Psoriasis and atopic dermatitis (AD) can impact quality of life (QOL) in pediatric patients, warranting early recognition and treatment.¹ Topical agents often are inadequate to treat moderate to severe disease, but the potential toxicity of systemic agents, which largely include immunosuppressives, limit their use in this population despite their effectiveness. Our expanding knowledge of the pathogenesis of psoriasis (tumor necrosis factor [TNF] α and IL-23/T_H17 pathways) and AD has led to targeted interventions, particularly monoclonal antibody biologics, which have revolutionized treatment for affected adults and more recently children. Several agents are approved by the US Food and Drug Administration (FDA) for pediatric psoriasis, and dupilumab is approved for pediatric AD. Herein, we discuss the latest developments in the treatment landscape for pediatric psoriasis and AD.

Pediatric Psoriasis

Methotrexate (MTX) and cyclosporine have been FDA approved for psoriasis in adults since 1972 and 1997, respectively.² Before biologics, MTX was the primary systemic agent used to treat pediatric psoriasis, given its lower toxicity vs cyclosporine. The TNF-α inhibitor etanercept became the first FDA-approved biologic for pediatric psoriasis in 2016. Adalimumab has been available in Europe for children since 2015 but is not FDA approved. Certolizumab, a pegylated TNF-α inhibitor that distinctly fails to cross the placental barrier currently is in clinical trials (ClinicalTrials.gov identifier NCT04123795). Tumor necrosis factor α inhibitors have shown more rapid onset and greater efficacy during the first 16 weeks of use than MTX, including a head-to-head trial comparing MTX to adalimumab.³ A recent real-world study showed that pediatric patients receiving biologics, primarily TNF-α inhibitors, were more likely to achieve psoriasis area and severity index (PASI) 75 or clear/almost clear status (similar to PASI 90) than MTX and had higher drug survival rates.⁴

Ustekinumab targets both IL-12 and IL-23, which share the IL-23 receptor p40 subunit. It was the first biologic to target IL-23, which promotes the proliferation and survival of helper T cells (T_H17). Ustekinumab has led to greater reductions in PASI scores than TNF-α inhibitors.^5,6 Pediatric trials of guselkumab, risankizumab, and tildrakizumab, all targeting the IL-23 receptor–specific p19 subunit, are completed or currently recruiting (NCT03451851, NCT03997786, NCT04435600). Ixekizumab is the first IL-17A–targeting biologic approved for children.⁷ Secukinumab and the IL-17 receptor inhibitor brodalumab are in pediatric trials (NCT03668613, NCT04305327, NCT03240809). One potential issue with T_H17 pathway inhibitors is their association with inflammatory bowel disease, a contraindication when considering if a patient is a potential candidate for treatment.

Skin disease can profoundly affect QOL during childhood and adolescence, a critical time for psychosocial development. In psoriasis, improvement in QOL is proportional to clearance and is greater when PASI 90 is achieved vs PASI 75.⁸ The high efficacy of IL-23 and IL-17A pathway inhibitors now makes achieving at least PASI 90 the new standard, which can be reached in most patients.

Pediatric AD

For AD in the pediatric population, systemic treatments primarily include corticosteroids, mycophenolate mofetil, azathioprine, cyclosporine, and MTX. Although cyclosporine was the favored systemic agent among pediatric dermatologists in one study,⁹ claims data analyses show that systemic corticosteroids are used much more often overall, prescribed in 24.4% (116,635 total cases) of children with AD vs nonsteroidal immunosuppressants in less than 0.5%.¹⁰ Systemic steroids are impractical given their side effects and risk for disease rebound; however, no immunosuppressants are safe for long-term use, and all require frequent laboratory monitoring. The development of biologics for AD largely involves targeting T_H2-driven inflammation.¹¹ Dupilumab is the only FDA-approved biologic for moderate to severe pediatric AD, including in patients as young as 6 years of age. Dupilumab inhibits activation of the IL-4Rα subunit, thereby blocking responses to its ligands, IL-4 and IL-13. Phase 3 trials are now underway in children aged 6 months to 5 years (NCT02612454, NCT03346434). The concomitant ameliorative effects of dupilumab on asthma and other allergic disorders, occurring in approximately 90% of children with moderate to severe AD, is an added benefit.¹² Although dupilumab does not appear to modify the disease course in children with AD, the possibility that early introduction could reduce the risk for later developing allergic disease is intriguing.

Adolescent trials have been started for lebrikizumab (NCT04392154) and have been completed for tralokinumab (NCT03160885). Both agents selectively target IL-13 to block T_H2 pathway inflammation. The only reported adverse effects of IL-4Rα and IL-13 inhibitors have been injection-site pain/reactions and increased conjunctivitis.¹³

The only other biologic for AD currently in clinical trials for adolescents is nemolizumab, targeting the receptor for IL-31, a predominantly T_H2 cytokine that causes pruritus (NCT03989349). In adults, nemolizumab has shown rapid and potent suppression of itch (but not inflammation) without adding topical corticosteroids.¹⁴

Advantages of Biologics and Laboratory Monitoring

By targeting specific cytokines, biologics have greater and more rapid efficacy, fewer side effects, fewer drug interactions, less frequent dosing, and less immunosuppression compared to other systemic agents.^3,4,15,16

Recent pediatric-specific guidelines for psoriasis recommend baseline monitoring for tuberculosis for all biologics but yearly tuberculosis testing only for TNF-α inhibitors unless the individual patient is at increased risk.² No tuberculosis testing is needed for dupilumab, and no other laboratory monitoring is recommended for any biologic in children unless warranted by risk. This difference in recommended monitoring suggests the safety of biologics and is advantageous in managing pediatric therapy.

