delivery systems, and self-management tools provide more options for ensuring that treatment is less disruptive and more effective than ever before. Inevitably, the advent of these major advances also brings new and serious challenges. Practices will need to transform to support the demands and the needs of our patients.

Practice transformation is necessary if primary care is to continue the delivery of high-quality diabetes care. The link between practice diabetes performance measures and the introduction of enhanced patient-centered care teams providing proactive outreach is clear.³

Our biggest challenge. Despite advances in the science, perhaps the biggest challenge in diabetes care is the inevitable inequity in access to new medications. The average wholesale price of glargine has soared to $340 per month, while the most effective new GLP-1 receptor agonists are close to $1000 per month.⁴

Continue to: Although primary care doctors...

Although primary care doctors have always tried to accommodate the uninsured, the stark differences between new and old medicines now resembles a 2-tiered system. We can all celebrate advances in diabetes care and work hard to learn when and how to best use them, but those advances are accompanied by an uncomfortable awareness of the enormous inequity of prescribing regimens that haven't been considered best practice since the 1990s to patients who simply can’t afford better medicine.

We can expect amplified inequities in diabetes clinical outcomes to continue unless we develop a better system of distributing these life-changing medicines to those Americans who need them. Some state legislatures have made progress by supporting limited access to affordable insulin. However, ensuring that all patients with diabetes have access to modern insulin and effective medications is a national responsibility that needs a national response. Universal access to the modern tools of basic health care is a long-overdue treatment for an expanding epidemic of inequity.

Primary care clinicians care for the vast majority of the 34 million individuals in the United States with type 2 diabetes; these patients make up about 11% of visits in most practices.^1,2 Maximizing their health requires that we make the most of the ever-growing number of medications and devices that can be used to manage diabetes, while being sensitive to the health care inequities that limit patient access to the best care we have to offer.

A growing number of effective Tx options. In the past few years, we have seen the number of new drug classes for treating type 2 diabetes climb steadily. Within-class effects and adverse effects vary widely, demanding familiarity with the proven benefits of each individual drug. The advent of oral and injectable agents that include glucagon-like peptide 1 (GLP-1) receptor agonists and sodium glucose cotransporter 2 (SGLT2) inhibitors now supplement an expanding list of reliable basal insulins. Never before have we had such effective drugs with fewer adverse effects to manage glycemic control. New evidence supports adding selected medicines from these categories to reduce the risk of cardiovascular disease, heart failure, or chronic kidney dis­ease in patients at risk—regardless of the level of glucose control.

The benefit of more achievable goals. When the ACCORD (Action to Control Cardiovascular Risk in Diabetes) trial began in 1999, the UKPDS (United Kingdom Prospective Diabetes Study) had just demonstrated that lower blood sugars resulted in lower morbidity in patients with type 2 diabetes. Colleagues insisted that an extrapolation of UKPDS results suggested that low blood sugars were better, and that it would be unethical to allow a patient to maintain an A1C of 7.5% if less than 6.0% was possible.

We can expect amplified inequities in diabetes clinical outcomes to continue unless we develop a better system of distributing these life-changing medicines to Americans who need them.

By 2008, the ACCORD trial demonstrated that more lives were saved with a less aggressive approach, and family physicians could breathe a sigh of relief as they addressed other important comorbidities of diabetes. However, the tools we used in ACCORD were rudimentary compared to today’s approaches. As glycemic control becomes safer and more effective, demands for further normalizing glycemic control to minimize complications are inevitable.

Devices have transformed care, too. A wide variety of new continuous monitoring devices, delivery systems, and self-management tools provide more options for ensuring that treatment is less disruptive and more effective than ever before. Inevitably, the advent of these major advances also brings new and serious challenges. Practices will need to transform to support the demands and the needs of our patients.

Practice transformation is necessary if primary care is to continue the delivery of high-quality diabetes care. The link between practice diabetes performance measures and the introduction of enhanced patient-centered care teams providing proactive outreach is clear.³

Our biggest challenge. Despite advances in the science, perhaps the biggest challenge in diabetes care is the inevitable inequity in access to new medications. The average wholesale price of glargine has soared to $340 per month, while the most effective new GLP-1 receptor agonists are close to $1000 per month.⁴

Continue to: Although primary care doctors...

Although primary care doctors have always tried to accommodate the uninsured, the stark differences between new and old medicines now resembles a 2-tiered system. We can all celebrate advances in diabetes care and work hard to learn when and how to best use them, but those advances are accompanied by an uncomfortable awareness of the enormous inequity of prescribing regimens that haven't been considered best practice since the 1990s to patients who simply can’t afford better medicine.

We can expect amplified inequities in diabetes clinical outcomes to continue unless we develop a better system of distributing these life-changing medicines to those Americans who need them. Some state legislatures have made progress by supporting limited access to affordable insulin. However, ensuring that all patients with diabetes have access to modern insulin and effective medications is a national responsibility that needs a national response. Universal access to the modern tools of basic health care is a long-overdue treatment for an expanding epidemic of inequity.

THE CASE

A 78-year-old man with a history of diabetes and hypertension was referred to the outpatient surgical office with a chief complaint of “tail bone pain” that had started after a fall a year earlier. The patient complained that the pain was worse when sitting and at nighttime. He also admitted to a 7-lb weight loss over the past 2 months without change in diet or appetite. He denied symptoms of incontinence, urinary retention, sharp stabbing pains in the lower extremities, night sweats, or anorexia.

The patient first visited an urgent care facility on the day after the fall because he was experiencing pain in his “tail bone” region while riding his lawn mower. A pelvic x-ray was performed at that time and showed no coccyx fracture. He received a steroid injection in the right sacroiliac joint, which provided some relief for a month. Throughout the course of the year, he was given 6 steroid injections into his sacroiliac joint by his primary care provider (PCP) and clinicians at his local urgent care facility. One year after the fall, the patient’s PCP ordered a computed tomography (CT) scan of the abdomen and pelvis, which revealed a 4.6 x 7.5–cm soft-tissue mass with bony destruction of the lower sacrum and coccyx that extended into the sacral and coccygeal canal (FIGURE 1).

On exam in our surgical office, the patient was found to be alert and oriented. His neurologic exam was unremarkable, with an intact motor and sensory exam and no symptoms of cauda equina syndrome. During palpation over the lower sacrum and coccyx, both tenderness and a boggy, soft mass were observed. Nerve impingement was most likely caused by the size of the mass.

THE DIAGNOSIS

Biopsy revealed a large tan-gray, gelatinous, soft-tissue mass that was necrotizing through the lower sacrum. The diagnosis of a sacral chordoma was confirmed with magnetic resonance imaging of the pelvis, which demonstrated a 4.6 × 8.1–cm destructive expansile sacrococcygeal tumor with an exophytic soft-tissue component (FIGURE 2). The tumor also involved the piriformis and gluteus maximus muscles bilaterally.

DISCUSSION

Chordomas are rare, malignant bone tumors that grow slowly and originate from embryonic remnants of the notochord.¹ They are most commonly seen in the sacrococcygeal segment (50%) but are also seen in the ­spheno-occipital synchondrosis (30%-35%) and other spinal segments such as C2 and lumbar spine.² Chordomas are typically seen in middle-aged patients, with sacral chordomas occurring predominantly in men compared to women (3:1).²

Slow to grow, slow to diagnose

The difficulty with diagnosing sacral chordomas lies in the tendency for these tumors to grow extremely slowly, making detection challenging due to a lack of symptoms in the early clinical course. Once the tumors cause noticeable symptoms, they are usually large and extensively locally invasive. As a result, most patients experience delayed diagnosis, with an average symptom duration of 2.3 years prior to diagnosis.³

Reexamining a common problem as a symptom of a rare condition

The most commonly manifesting symptom of sacral chordomas is lower back pain that is typically dull and worse with sitting.^3,4 Since lower back pain is the leading cause of disability, it is difficult to determine when back pain is simply a benign consequence of aging or muscular pain and when it is, in fact, pathologic.⁵ A thorough history and physical are crucial in making the distinction.

Continue to: Clinical red flags...

Clinical red flags include pain with neurologic symptoms (including paresthesia, urinary or bowel disturbances, and weakness in the lower limbs), pain in the lower back with or without coccyx pain that persists and gradually worsens over time, and pain that fails to resolve.³ These symptoms are collectively strong indicators of underlying sacral pathology and should warrant further investigation, including a CT and MRI of the involved area.

Survival rate is improved by surgery

The gold standard for treatment of sacral chordomas is surgical resection with adequate margins, as these tumors are both radio- and chemo-insensitive.⁶ It is generally accepted that achieving a wide surgical margin is the most important predictor of survival and of reducing local recurrence in patients with sacrococcygeal chordoma.^7-9

The survival rate varies after a posterior-only surgical approach; some studies cite the 5-year survival rate as 100% and others state the 7-year survival rate as 5%.⁴ The wide variation is likely due to small trial size, a lack of evidence, and how invasive the disease is at the time of surgery.

The recurrence rate 5 years after surgery is approximately 20%.⁴ The rate of urinary and fecal incontinence after surgery using a posterior-only approach is between 20% and 100%; some of this variation may be due to which spinal level is involved.⁴ If S3 is affected, there is almost always perineal anesthesia along with bowel and bladder incontinence.⁴

This patient was referred to Neurosurgery and underwent resection. He recovered well from surgery but suffered from some residual urinary incontinence. The patient did not receive chemotherapy or radiation, and further work-up revealed no evidence of metastasis.

Continue to: THE TAKEAWAY

The diagnosis of sacral chordoma remains challenging. A history of clinical red flags, especially persistent lower back pain with neuropathy, should prompt an aggressive investigation to rule out underlying pathology. Other signs on physical exam could include urinary or bowel disturbances, weakness in the lower limbs, saddle anesthesia, new foot drop, and/or laxity of the anal sphincter.⁵ Early detection and surgical intervention are crucial for these patients to experience a better prognosis and preserve maximum function.

CORRESPONDENCE
Ginger Poulton, MD, 123 Hendersonville Road, Asheville, NC 28803; [email protected]

THE CASE

A 78-year-old man with a history of diabetes and hypertension was referred to the outpatient surgical office with a chief complaint of “tail bone pain” that had started after a fall a year earlier. The patient complained that the pain was worse when sitting and at nighttime. He also admitted to a 7-lb weight loss over the past 2 months without change in diet or appetite. He denied symptoms of incontinence, urinary retention, sharp stabbing pains in the lower extremities, night sweats, or anorexia.

The patient first visited an urgent care facility on the day after the fall because he was experiencing pain in his “tail bone” region while riding his lawn mower. A pelvic x-ray was performed at that time and showed no coccyx fracture. He received a steroid injection in the right sacroiliac joint, which provided some relief for a month. Throughout the course of the year, he was given 6 steroid injections into his sacroiliac joint by his primary care provider (PCP) and clinicians at his local urgent care facility. One year after the fall, the patient’s PCP ordered a computed tomography (CT) scan of the abdomen and pelvis, which revealed a 4.6 x 7.5–cm soft-tissue mass with bony destruction of the lower sacrum and coccyx that extended into the sacral and coccygeal canal (FIGURE 1).

On exam in our surgical office, the patient was found to be alert and oriented. His neurologic exam was unremarkable, with an intact motor and sensory exam and no symptoms of cauda equina syndrome. During palpation over the lower sacrum and coccyx, both tenderness and a boggy, soft mass were observed. Nerve impingement was most likely caused by the size of the mass.

THE DIAGNOSIS

Biopsy revealed a large tan-gray, gelatinous, soft-tissue mass that was necrotizing through the lower sacrum. The diagnosis of a sacral chordoma was confirmed with magnetic resonance imaging of the pelvis, which demonstrated a 4.6 × 8.1–cm destructive expansile sacrococcygeal tumor with an exophytic soft-tissue component (FIGURE 2). The tumor also involved the piriformis and gluteus maximus muscles bilaterally.

DISCUSSION

Chordomas are rare, malignant bone tumors that grow slowly and originate from embryonic remnants of the notochord.¹ They are most commonly seen in the sacrococcygeal segment (50%) but are also seen in the ­spheno-occipital synchondrosis (30%-35%) and other spinal segments such as C2 and lumbar spine.² Chordomas are typically seen in middle-aged patients, with sacral chordomas occurring predominantly in men compared to women (3:1).²

Slow to grow, slow to diagnose

The difficulty with diagnosing sacral chordomas lies in the tendency for these tumors to grow extremely slowly, making detection challenging due to a lack of symptoms in the early clinical course. Once the tumors cause noticeable symptoms, they are usually large and extensively locally invasive. As a result, most patients experience delayed diagnosis, with an average symptom duration of 2.3 years prior to diagnosis.³

Reexamining a common problem as a symptom of a rare condition

The most commonly manifesting symptom of sacral chordomas is lower back pain that is typically dull and worse with sitting.^3,4 Since lower back pain is the leading cause of disability, it is difficult to determine when back pain is simply a benign consequence of aging or muscular pain and when it is, in fact, pathologic.⁵ A thorough history and physical are crucial in making the distinction.

Continue to: Clinical red flags...

Clinical red flags include pain with neurologic symptoms (including paresthesia, urinary or bowel disturbances, and weakness in the lower limbs), pain in the lower back with or without coccyx pain that persists and gradually worsens over time, and pain that fails to resolve.³ These symptoms are collectively strong indicators of underlying sacral pathology and should warrant further investigation, including a CT and MRI of the involved area.

Survival rate is improved by surgery

The gold standard for treatment of sacral chordomas is surgical resection with adequate margins, as these tumors are both radio- and chemo-insensitive.⁶ It is generally accepted that achieving a wide surgical margin is the most important predictor of survival and of reducing local recurrence in patients with sacrococcygeal chordoma.^7-9

The survival rate varies after a posterior-only surgical approach; some studies cite the 5-year survival rate as 100% and others state the 7-year survival rate as 5%.⁴ The wide variation is likely due to small trial size, a lack of evidence, and how invasive the disease is at the time of surgery.

The recurrence rate 5 years after surgery is approximately 20%.⁴ The rate of urinary and fecal incontinence after surgery using a posterior-only approach is between 20% and 100%; some of this variation may be due to which spinal level is involved.⁴ If S3 is affected, there is almost always perineal anesthesia along with bowel and bladder incontinence.⁴

This patient was referred to Neurosurgery and underwent resection. He recovered well from surgery but suffered from some residual urinary incontinence. The patient did not receive chemotherapy or radiation, and further work-up revealed no evidence of metastasis.

Continue to: THE TAKEAWAY

The diagnosis of sacral chordoma remains challenging. A history of clinical red flags, especially persistent lower back pain with neuropathy, should prompt an aggressive investigation to rule out underlying pathology. Other signs on physical exam could include urinary or bowel disturbances, weakness in the lower limbs, saddle anesthesia, new foot drop, and/or laxity of the anal sphincter.⁵ Early detection and surgical intervention are crucial for these patients to experience a better prognosis and preserve maximum function.

CORRESPONDENCE
Ginger Poulton, MD, 123 Hendersonville Road, Asheville, NC 28803; [email protected]

THE CASE

A 78-year-old man with a history of diabetes and hypertension was referred to the outpatient surgical office with a chief complaint of “tail bone pain” that had started after a fall a year earlier. The patient complained that the pain was worse when sitting and at nighttime. He also admitted to a 7-lb weight loss over the past 2 months without change in diet or appetite. He denied symptoms of incontinence, urinary retention, sharp stabbing pains in the lower extremities, night sweats, or anorexia.

The patient first visited an urgent care facility on the day after the fall because he was experiencing pain in his “tail bone” region while riding his lawn mower. A pelvic x-ray was performed at that time and showed no coccyx fracture. He received a steroid injection in the right sacroiliac joint, which provided some relief for a month. Throughout the course of the year, he was given 6 steroid injections into his sacroiliac joint by his primary care provider (PCP) and clinicians at his local urgent care facility. One year after the fall, the patient’s PCP ordered a computed tomography (CT) scan of the abdomen and pelvis, which revealed a 4.6 x 7.5–cm soft-tissue mass with bony destruction of the lower sacrum and coccyx that extended into the sacral and coccygeal canal (FIGURE 1).

On exam in our surgical office, the patient was found to be alert and oriented. His neurologic exam was unremarkable, with an intact motor and sensory exam and no symptoms of cauda equina syndrome. During palpation over the lower sacrum and coccyx, both tenderness and a boggy, soft mass were observed. Nerve impingement was most likely caused by the size of the mass.

THE DIAGNOSIS

Biopsy revealed a large tan-gray, gelatinous, soft-tissue mass that was necrotizing through the lower sacrum. The diagnosis of a sacral chordoma was confirmed with magnetic resonance imaging of the pelvis, which demonstrated a 4.6 × 8.1–cm destructive expansile sacrococcygeal tumor with an exophytic soft-tissue component (FIGURE 2). The tumor also involved the piriformis and gluteus maximus muscles bilaterally.

DISCUSSION

Chordomas are rare, malignant bone tumors that grow slowly and originate from embryonic remnants of the notochord.¹ They are most commonly seen in the sacrococcygeal segment (50%) but are also seen in the ­spheno-occipital synchondrosis (30%-35%) and other spinal segments such as C2 and lumbar spine.² Chordomas are typically seen in middle-aged patients, with sacral chordomas occurring predominantly in men compared to women (3:1).²

Slow to grow, slow to diagnose

The difficulty with diagnosing sacral chordomas lies in the tendency for these tumors to grow extremely slowly, making detection challenging due to a lack of symptoms in the early clinical course. Once the tumors cause noticeable symptoms, they are usually large and extensively locally invasive. As a result, most patients experience delayed diagnosis, with an average symptom duration of 2.3 years prior to diagnosis.³

Reexamining a common problem as a symptom of a rare condition

The most commonly manifesting symptom of sacral chordomas is lower back pain that is typically dull and worse with sitting.^3,4 Since lower back pain is the leading cause of disability, it is difficult to determine when back pain is simply a benign consequence of aging or muscular pain and when it is, in fact, pathologic.⁵ A thorough history and physical are crucial in making the distinction.

Continue to: Clinical red flags...

Clinical red flags include pain with neurologic symptoms (including paresthesia, urinary or bowel disturbances, and weakness in the lower limbs), pain in the lower back with or without coccyx pain that persists and gradually worsens over time, and pain that fails to resolve.³ These symptoms are collectively strong indicators of underlying sacral pathology and should warrant further investigation, including a CT and MRI of the involved area.

Survival rate is improved by surgery

The gold standard for treatment of sacral chordomas is surgical resection with adequate margins, as these tumors are both radio- and chemo-insensitive.⁶ It is generally accepted that achieving a wide surgical margin is the most important predictor of survival and of reducing local recurrence in patients with sacrococcygeal chordoma.^7-9

The survival rate varies after a posterior-only surgical approach; some studies cite the 5-year survival rate as 100% and others state the 7-year survival rate as 5%.⁴ The wide variation is likely due to small trial size, a lack of evidence, and how invasive the disease is at the time of surgery.

The recurrence rate 5 years after surgery is approximately 20%.⁴ The rate of urinary and fecal incontinence after surgery using a posterior-only approach is between 20% and 100%; some of this variation may be due to which spinal level is involved.⁴ If S3 is affected, there is almost always perineal anesthesia along with bowel and bladder incontinence.⁴

This patient was referred to Neurosurgery and underwent resection. He recovered well from surgery but suffered from some residual urinary incontinence. The patient did not receive chemotherapy or radiation, and further work-up revealed no evidence of metastasis.