Unanswered Questions: Vaccines and Antidrug Antibodies

Although administration of killed vaccines is considered safe with all approved biologics, questions remain about the safety of administering live vaccines while on biologics, a particularly pertinent issue in younger children treated with dupilumab and other biologics for AD. Another unanswered question is the potential reduction in clinical response and drug durability with intermittent use of biologics due to the potential development of neutralizing antidrug antibodies (ADAs). The ability to discontinue medication intermittently is desirable, both to determine the natural course of the underlying disease and give a holiday as tolerated. Newer biologics are thought to have lower immunogenicity and less frequent ADA development.^17-19 Even with TNF-α inhibitors, the presence of anti-ADAs is not temporally related to response in children with psoriasis.²⁰ Long-term outcomes of the use of biologics in adults have been reassuring, and safety profiles of biologics studied thus far appear to be similar in children.^21,22 However, understanding the potential long-term effects from the use of newly approved and emerging biologics in the pediatric population will require decades of study to ensure safety, including nonrandomized studies and postmarketing reports from regulatory agencies.

Cost Considerations

Biologics are disease and QOL altering for children with moderate to severe psoriasis or AD; however, access to biologics often is an obstacle for patients and practitioners. Biologics cost $30,000 to $60,000 annually, while conventional systemic treatments such as MTX, cyclosporine, and acitretin cost $100 to $3000 annually, raising the question of cost effectiveness. In 2016, the Institute for Clinical and Economic Review concluded that biologics for psoriasis had reasonably good value based on improved QOL and concluded in 2017 that dupilumab had a benefit that outweighed its cost.^23,24 Prior authorizations and multiple appeals have been necessary to obtain approval, especially in the pediatric population.²⁵ This difficulty highlights the need for programs to cover the cost of biologics for all children, as well as registries to further assess effectiveness and long-term safety, especially compared to traditional systemic agents.

On the Horizon

Clinical trials for other therapies for children and adolescents are ongoing. Details on recommended dosing, approval status, and efficacy in trials are provided in the eTable. Given their high efficacy in adults with psoriasis, IL-23–specific and T_H17 pathway biologics likely are similarly efficacious and raise the bar for the expectation of achieving PASI 90 and PASI 100 responses. The long-term safety, durability of responses, and ability to modify disease, particularly when started early in life (eg, preadolescence) and early in the disease course, remains to be determined.

Psoriasis and atopic dermatitis (AD) can impact quality of life (QOL) in pediatric patients, warranting early recognition and treatment.¹ Topical agents often are inadequate to treat moderate to severe disease, but the potential toxicity of systemic agents, which largely include immunosuppressives, limit their use in this population despite their effectiveness. Our expanding knowledge of the pathogenesis of psoriasis (tumor necrosis factor [TNF] α and IL-23/T_H17 pathways) and AD has led to targeted interventions, particularly monoclonal antibody biologics, which have revolutionized treatment for affected adults and more recently children. Several agents are approved by the US Food and Drug Administration (FDA) for pediatric psoriasis, and dupilumab is approved for pediatric AD. Herein, we discuss the latest developments in the treatment landscape for pediatric psoriasis and AD.

Pediatric Psoriasis

Methotrexate (MTX) and cyclosporine have been FDA approved for psoriasis in adults since 1972 and 1997, respectively.² Before biologics, MTX was the primary systemic agent used to treat pediatric psoriasis, given its lower toxicity vs cyclosporine. The TNF-α inhibitor etanercept became the first FDA-approved biologic for pediatric psoriasis in 2016. Adalimumab has been available in Europe for children since 2015 but is not FDA approved. Certolizumab, a pegylated TNF-α inhibitor that distinctly fails to cross the placental barrier currently is in clinical trials (ClinicalTrials.gov identifier NCT04123795). Tumor necrosis factor α inhibitors have shown more rapid onset and greater efficacy during the first 16 weeks of use than MTX, including a head-to-head trial comparing MTX to adalimumab.³ A recent real-world study showed that pediatric patients receiving biologics, primarily TNF-α inhibitors, were more likely to achieve psoriasis area and severity index (PASI) 75 or clear/almost clear status (similar to PASI 90) than MTX and had higher drug survival rates.⁴

Ustekinumab targets both IL-12 and IL-23, which share the IL-23 receptor p40 subunit. It was the first biologic to target IL-23, which promotes the proliferation and survival of helper T cells (T_H17). Ustekinumab has led to greater reductions in PASI scores than TNF-α inhibitors.^5,6 Pediatric trials of guselkumab, risankizumab, and tildrakizumab, all targeting the IL-23 receptor–specific p19 subunit, are completed or currently recruiting (NCT03451851, NCT03997786, NCT04435600). Ixekizumab is the first IL-17A–targeting biologic approved for children.⁷ Secukinumab and the IL-17 receptor inhibitor brodalumab are in pediatric trials (NCT03668613, NCT04305327, NCT03240809). One potential issue with T_H17 pathway inhibitors is their association with inflammatory bowel disease, a contraindication when considering if a patient is a potential candidate for treatment.

Skin disease can profoundly affect QOL during childhood and adolescence, a critical time for psychosocial development. In psoriasis, improvement in QOL is proportional to clearance and is greater when PASI 90 is achieved vs PASI 75.⁸ The high efficacy of IL-23 and IL-17A pathway inhibitors now makes achieving at least PASI 90 the new standard, which can be reached in most patients.

Pediatric AD

For AD in the pediatric population, systemic treatments primarily include corticosteroids, mycophenolate mofetil, azathioprine, cyclosporine, and MTX. Although cyclosporine was the favored systemic agent among pediatric dermatologists in one study,⁹ claims data analyses show that systemic corticosteroids are used much more often overall, prescribed in 24.4% (116,635 total cases) of children with AD vs nonsteroidal immunosuppressants in less than 0.5%.¹⁰ Systemic steroids are impractical given their side effects and risk for disease rebound; however, no immunosuppressants are safe for long-term use, and all require frequent laboratory monitoring. The development of biologics for AD largely involves targeting T_H2-driven inflammation.¹¹ Dupilumab is the only FDA-approved biologic for moderate to severe pediatric AD, including in patients as young as 6 years of age. Dupilumab inhibits activation of the IL-4Rα subunit, thereby blocking responses to its ligands, IL-4 and IL-13. Phase 3 trials are now underway in children aged 6 months to 5 years (NCT02612454, NCT03346434). The concomitant ameliorative effects of dupilumab on asthma and other allergic disorders, occurring in approximately 90% of children with moderate to severe AD, is an added benefit.¹² Although dupilumab does not appear to modify the disease course in children with AD, the possibility that early introduction could reduce the risk for later developing allergic disease is intriguing.

Adolescent trials have been started for lebrikizumab (NCT04392154) and have been completed for tralokinumab (NCT03160885). Both agents selectively target IL-13 to block T_H2 pathway inflammation. The only reported adverse effects of IL-4Rα and IL-13 inhibitors have been injection-site pain/reactions and increased conjunctivitis.¹³

The only other biologic for AD currently in clinical trials for adolescents is nemolizumab, targeting the receptor for IL-31, a predominantly T_H2 cytokine that causes pruritus (NCT03989349). In adults, nemolizumab has shown rapid and potent suppression of itch (but not inflammation) without adding topical corticosteroids.¹⁴

Advantages of Biologics and Laboratory Monitoring

By targeting specific cytokines, biologics have greater and more rapid efficacy, fewer side effects, fewer drug interactions, less frequent dosing, and less immunosuppression compared to other systemic agents.^3,4,15,16

Recent pediatric-specific guidelines for psoriasis recommend baseline monitoring for tuberculosis for all biologics but yearly tuberculosis testing only for TNF-α inhibitors unless the individual patient is at increased risk.² No tuberculosis testing is needed for dupilumab, and no other laboratory monitoring is recommended for any biologic in children unless warranted by risk. This difference in recommended monitoring suggests the safety of biologics and is advantageous in managing pediatric therapy.

Unanswered Questions: Vaccines and Antidrug Antibodies

Although administration of killed vaccines is considered safe with all approved biologics, questions remain about the safety of administering live vaccines while on biologics, a particularly pertinent issue in younger children treated with dupilumab and other biologics for AD. Another unanswered question is the potential reduction in clinical response and drug durability with intermittent use of biologics due to the potential development of neutralizing antidrug antibodies (ADAs). The ability to discontinue medication intermittently is desirable, both to determine the natural course of the underlying disease and give a holiday as tolerated. Newer biologics are thought to have lower immunogenicity and less frequent ADA development.^17-19 Even with TNF-α inhibitors, the presence of anti-ADAs is not temporally related to response in children with psoriasis.²⁰ Long-term outcomes of the use of biologics in adults have been reassuring, and safety profiles of biologics studied thus far appear to be similar in children.^21,22 However, understanding the potential long-term effects from the use of newly approved and emerging biologics in the pediatric population will require decades of study to ensure safety, including nonrandomized studies and postmarketing reports from regulatory agencies.

Cost Considerations

Biologics are disease and QOL altering for children with moderate to severe psoriasis or AD; however, access to biologics often is an obstacle for patients and practitioners. Biologics cost $30,000 to $60,000 annually, while conventional systemic treatments such as MTX, cyclosporine, and acitretin cost $100 to $3000 annually, raising the question of cost effectiveness. In 2016, the Institute for Clinical and Economic Review concluded that biologics for psoriasis had reasonably good value based on improved QOL and concluded in 2017 that dupilumab had a benefit that outweighed its cost.^23,24 Prior authorizations and multiple appeals have been necessary to obtain approval, especially in the pediatric population.²⁵ This difficulty highlights the need for programs to cover the cost of biologics for all children, as well as registries to further assess effectiveness and long-term safety, especially compared to traditional systemic agents.