Continue to: THE TAKEAWAY

The diagnosis of sacral chordoma remains challenging. A history of clinical red flags, especially persistent lower back pain with neuropathy, should prompt an aggressive investigation to rule out underlying pathology. Other signs on physical exam could include urinary or bowel disturbances, weakness in the lower limbs, saddle anesthesia, new foot drop, and/or laxity of the anal sphincter.⁵ Early detection and surgical intervention are crucial for these patients to experience a better prognosis and preserve maximum function.

CORRESPONDENCE
Ginger Poulton, MD, 123 Hendersonville Road, Asheville, NC 28803; [email protected]

The global prevalence of dyspepsia is approximately 20%,¹ and it is often associated with other comorbidities and overlapping gastrointestinal complaints. The effects on the patient’s quality of life, including societal impacts, are considerable. Symptoms and their response to treatment are highly variable, necessitating individualized management. While some patients’ symptoms may be refractory to standard medical treatment initially, evidence suggests that the strategies summarized in our guidance here—including the use of tricyclic antidepressants (TCAs), prokinetics, and adjunctive therapies—may alleviate symptoms and improve patients’ quality of life.

What dyspepsia is—and what it isn’t

Dyspepsia is a poorly characterized disorder often associated with nausea, heartburn, early satiety, and bloating. The American College of Gastroenterology (ACG) now advocates using a clinically relevant definition of dyspepsia as “predominant epigastric pain lasting at least a month” as long as epigastric pain is the patient's primary complaint.² Causes of dyspepsia are listed in TABLE 1.

Heartburn, a burning sensation in the chest, is not a dyspeptic symptom but the 2 may often coexist. In general, dyspepsia does not have a colicky or postural component. Symptoms that are relieved by evacuation of feces or gas generally should not be considered a part of dyspepsia.

Functional dyspepsia (FD) is a subset for which no structural pathology has been identified, accounting for up to 70% of all patients with dyspepsia.³ The Rome Foundation, in its recent update (Rome IV), has highlighted 4 key symptoms and 2 proposed subtypes (TABLE 2).⁴ The comorbidities of anxiety, depression, and somatization appear to be more prevalent in these dyspepsia patients than in those with organic issues. The incidence of gastric malignancy is low in this cohort.^3,5 Dyspepsia occurring after an acute infection is referred to as postinfectious functional dyspepsia.

Pathophysiology of functional dyspepsia. Dysmotility, visceral hypersensitivity, mucosal immune dysfunction, altered gut microbiota, and disturbed central nervous system processing contribute in varying degrees to the pathophysiology of FD. There is evidence that luminal factors have the potential to trigger local neuronal excitability.^6,7 Early life psychosocial factors may further influence illness behaviors, coping strategies, stress responses, and the intensity of symptoms perceived by the patient.⁸

Clues in the history and physical examination

Patients describe their discomfort using a variety of terms, including pain, gnawing, burning, gassiness, or queasiness. Although allergic reactions to food (swelling of lips and tongue with a rash) are rare in adults, food intolerances are common in patients with dyspepsia.⁹ Consumption of nonsteroidal ­anti-inflammatory drugs is a common cause of dyspepsia, even at over-the-counter strength, and may cause ulceration, gastrointestinal bleeding, and anemia. Narcotic and marijuana use and the anticholinergic effects of antidepressant medications are associated with gastrointestinal dysmotility, including gastroparesis.

Weight loss, night waking, and vomiting make functional dyspepsia less likely and deserve immediate consideration of abdominal imaging or endoscopic examination.

Patients with FD often exhibit symptoms of other functional abdominal disorders including irritable bowel syndrome, functional heartburn, bloating, or chronic nausea, and may have been previously diagnosed with overlapping conditions suggestive of visceral hypersensitivity, including depression, anxiety, fibromyalgia, migraine, and pelvic pain. During the patient’s office visit, be alert to any indication of an underlying psychological issue.

Continue to: The initial diagnostic challenge

The initial diagnostic challenge is to identify those patients who may have a structural disorder requiring expedited and targeted investigation. Weight loss, night waking, and vomiting are unusual in the setting of either FD or Helicobacter pylori gastritis. These and other features of concern (TABLE 3) make a diagnosis of a functional disorder less likely and should prompt immediate consideration of abdominal imaging or endoscopic examination. Epigastric tenderness on palpation is common in patients with FD and is not necessarily predictive of structural pathology—unless accompanied by other findings of concern. Abdominal scars or a history of trauma may be suggestive of abdominal wall pain. Abdominal pain that remains unchanged or increases when the muscles of the abdominal wall are tensed (Carnett sign) suggests abdominal wall pain.

Initial testing and Tx assessments focus on H pylori

All 3 of the major US gastroenterology organizations recommend a stepwise approach in patients without alarm symptoms, generally beginning (in those < 60 years) by testing for H pylori with either the stool antigen or urea breath test (UBT)—and initiating appropriate treatment if results are positive.^5,10 (The first step for those ≥ 60 years is discussed later.) Since the serum antibody test cannot differentiate between active and past infection, it is not recommended if other options are available.¹¹ The stool antigen test is preferred; it is a cost-effective option used for both diagnosis and confirmation of H pylori eradication.

The UBT identifies active infection with a sensitivity and specificity of > 95%¹² but is more labor intensive, employs an isotope, and is relatively expensive. Because proton pump inhibitors (PPIs), bismuth, and antibiotics may increase the false-negative rate for both the UBT and stool antigen test, we recommend that these medications be held for 2 to 4 weeks prior to testing.¹¹ H₂-receptor antagonists do not need to be restricted.

Treatment regimens containing clarithromycin have fallen into disfavor given the high rates of resistance that are now encountered. Fourteen-day regimens that can be used empirically (without susceptibility testing) are bismuth quadruple therapy (bismuth, metronidazole, tetracycline, and PPI) or rifabutin triple therapy (rifabutin, amoxicillin, and PPI).¹³ To confirm eradication, perform repeat testing with either stool antigen or UBT no sooner than 4 weeks after completion of therapy. If the first treatment fails, try a second regimen using different antibiotics.¹⁴ Although the impact of H pylori eradication on dyspeptic symptoms is only modest, this strategy is recommended also to reduce the risk of peptic ulceration and gastric neoplasia.

Next-step testing and Tx considerations

Given the heterogeneity of presenting symptoms of dyspepsia, some clinicians may be hesitant to diagnose a functional disorder at the first visit, preferring instead to conduct a limited range of investigations in concert with initial medical management. In these circumstances it would be reasonable, in addition to testing for H pylori, to order a complete blood count (CBC) and to measure serum lipase and liver enzymes. Keep in mind that liver enzymes may not be elevated in uncomplicated biliary colic.

Continue to: Consider ultrasound imaging...

Consider ultrasound imaging if gallstones are a consideration. A computerized tomography scan may not exclude uncomplicated and noncalcified gallstones, but it is an excellent modality for detecting suspected retroperitoneal pathology. Consider working with a gastroenterologist if the patient exhibits alarm features.

Empiric PPI therapy. A trial of daily PPI use over 4 weeks is recommended for patients without H pylori and for those whose symptoms continue despite eradication of the bacterium. A Cochrane meta-analysis found that PPI therapy was more effective than placebo (31% vs 26%; risk ratio, 0.88; number needed to treat [NNT] = 11; 95% CI 0.82 to 0.94; P < .001).¹⁵ PPI therapy appears to be slightly more effective than treatment with H₂-receptor antagonists. Both are proposed in the United Kingdom guideline.¹⁶ Both are generally safe and well tolerated but are not without potential adverse effects when used long term.

Dietary modification. Patients with dyspepsia commonly report that meals exacerbate symptoms. This is likely due to a combination of gastric distension and underlying visceral hypersensitivity rather than food composition.

The stool antigen test is preferred for diagnosing and confirming eradication of H pylori. The serum antibody test cannot differentiate between active and past infection.

There is no reliable “dyspepsia diet,” although a systematic review implicated wheat and high-fat foods as the 2 most common contributors to symptom onset.¹⁷ Recommended dietary modifications would be to consume smaller, more frequent meals and to eliminate recognized trigger foods. Patients with postprandial distress syndrome, a subset of FD, may want to consider reducing fat intake to help alleviate discomfort. If symptoms continue, evaluate for lactose intolerance. Also, consider a trial of a gluten-free diet. The low-FODMAP diet (restricting fermentable oligo-, di- and monosaccharides, as well as polyols) has shown benefit in patients with irritable bowel syndrome and may be considered in those with intractable FD, given the overlap in physiology of the disorders.

Upper gastrointestinal endoscopy. The ACG has suggested that esophagogastroduodenoscopy (EGD) be performed as the first investigative step for patients ≥ 60 years, while testing for H pylori be considered as the first step in younger patients, even if alarm symptoms are present² (FIGURE). This decision must be individualized, particularly in patients of Asian, Central or South American, or Caribbean descent, in whom the incidence of gastric cancer is higher with earlier onset.¹⁸

Continue to: Also consider EGD...

Also consider EGD for patients whose symptoms have not improved despite eradication of H pylori or an adequate trial of PPI therapy. While some guidelines do not require EGD in low-risk patients at this stage, other authorities would consider this step prudent, particularly when quality of life has been significantly impaired. An underlying organic cause, mainly erosive esophagitis or peptic ulcer disease, is found in 20% to 30% of patients with dyspepsia.⁵

Most patients without alarm features, with normal findings on upper endoscopy, who do not have H pylori gastritis, and whose symptoms continue despite a trial of PPI therapy, will have FD (FIGURE).²

Offer patients with functional dyspepsia supportive therapy

Neuromodulators

TCAs are superior to placebo in reducing dyspeptic symptoms with an NNT of 6 and are recommended for patients with ongoing symptoms despite PPI therapy or H pylori eradication.² Begin with a low dose and increase as tolerated. It may take a few weeks for improvement to be seen. Exercise caution in the presence of cardiac arrhythmias.

Mirtazapine, 7.5 to 15 mg every night at bedtime, reduces fullness and bloating in postprandial distress syndrome and is useful for patients who have lost weight. It’s important to note that TCAs and mirtazapine both have the potential for QT prolongation, as well as depression and suicidality in younger patients.¹⁹ The anxiolytic buspirone, 10 mg before meals, augments fundic relaxation, improves overall symptom severity, and helps alleviate early satiety, postprandial fullness, and upper abdominal bloating.²⁰

Prokinetics

A recent meta-analysis demonstrated significant benefit in symptom control in dyspeptic patients treated with prokinetics (NNT = 7).²¹ However, the benefit was predominantly due to cisapride, a drug that was withdrawn from the US market due to adverse effects. There are no clinical trials of metoclopramide or domperidone (not available in the United States) in FD. Nonetheless, the ACG has given a conditional recommendation, based on low-quality evidence, for the use of prokinetics in patients with FD not responding to PPI therapy, H pylori eradication, or TCA therapy.²

Continue to: A shortcoming of the established guidelines

A shortcoming of the established guidelines is that they do not provide guidance as to long-term management of those patients who respond to prescription medications. Our practice has been to continue medications for a minimum of 3 months, then begin a slow taper in order to establish the lowest efficacious dose. Some patients may relapse and require full dosage for a longer period of time.

Adjunctive therapies are worth considering

Complementary and alternative medicines. Products containing ginger, carraway oil, artichoke leaf extract, turmeric, and red pepper are readily available without prescription and have long been used with variable results for dyspepsia.²² The 9-herb combination STW-5 has demonstrated superiority over placebo in a number of studies and has a favorable safety profile.²³ The recommended dose is 10 to 20 drops tid. The European manufacturer has recently modified the package insert noting rare cases of hepatotoxicity.²⁴

Because PPIs, bismuth, and antibiotics may increase the false-negative rate for both the UBT and stool antigen test, we recommend that these medications be held for 2 to 4 weeks prior to testing.

A commercially available formulation (FDgard) containing L-menthol (a key component of peppermint oil) and caraway has been found to reduce the intensity of symptoms in patients with FD. Potential adverse effects include nausea, contact dermatitis, bronchospasm, and atrial fibrillation. Cayenne, a red pepper extract, is available over the counter for the benefit for epigastric pain and bloating. Begin with a 500-mg dose before breakfast and a 1000-mg dose before dinner, increasing to 2500 mg/d as tolerated. Cayenne preparations may trigger drug toxicities and are best avoided in patients taking antihypertensives, theophylline, or anticoagulants.

Cognitive behavioral therapy, acupuncture, and hypnosis. These modalities are time consuming, are often expensive, are not always covered by insurance, and require significant motivation. A systematic review found no benefit.²⁵ Subsequent studies summarized in the ACG guidelines² reported benefit; however, a lack of blinding and significant heterogeneity among the groups detract from the quality of the data. It remains unclear whether these are effective strategies for FD, and therefore they cannot be recommended on a routine basis.

CORRESPONDENCE
Norman H. Gilinsky, MD, Division of Digestive Diseases, University of Cincinnati College of Medicine, 231 Albert Sabin Way, Cincinnati, OH 45267-0595; norman.gilinsky@ uc.edu

The global prevalence of dyspepsia is approximately 20%,¹ and it is often associated with other comorbidities and overlapping gastrointestinal complaints. The effects on the patient’s quality of life, including societal impacts, are considerable. Symptoms and their response to treatment are highly variable, necessitating individualized management. While some patients’ symptoms may be refractory to standard medical treatment initially, evidence suggests that the strategies summarized in our guidance here—including the use of tricyclic antidepressants (TCAs), prokinetics, and adjunctive therapies—may alleviate symptoms and improve patients’ quality of life.

What dyspepsia is—and what it isn’t

Dyspepsia is a poorly characterized disorder often associated with nausea, heartburn, early satiety, and bloating. The American College of Gastroenterology (ACG) now advocates using a clinically relevant definition of dyspepsia as “predominant epigastric pain lasting at least a month” as long as epigastric pain is the patient's primary complaint.² Causes of dyspepsia are listed in TABLE 1.

Heartburn, a burning sensation in the chest, is not a dyspeptic symptom but the 2 may often coexist. In general, dyspepsia does not have a colicky or postural component. Symptoms that are relieved by evacuation of feces or gas generally should not be considered a part of dyspepsia.

Functional dyspepsia (FD) is a subset for which no structural pathology has been identified, accounting for up to 70% of all patients with dyspepsia.³ The Rome Foundation, in its recent update (Rome IV), has highlighted 4 key symptoms and 2 proposed subtypes (TABLE 2).⁴ The comorbidities of anxiety, depression, and somatization appear to be more prevalent in these dyspepsia patients than in those with organic issues. The incidence of gastric malignancy is low in this cohort.^3,5 Dyspepsia occurring after an acute infection is referred to as postinfectious functional dyspepsia.

Pathophysiology of functional dyspepsia. Dysmotility, visceral hypersensitivity, mucosal immune dysfunction, altered gut microbiota, and disturbed central nervous system processing contribute in varying degrees to the pathophysiology of FD. There is evidence that luminal factors have the potential to trigger local neuronal excitability.^6,7 Early life psychosocial factors may further influence illness behaviors, coping strategies, stress responses, and the intensity of symptoms perceived by the patient.⁸

Clues in the history and physical examination

Patients describe their discomfort using a variety of terms, including pain, gnawing, burning, gassiness, or queasiness. Although allergic reactions to food (swelling of lips and tongue with a rash) are rare in adults, food intolerances are common in patients with dyspepsia.⁹ Consumption of nonsteroidal ­anti-inflammatory drugs is a common cause of dyspepsia, even at over-the-counter strength, and may cause ulceration, gastrointestinal bleeding, and anemia. Narcotic and marijuana use and the anticholinergic effects of antidepressant medications are associated with gastrointestinal dysmotility, including gastroparesis.

Weight loss, night waking, and vomiting make functional dyspepsia less likely and deserve immediate consideration of abdominal imaging or endoscopic examination.

Patients with FD often exhibit symptoms of other functional abdominal disorders including irritable bowel syndrome, functional heartburn, bloating, or chronic nausea, and may have been previously diagnosed with overlapping conditions suggestive of visceral hypersensitivity, including depression, anxiety, fibromyalgia, migraine, and pelvic pain. During the patient’s office visit, be alert to any indication of an underlying psychological issue.

Continue to: The initial diagnostic challenge

The initial diagnostic challenge is to identify those patients who may have a structural disorder requiring expedited and targeted investigation. Weight loss, night waking, and vomiting are unusual in the setting of either FD or Helicobacter pylori gastritis. These and other features of concern (TABLE 3) make a diagnosis of a functional disorder less likely and should prompt immediate consideration of abdominal imaging or endoscopic examination. Epigastric tenderness on palpation is common in patients with FD and is not necessarily predictive of structural pathology—unless accompanied by other findings of concern. Abdominal scars or a history of trauma may be suggestive of abdominal wall pain. Abdominal pain that remains unchanged or increases when the muscles of the abdominal wall are tensed (Carnett sign) suggests abdominal wall pain.

Initial testing and Tx assessments focus on H pylori

All 3 of the major US gastroenterology organizations recommend a stepwise approach in patients without alarm symptoms, generally beginning (in those < 60 years) by testing for H pylori with either the stool antigen or urea breath test (UBT)—and initiating appropriate treatment if results are positive.^5,10 (The first step for those ≥ 60 years is discussed later.) Since the serum antibody test cannot differentiate between active and past infection, it is not recommended if other options are available.¹¹ The stool antigen test is preferred; it is a cost-effective option used for both diagnosis and confirmation of H pylori eradication.

The UBT identifies active infection with a sensitivity and specificity of > 95%¹² but is more labor intensive, employs an isotope, and is relatively expensive. Because proton pump inhibitors (PPIs), bismuth, and antibiotics may increase the false-negative rate for both the UBT and stool antigen test, we recommend that these medications be held for 2 to 4 weeks prior to testing.¹¹ H₂-receptor antagonists do not need to be restricted.

Treatment regimens containing clarithromycin have fallen into disfavor given the high rates of resistance that are now encountered. Fourteen-day regimens that can be used empirically (without susceptibility testing) are bismuth quadruple therapy (bismuth, metronidazole, tetracycline, and PPI) or rifabutin triple therapy (rifabutin, amoxicillin, and PPI).¹³ To confirm eradication, perform repeat testing with either stool antigen or UBT no sooner than 4 weeks after completion of therapy. If the first treatment fails, try a second regimen using different antibiotics.¹⁴ Although the impact of H pylori eradication on dyspeptic symptoms is only modest, this strategy is recommended also to reduce the risk of peptic ulceration and gastric neoplasia.

Next-step testing and Tx considerations

Given the heterogeneity of presenting symptoms of dyspepsia, some clinicians may be hesitant to diagnose a functional disorder at the first visit, preferring instead to conduct a limited range of investigations in concert with initial medical management. In these circumstances it would be reasonable, in addition to testing for H pylori, to order a complete blood count (CBC) and to measure serum lipase and liver enzymes. Keep in mind that liver enzymes may not be elevated in uncomplicated biliary colic.

Continue to: Consider ultrasound imaging...

Consider ultrasound imaging if gallstones are a consideration. A computerized tomography scan may not exclude uncomplicated and noncalcified gallstones, but it is an excellent modality for detecting suspected retroperitoneal pathology. Consider working with a gastroenterologist if the patient exhibits alarm features.