On the Horizon

Clinical trials for other therapies for children and adolescents are ongoing. Details on recommended dosing, approval status, and efficacy in trials are provided in the eTable. Given their high efficacy in adults with psoriasis, IL-23–specific and T_H17 pathway biologics likely are similarly efficacious and raise the bar for the expectation of achieving PASI 90 and PASI 100 responses. The long-term safety, durability of responses, and ability to modify disease, particularly when started early in life (eg, preadolescence) and early in the disease course, remains to be determined.

Psoriasis and atopic dermatitis (AD) can impact quality of life (QOL) in pediatric patients, warranting early recognition and treatment.¹ Topical agents often are inadequate to treat moderate to severe disease, but the potential toxicity of systemic agents, which largely include immunosuppressives, limit their use in this population despite their effectiveness. Our expanding knowledge of the pathogenesis of psoriasis (tumor necrosis factor [TNF] α and IL-23/T_H17 pathways) and AD has led to targeted interventions, particularly monoclonal antibody biologics, which have revolutionized treatment for affected adults and more recently children. Several agents are approved by the US Food and Drug Administration (FDA) for pediatric psoriasis, and dupilumab is approved for pediatric AD. Herein, we discuss the latest developments in the treatment landscape for pediatric psoriasis and AD.

Pediatric Psoriasis

Methotrexate (MTX) and cyclosporine have been FDA approved for psoriasis in adults since 1972 and 1997, respectively.² Before biologics, MTX was the primary systemic agent used to treat pediatric psoriasis, given its lower toxicity vs cyclosporine. The TNF-α inhibitor etanercept became the first FDA-approved biologic for pediatric psoriasis in 2016. Adalimumab has been available in Europe for children since 2015 but is not FDA approved. Certolizumab, a pegylated TNF-α inhibitor that distinctly fails to cross the placental barrier currently is in clinical trials (ClinicalTrials.gov identifier NCT04123795). Tumor necrosis factor α inhibitors have shown more rapid onset and greater efficacy during the first 16 weeks of use than MTX, including a head-to-head trial comparing MTX to adalimumab.³ A recent real-world study showed that pediatric patients receiving biologics, primarily TNF-α inhibitors, were more likely to achieve psoriasis area and severity index (PASI) 75 or clear/almost clear status (similar to PASI 90) than MTX and had higher drug survival rates.⁴

Ustekinumab targets both IL-12 and IL-23, which share the IL-23 receptor p40 subunit. It was the first biologic to target IL-23, which promotes the proliferation and survival of helper T cells (T_H17). Ustekinumab has led to greater reductions in PASI scores than TNF-α inhibitors.^5,6 Pediatric trials of guselkumab, risankizumab, and tildrakizumab, all targeting the IL-23 receptor–specific p19 subunit, are completed or currently recruiting (NCT03451851, NCT03997786, NCT04435600). Ixekizumab is the first IL-17A–targeting biologic approved for children.⁷ Secukinumab and the IL-17 receptor inhibitor brodalumab are in pediatric trials (NCT03668613, NCT04305327, NCT03240809). One potential issue with T_H17 pathway inhibitors is their association with inflammatory bowel disease, a contraindication when considering if a patient is a potential candidate for treatment.

Skin disease can profoundly affect QOL during childhood and adolescence, a critical time for psychosocial development. In psoriasis, improvement in QOL is proportional to clearance and is greater when PASI 90 is achieved vs PASI 75.⁸ The high efficacy of IL-23 and IL-17A pathway inhibitors now makes achieving at least PASI 90 the new standard, which can be reached in most patients.

Pediatric AD

For AD in the pediatric population, systemic treatments primarily include corticosteroids, mycophenolate mofetil, azathioprine, cyclosporine, and MTX. Although cyclosporine was the favored systemic agent among pediatric dermatologists in one study,⁹ claims data analyses show that systemic corticosteroids are used much more often overall, prescribed in 24.4% (116,635 total cases) of children with AD vs nonsteroidal immunosuppressants in less than 0.5%.¹⁰ Systemic steroids are impractical given their side effects and risk for disease rebound; however, no immunosuppressants are safe for long-term use, and all require frequent laboratory monitoring. The development of biologics for AD largely involves targeting T_H2-driven inflammation.¹¹ Dupilumab is the only FDA-approved biologic for moderate to severe pediatric AD, including in patients as young as 6 years of age. Dupilumab inhibits activation of the IL-4Rα subunit, thereby blocking responses to its ligands, IL-4 and IL-13. Phase 3 trials are now underway in children aged 6 months to 5 years (NCT02612454, NCT03346434). The concomitant ameliorative effects of dupilumab on asthma and other allergic disorders, occurring in approximately 90% of children with moderate to severe AD, is an added benefit.¹² Although dupilumab does not appear to modify the disease course in children with AD, the possibility that early introduction could reduce the risk for later developing allergic disease is intriguing.

Adolescent trials have been started for lebrikizumab (NCT04392154) and have been completed for tralokinumab (NCT03160885). Both agents selectively target IL-13 to block T_H2 pathway inflammation. The only reported adverse effects of IL-4Rα and IL-13 inhibitors have been injection-site pain/reactions and increased conjunctivitis.¹³

The only other biologic for AD currently in clinical trials for adolescents is nemolizumab, targeting the receptor for IL-31, a predominantly T_H2 cytokine that causes pruritus (NCT03989349). In adults, nemolizumab has shown rapid and potent suppression of itch (but not inflammation) without adding topical corticosteroids.¹⁴

Advantages of Biologics and Laboratory Monitoring

By targeting specific cytokines, biologics have greater and more rapid efficacy, fewer side effects, fewer drug interactions, less frequent dosing, and less immunosuppression compared to other systemic agents.^3,4,15,16

Recent pediatric-specific guidelines for psoriasis recommend baseline monitoring for tuberculosis for all biologics but yearly tuberculosis testing only for TNF-α inhibitors unless the individual patient is at increased risk.² No tuberculosis testing is needed for dupilumab, and no other laboratory monitoring is recommended for any biologic in children unless warranted by risk. This difference in recommended monitoring suggests the safety of biologics and is advantageous in managing pediatric therapy.

Unanswered Questions: Vaccines and Antidrug Antibodies

Although administration of killed vaccines is considered safe with all approved biologics, questions remain about the safety of administering live vaccines while on biologics, a particularly pertinent issue in younger children treated with dupilumab and other biologics for AD. Another unanswered question is the potential reduction in clinical response and drug durability with intermittent use of biologics due to the potential development of neutralizing antidrug antibodies (ADAs). The ability to discontinue medication intermittently is desirable, both to determine the natural course of the underlying disease and give a holiday as tolerated. Newer biologics are thought to have lower immunogenicity and less frequent ADA development.^17-19 Even with TNF-α inhibitors, the presence of anti-ADAs is not temporally related to response in children with psoriasis.²⁰ Long-term outcomes of the use of biologics in adults have been reassuring, and safety profiles of biologics studied thus far appear to be similar in children.^21,22 However, understanding the potential long-term effects from the use of newly approved and emerging biologics in the pediatric population will require decades of study to ensure safety, including nonrandomized studies and postmarketing reports from regulatory agencies.

Cost Considerations

Biologics are disease and QOL altering for children with moderate to severe psoriasis or AD; however, access to biologics often is an obstacle for patients and practitioners. Biologics cost $30,000 to $60,000 annually, while conventional systemic treatments such as MTX, cyclosporine, and acitretin cost $100 to $3000 annually, raising the question of cost effectiveness. In 2016, the Institute for Clinical and Economic Review concluded that biologics for psoriasis had reasonably good value based on improved QOL and concluded in 2017 that dupilumab had a benefit that outweighed its cost.^23,24 Prior authorizations and multiple appeals have been necessary to obtain approval, especially in the pediatric population.²⁵ This difficulty highlights the need for programs to cover the cost of biologics for all children, as well as registries to further assess effectiveness and long-term safety, especially compared to traditional systemic agents.

On the Horizon

Clinical trials for other therapies for children and adolescents are ongoing. Details on recommended dosing, approval status, and efficacy in trials are provided in the eTable. Given their high efficacy in adults with psoriasis, IL-23–specific and T_H17 pathway biologics likely are similarly efficacious and raise the bar for the expectation of achieving PASI 90 and PASI 100 responses. The long-term safety, durability of responses, and ability to modify disease, particularly when started early in life (eg, preadolescence) and early in the disease course, remains to be determined.

The age of antiretroviral therapy (ART) for HIV is in its third decade, and many of the patients who live in areas of the world fortunate enough to have had early access to therapy have now lived for several decades with complications of HIV and viral suppressive therapy.

But while the life-expectancy of persons with HIV has approached that of noninfected persons over the last 20 years, the higher burden of comorbidities for aging patients with HIV has remained largely the same, according to an epidemiologist who specializes in HIV/AIDS research and aging.

“The pathways from HIV and its treatments to comorbidities are very long and winding, spanning a life course. Social determinants of health and individual risk factors also play an important role, and must be considered,” said Keri N. Althoff, PhD, MPH, of Johns Hopkins University, Baltimore.

Dr. Althoff discussed long-term complications of HIV and its treatment in a virtual symposium during an annual scientific meeting on infectious diseases.

“Many urban HIV providers have an increased proportion of patients who are older long-term survivors of the epidemic. Many, but not all of the comorbidities (including cardiovascular, neurocognitive, renal, and malignancies) have been associated with age, long-term HIV infection, especially uncontrolled HIV infection, and low CD4 nadirs,” commented Harry Lampiris, MD, professor of clinical medicine at the University of California, San Francisco.