Empiric PPI therapy. A trial of daily PPI use over 4 weeks is recommended for patients without H pylori and for those whose symptoms continue despite eradication of the bacterium. A Cochrane meta-analysis found that PPI therapy was more effective than placebo (31% vs 26%; risk ratio, 0.88; number needed to treat [NNT] = 11; 95% CI 0.82 to 0.94; P < .001).¹⁵ PPI therapy appears to be slightly more effective than treatment with H₂-receptor antagonists. Both are proposed in the United Kingdom guideline.¹⁶ Both are generally safe and well tolerated but are not without potential adverse effects when used long term.

Dietary modification. Patients with dyspepsia commonly report that meals exacerbate symptoms. This is likely due to a combination of gastric distension and underlying visceral hypersensitivity rather than food composition.

The stool antigen test is preferred for diagnosing and confirming eradication of H pylori. The serum antibody test cannot differentiate between active and past infection.

There is no reliable “dyspepsia diet,” although a systematic review implicated wheat and high-fat foods as the 2 most common contributors to symptom onset.¹⁷ Recommended dietary modifications would be to consume smaller, more frequent meals and to eliminate recognized trigger foods. Patients with postprandial distress syndrome, a subset of FD, may want to consider reducing fat intake to help alleviate discomfort. If symptoms continue, evaluate for lactose intolerance. Also, consider a trial of a gluten-free diet. The low-FODMAP diet (restricting fermentable oligo-, di- and monosaccharides, as well as polyols) has shown benefit in patients with irritable bowel syndrome and may be considered in those with intractable FD, given the overlap in physiology of the disorders.

Upper gastrointestinal endoscopy. The ACG has suggested that esophagogastroduodenoscopy (EGD) be performed as the first investigative step for patients ≥ 60 years, while testing for H pylori be considered as the first step in younger patients, even if alarm symptoms are present² (FIGURE). This decision must be individualized, particularly in patients of Asian, Central or South American, or Caribbean descent, in whom the incidence of gastric cancer is higher with earlier onset.¹⁸

Continue to: Also consider EGD...

Also consider EGD for patients whose symptoms have not improved despite eradication of H pylori or an adequate trial of PPI therapy. While some guidelines do not require EGD in low-risk patients at this stage, other authorities would consider this step prudent, particularly when quality of life has been significantly impaired. An underlying organic cause, mainly erosive esophagitis or peptic ulcer disease, is found in 20% to 30% of patients with dyspepsia.⁵

Most patients without alarm features, with normal findings on upper endoscopy, who do not have H pylori gastritis, and whose symptoms continue despite a trial of PPI therapy, will have FD (FIGURE).²

Offer patients with functional dyspepsia supportive therapy

Neuromodulators

TCAs are superior to placebo in reducing dyspeptic symptoms with an NNT of 6 and are recommended for patients with ongoing symptoms despite PPI therapy or H pylori eradication.² Begin with a low dose and increase as tolerated. It may take a few weeks for improvement to be seen. Exercise caution in the presence of cardiac arrhythmias.

Mirtazapine, 7.5 to 15 mg every night at bedtime, reduces fullness and bloating in postprandial distress syndrome and is useful for patients who have lost weight. It’s important to note that TCAs and mirtazapine both have the potential for QT prolongation, as well as depression and suicidality in younger patients.¹⁹ The anxiolytic buspirone, 10 mg before meals, augments fundic relaxation, improves overall symptom severity, and helps alleviate early satiety, postprandial fullness, and upper abdominal bloating.²⁰

Prokinetics

A recent meta-analysis demonstrated significant benefit in symptom control in dyspeptic patients treated with prokinetics (NNT = 7).²¹ However, the benefit was predominantly due to cisapride, a drug that was withdrawn from the US market due to adverse effects. There are no clinical trials of metoclopramide or domperidone (not available in the United States) in FD. Nonetheless, the ACG has given a conditional recommendation, based on low-quality evidence, for the use of prokinetics in patients with FD not responding to PPI therapy, H pylori eradication, or TCA therapy.²

Continue to: A shortcoming of the established guidelines

A shortcoming of the established guidelines is that they do not provide guidance as to long-term management of those patients who respond to prescription medications. Our practice has been to continue medications for a minimum of 3 months, then begin a slow taper in order to establish the lowest efficacious dose. Some patients may relapse and require full dosage for a longer period of time.

Adjunctive therapies are worth considering

Complementary and alternative medicines. Products containing ginger, carraway oil, artichoke leaf extract, turmeric, and red pepper are readily available without prescription and have long been used with variable results for dyspepsia.²² The 9-herb combination STW-5 has demonstrated superiority over placebo in a number of studies and has a favorable safety profile.²³ The recommended dose is 10 to 20 drops tid. The European manufacturer has recently modified the package insert noting rare cases of hepatotoxicity.²⁴

Because PPIs, bismuth, and antibiotics may increase the false-negative rate for both the UBT and stool antigen test, we recommend that these medications be held for 2 to 4 weeks prior to testing.

A commercially available formulation (FDgard) containing L-menthol (a key component of peppermint oil) and caraway has been found to reduce the intensity of symptoms in patients with FD. Potential adverse effects include nausea, contact dermatitis, bronchospasm, and atrial fibrillation. Cayenne, a red pepper extract, is available over the counter for the benefit for epigastric pain and bloating. Begin with a 500-mg dose before breakfast and a 1000-mg dose before dinner, increasing to 2500 mg/d as tolerated. Cayenne preparations may trigger drug toxicities and are best avoided in patients taking antihypertensives, theophylline, or anticoagulants.

Cognitive behavioral therapy, acupuncture, and hypnosis. These modalities are time consuming, are often expensive, are not always covered by insurance, and require significant motivation. A systematic review found no benefit.²⁵ Subsequent studies summarized in the ACG guidelines² reported benefit; however, a lack of blinding and significant heterogeneity among the groups detract from the quality of the data. It remains unclear whether these are effective strategies for FD, and therefore they cannot be recommended on a routine basis.

CORRESPONDENCE
Norman H. Gilinsky, MD, Division of Digestive Diseases, University of Cincinnati College of Medicine, 231 Albert Sabin Way, Cincinnati, OH 45267-0595; norman.gilinsky@ uc.edu

The global prevalence of dyspepsia is approximately 20%,¹ and it is often associated with other comorbidities and overlapping gastrointestinal complaints. The effects on the patient’s quality of life, including societal impacts, are considerable. Symptoms and their response to treatment are highly variable, necessitating individualized management. While some patients’ symptoms may be refractory to standard medical treatment initially, evidence suggests that the strategies summarized in our guidance here—including the use of tricyclic antidepressants (TCAs), prokinetics, and adjunctive therapies—may alleviate symptoms and improve patients’ quality of life.

What dyspepsia is—and what it isn’t

Dyspepsia is a poorly characterized disorder often associated with nausea, heartburn, early satiety, and bloating. The American College of Gastroenterology (ACG) now advocates using a clinically relevant definition of dyspepsia as “predominant epigastric pain lasting at least a month” as long as epigastric pain is the patient's primary complaint.² Causes of dyspepsia are listed in TABLE 1.

Heartburn, a burning sensation in the chest, is not a dyspeptic symptom but the 2 may often coexist. In general, dyspepsia does not have a colicky or postural component. Symptoms that are relieved by evacuation of feces or gas generally should not be considered a part of dyspepsia.

Functional dyspepsia (FD) is a subset for which no structural pathology has been identified, accounting for up to 70% of all patients with dyspepsia.³ The Rome Foundation, in its recent update (Rome IV), has highlighted 4 key symptoms and 2 proposed subtypes (TABLE 2).⁴ The comorbidities of anxiety, depression, and somatization appear to be more prevalent in these dyspepsia patients than in those with organic issues. The incidence of gastric malignancy is low in this cohort.^3,5 Dyspepsia occurring after an acute infection is referred to as postinfectious functional dyspepsia.

Pathophysiology of functional dyspepsia. Dysmotility, visceral hypersensitivity, mucosal immune dysfunction, altered gut microbiota, and disturbed central nervous system processing contribute in varying degrees to the pathophysiology of FD. There is evidence that luminal factors have the potential to trigger local neuronal excitability.^6,7 Early life psychosocial factors may further influence illness behaviors, coping strategies, stress responses, and the intensity of symptoms perceived by the patient.⁸

Clues in the history and physical examination

Patients describe their discomfort using a variety of terms, including pain, gnawing, burning, gassiness, or queasiness. Although allergic reactions to food (swelling of lips and tongue with a rash) are rare in adults, food intolerances are common in patients with dyspepsia.⁹ Consumption of nonsteroidal ­anti-inflammatory drugs is a common cause of dyspepsia, even at over-the-counter strength, and may cause ulceration, gastrointestinal bleeding, and anemia. Narcotic and marijuana use and the anticholinergic effects of antidepressant medications are associated with gastrointestinal dysmotility, including gastroparesis.

Weight loss, night waking, and vomiting make functional dyspepsia less likely and deserve immediate consideration of abdominal imaging or endoscopic examination.

Patients with FD often exhibit symptoms of other functional abdominal disorders including irritable bowel syndrome, functional heartburn, bloating, or chronic nausea, and may have been previously diagnosed with overlapping conditions suggestive of visceral hypersensitivity, including depression, anxiety, fibromyalgia, migraine, and pelvic pain. During the patient’s office visit, be alert to any indication of an underlying psychological issue.

Continue to: The initial diagnostic challenge

The initial diagnostic challenge is to identify those patients who may have a structural disorder requiring expedited and targeted investigation. Weight loss, night waking, and vomiting are unusual in the setting of either FD or Helicobacter pylori gastritis. These and other features of concern (TABLE 3) make a diagnosis of a functional disorder less likely and should prompt immediate consideration of abdominal imaging or endoscopic examination. Epigastric tenderness on palpation is common in patients with FD and is not necessarily predictive of structural pathology—unless accompanied by other findings of concern. Abdominal scars or a history of trauma may be suggestive of abdominal wall pain. Abdominal pain that remains unchanged or increases when the muscles of the abdominal wall are tensed (Carnett sign) suggests abdominal wall pain.

Initial testing and Tx assessments focus on H pylori

All 3 of the major US gastroenterology organizations recommend a stepwise approach in patients without alarm symptoms, generally beginning (in those < 60 years) by testing for H pylori with either the stool antigen or urea breath test (UBT)—and initiating appropriate treatment if results are positive.^5,10 (The first step for those ≥ 60 years is discussed later.) Since the serum antibody test cannot differentiate between active and past infection, it is not recommended if other options are available.¹¹ The stool antigen test is preferred; it is a cost-effective option used for both diagnosis and confirmation of H pylori eradication.

The UBT identifies active infection with a sensitivity and specificity of > 95%¹² but is more labor intensive, employs an isotope, and is relatively expensive. Because proton pump inhibitors (PPIs), bismuth, and antibiotics may increase the false-negative rate for both the UBT and stool antigen test, we recommend that these medications be held for 2 to 4 weeks prior to testing.¹¹ H₂-receptor antagonists do not need to be restricted.

Treatment regimens containing clarithromycin have fallen into disfavor given the high rates of resistance that are now encountered. Fourteen-day regimens that can be used empirically (without susceptibility testing) are bismuth quadruple therapy (bismuth, metronidazole, tetracycline, and PPI) or rifabutin triple therapy (rifabutin, amoxicillin, and PPI).¹³ To confirm eradication, perform repeat testing with either stool antigen or UBT no sooner than 4 weeks after completion of therapy. If the first treatment fails, try a second regimen using different antibiotics.¹⁴ Although the impact of H pylori eradication on dyspeptic symptoms is only modest, this strategy is recommended also to reduce the risk of peptic ulceration and gastric neoplasia.

Next-step testing and Tx considerations

Given the heterogeneity of presenting symptoms of dyspepsia, some clinicians may be hesitant to diagnose a functional disorder at the first visit, preferring instead to conduct a limited range of investigations in concert with initial medical management. In these circumstances it would be reasonable, in addition to testing for H pylori, to order a complete blood count (CBC) and to measure serum lipase and liver enzymes. Keep in mind that liver enzymes may not be elevated in uncomplicated biliary colic.

Continue to: Consider ultrasound imaging...

Consider ultrasound imaging if gallstones are a consideration. A computerized tomography scan may not exclude uncomplicated and noncalcified gallstones, but it is an excellent modality for detecting suspected retroperitoneal pathology. Consider working with a gastroenterologist if the patient exhibits alarm features.

Empiric PPI therapy. A trial of daily PPI use over 4 weeks is recommended for patients without H pylori and for those whose symptoms continue despite eradication of the bacterium. A Cochrane meta-analysis found that PPI therapy was more effective than placebo (31% vs 26%; risk ratio, 0.88; number needed to treat [NNT] = 11; 95% CI 0.82 to 0.94; P < .001).¹⁵ PPI therapy appears to be slightly more effective than treatment with H₂-receptor antagonists. Both are proposed in the United Kingdom guideline.¹⁶ Both are generally safe and well tolerated but are not without potential adverse effects when used long term.

Dietary modification. Patients with dyspepsia commonly report that meals exacerbate symptoms. This is likely due to a combination of gastric distension and underlying visceral hypersensitivity rather than food composition.

The stool antigen test is preferred for diagnosing and confirming eradication of H pylori. The serum antibody test cannot differentiate between active and past infection.

There is no reliable “dyspepsia diet,” although a systematic review implicated wheat and high-fat foods as the 2 most common contributors to symptom onset.¹⁷ Recommended dietary modifications would be to consume smaller, more frequent meals and to eliminate recognized trigger foods. Patients with postprandial distress syndrome, a subset of FD, may want to consider reducing fat intake to help alleviate discomfort. If symptoms continue, evaluate for lactose intolerance. Also, consider a trial of a gluten-free diet. The low-FODMAP diet (restricting fermentable oligo-, di- and monosaccharides, as well as polyols) has shown benefit in patients with irritable bowel syndrome and may be considered in those with intractable FD, given the overlap in physiology of the disorders.

Upper gastrointestinal endoscopy. The ACG has suggested that esophagogastroduodenoscopy (EGD) be performed as the first investigative step for patients ≥ 60 years, while testing for H pylori be considered as the first step in younger patients, even if alarm symptoms are present² (FIGURE). This decision must be individualized, particularly in patients of Asian, Central or South American, or Caribbean descent, in whom the incidence of gastric cancer is higher with earlier onset.¹⁸

Continue to: Also consider EGD...

Also consider EGD for patients whose symptoms have not improved despite eradication of H pylori or an adequate trial of PPI therapy. While some guidelines do not require EGD in low-risk patients at this stage, other authorities would consider this step prudent, particularly when quality of life has been significantly impaired. An underlying organic cause, mainly erosive esophagitis or peptic ulcer disease, is found in 20% to 30% of patients with dyspepsia.⁵

Most patients without alarm features, with normal findings on upper endoscopy, who do not have H pylori gastritis, and whose symptoms continue despite a trial of PPI therapy, will have FD (FIGURE).²

Offer patients with functional dyspepsia supportive therapy

Neuromodulators

TCAs are superior to placebo in reducing dyspeptic symptoms with an NNT of 6 and are recommended for patients with ongoing symptoms despite PPI therapy or H pylori eradication.² Begin with a low dose and increase as tolerated. It may take a few weeks for improvement to be seen. Exercise caution in the presence of cardiac arrhythmias.

Mirtazapine, 7.5 to 15 mg every night at bedtime, reduces fullness and bloating in postprandial distress syndrome and is useful for patients who have lost weight. It’s important to note that TCAs and mirtazapine both have the potential for QT prolongation, as well as depression and suicidality in younger patients.¹⁹ The anxiolytic buspirone, 10 mg before meals, augments fundic relaxation, improves overall symptom severity, and helps alleviate early satiety, postprandial fullness, and upper abdominal bloating.²⁰

Prokinetics

A recent meta-analysis demonstrated significant benefit in symptom control in dyspeptic patients treated with prokinetics (NNT = 7).²¹ However, the benefit was predominantly due to cisapride, a drug that was withdrawn from the US market due to adverse effects. There are no clinical trials of metoclopramide or domperidone (not available in the United States) in FD. Nonetheless, the ACG has given a conditional recommendation, based on low-quality evidence, for the use of prokinetics in patients with FD not responding to PPI therapy, H pylori eradication, or TCA therapy.²

Continue to: A shortcoming of the established guidelines

A shortcoming of the established guidelines is that they do not provide guidance as to long-term management of those patients who respond to prescription medications. Our practice has been to continue medications for a minimum of 3 months, then begin a slow taper in order to establish the lowest efficacious dose. Some patients may relapse and require full dosage for a longer period of time.

Adjunctive therapies are worth considering

Complementary and alternative medicines. Products containing ginger, carraway oil, artichoke leaf extract, turmeric, and red pepper are readily available without prescription and have long been used with variable results for dyspepsia.²² The 9-herb combination STW-5 has demonstrated superiority over placebo in a number of studies and has a favorable safety profile.²³ The recommended dose is 10 to 20 drops tid. The European manufacturer has recently modified the package insert noting rare cases of hepatotoxicity.²⁴

Because PPIs, bismuth, and antibiotics may increase the false-negative rate for both the UBT and stool antigen test, we recommend that these medications be held for 2 to 4 weeks prior to testing.

A commercially available formulation (FDgard) containing L-menthol (a key component of peppermint oil) and caraway has been found to reduce the intensity of symptoms in patients with FD. Potential adverse effects include nausea, contact dermatitis, bronchospasm, and atrial fibrillation. Cayenne, a red pepper extract, is available over the counter for the benefit for epigastric pain and bloating. Begin with a 500-mg dose before breakfast and a 1000-mg dose before dinner, increasing to 2500 mg/d as tolerated. Cayenne preparations may trigger drug toxicities and are best avoided in patients taking antihypertensives, theophylline, or anticoagulants.

Cognitive behavioral therapy, acupuncture, and hypnosis. These modalities are time consuming, are often expensive, are not always covered by insurance, and require significant motivation. A systematic review found no benefit.²⁵ Subsequent studies summarized in the ACG guidelines² reported benefit; however, a lack of blinding and significant heterogeneity among the groups detract from the quality of the data. It remains unclear whether these are effective strategies for FD, and therefore they cannot be recommended on a routine basis.

CORRESPONDENCE
Norman H. Gilinsky, MD, Division of Digestive Diseases, University of Cincinnati College of Medicine, 231 Albert Sabin Way, Cincinnati, OH 45267-0595; norman.gilinsky@ uc.edu

In North America and Europe, penicillin allergy is the most common drug-allergy label.¹ Carrying a penicillin-allergy label, which has recently gained more attention in health care systems, leads to suboptimal outcomes, increased use of broad-spectrum antibiotics, increased risk of adverse reactions, and increased cost of care.^2,3 Despite the high rate of reported reactions, clinically significant immunoglobulin E (IgE)-mediated and T cell–mediated hypersensitivity reactions to penicillins are uncommon.²

Through the Choosing Wisely initiative of the American Board of Internal Medicine Foundation, the American Academy of Allergy, Asthma, and Immunology has issued a recommendation: “Don’t overuse non-beta lactam antibiotics in patients with a history of penicillin allergy without an appropriate evaluation.”⁴ The primary care physician (PCP) plays a critical role in the appropriate evaluation and accurate initial labeling of penicillin allergy. Furthermore, the PCP plays an integral part, in conjunction with the allergist, in removing the “penicillin allergy” label from a patient’s chart when feasible.