“An increasing number of patients are experiencing geriatric syndromes (especially problems with mobility, cognitive decline, food insecurity, polypharmacy, and social isolation) at younger ages than HIV-negative populations,” he added.

Dr. Lampiris, who moderated the session where Dr. Althoff presented her findings, commented on it in an interview, but was not involved in her research.
 

Pathways to comorbidity

The three primary pathways to comorbidities in people with HIV infections are as follows, according to Dr. Athloff:

• The virus itself, with its associated inflammation, immunosuppression, immune activation, and AIDS.
• HIV therapies, beginning with the notoriously toxic dideoxynucleoside analogues or “d-drugs,” and following with subsequent generations of newer, less toxic agents.
• Individual risk factors, including smoking, stress, diet, exercise, and environment.

Cardiovascular and renal complications

Persons with HIV have an approximately twofold higher risk for major adverse cardiovascular events (myocardial infarction, stroke) compared with persons without HIV. Conditions contributing to cardiovascular disease including hypertension, diabetes, and hyperlipidemia are also significantly higher among persons with HIV, Dr. Althoff said.

Hypertension among persons with HIV from the ages 60-69 years is especially high for Black men and to a lesser degree non-Black men, compared with either White or Black women, she noted.

Pathways to renal disease in persons with HIV include diabetes and hypertension, as well as therapies to treat them, hepatitis B and C coinfection, HIV-associated nephropathy, and immune complex kidney disease, as well as chronic kidney disease resulting from acute kidney injury related to therapy.

“Cardiovascular disease and kidney disease are excellent examples of why the life-course perspective is essential when caring for people with HIV. For those diagnosed with HIV at younger ages, there are points of intervention along the decades-long path, and the timing and implementation of the most effective intervention may preserve comorbidity-free years,” Dr. Althoff said.

Prevention and screening interventions to lower risk for future heart- and kidney-related comorbidities include smoking cessation and lifestyle optimization (diet, exercise, mental health), as well as lipid-lowering medications to lower risk for cardiovascular events.
 

Liver comorbidities

“Primary drivers of liver disease are social determinants of health and individual lifestyle risk factors that share the same pathways as HIV, resulting in this increased burden of liver disease in people with HIV,” she said.

Risk factors include alcoholic liver disease, nonalcoholic fatty liver disease, hepatitis B and C coinfection, drug use, autoimmune disease, and aging. These risk factors contribute to oxidative stress, mitochondrial injury, lipotoxicity, cytotoxicity, and other mechanisms that can lead to fibrosis, cirrhosis, hepatocellular carcinoma, and end-stage liver disease.

“I want to be sure to acknowledge the importance of liver disease as a comorbidity among people with HIV. Liver disease accounts for nearly 20% of mortality in persons with HIV,” she said.
 

Neurocognitive problems

HIV has been linked to neurocognitive decline since the beginning of the epidemic, Dr. Althoff noted. The term HIV-associated neurocognitive disorders encompasses the broad spectrum of cognitive effects of HIV, from asymptomatic illness to AIDS-related dementia. Estimates of cognitive impairment in people with HIV range from 14% to 64% across various study populations, but diagnosing and treating it in the community can be challenging.

“Routine monitoring of cognition is often just out of reach in the clinical setting, due to the time it takes to use validated tools. We need a deeper toolbox of quick and validated tools calibrated to people with HIV in order to accurately monitor cognition,” she said.

She noted that the average age of onset of Alzheimer’s disease in the general population is 80 years, and that relatively few people with HIV infection have reached that age.

“But before the population age distribution shifts to the older ages, we can do more to monitor cognition in people with HIV,” she added.

In addition to HIV, factors that can contribute to worse neurocognitive outcomes include major depressive disorder, occurring in and estimated 20%-40% of adults with HIV versus 8% of the U.S. population, generalized anxiety disorder (10%-25% vs. 3%), bipolar disorder (3%-9% vs. 3%), schizophrenia (4%-15% vs. 1%), and posttraumatic stress disorder (10%-30% vs. 8%).

Substance use and polypharmacy, common among adults with HIV, can also contribute to cognitive decline, she said.
 

Decreased mobility

The Multicenter AIDS Cohort Study (MACS) showed that decreased mobility, defined as a gait speed less than 1 m/sec, occurred earlier in life among HIV-positive men than in HIV-negative men.

In the general aging population, slow gait speed is a predictor for lower extremity limitations, hospitalization, and death, and in more recent MACS studies was associated with increased hemoglobin A_1C levels, as well as neurocognitive impairment.

“Hemoglobin A_1C is an intervenable target, and perhaps it will help to slow the decline in gait speed,” Dr. Althoff said.
 

Reduce ‘healthspan’ disparities

The goal for treating aging adults with HIV “is to reduce the disparity in healthspan between people with HIV compared to people without HIV by delaying or eliminating the onset of comorbidities among people with HIV,” she said.

The gerontological concept of extending “healthspan” – the duration of life without significant comorbidities – is to target common mechanisms of aging, thereby delaying the onset of more than one age-related disease at the same time.

“Crude translation of this concept to the population of aging with HIV includes reducing that gap in comorbidity-free survival in people with versus without HIV,” she said.