The history of penicillin and prevalence of allergy

History. Penicillin, the first antibiotic, was discovered in 1928 by physician and microbiologist Alexander Fleming when he observed that a mold of the Penicillium genus inhibited growth of gram-positive pathogens.⁵ Along with pharmacologist Howard Florey and chemist Ernst Chain, both of whom assisted in the large-scale isolation and production of the antibiotic, Fleming won the Nobel Prize in Physiology or Medicine in 1945 for this discovery.⁵

Studies have confirmed that as many as 90% of patients who report penicillin allergy are, in fact, able to tolerate penicillins.

Antibiotics transformed the practice of medicine across a spectrum, including safer childbirth, surgical procedures, and transplantation.⁶ Penicillin remains first-line therapy for many infections, such as streptococcal pharyngitis,⁷ and is the only recommended medication for treating syphilis during pregnancy.⁸ Continued effectiveness of penicillin in these cases allows broad-spectrum antibiotics to be reserved for more severe infections. Regrettably, incorrect antibiotic allergy labeling poses a significant risk to the patient and health care system.

Epidemiology. As with all medications, the potential for anaphylaxis exists after administration of penicillin. Because its use is widespread, penicillin is the most common cause of drug-induced anaphylaxis. However, the incidence of penicillin-induced anaphylaxis is low⁹: A 1968 World Health Organization report stated that the rate of penicillin anaphylaxis was between 0.015% and 0.04%.¹⁰ A more recent study reported an incidence of 1 in 207,191 patients after an oral dose and 1 in 95,298 after a parenteral dose.¹¹ The most common reactions to penicillins are urticaria and delayed maculopapular rash.⁸

In the United States, the prevalence of reported penicillin allergy is approximately 10% (estimated range, 8% to 12%)^3,12-15; among hospitalized patients, that prevalence is estimated to be as high as 15%.^13,15 However, the prevalence of confirmed penicillin allergy is low and has decreased over time—demonstrated in a longitudinal study in which the rate of a positive skin test fell from 15% in 1995 to 0.8% in 2013.^16,17

Studies have confirmed that as many as 90% of patients who report penicillin allergy are, in fact, able to tolerate penicillins.^14,18-20 This finding might be a consequence of initial mislabeling of penicillin allergy; often, adverse reactions are documented as “allergy” when no risk of anaphylaxis exists. Furthermore, patients can outgrow IgE-mediated penicillin allergy because the presence of penicillin IgE antibodies wanes over time.^14,15

Continue to: Consequences of mislabeling

Consequences of mislabeling

Clinical consequences. A multitude of clinical consequences result from carrying a “penicillin allergy” label.

Use of broad-spectrum antibiotics leads to increased risk of Clostridium difficile infection and to development of resistant bacteria, such as methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococcus.^2,15

Alternative antibiotics used in the setting of a “penicillin allergy” label might be less efficacious and result in suboptimal outcomes.

Alternative antibiotics used in the setting of a “penicillin allergy” label might be less efficacious and result in suboptimal outcomes. For example, vancomycin is less effective against methicillin-sensitive S aureus bacteremia than nafcillin or cefazolin.^2,21 Beta-­lactam antibiotics—in particular, cefazolin—are often first-line for perioperative prophylaxis; patients with reported penicillin allergy often receive a less-optimal alternative, such as clindamycin, vancomycin, or gentamicin.²² These patients are at increased risk of surgical site infection.^2,22

In addition, using penicillin alternatives can result in greater risk of drug reactions and adverse effects.²

Increased health care costs. Primarily through observational studies, penicillin allergy has been associated with higher health care costs.²³ Patients with reported penicillin allergy had, on average, a longer inpatient stay than patients without penicillin allergy, at a 3-year total estimated additional cost of $64.6 million.²⁴ Inpatients with a listed penicillin allergy had direct drug costs ranging from “no difference” to $609 per patient more than patients without a listed penicillin allergy. Outpatient prescription costs were $14 to $193 higher per patient for patients with a listed penicillin allergy.²³

Continue to: Considerations in special populations

Considerations in special populations. Evaluating penicillin allergy during routine care is key to decreasing the necessity for urgent penicillin evaluation and possible desensitization at the time of serious infection. Certain patient populations pose specific challenges:

• Pregnant patients. Unverified penicillin allergy during pregnancy is associated with an increased rate of cesarean section and longer postpartum hospitalization.²⁵ Additionally, group B streptococcus-positive women have increased exposure to alternative antibiotics and an increased incidence of adverse drug reactions.²⁵
• Elderly patients. Drug allergy increases with aging.¹ Elderly patients in a long-term care facility are more likely to experience adverse drug effects or drug–drug interactions from the use of penicillin alternatives, such as clindamycin, vancomycin, and fluoroquinolones.²
• Oncology patients often require antibiotic prophylaxis as well as treatment for illnesses, such as neutropenic fever, for which beta-lactam antibiotics are often used as initial treatment.^2,26
• Other important populations that present specific challenges include hospitalized patients, pediatric patients, and patients with a sexually transmitted infection.²

Active management of a penicillin-allergy label

Greater recognition of the consequences of penicillin allergy in recent years has led to efforts by hospitals and other health care organizations to develop processes by which patients can be successfully de-labeled as part of antibiotic stewardship programs⁹ and other initiatives. Ideally, every patient who has a “penicillin allergy” label would be referred to an allergist for evaluation; however, the number of allergy specialists is limited, and access to such specialists might be restricted in some areas, making this approach impracticable. Active management of penicillin allergy requires strategies to both test and de-label patients, as well as proactive approaches to prevent incorrect labeling. These proactive approaches require involvement of all members of the health care team—especially PCPs.

Preventing incorrect labeling. PCPs are the most likely to initially label a patient as allergic to penicillin.²⁷ Most physicians rely on a reported history of allergy alone when selecting medication¹²; once a patient has been labeled “penicillin allergic,” they often retain that mislabel through adulthood.^27,28 A qualitative study of PCPs’ views on prescribing penicillin found that many were aware that documented allergies were incorrect but were uncomfortable using their clinical judgment to prescribe a penicillin or change the record, for fear of a future anaphylactic reaction.²⁹ The first step in the case of any reported reaction should be for you to elicit an accurate drug allergy history (TABLE 1).

As with other drug reactions, you should consider the context surrounding the reaction to a penicillin. Take care to review signs and symptoms of the reaction to look for clues that make a true allergic reaction more, or less, likely.

Symptoms can generally be divided into low-risk and high-risk categories²⁷ (TABLE 2). An example of a commonly reported low-risk symptom is diarrhea that develops after several doses of a penicillin. In the absence of other symptoms, this finding is most likely due to elimination of normal gut flora,³⁰ not to an allergic reaction to the medication. Symptoms of intolerance to the medication, such as headache and nausea, are also low risk.^27,31 In contrast, immediate onset of abdominal pain after a dose of penicillin and lip or throat swelling are considered high risk.

Continue to: Patients presenting with urticaria...

Patients presenting with urticaria or maculopapular rash after taking penicillin are particularly challenging.³⁰ A study of patients in a primary care pediatrics practice found that 7.4% of children receiving a prescription for a penicillin reported a rash.³² Here, timing of onset of symptoms provides some clarity about the likelihood of true allergy. Rashes that manifest during the first hours after exposure are more likely to be IgE mediated, particularly when accompanied by other systemic symptoms; they should be considered high risk. Delayed-onset rashes (> 72 hours after exposure) are usually non-IgE mediated and therefore are generally lower risk,^8,30,33 except when associated with certain features, such as mucosal involvement and skin peeling.

Despite acknowledging viral exanthems in the differential, many physicians still label patients presenting with any rash as “allergic.”²⁸ Take care to look for other potential causes of a rash; for example, patients taking amoxicillin who have concurrent Epstein-Barr virus infection frequently develop a maculopapular rash.³⁴ Caubet and colleagues found that 56% of pediatric patients with a history of nonimmediate rash and a negative oral challenge to amoxicillin tested positive for viral infection.²⁸

A family history of penicillin allergy alone should not preclude the use of penicillin.^8,27,31 Similarly, if a patient has already received and tolerated a subsequent course of the same penicillin derivative after the initial reaction, the “penicillin allergy” label can be removed. If the reaction history is unknown, refer the patient to an allergist for further evaluation.

Accurate charting is key. With most hospital systems and physician practices now documenting in an electronic health record, there exists the ability to document, in great detail, patients’ reactions to medications. Previous studies have found, however, that such documentation is often done poorly, or not done at all. One such study found that (1) > 20% of patients with a “penicillin allergy” label did not have reaction details listed and (2) when reactions were listed, many were incorrectly labeled as “allergy,” not “intolerance.”³⁵

Many electronic health record systems lump drug allergies, adverse effects, and food and environmental allergies into a single section, leading to a lack of distinction between adverse reactions and true allergy.³¹ Although many PCPs report that it is easy to change a patient’s allergy label in the record,²⁹ more often, a nurse, resident, or consultant actually documents the reaction.³⁵

Continue to: Documentation at the time of the reaction...

Documentation at the time of the reaction, within the encounter note and the allergy tab, is essential, so that other physicians caring for the patient, in the future, will be knowledgeable about the details of the reaction. Make it your responsibility to accurately document penicillin allergy in patients’ charts, including removing the “penicillin allergy” label from the chart of patients whose history is inconsistent with allergy, who have tolerated subsequent courses of the same penicillin derivative, or who have passed testing in an allergist’s office. In a study of 639 patients who tested negative for penicillin allergy, 51% still had a “penicillin allergy” label in their chart more than 4 years later.³⁶

Penicillin allergy evaluation. When a patient cannot be cleared of a “penicillin allergy” label by history alone, and in the absence of severe features such as mucous membrane involvement, they should be further evaluated through objective testing for potential IgE-mediated allergy. This assessment includes penicillin skin testing or an oral challenge, or both.

Skin testing involves skin-prick testing of major and minor determinants of penicillin; when skin-prick testing is negative, intradermal testing of major and minor determinants should follow. The negative predictive value of penicillin skin testing is high: In a prospective, multicenter investigation, researchers demonstrated that, when both the major penicillin determinant and a minor determinant mixture were used, negative predictive value was 97.9%.³⁷

Rashes manifesting during the first hours after exposure are more likely to be IgE mediated, particularly when accompanied by other systemic symptoms; consider them a high-risk sign.

However, a minor determinant mixture is not commercially available in the United States; therefore, penicillin G is often used alone as the minor determinant. Typically, if a patient passes skin testing, a challenge dose of penicillin or amoxicillin is administered, followed by an observation period. The risk of re-sensitization after oral penicillin is thought to be low and does not preclude future use.³⁸

Although drug testing is most often performed in an allergist’s office, several groups have developed protocols that allow for limited testing of low-risk patients in a primary care setting.^8,31 For example, several studies have demonstrated that patients presenting with low-risk skin rash can be safely tested with a supervised oral challenge alone.^18,28 The FIGURE^{8,27,30,31,33,34} outlines our proposed workflow for risk stratification and subsequent management of patients with a “penicillin allergy” label.

Continue to: De-labeling requires a systems approach

De-labeling requires a systems approach. Given the mismatch between the large number of patients labeled “penicillin allergic” and the few allergy specialists, referral alone is not enough to solve the problem of mislabeling. Targeting specific populations for testing, such as patients presenting to an inner-city sexually transmitted infection clinic¹⁹ or preoperative patients, as is done at the Mayo Clinic,⁹ has been successful. Skin testing in an inpatient setting has also been shown to be safe and effective,¹³ allowing for protocol-driven testing under the supervision of trained pharmacists (and others), to relieve the burden on allergy specialists.⁹

CORRESPONDENCE
Andrew Lutzkanin, MD, 500 University Drive, PO Box 850, Hershey, PA 17033; [email protected]

In North America and Europe, penicillin allergy is the most common drug-allergy label.¹ Carrying a penicillin-allergy label, which has recently gained more attention in health care systems, leads to suboptimal outcomes, increased use of broad-spectrum antibiotics, increased risk of adverse reactions, and increased cost of care.^2,3 Despite the high rate of reported reactions, clinically significant immunoglobulin E (IgE)-mediated and T cell–mediated hypersensitivity reactions to penicillins are uncommon.²

Through the Choosing Wisely initiative of the American Board of Internal Medicine Foundation, the American Academy of Allergy, Asthma, and Immunology has issued a recommendation: “Don’t overuse non-beta lactam antibiotics in patients with a history of penicillin allergy without an appropriate evaluation.”⁴ The primary care physician (PCP) plays a critical role in the appropriate evaluation and accurate initial labeling of penicillin allergy. Furthermore, the PCP plays an integral part, in conjunction with the allergist, in removing the “penicillin allergy” label from a patient’s chart when feasible.

The history of penicillin and prevalence of allergy

History. Penicillin, the first antibiotic, was discovered in 1928 by physician and microbiologist Alexander Fleming when he observed that a mold of the Penicillium genus inhibited growth of gram-positive pathogens.⁵ Along with pharmacologist Howard Florey and chemist Ernst Chain, both of whom assisted in the large-scale isolation and production of the antibiotic, Fleming won the Nobel Prize in Physiology or Medicine in 1945 for this discovery.⁵

Studies have confirmed that as many as 90% of patients who report penicillin allergy are, in fact, able to tolerate penicillins.

Antibiotics transformed the practice of medicine across a spectrum, including safer childbirth, surgical procedures, and transplantation.⁶ Penicillin remains first-line therapy for many infections, such as streptococcal pharyngitis,⁷ and is the only recommended medication for treating syphilis during pregnancy.⁸ Continued effectiveness of penicillin in these cases allows broad-spectrum antibiotics to be reserved for more severe infections. Regrettably, incorrect antibiotic allergy labeling poses a significant risk to the patient and health care system.

Epidemiology. As with all medications, the potential for anaphylaxis exists after administration of penicillin. Because its use is widespread, penicillin is the most common cause of drug-induced anaphylaxis. However, the incidence of penicillin-induced anaphylaxis is low⁹: A 1968 World Health Organization report stated that the rate of penicillin anaphylaxis was between 0.015% and 0.04%.¹⁰ A more recent study reported an incidence of 1 in 207,191 patients after an oral dose and 1 in 95,298 after a parenteral dose.¹¹ The most common reactions to penicillins are urticaria and delayed maculopapular rash.⁸

In the United States, the prevalence of reported penicillin allergy is approximately 10% (estimated range, 8% to 12%)^3,12-15; among hospitalized patients, that prevalence is estimated to be as high as 15%.^13,15 However, the prevalence of confirmed penicillin allergy is low and has decreased over time—demonstrated in a longitudinal study in which the rate of a positive skin test fell from 15% in 1995 to 0.8% in 2013.^16,17

Studies have confirmed that as many as 90% of patients who report penicillin allergy are, in fact, able to tolerate penicillins.^14,18-20 This finding might be a consequence of initial mislabeling of penicillin allergy; often, adverse reactions are documented as “allergy” when no risk of anaphylaxis exists. Furthermore, patients can outgrow IgE-mediated penicillin allergy because the presence of penicillin IgE antibodies wanes over time.^14,15

Continue to: Consequences of mislabeling

Consequences of mislabeling

Clinical consequences. A multitude of clinical consequences result from carrying a “penicillin allergy” label.

Use of broad-spectrum antibiotics leads to increased risk of Clostridium difficile infection and to development of resistant bacteria, such as methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococcus.^2,15

Alternative antibiotics used in the setting of a “penicillin allergy” label might be less efficacious and result in suboptimal outcomes.

Alternative antibiotics used in the setting of a “penicillin allergy” label might be less efficacious and result in suboptimal outcomes. For example, vancomycin is less effective against methicillin-sensitive S aureus bacteremia than nafcillin or cefazolin.^2,21 Beta-­lactam antibiotics—in particular, cefazolin—are often first-line for perioperative prophylaxis; patients with reported penicillin allergy often receive a less-optimal alternative, such as clindamycin, vancomycin, or gentamicin.²² These patients are at increased risk of surgical site infection.^2,22

In addition, using penicillin alternatives can result in greater risk of drug reactions and adverse effects.²

Increased health care costs. Primarily through observational studies, penicillin allergy has been associated with higher health care costs.²³ Patients with reported penicillin allergy had, on average, a longer inpatient stay than patients without penicillin allergy, at a 3-year total estimated additional cost of $64.6 million.²⁴ Inpatients with a listed penicillin allergy had direct drug costs ranging from “no difference” to $609 per patient more than patients without a listed penicillin allergy. Outpatient prescription costs were $14 to $193 higher per patient for patients with a listed penicillin allergy.²³

Continue to: Considerations in special populations

Considerations in special populations. Evaluating penicillin allergy during routine care is key to decreasing the necessity for urgent penicillin evaluation and possible desensitization at the time of serious infection. Certain patient populations pose specific challenges:

• Pregnant patients. Unverified penicillin allergy during pregnancy is associated with an increased rate of cesarean section and longer postpartum hospitalization.²⁵ Additionally, group B streptococcus-positive women have increased exposure to alternative antibiotics and an increased incidence of adverse drug reactions.²⁵
• Elderly patients. Drug allergy increases with aging.¹ Elderly patients in a long-term care facility are more likely to experience adverse drug effects or drug–drug interactions from the use of penicillin alternatives, such as clindamycin, vancomycin, and fluoroquinolones.²
• Oncology patients often require antibiotic prophylaxis as well as treatment for illnesses, such as neutropenic fever, for which beta-lactam antibiotics are often used as initial treatment.^2,26
• Other important populations that present specific challenges include hospitalized patients, pediatric patients, and patients with a sexually transmitted infection.²

Active management of a penicillin-allergy label

Greater recognition of the consequences of penicillin allergy in recent years has led to efforts by hospitals and other health care organizations to develop processes by which patients can be successfully de-labeled as part of antibiotic stewardship programs⁹ and other initiatives. Ideally, every patient who has a “penicillin allergy” label would be referred to an allergist for evaluation; however, the number of allergy specialists is limited, and access to such specialists might be restricted in some areas, making this approach impracticable. Active management of penicillin allergy requires strategies to both test and de-label patients, as well as proactive approaches to prevent incorrect labeling. These proactive approaches require involvement of all members of the health care team—especially PCPs.

Preventing incorrect labeling. PCPs are the most likely to initially label a patient as allergic to penicillin.²⁷ Most physicians rely on a reported history of allergy alone when selecting medication¹²; once a patient has been labeled “penicillin allergic,” they often retain that mislabel through adulthood.^27,28 A qualitative study of PCPs’ views on prescribing penicillin found that many were aware that documented allergies were incorrect but were uncomfortable using their clinical judgment to prescribe a penicillin or change the record, for fear of a future anaphylactic reaction.²⁹ The first step in the case of any reported reaction should be for you to elicit an accurate drug allergy history (TABLE 1).

As with other drug reactions, you should consider the context surrounding the reaction to a penicillin. Take care to review signs and symptoms of the reaction to look for clues that make a true allergic reaction more, or less, likely.

Symptoms can generally be divided into low-risk and high-risk categories²⁷ (TABLE 2). An example of a commonly reported low-risk symptom is diarrhea that develops after several doses of a penicillin. In the absence of other symptoms, this finding is most likely due to elimination of normal gut flora,³⁰ not to an allergic reaction to the medication. Symptoms of intolerance to the medication, such as headache and nausea, are also low risk.^27,31 In contrast, immediate onset of abdominal pain after a dose of penicillin and lip or throat swelling are considered high risk.

Continue to: Patients presenting with urticaria...