Modification of care models from geriatrics may help infectious disease specialists manage adults with HIV who have increasingly complex needs.

For example, the geriatric “5 M” model emphasizes focusing on issues of mind (mentation, dementia, delirium, depression), mobility (impaired gait and balance, as well as fall prevention), medications (reducing polypharmacy, optimal prescribing), multicomplexity (multiple morbidities and complex bio-psycho-social situations), and “matters most” (each patient’s individual meaningful health outcome goals and care preferences).

Changing exposures that may influence the pattern of comorbidities for patients with HIV in the future include earlier start on ART, shorter duration of uncontrolled viremia, compared with older populations, newer and less toxic ARTs, long-term viral suppression, and risk factor interventions, Dr. Althoff concluded.

Dr. Lampiris noted that “patients who have initiated therapy in the last 5-10 years are more likely to initiate antiretroviral therapy at higher CD4 counts, and less likely to experience long-term toxicities of antiretroviral therapy. However, African Americans, Hispanics and HIV-positive women continue to lag behind others with regard to timely initiation of treatment.

“In addition there are toxicities associated with the newer agents, particularly weight gain, which disproportionately affect African Americans and women and which may be made worse by poverty, food insecurity, and other health-related behaviors.”

Dr. Athloff’s work is supported by grants from the National Institutes for Health. She disclosed serving as a consultant to the NIH-funded All of US study and to MediQ, and as an adviser to TrioHealth. Dr. Lampiris reported having no disclosures.

The age of antiretroviral therapy (ART) for HIV is in its third decade, and many of the patients who live in areas of the world fortunate enough to have had early access to therapy have now lived for several decades with complications of HIV and viral suppressive therapy.

But while the life-expectancy of persons with HIV has approached that of noninfected persons over the last 20 years, the higher burden of comorbidities for aging patients with HIV has remained largely the same, according to an epidemiologist who specializes in HIV/AIDS research and aging.

“The pathways from HIV and its treatments to comorbidities are very long and winding, spanning a life course. Social determinants of health and individual risk factors also play an important role, and must be considered,” said Keri N. Althoff, PhD, MPH, of Johns Hopkins University, Baltimore.

Dr. Althoff discussed long-term complications of HIV and its treatment in a virtual symposium during an annual scientific meeting on infectious diseases.

“Many urban HIV providers have an increased proportion of patients who are older long-term survivors of the epidemic. Many, but not all of the comorbidities (including cardiovascular, neurocognitive, renal, and malignancies) have been associated with age, long-term HIV infection, especially uncontrolled HIV infection, and low CD4 nadirs,” commented Harry Lampiris, MD, professor of clinical medicine at the University of California, San Francisco.

“An increasing number of patients are experiencing geriatric syndromes (especially problems with mobility, cognitive decline, food insecurity, polypharmacy, and social isolation) at younger ages than HIV-negative populations,” he added.

Dr. Lampiris, who moderated the session where Dr. Althoff presented her findings, commented on it in an interview, but was not involved in her research.
 

Pathways to comorbidity

The three primary pathways to comorbidities in people with HIV infections are as follows, according to Dr. Athloff:

• The virus itself, with its associated inflammation, immunosuppression, immune activation, and AIDS.
• HIV therapies, beginning with the notoriously toxic dideoxynucleoside analogues or “d-drugs,” and following with subsequent generations of newer, less toxic agents.
• Individual risk factors, including smoking, stress, diet, exercise, and environment.

Cardiovascular and renal complications

Persons with HIV have an approximately twofold higher risk for major adverse cardiovascular events (myocardial infarction, stroke) compared with persons without HIV. Conditions contributing to cardiovascular disease including hypertension, diabetes, and hyperlipidemia are also significantly higher among persons with HIV, Dr. Althoff said.

Hypertension among persons with HIV from the ages 60-69 years is especially high for Black men and to a lesser degree non-Black men, compared with either White or Black women, she noted.

Pathways to renal disease in persons with HIV include diabetes and hypertension, as well as therapies to treat them, hepatitis B and C coinfection, HIV-associated nephropathy, and immune complex kidney disease, as well as chronic kidney disease resulting from acute kidney injury related to therapy.

“Cardiovascular disease and kidney disease are excellent examples of why the life-course perspective is essential when caring for people with HIV. For those diagnosed with HIV at younger ages, there are points of intervention along the decades-long path, and the timing and implementation of the most effective intervention may preserve comorbidity-free years,” Dr. Althoff said.

Prevention and screening interventions to lower risk for future heart- and kidney-related comorbidities include smoking cessation and lifestyle optimization (diet, exercise, mental health), as well as lipid-lowering medications to lower risk for cardiovascular events.
 

Liver comorbidities

“Primary drivers of liver disease are social determinants of health and individual lifestyle risk factors that share the same pathways as HIV, resulting in this increased burden of liver disease in people with HIV,” she said.