Patients presenting with urticaria or maculopapular rash after taking penicillin are particularly challenging.³⁰ A study of patients in a primary care pediatrics practice found that 7.4% of children receiving a prescription for a penicillin reported a rash.³² Here, timing of onset of symptoms provides some clarity about the likelihood of true allergy. Rashes that manifest during the first hours after exposure are more likely to be IgE mediated, particularly when accompanied by other systemic symptoms; they should be considered high risk. Delayed-onset rashes (> 72 hours after exposure) are usually non-IgE mediated and therefore are generally lower risk,^8,30,33 except when associated with certain features, such as mucosal involvement and skin peeling.

Despite acknowledging viral exanthems in the differential, many physicians still label patients presenting with any rash as “allergic.”²⁸ Take care to look for other potential causes of a rash; for example, patients taking amoxicillin who have concurrent Epstein-Barr virus infection frequently develop a maculopapular rash.³⁴ Caubet and colleagues found that 56% of pediatric patients with a history of nonimmediate rash and a negative oral challenge to amoxicillin tested positive for viral infection.²⁸

A family history of penicillin allergy alone should not preclude the use of penicillin.^8,27,31 Similarly, if a patient has already received and tolerated a subsequent course of the same penicillin derivative after the initial reaction, the “penicillin allergy” label can be removed. If the reaction history is unknown, refer the patient to an allergist for further evaluation.

Accurate charting is key. With most hospital systems and physician practices now documenting in an electronic health record, there exists the ability to document, in great detail, patients’ reactions to medications. Previous studies have found, however, that such documentation is often done poorly, or not done at all. One such study found that (1) > 20% of patients with a “penicillin allergy” label did not have reaction details listed and (2) when reactions were listed, many were incorrectly labeled as “allergy,” not “intolerance.”³⁵

Many electronic health record systems lump drug allergies, adverse effects, and food and environmental allergies into a single section, leading to a lack of distinction between adverse reactions and true allergy.³¹ Although many PCPs report that it is easy to change a patient’s allergy label in the record,²⁹ more often, a nurse, resident, or consultant actually documents the reaction.³⁵

Continue to: Documentation at the time of the reaction...

Documentation at the time of the reaction, within the encounter note and the allergy tab, is essential, so that other physicians caring for the patient, in the future, will be knowledgeable about the details of the reaction. Make it your responsibility to accurately document penicillin allergy in patients’ charts, including removing the “penicillin allergy” label from the chart of patients whose history is inconsistent with allergy, who have tolerated subsequent courses of the same penicillin derivative, or who have passed testing in an allergist’s office. In a study of 639 patients who tested negative for penicillin allergy, 51% still had a “penicillin allergy” label in their chart more than 4 years later.³⁶

Penicillin allergy evaluation. When a patient cannot be cleared of a “penicillin allergy” label by history alone, and in the absence of severe features such as mucous membrane involvement, they should be further evaluated through objective testing for potential IgE-mediated allergy. This assessment includes penicillin skin testing or an oral challenge, or both.

Skin testing involves skin-prick testing of major and minor determinants of penicillin; when skin-prick testing is negative, intradermal testing of major and minor determinants should follow. The negative predictive value of penicillin skin testing is high: In a prospective, multicenter investigation, researchers demonstrated that, when both the major penicillin determinant and a minor determinant mixture were used, negative predictive value was 97.9%.³⁷

Rashes manifesting during the first hours after exposure are more likely to be IgE mediated, particularly when accompanied by other systemic symptoms; consider them a high-risk sign.

However, a minor determinant mixture is not commercially available in the United States; therefore, penicillin G is often used alone as the minor determinant. Typically, if a patient passes skin testing, a challenge dose of penicillin or amoxicillin is administered, followed by an observation period. The risk of re-sensitization after oral penicillin is thought to be low and does not preclude future use.³⁸

Although drug testing is most often performed in an allergist’s office, several groups have developed protocols that allow for limited testing of low-risk patients in a primary care setting.^8,31 For example, several studies have demonstrated that patients presenting with low-risk skin rash can be safely tested with a supervised oral challenge alone.^18,28 The FIGURE^{8,27,30,31,33,34} outlines our proposed workflow for risk stratification and subsequent management of patients with a “penicillin allergy” label.

Continue to: De-labeling requires a systems approach

De-labeling requires a systems approach. Given the mismatch between the large number of patients labeled “penicillin allergic” and the few allergy specialists, referral alone is not enough to solve the problem of mislabeling. Targeting specific populations for testing, such as patients presenting to an inner-city sexually transmitted infection clinic¹⁹ or preoperative patients, as is done at the Mayo Clinic,⁹ has been successful. Skin testing in an inpatient setting has also been shown to be safe and effective,¹³ allowing for protocol-driven testing under the supervision of trained pharmacists (and others), to relieve the burden on allergy specialists.⁹

CORRESPONDENCE
Andrew Lutzkanin, MD, 500 University Drive, PO Box 850, Hershey, PA 17033; [email protected]

In North America and Europe, penicillin allergy is the most common drug-allergy label.¹ Carrying a penicillin-allergy label, which has recently gained more attention in health care systems, leads to suboptimal outcomes, increased use of broad-spectrum antibiotics, increased risk of adverse reactions, and increased cost of care.^2,3 Despite the high rate of reported reactions, clinically significant immunoglobulin E (IgE)-mediated and T cell–mediated hypersensitivity reactions to penicillins are uncommon.²

Through the Choosing Wisely initiative of the American Board of Internal Medicine Foundation, the American Academy of Allergy, Asthma, and Immunology has issued a recommendation: “Don’t overuse non-beta lactam antibiotics in patients with a history of penicillin allergy without an appropriate evaluation.”⁴ The primary care physician (PCP) plays a critical role in the appropriate evaluation and accurate initial labeling of penicillin allergy. Furthermore, the PCP plays an integral part, in conjunction with the allergist, in removing the “penicillin allergy” label from a patient’s chart when feasible.

The history of penicillin and prevalence of allergy

History. Penicillin, the first antibiotic, was discovered in 1928 by physician and microbiologist Alexander Fleming when he observed that a mold of the Penicillium genus inhibited growth of gram-positive pathogens.⁵ Along with pharmacologist Howard Florey and chemist Ernst Chain, both of whom assisted in the large-scale isolation and production of the antibiotic, Fleming won the Nobel Prize in Physiology or Medicine in 1945 for this discovery.⁵

Studies have confirmed that as many as 90% of patients who report penicillin allergy are, in fact, able to tolerate penicillins.

Antibiotics transformed the practice of medicine across a spectrum, including safer childbirth, surgical procedures, and transplantation.⁶ Penicillin remains first-line therapy for many infections, such as streptococcal pharyngitis,⁷ and is the only recommended medication for treating syphilis during pregnancy.⁸ Continued effectiveness of penicillin in these cases allows broad-spectrum antibiotics to be reserved for more severe infections. Regrettably, incorrect antibiotic allergy labeling poses a significant risk to the patient and health care system.

Epidemiology. As with all medications, the potential for anaphylaxis exists after administration of penicillin. Because its use is widespread, penicillin is the most common cause of drug-induced anaphylaxis. However, the incidence of penicillin-induced anaphylaxis is low⁹: A 1968 World Health Organization report stated that the rate of penicillin anaphylaxis was between 0.015% and 0.04%.¹⁰ A more recent study reported an incidence of 1 in 207,191 patients after an oral dose and 1 in 95,298 after a parenteral dose.¹¹ The most common reactions to penicillins are urticaria and delayed maculopapular rash.⁸

In the United States, the prevalence of reported penicillin allergy is approximately 10% (estimated range, 8% to 12%)^3,12-15; among hospitalized patients, that prevalence is estimated to be as high as 15%.^13,15 However, the prevalence of confirmed penicillin allergy is low and has decreased over time—demonstrated in a longitudinal study in which the rate of a positive skin test fell from 15% in 1995 to 0.8% in 2013.^16,17

Studies have confirmed that as many as 90% of patients who report penicillin allergy are, in fact, able to tolerate penicillins.^14,18-20 This finding might be a consequence of initial mislabeling of penicillin allergy; often, adverse reactions are documented as “allergy” when no risk of anaphylaxis exists. Furthermore, patients can outgrow IgE-mediated penicillin allergy because the presence of penicillin IgE antibodies wanes over time.^14,15

Continue to: Consequences of mislabeling

Consequences of mislabeling

Clinical consequences. A multitude of clinical consequences result from carrying a “penicillin allergy” label.

Use of broad-spectrum antibiotics leads to increased risk of Clostridium difficile infection and to development of resistant bacteria, such as methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococcus.^2,15

Alternative antibiotics used in the setting of a “penicillin allergy” label might be less efficacious and result in suboptimal outcomes.

Alternative antibiotics used in the setting of a “penicillin allergy” label might be less efficacious and result in suboptimal outcomes. For example, vancomycin is less effective against methicillin-sensitive S aureus bacteremia than nafcillin or cefazolin.^2,21 Beta-­lactam antibiotics—in particular, cefazolin—are often first-line for perioperative prophylaxis; patients with reported penicillin allergy often receive a less-optimal alternative, such as clindamycin, vancomycin, or gentamicin.²² These patients are at increased risk of surgical site infection.^2,22

In addition, using penicillin alternatives can result in greater risk of drug reactions and adverse effects.²

Increased health care costs. Primarily through observational studies, penicillin allergy has been associated with higher health care costs.²³ Patients with reported penicillin allergy had, on average, a longer inpatient stay than patients without penicillin allergy, at a 3-year total estimated additional cost of $64.6 million.²⁴ Inpatients with a listed penicillin allergy had direct drug costs ranging from “no difference” to $609 per patient more than patients without a listed penicillin allergy. Outpatient prescription costs were $14 to $193 higher per patient for patients with a listed penicillin allergy.²³

Continue to: Considerations in special populations

Considerations in special populations. Evaluating penicillin allergy during routine care is key to decreasing the necessity for urgent penicillin evaluation and possible desensitization at the time of serious infection. Certain patient populations pose specific challenges:

• Pregnant patients. Unverified penicillin allergy during pregnancy is associated with an increased rate of cesarean section and longer postpartum hospitalization.²⁵ Additionally, group B streptococcus-positive women have increased exposure to alternative antibiotics and an increased incidence of adverse drug reactions.²⁵
• Elderly patients. Drug allergy increases with aging.¹ Elderly patients in a long-term care facility are more likely to experience adverse drug effects or drug–drug interactions from the use of penicillin alternatives, such as clindamycin, vancomycin, and fluoroquinolones.²
• Oncology patients often require antibiotic prophylaxis as well as treatment for illnesses, such as neutropenic fever, for which beta-lactam antibiotics are often used as initial treatment.^2,26
• Other important populations that present specific challenges include hospitalized patients, pediatric patients, and patients with a sexually transmitted infection.²

Active management of a penicillin-allergy label

Greater recognition of the consequences of penicillin allergy in recent years has led to efforts by hospitals and other health care organizations to develop processes by which patients can be successfully de-labeled as part of antibiotic stewardship programs⁹ and other initiatives. Ideally, every patient who has a “penicillin allergy” label would be referred to an allergist for evaluation; however, the number of allergy specialists is limited, and access to such specialists might be restricted in some areas, making this approach impracticable. Active management of penicillin allergy requires strategies to both test and de-label patients, as well as proactive approaches to prevent incorrect labeling. These proactive approaches require involvement of all members of the health care team—especially PCPs.

Preventing incorrect labeling. PCPs are the most likely to initially label a patient as allergic to penicillin.²⁷ Most physicians rely on a reported history of allergy alone when selecting medication¹²; once a patient has been labeled “penicillin allergic,” they often retain that mislabel through adulthood.^27,28 A qualitative study of PCPs’ views on prescribing penicillin found that many were aware that documented allergies were incorrect but were uncomfortable using their clinical judgment to prescribe a penicillin or change the record, for fear of a future anaphylactic reaction.²⁹ The first step in the case of any reported reaction should be for you to elicit an accurate drug allergy history (TABLE 1).

As with other drug reactions, you should consider the context surrounding the reaction to a penicillin. Take care to review signs and symptoms of the reaction to look for clues that make a true allergic reaction more, or less, likely.

Symptoms can generally be divided into low-risk and high-risk categories²⁷ (TABLE 2). An example of a commonly reported low-risk symptom is diarrhea that develops after several doses of a penicillin. In the absence of other symptoms, this finding is most likely due to elimination of normal gut flora,³⁰ not to an allergic reaction to the medication. Symptoms of intolerance to the medication, such as headache and nausea, are also low risk.^27,31 In contrast, immediate onset of abdominal pain after a dose of penicillin and lip or throat swelling are considered high risk.

Continue to: Patients presenting with urticaria...

Patients presenting with urticaria or maculopapular rash after taking penicillin are particularly challenging.³⁰ A study of patients in a primary care pediatrics practice found that 7.4% of children receiving a prescription for a penicillin reported a rash.³² Here, timing of onset of symptoms provides some clarity about the likelihood of true allergy. Rashes that manifest during the first hours after exposure are more likely to be IgE mediated, particularly when accompanied by other systemic symptoms; they should be considered high risk. Delayed-onset rashes (> 72 hours after exposure) are usually non-IgE mediated and therefore are generally lower risk,^8,30,33 except when associated with certain features, such as mucosal involvement and skin peeling.

Despite acknowledging viral exanthems in the differential, many physicians still label patients presenting with any rash as “allergic.”²⁸ Take care to look for other potential causes of a rash; for example, patients taking amoxicillin who have concurrent Epstein-Barr virus infection frequently develop a maculopapular rash.³⁴ Caubet and colleagues found that 56% of pediatric patients with a history of nonimmediate rash and a negative oral challenge to amoxicillin tested positive for viral infection.²⁸

A family history of penicillin allergy alone should not preclude the use of penicillin.^8,27,31 Similarly, if a patient has already received and tolerated a subsequent course of the same penicillin derivative after the initial reaction, the “penicillin allergy” label can be removed. If the reaction history is unknown, refer the patient to an allergist for further evaluation.

Accurate charting is key. With most hospital systems and physician practices now documenting in an electronic health record, there exists the ability to document, in great detail, patients’ reactions to medications. Previous studies have found, however, that such documentation is often done poorly, or not done at all. One such study found that (1) > 20% of patients with a “penicillin allergy” label did not have reaction details listed and (2) when reactions were listed, many were incorrectly labeled as “allergy,” not “intolerance.”³⁵

Many electronic health record systems lump drug allergies, adverse effects, and food and environmental allergies into a single section, leading to a lack of distinction between adverse reactions and true allergy.³¹ Although many PCPs report that it is easy to change a patient’s allergy label in the record,²⁹ more often, a nurse, resident, or consultant actually documents the reaction.³⁵

Continue to: Documentation at the time of the reaction...

Documentation at the time of the reaction, within the encounter note and the allergy tab, is essential, so that other physicians caring for the patient, in the future, will be knowledgeable about the details of the reaction. Make it your responsibility to accurately document penicillin allergy in patients’ charts, including removing the “penicillin allergy” label from the chart of patients whose history is inconsistent with allergy, who have tolerated subsequent courses of the same penicillin derivative, or who have passed testing in an allergist’s office. In a study of 639 patients who tested negative for penicillin allergy, 51% still had a “penicillin allergy” label in their chart more than 4 years later.³⁶

Penicillin allergy evaluation. When a patient cannot be cleared of a “penicillin allergy” label by history alone, and in the absence of severe features such as mucous membrane involvement, they should be further evaluated through objective testing for potential IgE-mediated allergy. This assessment includes penicillin skin testing or an oral challenge, or both.

Skin testing involves skin-prick testing of major and minor determinants of penicillin; when skin-prick testing is negative, intradermal testing of major and minor determinants should follow. The negative predictive value of penicillin skin testing is high: In a prospective, multicenter investigation, researchers demonstrated that, when both the major penicillin determinant and a minor determinant mixture were used, negative predictive value was 97.9%.³⁷

Rashes manifesting during the first hours after exposure are more likely to be IgE mediated, particularly when accompanied by other systemic symptoms; consider them a high-risk sign.

However, a minor determinant mixture is not commercially available in the United States; therefore, penicillin G is often used alone as the minor determinant. Typically, if a patient passes skin testing, a challenge dose of penicillin or amoxicillin is administered, followed by an observation period. The risk of re-sensitization after oral penicillin is thought to be low and does not preclude future use.³⁸

Although drug testing is most often performed in an allergist’s office, several groups have developed protocols that allow for limited testing of low-risk patients in a primary care setting.^8,31 For example, several studies have demonstrated that patients presenting with low-risk skin rash can be safely tested with a supervised oral challenge alone.^18,28 The FIGURE^{8,27,30,31,33,34} outlines our proposed workflow for risk stratification and subsequent management of patients with a “penicillin allergy” label.

Continue to: De-labeling requires a systems approach

De-labeling requires a systems approach. Given the mismatch between the large number of patients labeled “penicillin allergic” and the few allergy specialists, referral alone is not enough to solve the problem of mislabeling. Targeting specific populations for testing, such as patients presenting to an inner-city sexually transmitted infection clinic¹⁹ or preoperative patients, as is done at the Mayo Clinic,⁹ has been successful. Skin testing in an inpatient setting has also been shown to be safe and effective,¹³ allowing for protocol-driven testing under the supervision of trained pharmacists (and others), to relieve the burden on allergy specialists.⁹

CORRESPONDENCE
Andrew Lutzkanin, MD, 500 University Drive, PO Box 850, Hershey, PA 17033; [email protected]

Weekly cases of COVID-19 in children dropped for the first time since June, and daily hospitalizations appear to be falling, even as the pace of vaccinations continues to slow among the youngest eligible recipients, according to new data.

Despite the 3.3% decline from the previous week’s record high, the new-case count still topped 243,000 for the week of Sept. 3-9, putting the total number of cases in children at almost 5.3 million since the pandemic began. Children’s share of all COVID cases for Sept. 3-9, nearly 29%, is the highest recorded for a single week, based on a report from the American Academy of Pediatrics and the Children’s Hospital Association.

Hospitalizations seem to have peaked on Sept. 4, when the rate for children aged 0-17 years reached 0.51 per 100,000 population. The admission rate for confirmed COVID-19 has dropped steadily since then and was down to 0.45 per 100,000 on Sept. 11, the last day for which preliminary data from the Centers for Disease Control and Prevention were available.

On the prevention side, fully vaccinated children aged 12-17 years represented 5.5% of all Americans who had completed the vaccine regimen as of Sept. 13. Vaccine initiation, however, has dropped for 5 consecutive weeks in 12- to 15-year-olds and in 4 of the last 5 weeks among 16- and 17-year-olds, the CDC said on its COVID Data Tracker.

Just under 199,000 children aged 12-15 received their first dose of the COVID-19 vaccine during the week of Sept. 7-13. That’s down by 18.5% from the week before and by 51.6% since Aug. 9, the last week that vaccine initiation increased for the age group. Among 16- and 17-year-olds, the 83,000 new recipients that week was a decrease of 25.7% from the previous week and a decline of 47% since the summer peak of Aug. 9, the CDC data show.

Those newest recipients bring at-least-one-dose status to 52.0% of those aged 12-15 and 59.9% of the 16- and 17-year-olds, while 40.3% and 48.9% were fully vaccinated as of Sept. 13. Corresponding figures for some of the older groups are 61.6%/49.7% (age 18-24 years), 73.8%/63.1% (40-49 years), and 95.1%/84.5% (65-74 years), the CDC said.

Vaccine coverage for children at the state level deviates considerably from the national averages. The highest rates for children aged 12-17 are to be found in Vermont, where 76% have received at least one dose, the AAP reported in a separate analysis. Massachusetts is just below that but also comes in at 76% by virtue of a rounding error. The other states in the top five are Connecticut (74%), Hawaii (73%), and Rhode Island (71%).

The lowest vaccination rate for children comes from Wyoming (29%), which is preceded by North Dakota (33%), West Virginia (33%), Alabama (33%), and Mississippi (34%). the AAP said based on data from the CDC, which does not include Idaho.

In a bit of a side note, West Virginia’s Republican governor, Jim Justice, recently said this about vaccine reluctance in his state: “For God’s sakes a livin’, how difficult is this to understand? Why in the world do we have to come up with these crazy ideas – and they’re crazy ideas – that the vaccine’s got something in it and it’s tracing people wherever they go? And the same very people that are saying that are carrying their cellphones around. I mean, come on. Come on.”

Over the last 3 weeks, the District of Columbia has had the largest increase in children having received at least one dose: 10 percentage points, as it went from 58% to 68%. The next-largest improvement – 7 percentage points – occurred in Georgia (34% to 41%), New Mexico (61% to 68%), New York (55% to 62%), and Washington (57% to 64%), the AAP said in its weekly vaccination trends report.

[email protected]

Weekly cases of COVID-19 in children dropped for the first time since June, and daily hospitalizations appear to be falling, even as the pace of vaccinations continues to slow among the youngest eligible recipients, according to new data.

Despite the 3.3% decline from the previous week’s record high, the new-case count still topped 243,000 for the week of Sept. 3-9, putting the total number of cases in children at almost 5.3 million since the pandemic began. Children’s share of all COVID cases for Sept. 3-9, nearly 29%, is the highest recorded for a single week, based on a report from the American Academy of Pediatrics and the Children’s Hospital Association.

Hospitalizations seem to have peaked on Sept. 4, when the rate for children aged 0-17 years reached 0.51 per 100,000 population. The admission rate for confirmed COVID-19 has dropped steadily since then and was down to 0.45 per 100,000 on Sept. 11, the last day for which preliminary data from the Centers for Disease Control and Prevention were available.

On the prevention side, fully vaccinated children aged 12-17 years represented 5.5% of all Americans who had completed the vaccine regimen as of Sept. 13. Vaccine initiation, however, has dropped for 5 consecutive weeks in 12- to 15-year-olds and in 4 of the last 5 weeks among 16- and 17-year-olds, the CDC said on its COVID Data Tracker.

Just under 199,000 children aged 12-15 received their first dose of the COVID-19 vaccine during the week of Sept. 7-13. That’s down by 18.5% from the week before and by 51.6% since Aug. 9, the last week that vaccine initiation increased for the age group. Among 16- and 17-year-olds, the 83,000 new recipients that week was a decrease of 25.7% from the previous week and a decline of 47% since the summer peak of Aug. 9, the CDC data show.

Those newest recipients bring at-least-one-dose status to 52.0% of those aged 12-15 and 59.9% of the 16- and 17-year-olds, while 40.3% and 48.9% were fully vaccinated as of Sept. 13. Corresponding figures for some of the older groups are 61.6%/49.7% (age 18-24 years), 73.8%/63.1% (40-49 years), and 95.1%/84.5% (65-74 years), the CDC said.

Vaccine coverage for children at the state level deviates considerably from the national averages. The highest rates for children aged 12-17 are to be found in Vermont, where 76% have received at least one dose, the AAP reported in a separate analysis. Massachusetts is just below that but also comes in at 76% by virtue of a rounding error. The other states in the top five are Connecticut (74%), Hawaii (73%), and Rhode Island (71%).

The lowest vaccination rate for children comes from Wyoming (29%), which is preceded by North Dakota (33%), West Virginia (33%), Alabama (33%), and Mississippi (34%). the AAP said based on data from the CDC, which does not include Idaho.

In a bit of a side note, West Virginia’s Republican governor, Jim Justice, recently said this about vaccine reluctance in his state: “For God’s sakes a livin’, how difficult is this to understand? Why in the world do we have to come up with these crazy ideas – and they’re crazy ideas – that the vaccine’s got something in it and it’s tracing people wherever they go? And the same very people that are saying that are carrying their cellphones around. I mean, come on. Come on.”

Over the last 3 weeks, the District of Columbia has had the largest increase in children having received at least one dose: 10 percentage points, as it went from 58% to 68%. The next-largest improvement – 7 percentage points – occurred in Georgia (34% to 41%), New Mexico (61% to 68%), New York (55% to 62%), and Washington (57% to 64%), the AAP said in its weekly vaccination trends report.

[email protected]

Weekly cases of COVID-19 in children dropped for the first time since June, and daily hospitalizations appear to be falling, even as the pace of vaccinations continues to slow among the youngest eligible recipients, according to new data.

Despite the 3.3% decline from the previous week’s record high, the new-case count still topped 243,000 for the week of Sept. 3-9, putting the total number of cases in children at almost 5.3 million since the pandemic began. Children’s share of all COVID cases for Sept. 3-9, nearly 29%, is the highest recorded for a single week, based on a report from the American Academy of Pediatrics and the Children’s Hospital Association.

Hospitalizations seem to have peaked on Sept. 4, when the rate for children aged 0-17 years reached 0.51 per 100,000 population. The admission rate for confirmed COVID-19 has dropped steadily since then and was down to 0.45 per 100,000 on Sept. 11, the last day for which preliminary data from the Centers for Disease Control and Prevention were available.

On the prevention side, fully vaccinated children aged 12-17 years represented 5.5% of all Americans who had completed the vaccine regimen as of Sept. 13. Vaccine initiation, however, has dropped for 5 consecutive weeks in 12- to 15-year-olds and in 4 of the last 5 weeks among 16- and 17-year-olds, the CDC said on its COVID Data Tracker.

Just under 199,000 children aged 12-15 received their first dose of the COVID-19 vaccine during the week of Sept. 7-13. That’s down by 18.5% from the week before and by 51.6% since Aug. 9, the last week that vaccine initiation increased for the age group. Among 16- and 17-year-olds, the 83,000 new recipients that week was a decrease of 25.7% from the previous week and a decline of 47% since the summer peak of Aug. 9, the CDC data show.

Those newest recipients bring at-least-one-dose status to 52.0% of those aged 12-15 and 59.9% of the 16- and 17-year-olds, while 40.3% and 48.9% were fully vaccinated as of Sept. 13. Corresponding figures for some of the older groups are 61.6%/49.7% (age 18-24 years), 73.8%/63.1% (40-49 years), and 95.1%/84.5% (65-74 years), the CDC said.

Vaccine coverage for children at the state level deviates considerably from the national averages. The highest rates for children aged 12-17 are to be found in Vermont, where 76% have received at least one dose, the AAP reported in a separate analysis. Massachusetts is just below that but also comes in at 76% by virtue of a rounding error. The other states in the top five are Connecticut (74%), Hawaii (73%), and Rhode Island (71%).

The lowest vaccination rate for children comes from Wyoming (29%), which is preceded by North Dakota (33%), West Virginia (33%), Alabama (33%), and Mississippi (34%). the AAP said based on data from the CDC, which does not include Idaho.

In a bit of a side note, West Virginia’s Republican governor, Jim Justice, recently said this about vaccine reluctance in his state: “For God’s sakes a livin’, how difficult is this to understand? Why in the world do we have to come up with these crazy ideas – and they’re crazy ideas – that the vaccine’s got something in it and it’s tracing people wherever they go? And the same very people that are saying that are carrying their cellphones around. I mean, come on. Come on.”

Over the last 3 weeks, the District of Columbia has had the largest increase in children having received at least one dose: 10 percentage points, as it went from 58% to 68%. The next-largest improvement – 7 percentage points – occurred in Georgia (34% to 41%), New Mexico (61% to 68%), New York (55% to 62%), and Washington (57% to 64%), the AAP said in its weekly vaccination trends report.

[email protected]

PHM 2021 session

Accelerating Patient Care and Healthcare Workforce Diversity and Inclusion

Presenter

Julie Silver, MD

Session summary

Gender inequity in medicine has been well documented and further highlighted by the tremendous impact of the COVID-19 pandemic on women in medicine. While more women than men are entering medical schools across the U.S., women still struggle to reach the highest levels of academic rank, achieve leadership positions of power and influence, receive fair equitable pay, attain leadership roles in national societies, and receive funding from national agencies. They also continue to face discrimination and implicit and explicit biases. Women of color or from other minority backgrounds face even greater barriers and biases. Despite being a specialty in which women represent almost 70% of the workforce, pediatrics is not immune to these disparities.

In her PHM21 plenary on Aug. 3, 2021, Dr. Julie Silver, a national expert in gender equity disparities, detailed the landscape for women in medicine and proposed some solutions to accelerate systemic change for gender equity. In order to understand and mitigate gender inequity, Dr. Silver encouraged the PHM community to identify influential “gatekeepers” of promotion, advancement, and salary compensation. In academic medicine medical schools, funding agencies, professional societies, and journals are the gatekeepers to advancement and compensation for women. Women are traditionally underrepresented as members and influential leaders of these gatekeeping organizations and in their recognition structures, therefore their advancement, compensation, and wellbeing are hindered.

Key takeaways

• Critical mass theory will not help alleviate gender inequity in medicine, as women make up a critical mass in pediatrics and are still experiencing stark inequities. Critical actor leaders are needed to highlight disparities and drive change even once a critical mass is reached.
• Our current diversity, equity, and inclusion (DEI) efforts are ineffective and are creating an “illusion of fairness that causes majority group members to become less sensitive to recognizing discrimination against minorities.” Many of the activities that are considered citizenship, including committees focused on DEI efforts, should be counted as scholarship, and appropriately compensated to ensure promotion of our women and minority colleagues.
• Male allies are critical to documenting, disseminating, and addressing gender inequality. Without the support of men in the field, we will see little progress.
• While there are numerous advocacy angles we can take when advocating for gender equity, the most effective will be the financial angle. Gender pay gaps at the start of a career can lead to roughly 2 million dollars of salary loss for a woman over the course of her career. In order to alleviate those salary pay gaps our institutions must not expect women to negotiate for fair pay, make salary benchmarks transparent, continue to monitor and conduct research on compensation disparities, and attempt to alleviate the weight of educational debt.
• COVID-19 is causing immense stress on women in medicine, and the impact could be disastrous. We must recognize and reward the “4th shift” women are working for COVID-19–related activities at home and at work, and put measures in place to #GiveHerAReasonToStay in health care.
• Men and other women leaders have a responsibility to sponsor the many and well-qualified women in medicine for awards, committees, and speaking engagements. These opportunities are key markers of success in academic medicine and are critical to advancement and salary compensation.

Dr. Casillas is the internal medicine-pediatric chief resident for the University of Cincinnati/Cincinnati Children’s Internal Medicine-Pediatric program. His career goal is to serve as a hospitalist for children and adults, and he is interested in health equity and Latinx health. Dr. O’Toole is a pediatric and adult hospitalist at Cincinnati Children’s Hospital Medical Center and University of Cincinnati Medical Center, and a professor of pediatrics and internal medicine at the University of Cincinnati College of Medicine. She serves as program director of Cincinnati’s Combined Internal Medicine and Pediatrics Residency Program.

PHM 2021 session

Accelerating Patient Care and Healthcare Workforce Diversity and Inclusion

Presenter

Julie Silver, MD

Session summary

Gender inequity in medicine has been well documented and further highlighted by the tremendous impact of the COVID-19 pandemic on women in medicine. While more women than men are entering medical schools across the U.S., women still struggle to reach the highest levels of academic rank, achieve leadership positions of power and influence, receive fair equitable pay, attain leadership roles in national societies, and receive funding from national agencies. They also continue to face discrimination and implicit and explicit biases. Women of color or from other minority backgrounds face even greater barriers and biases. Despite being a specialty in which women represent almost 70% of the workforce, pediatrics is not immune to these disparities.

In her PHM21 plenary on Aug. 3, 2021, Dr. Julie Silver, a national expert in gender equity disparities, detailed the landscape for women in medicine and proposed some solutions to accelerate systemic change for gender equity. In order to understand and mitigate gender inequity, Dr. Silver encouraged the PHM community to identify influential “gatekeepers” of promotion, advancement, and salary compensation. In academic medicine medical schools, funding agencies, professional societies, and journals are the gatekeepers to advancement and compensation for women. Women are traditionally underrepresented as members and influential leaders of these gatekeeping organizations and in their recognition structures, therefore their advancement, compensation, and wellbeing are hindered.

Key takeaways

• Critical mass theory will not help alleviate gender inequity in medicine, as women make up a critical mass in pediatrics and are still experiencing stark inequities. Critical actor leaders are needed to highlight disparities and drive change even once a critical mass is reached.
• Our current diversity, equity, and inclusion (DEI) efforts are ineffective and are creating an “illusion of fairness that causes majority group members to become less sensitive to recognizing discrimination against minorities.” Many of the activities that are considered citizenship, including committees focused on DEI efforts, should be counted as scholarship, and appropriately compensated to ensure promotion of our women and minority colleagues.
• Male allies are critical to documenting, disseminating, and addressing gender inequality. Without the support of men in the field, we will see little progress.
• While there are numerous advocacy angles we can take when advocating for gender equity, the most effective will be the financial angle. Gender pay gaps at the start of a career can lead to roughly 2 million dollars of salary loss for a woman over the course of her career. In order to alleviate those salary pay gaps our institutions must not expect women to negotiate for fair pay, make salary benchmarks transparent, continue to monitor and conduct research on compensation disparities, and attempt to alleviate the weight of educational debt.
• COVID-19 is causing immense stress on women in medicine, and the impact could be disastrous. We must recognize and reward the “4th shift” women are working for COVID-19–related activities at home and at work, and put measures in place to #GiveHerAReasonToStay in health care.
• Men and other women leaders have a responsibility to sponsor the many and well-qualified women in medicine for awards, committees, and speaking engagements. These opportunities are key markers of success in academic medicine and are critical to advancement and salary compensation.

Dr. Casillas is the internal medicine-pediatric chief resident for the University of Cincinnati/Cincinnati Children’s Internal Medicine-Pediatric program. His career goal is to serve as a hospitalist for children and adults, and he is interested in health equity and Latinx health. Dr. O’Toole is a pediatric and adult hospitalist at Cincinnati Children’s Hospital Medical Center and University of Cincinnati Medical Center, and a professor of pediatrics and internal medicine at the University of Cincinnati College of Medicine. She serves as program director of Cincinnati’s Combined Internal Medicine and Pediatrics Residency Program.

PHM 2021 session

Accelerating Patient Care and Healthcare Workforce Diversity and Inclusion

Presenter

Julie Silver, MD

Session summary

Gender inequity in medicine has been well documented and further highlighted by the tremendous impact of the COVID-19 pandemic on women in medicine. While more women than men are entering medical schools across the U.S., women still struggle to reach the highest levels of academic rank, achieve leadership positions of power and influence, receive fair equitable pay, attain leadership roles in national societies, and receive funding from national agencies. They also continue to face discrimination and implicit and explicit biases. Women of color or from other minority backgrounds face even greater barriers and biases. Despite being a specialty in which women represent almost 70% of the workforce, pediatrics is not immune to these disparities.

In her PHM21 plenary on Aug. 3, 2021, Dr. Julie Silver, a national expert in gender equity disparities, detailed the landscape for women in medicine and proposed some solutions to accelerate systemic change for gender equity. In order to understand and mitigate gender inequity, Dr. Silver encouraged the PHM community to identify influential “gatekeepers” of promotion, advancement, and salary compensation. In academic medicine medical schools, funding agencies, professional societies, and journals are the gatekeepers to advancement and compensation for women. Women are traditionally underrepresented as members and influential leaders of these gatekeeping organizations and in their recognition structures, therefore their advancement, compensation, and wellbeing are hindered.

Key takeaways

• Critical mass theory will not help alleviate gender inequity in medicine, as women make up a critical mass in pediatrics and are still experiencing stark inequities. Critical actor leaders are needed to highlight disparities and drive change even once a critical mass is reached.
• Our current diversity, equity, and inclusion (DEI) efforts are ineffective and are creating an “illusion of fairness that causes majority group members to become less sensitive to recognizing discrimination against minorities.” Many of the activities that are considered citizenship, including committees focused on DEI efforts, should be counted as scholarship, and appropriately compensated to ensure promotion of our women and minority colleagues.
• Male allies are critical to documenting, disseminating, and addressing gender inequality. Without the support of men in the field, we will see little progress.
• While there are numerous advocacy angles we can take when advocating for gender equity, the most effective will be the financial angle. Gender pay gaps at the start of a career can lead to roughly 2 million dollars of salary loss for a woman over the course of her career. In order to alleviate those salary pay gaps our institutions must not expect women to negotiate for fair pay, make salary benchmarks transparent, continue to monitor and conduct research on compensation disparities, and attempt to alleviate the weight of educational debt.
• COVID-19 is causing immense stress on women in medicine, and the impact could be disastrous. We must recognize and reward the “4th shift” women are working for COVID-19–related activities at home and at work, and put measures in place to #GiveHerAReasonToStay in health care.
• Men and other women leaders have a responsibility to sponsor the many and well-qualified women in medicine for awards, committees, and speaking engagements. These opportunities are key markers of success in academic medicine and are critical to advancement and salary compensation.

Dr. Casillas is the internal medicine-pediatric chief resident for the University of Cincinnati/Cincinnati Children’s Internal Medicine-Pediatric program. His career goal is to serve as a hospitalist for children and adults, and he is interested in health equity and Latinx health. Dr. O’Toole is a pediatric and adult hospitalist at Cincinnati Children’s Hospital Medical Center and University of Cincinnati Medical Center, and a professor of pediatrics and internal medicine at the University of Cincinnati College of Medicine. She serves as program director of Cincinnati’s Combined Internal Medicine and Pediatrics Residency Program.

In a little-noticed action last month, the Centers for Medicare & Medicaid Services (CMS) published a regulation requiring hospitals to attest that they have completed an annual safety assessment of their electronic health record (EHR) products so as to meet an objective of the Medicare Promoting Interoperability Program, starting next year.

©daoleduc/ThinkStock.com

Experts praised the move but said that EHR developers should share the responsibility for ensuring that the use of their products doesn’t harm patients.

A number of safety problems are associated with hospital EHR systems, ranging from insufficient protection against medication errors and inadvertent turnoffs of drug interaction checkers to allowing physicians to use free text instead of coded data for key patient indicators. Although hospitals aren’t required to do anything about safety problems that turn up in their self-audits, practitioners who perform the self-assessment will likely encounter challenges that they were previously unaware of and will fix them, experts say.

Studies over the past decade have shown that improper configuration and use of EHRs, as well as design flaws in the systems, can cause avoidable patient injuries or can fail to prevent them. For example, one large study found that clinical decision support (CDS) features in EHRs prevented adverse drug events (ADEs) in only 61.6% of cases in 2016. That was an improvement over the ADE prevention rate of 54% in 2009. Nevertheless, nearly 40% of ADEs were not averted.

Another study, sponsored by the Leapfrog Group, found that EHRs used in U.S. hospitals failed to detect up to 1 in 3 potentially harmful drug interactions and other medication errors. In this study, about 10% of the detection failures were attributed to design problems in EHRs.

The new CMS measure requires hospitals to evaluate their EHRs using safety guides that were developed in 2014 and were revised in 2016 by the Office of the National Coordinator for Health IT (ONC). Known as the Safety Assurance Factors for Resilience (SAFER) guides, they include a set of recommendations to help health care organizations optimize the safety of EHRs.
 

Surprises in store for hospitals

Dean Sittig, PhD, a professor at the University of Texas Health Science Center, Houston, told this news organization that a 2018 study he conducted with his colleague Hardeep Singh, MD, MPH, found that eight surveyed health care organizations were following about 75% of the SAFER recommendations.

He said that when hospitals and health care systems start to assess their systems, many will be surprised at what they are not doing or not doing right. Although the new CMS rule doesn’t require them to correct deficiencies, he expects that many will.

For this reason, Dr. Sittig believes the requirement will have a positive effect on patient safety. But the regulation may not go far enough because it doesn’t impose any requirements on EHR vendors, he said.

In a commentary published in JAMA, Dr. Sittig and Dr. Hardeep, a professor at the Michael E. DeBakey VA Medical Center and Baylor College of Medicine, cite a study showing that 40% of “EHR-related products” had “nonconformities” with EHR certification regulations that could potentially harm patients. “Many nonconformities could have been identified by the developer prior to product release,” they say.
 

Shared responsibility

According to the JAMA commentary, the SAFER guides were developed “to help health care organizations and EHR developers conduct voluntary self-assessments to help eliminate or minimize EHR-related safety risks and hazards.”

In response to a query from this news organization, ONC confirmed that the SAFER guides were intended for use by developers as well as practitioners. ONC said it supports CMS’s approach to incentivize collaborations between EHR vendors and health care organizations. It noted that some entities have already teamed up to the meet the SAFER guides’ recommendations.

Hospitals and EHR developers must share responsibility for safety, Dr. Sittig and Dr. Singh argue, because many SAFER recommendations are based on EHR features that have to be programmed by developers.

For example, one recommendation is that patient identification information be displayed on all portions of the EHR user interface, wristbands, and printouts. Hospitals can’t implement this feature if the developer hasn’t built it into its product.

Dr. Sittig and Dr. Singh suggest three strategies to complement CMS’s new regulation:

• Because in their view, ONC’s EHR certification criteria are insufficient to address many patient safety concerns, CMS should require EHR developers to assess their products annually.
• ONC should conduct annual reviews of the SAFER recommendations with input from EHR developers and safety experts.
• EHR vendors should disseminate guidance to their customers on how to address safety practices, perhaps including EHR configuration guides related to safety.

Safety in EHR certification

At a recent press conference that ONC held to update reporters on its current plans, officials were asked to comment on Dr. Sittig’s and Dr. Singh’s proposition that EHR developers, as well as hospitals, do more to ensure system safety.

Steve Posnack, deputy national coordinator of health IT, noted that the ONC-supervised certification process requires developers to pay attention to how they “implement and integrate safety practices in their software design. We have certification criteria ... around what’s called safety-enhanced design – specific capabilities in the EHR that are sensitive to safety in areas like e-prescribing, medication, and high-risk events, where you want to make sure there’s more attention paid to the safety-related dynamics.”

After the conference, ONC told this news organization that among the safety-related certification criteria is one on user-centered design, which must be used in programming certain EHR features. Another is on the use of a quality management system to guide the creation of each EHR capability.

Nevertheless, there is evidence that not all EHR developers have paid sufficient attention to safety in their products. This is shown in the corporate integrity agreements with the Office of the Inspector General (OIG) of the Department of Health and Human Services (HHS) that developers eClinicalWorks and Greenway agreed to sign because, according to the government, they had not met all of the certification criteria they’d claimed to satisfy.

Under these agreements, the vendors agreed to follow “relevant standards, checklists, self-assessment tools, and other practices identified in the ONC SAFER guides and the ICE Report(s) to optimize the safety and safe use of EHRs” in a number of specific areas.

Even if all EHRs conformed to the certification requirements for safety, they would fall short of the SAFER recommendations, Dr. Sittig says. “Those certification criteria are pretty general and not as comprehensive as the SAFER guides. Some SAFER guide recommendations are in existing certification requirements, like you’re supposed to have drug-drug interaction checking capabilities, and they’re supposed to be on. But it doesn’t say you need to have the patient’s identification on every screen. It’s easy to assume good software design, development, and testing principles are a given, but our experience suggests otherwise.”
 

Configuration problems

A handful of vendors are working on what the JAMA article suggests, but there are about 1,000 EHR developers, Dr. Sittig notes. Moreover, there are configuration problems in the design of many EHRs, even if the products have the recommended features.

“For example, it’s often possible to meet the SAFER recommendations, but not all the vendors make that the default setting. That’s one of the things our paper says they should do,” Dr. Sittig says.

Conversely, some hospitals turn off certain features because they annoy doctors, he notes. For instance, the SAFER guides recommend that allergies, problem list entries, and diagnostic test results be entered and stored using standard, coded data elements in the EHR, but often the EHR makes it easier to enter free text data.

Default settings can be wiped out during system upgrades, he added. That has happened with drug interaction checkers. “If you don’t test the system after upgrades and reassess it annually, you might go several months without your drug-drug interaction checker on. And your doctors aren’t complaining about not getting alerts. Those kinds of mistakes are hard to catch.”

Some errors in an EHR may be caught fairly quickly, but in a health system that treats thousands of patients at any given time, those mistakes can still cause a lot of potential patient harm, Dr. Sittig points out. Some vendors, he says, are building tools to help health care organizations catch those errors through what is called “anomaly detection.” This is similar to what credit card companies do when they notice you’ve bought a carpet in Saudi Arabia, although you’ve never traveled abroad, he notes.

“You can look at alert firing data and notice that all of a sudden an alert fired 500 times today when it usually fires 10 times, or it stopped firing,” Dr. Sittig observes. “Those kinds of things should be built into all EHRs. That would be an excellent step forward.”

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

In a little-noticed action last month, the Centers for Medicare & Medicaid Services (CMS) published a regulation requiring hospitals to attest that they have completed an annual safety assessment of their electronic health record (EHR) products so as to meet an objective of the Medicare Promoting Interoperability Program, starting next year.

©daoleduc/ThinkStock.com

Experts praised the move but said that EHR developers should share the responsibility for ensuring that the use of their products doesn’t harm patients.

A number of safety problems are associated with hospital EHR systems, ranging from insufficient protection against medication errors and inadvertent turnoffs of drug interaction checkers to allowing physicians to use free text instead of coded data for key patient indicators. Although hospitals aren’t required to do anything about safety problems that turn up in their self-audits, practitioners who perform the self-assessment will likely encounter challenges that they were previously unaware of and will fix them, experts say.

Studies over the past decade have shown that improper configuration and use of EHRs, as well as design flaws in the systems, can cause avoidable patient injuries or can fail to prevent them. For example, one large study found that clinical decision support (CDS) features in EHRs prevented adverse drug events (ADEs) in only 61.6% of cases in 2016. That was an improvement over the ADE prevention rate of 54% in 2009. Nevertheless, nearly 40% of ADEs were not averted.

Another study, sponsored by the Leapfrog Group, found that EHRs used in U.S. hospitals failed to detect up to 1 in 3 potentially harmful drug interactions and other medication errors. In this study, about 10% of the detection failures were attributed to design problems in EHRs.

The new CMS measure requires hospitals to evaluate their EHRs using safety guides that were developed in 2014 and were revised in 2016 by the Office of the National Coordinator for Health IT (ONC). Known as the Safety Assurance Factors for Resilience (SAFER) guides, they include a set of recommendations to help health care organizations optimize the safety of EHRs.
 

Surprises in store for hospitals

Dean Sittig, PhD, a professor at the University of Texas Health Science Center, Houston, told this news organization that a 2018 study he conducted with his colleague Hardeep Singh, MD, MPH, found that eight surveyed health care organizations were following about 75% of the SAFER recommendations.

He said that when hospitals and health care systems start to assess their systems, many will be surprised at what they are not doing or not doing right. Although the new CMS rule doesn’t require them to correct deficiencies, he expects that many will.

For this reason, Dr. Sittig believes the requirement will have a positive effect on patient safety. But the regulation may not go far enough because it doesn’t impose any requirements on EHR vendors, he said.

In a commentary published in JAMA, Dr. Sittig and Dr. Hardeep, a professor at the Michael E. DeBakey VA Medical Center and Baylor College of Medicine, cite a study showing that 40% of “EHR-related products” had “nonconformities” with EHR certification regulations that could potentially harm patients. “Many nonconformities could have been identified by the developer prior to product release,” they say.
 

Shared responsibility

According to the JAMA commentary, the SAFER guides were developed “to help health care organizations and EHR developers conduct voluntary self-assessments to help eliminate or minimize EHR-related safety risks and hazards.”

In response to a query from this news organization, ONC confirmed that the SAFER guides were intended for use by developers as well as practitioners. ONC said it supports CMS’s approach to incentivize collaborations between EHR vendors and health care organizations. It noted that some entities have already teamed up to the meet the SAFER guides’ recommendations.

Hospitals and EHR developers must share responsibility for safety, Dr. Sittig and Dr. Singh argue, because many SAFER recommendations are based on EHR features that have to be programmed by developers.

For example, one recommendation is that patient identification information be displayed on all portions of the EHR user interface, wristbands, and printouts. Hospitals can’t implement this feature if the developer hasn’t built it into its product.

Dr. Sittig and Dr. Singh suggest three strategies to complement CMS’s new regulation:

• Because in their view, ONC’s EHR certification criteria are insufficient to address many patient safety concerns, CMS should require EHR developers to assess their products annually.
• ONC should conduct annual reviews of the SAFER recommendations with input from EHR developers and safety experts.
• EHR vendors should disseminate guidance to their customers on how to address safety practices, perhaps including EHR configuration guides related to safety.

Safety in EHR certification

At a recent press conference that ONC held to update reporters on its current plans, officials were asked to comment on Dr. Sittig’s and Dr. Singh’s proposition that EHR developers, as well as hospitals, do more to ensure system safety.

Steve Posnack, deputy national coordinator of health IT, noted that the ONC-supervised certification process requires developers to pay attention to how they “implement and integrate safety practices in their software design. We have certification criteria ... around what’s called safety-enhanced design – specific capabilities in the EHR that are sensitive to safety in areas like e-prescribing, medication, and high-risk events, where you want to make sure there’s more attention paid to the safety-related dynamics.”

After the conference, ONC told this news organization that among the safety-related certification criteria is one on user-centered design, which must be used in programming certain EHR features. Another is on the use of a quality management system to guide the creation of each EHR capability.

Nevertheless, there is evidence that not all EHR developers have paid sufficient attention to safety in their products. This is shown in the corporate integrity agreements with the Office of the Inspector General (OIG) of the Department of Health and Human Services (HHS) that developers eClinicalWorks and Greenway agreed to sign because, according to the government, they had not met all of the certification criteria they’d claimed to satisfy.

Under these agreements, the vendors agreed to follow “relevant standards, checklists, self-assessment tools, and other practices identified in the ONC SAFER guides and the ICE Report(s) to optimize the safety and safe use of EHRs” in a number of specific areas.

Even if all EHRs conformed to the certification requirements for safety, they would fall short of the SAFER recommendations, Dr. Sittig says. “Those certification criteria are pretty general and not as comprehensive as the SAFER guides. Some SAFER guide recommendations are in existing certification requirements, like you’re supposed to have drug-drug interaction checking capabilities, and they’re supposed to be on. But it doesn’t say you need to have the patient’s identification on every screen. It’s easy to assume good software design, development, and testing principles are a given, but our experience suggests otherwise.”
 

Configuration problems

A handful of vendors are working on what the JAMA article suggests, but there are about 1,000 EHR developers, Dr. Sittig notes. Moreover, there are configuration problems in the design of many EHRs, even if the products have the recommended features.

“For example, it’s often possible to meet the SAFER recommendations, but not all the vendors make that the default setting. That’s one of the things our paper says they should do,” Dr. Sittig says.

Conversely, some hospitals turn off certain features because they annoy doctors, he notes. For instance, the SAFER guides recommend that allergies, problem list entries, and diagnostic test results be entered and stored using standard, coded data elements in the EHR, but often the EHR makes it easier to enter free text data.

Default settings can be wiped out during system upgrades, he added. That has happened with drug interaction checkers. “If you don’t test the system after upgrades and reassess it annually, you might go several months without your drug-drug interaction checker on. And your doctors aren’t complaining about not getting alerts. Those kinds of mistakes are hard to catch.”

Some errors in an EHR may be caught fairly quickly, but in a health system that treats thousands of patients at any given time, those mistakes can still cause a lot of potential patient harm, Dr. Sittig points out. Some vendors, he says, are building tools to help health care organizations catch those errors through what is called “anomaly detection.” This is similar to what credit card companies do when they notice you’ve bought a carpet in Saudi Arabia, although you’ve never traveled abroad, he notes.

“You can look at alert firing data and notice that all of a sudden an alert fired 500 times today when it usually fires 10 times, or it stopped firing,” Dr. Sittig observes. “Those kinds of things should be built into all EHRs. That would be an excellent step forward.”

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

In a little-noticed action last month, the Centers for Medicare & Medicaid Services (CMS) published a regulation requiring hospitals to attest that they have completed an annual safety assessment of their electronic health record (EHR) products so as to meet an objective of the Medicare Promoting Interoperability Program, starting next year.

©daoleduc/ThinkStock.com

Experts praised the move but said that EHR developers should share the responsibility for ensuring that the use of their products doesn’t harm patients.

A number of safety problems are associated with hospital EHR systems, ranging from insufficient protection against medication errors and inadvertent turnoffs of drug interaction checkers to allowing physicians to use free text instead of coded data for key patient indicators. Although hospitals aren’t required to do anything about safety problems that turn up in their self-audits, practitioners who perform the self-assessment will likely encounter challenges that they were previously unaware of and will fix them, experts say.

Studies over the past decade have shown that improper configuration and use of EHRs, as well as design flaws in the systems, can cause avoidable patient injuries or can fail to prevent them. For example, one large study found that clinical decision support (CDS) features in EHRs prevented adverse drug events (ADEs) in only 61.6% of cases in 2016. That was an improvement over the ADE prevention rate of 54% in 2009. Nevertheless, nearly 40% of ADEs were not averted.

Another study, sponsored by the Leapfrog Group, found that EHRs used in U.S. hospitals failed to detect up to 1 in 3 potentially harmful drug interactions and other medication errors. In this study, about 10% of the detection failures were attributed to design problems in EHRs.

The new CMS measure requires hospitals to evaluate their EHRs using safety guides that were developed in 2014 and were revised in 2016 by the Office of the National Coordinator for Health IT (ONC). Known as the Safety Assurance Factors for Resilience (SAFER) guides, they include a set of recommendations to help health care organizations optimize the safety of EHRs.
 

Surprises in store for hospitals

Dean Sittig, PhD, a professor at the University of Texas Health Science Center, Houston, told this news organization that a 2018 study he conducted with his colleague Hardeep Singh, MD, MPH, found that eight surveyed health care organizations were following about 75% of the SAFER recommendations.

He said that when hospitals and health care systems start to assess their systems, many will be surprised at what they are not doing or not doing right. Although the new CMS rule doesn’t require them to correct deficiencies, he expects that many will.

For this reason, Dr. Sittig believes the requirement will have a positive effect on patient safety. But the regulation may not go far enough because it doesn’t impose any requirements on EHR vendors, he said.

In a commentary published in JAMA, Dr. Sittig and Dr. Hardeep, a professor at the Michael E. DeBakey VA Medical Center and Baylor College of Medicine, cite a study showing that 40% of “EHR-related products” had “nonconformities” with EHR certification regulations that could potentially harm patients. “Many nonconformities could have been identified by the developer prior to product release,” they say.
 

Shared responsibility

According to the JAMA commentary, the SAFER guides were developed “to help health care organizations and EHR developers conduct voluntary self-assessments to help eliminate or minimize EHR-related safety risks and hazards.”

In response to a query from this news organization, ONC confirmed that the SAFER guides were intended for use by developers as well as practitioners. ONC said it supports CMS’s approach to incentivize collaborations between EHR vendors and health care organizations. It noted that some entities have already teamed up to the meet the SAFER guides’ recommendations.

Hospitals and EHR developers must share responsibility for safety, Dr. Sittig and Dr. Singh argue, because many SAFER recommendations are based on EHR features that have to be programmed by developers.

For example, one recommendation is that patient identification information be displayed on all portions of the EHR user interface, wristbands, and printouts. Hospitals can’t implement this feature if the developer hasn’t built it into its product.

Dr. Sittig and Dr. Singh suggest three strategies to complement CMS’s new regulation:

• Because in their view, ONC’s EHR certification criteria are insufficient to address many patient safety concerns, CMS should require EHR developers to assess their products annually.
• ONC should conduct annual reviews of the SAFER recommendations with input from EHR developers and safety experts.
• EHR vendors should disseminate guidance to their customers on how to address safety practices, perhaps including EHR configuration guides related to safety.

Safety in EHR certification

At a recent press conference that ONC held to update reporters on its current plans, officials were asked to comment on Dr. Sittig’s and Dr. Singh’s proposition that EHR developers, as well as hospitals, do more to ensure system safety.

Steve Posnack, deputy national coordinator of health IT, noted that the ONC-supervised certification process requires developers to pay attention to how they “implement and integrate safety practices in their software design. We have certification criteria ... around what’s called safety-enhanced design – specific capabilities in the EHR that are sensitive to safety in areas like e-prescribing, medication, and high-risk events, where you want to make sure there’s more attention paid to the safety-related dynamics.”

After the conference, ONC told this news organization that among the safety-related certification criteria is one on user-centered design, which must be used in programming certain EHR features. Another is on the use of a quality management system to guide the creation of each EHR capability.

Nevertheless, there is evidence that not all EHR developers have paid sufficient attention to safety in their products. This is shown in the corporate integrity agreements with the Office of the Inspector General (OIG) of the Department of Health and Human Services (HHS) that developers eClinicalWorks and Greenway agreed to sign because, according to the government, they had not met all of the certification criteria they’d claimed to satisfy.

Under these agreements, the vendors agreed to follow “relevant standards, checklists, self-assessment tools, and other practices identified in the ONC SAFER guides and the ICE Report(s) to optimize the safety and safe use of EHRs” in a number of specific areas.

Even if all EHRs conformed to the certification requirements for safety, they would fall short of the SAFER recommendations, Dr. Sittig says. “Those certification criteria are pretty general and not as comprehensive as the SAFER guides. Some SAFER guide recommendations are in existing certification requirements, like you’re supposed to have drug-drug interaction checking capabilities, and they’re supposed to be on. But it doesn’t say you need to have the patient’s identification on every screen. It’s easy to assume good software design, development, and testing principles are a given, but our experience suggests otherwise.”
 

Configuration problems

A handful of vendors are working on what the JAMA article suggests, but there are about 1,000 EHR developers, Dr. Sittig notes. Moreover, there are configuration problems in the design of many EHRs, even if the products have the recommended features.

“For example, it’s often possible to meet the SAFER recommendations, but not all the vendors make that the default setting. That’s one of the things our paper says they should do,” Dr. Sittig says.

Conversely, some hospitals turn off certain features because they annoy doctors, he notes. For instance, the SAFER guides recommend that allergies, problem list entries, and diagnostic test results be entered and stored using standard, coded data elements in the EHR, but often the EHR makes it easier to enter free text data.

Default settings can be wiped out during system upgrades, he added. That has happened with drug interaction checkers. “If you don’t test the system after upgrades and reassess it annually, you might go several months without your drug-drug interaction checker on. And your doctors aren’t complaining about not getting alerts. Those kinds of mistakes are hard to catch.”

Some errors in an EHR may be caught fairly quickly, but in a health system that treats thousands of patients at any given time, those mistakes can still cause a lot of potential patient harm, Dr. Sittig points out. Some vendors, he says, are building tools to help health care organizations catch those errors through what is called “anomaly detection.” This is similar to what credit card companies do when they notice you’ve bought a carpet in Saudi Arabia, although you’ve never traveled abroad, he notes.

“You can look at alert firing data and notice that all of a sudden an alert fired 500 times today when it usually fires 10 times, or it stopped firing,” Dr. Sittig observes. “Those kinds of things should be built into all EHRs. That would be an excellent step forward.”

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

Another study has shown an association between antibiotic use and an increased risk for colon cancer.

The latest data come from a Swedish population study. Investigators analyzed data from more than 40,000 colorectal cancer patients and 200,000 cancer-free control persons.

Sheep purple/flickr/CC BY 2.0 /en.wikipedia/CC BY-SA 4.0

They found that moderate use of antibiotics increased the risk for proximal colon cancer by 9% and that very high antibiotic use increased the risk by 17%.

In contrast, the risk for rectal cancer was reduced by 4% with moderate use and 9% with very high use, but this association was confined to women.

Antibiotic use was categorized as no use (no reported use of antibiotics during the study period), low (use during a period of 1-10 days), moderate (11-60 days), high (61-180 days), and very high (>180 days).

The study, led by Sophia Harlid, PhD, department of radiation sciences, oncology, Umeå University, Sweden, was published online on Sept. 1 in the Journal of the National Cancer Institute.

The results complement findings from a recent study from Scotland, which found that a history of antibiotic use among individuals younger than 50 appeared to increase the risk of developing colon cancer but not rectal cancer by 49%.

The new data from Sweden “strengthen prior evidence and provide new insights into site-specific carcinogenesis as well as indirect support for the role of gut microbiota,” lead author Dr. Dr. Harlid commented in an interview.

“The positive associations between antibiotics use and proximal colon cancer began at the lowest level of antibiotics use, providing a potential justification for reducing antibiotics prescriptions in clinical practice,” she added.

In their article, the team suggests that the increased risk could be a result of antibiotics having a “disruptive effect” on the gut microbiome.

The finding of an increased risk for cancer in the proximal colon but not further along the alimentary tract “is consistent with a high microbial impact in the proximal colon and a decreasing concentration of short-chain fatty acids along the colon,” the authors comment.

This results “in higher bacterial activity, biofilm formation, and fermentation in the proximal compared with the distal colon and rectum.”

A further analysis showed that the use of quinolones and sulfonamides and/or trimethoprims was associated with an increased risk for proximal colon cancer, whereas use of nitrofurantoins, macrolides and/or lincosamides, and metronidazoles and/or tinidazoles was inversely associated with rectal cancer.

Details of the study findings

For their study, the team analyzed complete-population data from Swedish national registers for the period July 1, 2005 to Dec. 31, 2016.

They matched case patients who were diagnosed with colorectal cancer from Jan. 1, 2010 to Dec. 31, 2016 with cancer-free control persons in a 1:5 ratio. Data on antibiotic use were extracted from the Swedish Prescribed Drug Register.

Other variables, such as socioeconomic factors and health care utilization, were obtained from the Swedish Inpatient Register and the Longitudinal Integration Database for Health Insurance and Labor Market Studies.

The team identified 40,545 patients with colorectal cancer cases; there were 202,720 control persons. Just over half (52.9%) of the participants were men; the mean age at cancer diagnosis was 72 years. Among the cases, 36.4% were proximal colon cancers, 29.3% were distal colon cancers, and 33.0% rectal cancers.

Control patients were more likely to have been prescribed no antibiotics, at 22.4% versus 18.7% for case patients. Case patients were more likely than control persons to have used antibiotics for more than 2 months, at 20.8% versus 19.3% (P < .001).

Overall, antibiotic use was positively associated with colorectal cancer. In comparison with no use, the odds ratio for moderate use was 1.15; for very high use, it was 1.17 (P < .001 for trend).

Excluding all antibiotic use during the 2 years prior to a colorectal cancer diagnosis attenuated the association, such that it was no longer significant for very high use versus no antibiotic use.

Applying this cutoff to the remaining analyses, the team found that the dose-response relationship between antibiotic use and colorectal cancer was largely confined to proximal colon cancer, at an odds ratio of 1.09 for moderate use and 1.17 for very high use in comparison with no use (P < .001 for trend).

For distal colon cancer, the relationship was “close to null.”

There was a slight inverse relationship between rectal cancer and antibiotic use, at an odds rate of 0.96 for moderate use and 0.91 for very high use versus no use (P < .001 for trend). This association was found in women only, whereas the other associations were seen in both men and women.

The study was supported by the Lion’s Cancer Research Foundation, Umeå University, and Region Västerbotten. Dr. Harlid has disclosed no relevant financial relationships. Three coauthors report various relationships with industry, as noted in the original article.

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

Another study has shown an association between antibiotic use and an increased risk for colon cancer.

The latest data come from a Swedish population study. Investigators analyzed data from more than 40,000 colorectal cancer patients and 200,000 cancer-free control persons.

Sheep purple/flickr/CC BY 2.0 /en.wikipedia/CC BY-SA 4.0

They found that moderate use of antibiotics increased the risk for proximal colon cancer by 9% and that very high antibiotic use increased the risk by 17%.

In contrast, the risk for rectal cancer was reduced by 4% with moderate use and 9% with very high use, but this association was confined to women.

Antibiotic use was categorized as no use (no reported use of antibiotics during the study period), low (use during a period of 1-10 days), moderate (11-60 days), high (61-180 days), and very high (>180 days).

The study, led by Sophia Harlid, PhD, department of radiation sciences, oncology, Umeå University, Sweden, was published online on Sept. 1 in the Journal of the National Cancer Institute.

The results complement findings from a recent study from Scotland, which found that a history of antibiotic use among individuals younger than 50 appeared to increase the risk of developing colon cancer but not rectal cancer by 49%.

The new data from Sweden “strengthen prior evidence and provide new insights into site-specific carcinogenesis as well as indirect support for the role of gut microbiota,” lead author Dr. Dr. Harlid commented in an interview.

“The positive associations between antibiotics use and proximal colon cancer began at the lowest level of antibiotics use, providing a potential justification for reducing antibiotics prescriptions in clinical practice,” she added.

In their article, the team suggests that the increased risk could be a result of antibiotics having a “disruptive effect” on the gut microbiome.

The finding of an increased risk for cancer in the proximal colon but not further along the alimentary tract “is consistent with a high microbial impact in the proximal colon and a decreasing concentration of short-chain fatty acids along the colon,” the authors comment.

This results “in higher bacterial activity, biofilm formation, and fermentation in the proximal compared with the distal colon and rectum.”

A further analysis showed that the use of quinolones and sulfonamides and/or trimethoprims was associated with an increased risk for proximal colon cancer, whereas use of nitrofurantoins, macrolides and/or lincosamides, and metronidazoles and/or tinidazoles was inversely associated with rectal cancer.

Details of the study findings

For their study, the team analyzed complete-population data from Swedish national registers for the period July 1, 2005 to Dec. 31, 2016.

They matched case patients who were diagnosed with colorectal cancer from Jan. 1, 2010 to Dec. 31, 2016 with cancer-free control persons in a 1:5 ratio. Data on antibiotic use were extracted from the Swedish Prescribed Drug Register.

Other variables, such as socioeconomic factors and health care utilization, were obtained from the Swedish Inpatient Register and the Longitudinal Integration Database for Health Insurance and Labor Market Studies.

The team identified 40,545 patients with colorectal cancer cases; there were 202,720 control persons. Just over half (52.9%) of the participants were men; the mean age at cancer diagnosis was 72 years. Among the cases, 36.4% were proximal colon cancers, 29.3% were distal colon cancers, and 33.0% rectal cancers.

Control patients were more likely to have been prescribed no antibiotics, at 22.4% versus 18.7% for case patients. Case patients were more likely than control persons to have used antibiotics for more than 2 months, at 20.8% versus 19.3% (P < .001).

Overall, antibiotic use was positively associated with colorectal cancer. In comparison with no use, the odds ratio for moderate use was 1.15; for very high use, it was 1.17 (P < .001 for trend).

Excluding all antibiotic use during the 2 years prior to a colorectal cancer diagnosis attenuated the association, such that it was no longer significant for very high use versus no antibiotic use.

Applying this cutoff to the remaining analyses, the team found that the dose-response relationship between antibiotic use and colorectal cancer was largely confined to proximal colon cancer, at an odds ratio of 1.09 for moderate use and 1.17 for very high use in comparison with no use (P < .001 for trend).

For distal colon cancer, the relationship was “close to null.”

There was a slight inverse relationship between rectal cancer and antibiotic use, at an odds rate of 0.96 for moderate use and 0.91 for very high use versus no use (P < .001 for trend). This association was found in women only, whereas the other associations were seen in both men and women.

The study was supported by the Lion’s Cancer Research Foundation, Umeå University, and Region Västerbotten. Dr. Harlid has disclosed no relevant financial relationships. Three coauthors report various relationships with industry, as noted in the original article.

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

Another study has shown an association between antibiotic use and an increased risk for colon cancer.

The latest data come from a Swedish population study. Investigators analyzed data from more than 40,000 colorectal cancer patients and 200,000 cancer-free control persons.

Sheep purple/flickr/CC BY 2.0 /en.wikipedia/CC BY-SA 4.0

They found that moderate use of antibiotics increased the risk for proximal colon cancer by 9% and that very high antibiotic use increased the risk by 17%.

In contrast, the risk for rectal cancer was reduced by 4% with moderate use and 9% with very high use, but this association was confined to women.

Antibiotic use was categorized as no use (no reported use of antibiotics during the study period), low (use during a period of 1-10 days), moderate (11-60 days), high (61-180 days), and very high (>180 days).

The study, led by Sophia Harlid, PhD, department of radiation sciences, oncology, Umeå University, Sweden, was published online on Sept. 1 in the Journal of the National Cancer Institute.

The results complement findings from a recent study from Scotland, which found that a history of antibiotic use among individuals younger than 50 appeared to increase the risk of developing colon cancer but not rectal cancer by 49%.

The new data from Sweden “strengthen prior evidence and provide new insights into site-specific carcinogenesis as well as indirect support for the role of gut microbiota,” lead author Dr. Dr. Harlid commented in an interview.

“The positive associations between antibiotics use and proximal colon cancer began at the lowest level of antibiotics use, providing a potential justification for reducing antibiotics prescriptions in clinical practice,” she added.

In their article, the team suggests that the increased risk could be a result of antibiotics having a “disruptive effect” on the gut microbiome.

The finding of an increased risk for cancer in the proximal colon but not further along the alimentary tract “is consistent with a high microbial impact in the proximal colon and a decreasing concentration of short-chain fatty acids along the colon,” the authors comment.

This results “in higher bacterial activity, biofilm formation, and fermentation in the proximal compared with the distal colon and rectum.”

A further analysis showed that the use of quinolones and sulfonamides and/or trimethoprims was associated with an increased risk for proximal colon cancer, whereas use of nitrofurantoins, macrolides and/or lincosamides, and metronidazoles and/or tinidazoles was inversely associated with rectal cancer.

Details of the study findings

For their study, the team analyzed complete-population data from Swedish national registers for the period July 1, 2005 to Dec. 31, 2016.

They matched case patients who were diagnosed with colorectal cancer from Jan. 1, 2010 to Dec. 31, 2016 with cancer-free control persons in a 1:5 ratio. Data on antibiotic use were extracted from the Swedish Prescribed Drug Register.

Other variables, such as socioeconomic factors and health care utilization, were obtained from the Swedish Inpatient Register and the Longitudinal Integration Database for Health Insurance and Labor Market Studies.

The team identified 40,545 patients with colorectal cancer cases; there were 202,720 control persons. Just over half (52.9%) of the participants were men; the mean age at cancer diagnosis was 72 years. Among the cases, 36.4% were proximal colon cancers, 29.3% were distal colon cancers, and 33.0% rectal cancers.

Control patients were more likely to have been prescribed no antibiotics, at 22.4% versus 18.7% for case patients. Case patients were more likely than control persons to have used antibiotics for more than 2 months, at 20.8% versus 19.3% (P < .001).

Overall, antibiotic use was positively associated with colorectal cancer. In comparison with no use, the odds ratio for moderate use was 1.15; for very high use, it was 1.17 (P < .001 for trend).

Excluding all antibiotic use during the 2 years prior to a colorectal cancer diagnosis attenuated the association, such that it was no longer significant for very high use versus no antibiotic use.

Applying this cutoff to the remaining analyses, the team found that the dose-response relationship between antibiotic use and colorectal cancer was largely confined to proximal colon cancer, at an odds ratio of 1.09 for moderate use and 1.17 for very high use in comparison with no use (P < .001 for trend).

For distal colon cancer, the relationship was “close to null.”

There was a slight inverse relationship between rectal cancer and antibiotic use, at an odds rate of 0.96 for moderate use and 0.91 for very high use versus no use (P < .001 for trend). This association was found in women only, whereas the other associations were seen in both men and women.

The study was supported by the Lion’s Cancer Research Foundation, Umeå University, and Region Västerbotten. Dr. Harlid has disclosed no relevant financial relationships. Three coauthors report various relationships with industry, as noted in the original article.

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

The family of an Alabama man used his obituary to plead with people to become vaccinated against COVID-19.

Ray Martin DeMonia, 73, of Cullman, Alabama, ran an antiques business for 40 years and served as an auctioneer at charity events, the obituary said.

He had a stroke in 2020 during the first months of the COVID pandemic and made sure to get vaccinated, his daughter, Raven DeMonia, told The Washington Post.

“He knew what the vaccine meant for his health and what it meant to staying alive,” she said. “He said, ‘I just want to get back to shaking hands with people, selling stuff, and talking antiques.’”

His daughter told the Post that her father went to Cullman Regional Medical Center on Aug. 23 with heart problems.

About 12 hours after he was admitted, her mother got a call from the hospital saying they’d called 43 hospitals and were unable to find a “specialized cardiac ICU bed” for him, Ms. DeMonia told the Post.

He was finally airlifted to Rush Foundation Hospital in Meridian, Mississippi, almost 200 miles from his home, but died there Sept. 1. His family decided to make a plea for increased vaccinations in his obituary.

“In honor of Ray, please get vaccinated if you have not, in an effort to free up resources for non COVID related emergencies,” the obit said. “Due to COVID 19, CRMC emergency staff contacted 43 hospitals in 3 states in search of a Cardiac ICU bed and finally located one in Meridian, MS. He would not want any other family to go through what his did.”

Mr. DeMonia is survived by his wife, daughter, grandson, and other family members.

The Alabama Hospital Association says state hospitals are still short of ICU beds. On Sept. 12, the AHA website said the state had 1,530 staffed ICU beds to accommodate 1,541 ICU patients.

The AHA said 83% of COVID patients in ICU had not been vaccinated against COVID, 4% were partially vaccinated, and 13% were fully vaccinated. Alabama trails other states in vaccination rates. Newsweek, citing CDC data, said 53.7% of people in Alabama were fully vaccinated. In comparison, 53.8% of all Americans nationally are fully vaccinated.

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

The family of an Alabama man used his obituary to plead with people to become vaccinated against COVID-19.

Ray Martin DeMonia, 73, of Cullman, Alabama, ran an antiques business for 40 years and served as an auctioneer at charity events, the obituary said.

He had a stroke in 2020 during the first months of the COVID pandemic and made sure to get vaccinated, his daughter, Raven DeMonia, told The Washington Post.

“He knew what the vaccine meant for his health and what it meant to staying alive,” she said. “He said, ‘I just want to get back to shaking hands with people, selling stuff, and talking antiques.’”

His daughter told the Post that her father went to Cullman Regional Medical Center on Aug. 23 with heart problems.

About 12 hours after he was admitted, her mother got a call from the hospital saying they’d called 43 hospitals and were unable to find a “specialized cardiac ICU bed” for him, Ms. DeMonia told the Post.

He was finally airlifted to Rush Foundation Hospital in Meridian, Mississippi, almost 200 miles from his home, but died there Sept. 1. His family decided to make a plea for increased vaccinations in his obituary.

“In honor of Ray, please get vaccinated if you have not, in an effort to free up resources for non COVID related emergencies,” the obit said. “Due to COVID 19, CRMC emergency staff contacted 43 hospitals in 3 states in search of a Cardiac ICU bed and finally located one in Meridian, MS. He would not want any other family to go through what his did.”

Mr. DeMonia is survived by his wife, daughter, grandson, and other family members.

The Alabama Hospital Association says state hospitals are still short of ICU beds. On Sept. 12, the AHA website said the state had 1,530 staffed ICU beds to accommodate 1,541 ICU patients.

The AHA said 83% of COVID patients in ICU had not been vaccinated against COVID, 4% were partially vaccinated, and 13% were fully vaccinated. Alabama trails other states in vaccination rates. Newsweek, citing CDC data, said 53.7% of people in Alabama were fully vaccinated. In comparison, 53.8% of all Americans nationally are fully vaccinated.

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

The family of an Alabama man used his obituary to plead with people to become vaccinated against COVID-19.

Ray Martin DeMonia, 73, of Cullman, Alabama, ran an antiques business for 40 years and served as an auctioneer at charity events, the obituary said.

He had a stroke in 2020 during the first months of the COVID pandemic and made sure to get vaccinated, his daughter, Raven DeMonia, told The Washington Post.

“He knew what the vaccine meant for his health and what it meant to staying alive,” she said. “He said, ‘I just want to get back to shaking hands with people, selling stuff, and talking antiques.’”

His daughter told the Post that her father went to Cullman Regional Medical Center on Aug. 23 with heart problems.

About 12 hours after he was admitted, her mother got a call from the hospital saying they’d called 43 hospitals and were unable to find a “specialized cardiac ICU bed” for him, Ms. DeMonia told the Post.

He was finally airlifted to Rush Foundation Hospital in Meridian, Mississippi, almost 200 miles from his home, but died there Sept. 1. His family decided to make a plea for increased vaccinations in his obituary.

“In honor of Ray, please get vaccinated if you have not, in an effort to free up resources for non COVID related emergencies,” the obit said. “Due to COVID 19, CRMC emergency staff contacted 43 hospitals in 3 states in search of a Cardiac ICU bed and finally located one in Meridian, MS. He would not want any other family to go through what his did.”

Mr. DeMonia is survived by his wife, daughter, grandson, and other family members.

The Alabama Hospital Association says state hospitals are still short of ICU beds. On Sept. 12, the AHA website said the state had 1,530 staffed ICU beds to accommodate 1,541 ICU patients.

The AHA said 83% of COVID patients in ICU had not been vaccinated against COVID, 4% were partially vaccinated, and 13% were fully vaccinated. Alabama trails other states in vaccination rates. Newsweek, citing CDC data, said 53.7% of people in Alabama were fully vaccinated. In comparison, 53.8% of all Americans nationally are fully vaccinated.

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