Risk factors include alcoholic liver disease, nonalcoholic fatty liver disease, hepatitis B and C coinfection, drug use, autoimmune disease, and aging. These risk factors contribute to oxidative stress, mitochondrial injury, lipotoxicity, cytotoxicity, and other mechanisms that can lead to fibrosis, cirrhosis, hepatocellular carcinoma, and end-stage liver disease.

“I want to be sure to acknowledge the importance of liver disease as a comorbidity among people with HIV. Liver disease accounts for nearly 20% of mortality in persons with HIV,” she said.
 

Neurocognitive problems

HIV has been linked to neurocognitive decline since the beginning of the epidemic, Dr. Althoff noted. The term HIV-associated neurocognitive disorders encompasses the broad spectrum of cognitive effects of HIV, from asymptomatic illness to AIDS-related dementia. Estimates of cognitive impairment in people with HIV range from 14% to 64% across various study populations, but diagnosing and treating it in the community can be challenging.

“Routine monitoring of cognition is often just out of reach in the clinical setting, due to the time it takes to use validated tools. We need a deeper toolbox of quick and validated tools calibrated to people with HIV in order to accurately monitor cognition,” she said.

She noted that the average age of onset of Alzheimer’s disease in the general population is 80 years, and that relatively few people with HIV infection have reached that age.

“But before the population age distribution shifts to the older ages, we can do more to monitor cognition in people with HIV,” she added.

In addition to HIV, factors that can contribute to worse neurocognitive outcomes include major depressive disorder, occurring in and estimated 20%-40% of adults with HIV versus 8% of the U.S. population, generalized anxiety disorder (10%-25% vs. 3%), bipolar disorder (3%-9% vs. 3%), schizophrenia (4%-15% vs. 1%), and posttraumatic stress disorder (10%-30% vs. 8%).

Substance use and polypharmacy, common among adults with HIV, can also contribute to cognitive decline, she said.
 

Decreased mobility

The Multicenter AIDS Cohort Study (MACS) showed that decreased mobility, defined as a gait speed less than 1 m/sec, occurred earlier in life among HIV-positive men than in HIV-negative men.

In the general aging population, slow gait speed is a predictor for lower extremity limitations, hospitalization, and death, and in more recent MACS studies was associated with increased hemoglobin A_1C levels, as well as neurocognitive impairment.

“Hemoglobin A_1C is an intervenable target, and perhaps it will help to slow the decline in gait speed,” Dr. Althoff said.
 

Reduce ‘healthspan’ disparities

The goal for treating aging adults with HIV “is to reduce the disparity in healthspan between people with HIV compared to people without HIV by delaying or eliminating the onset of comorbidities among people with HIV,” she said.

The gerontological concept of extending “healthspan” – the duration of life without significant comorbidities – is to target common mechanisms of aging, thereby delaying the onset of more than one age-related disease at the same time.

“Crude translation of this concept to the population of aging with HIV includes reducing that gap in comorbidity-free survival in people with versus without HIV,” she said.

Modification of care models from geriatrics may help infectious disease specialists manage adults with HIV who have increasingly complex needs.

For example, the geriatric “5 M” model emphasizes focusing on issues of mind (mentation, dementia, delirium, depression), mobility (impaired gait and balance, as well as fall prevention), medications (reducing polypharmacy, optimal prescribing), multicomplexity (multiple morbidities and complex bio-psycho-social situations), and “matters most” (each patient’s individual meaningful health outcome goals and care preferences).

Changing exposures that may influence the pattern of comorbidities for patients with HIV in the future include earlier start on ART, shorter duration of uncontrolled viremia, compared with older populations, newer and less toxic ARTs, long-term viral suppression, and risk factor interventions, Dr. Althoff concluded.

Dr. Lampiris noted that “patients who have initiated therapy in the last 5-10 years are more likely to initiate antiretroviral therapy at higher CD4 counts, and less likely to experience long-term toxicities of antiretroviral therapy. However, African Americans, Hispanics and HIV-positive women continue to lag behind others with regard to timely initiation of treatment.

“In addition there are toxicities associated with the newer agents, particularly weight gain, which disproportionately affect African Americans and women and which may be made worse by poverty, food insecurity, and other health-related behaviors.”

Dr. Athloff’s work is supported by grants from the National Institutes for Health. She disclosed serving as a consultant to the NIH-funded All of US study and to MediQ, and as an adviser to TrioHealth. Dr. Lampiris reported having no disclosures.

The age of antiretroviral therapy (ART) for HIV is in its third decade, and many of the patients who live in areas of the world fortunate enough to have had early access to therapy have now lived for several decades with complications of HIV and viral suppressive therapy.

But while the life-expectancy of persons with HIV has approached that of noninfected persons over the last 20 years, the higher burden of comorbidities for aging patients with HIV has remained largely the same, according to an epidemiologist who specializes in HIV/AIDS research and aging.

“The pathways from HIV and its treatments to comorbidities are very long and winding, spanning a life course. Social determinants of health and individual risk factors also play an important role, and must be considered,” said Keri N. Althoff, PhD, MPH, of Johns Hopkins University, Baltimore.

Dr. Althoff discussed long-term complications of HIV and its treatment in a virtual symposium during an annual scientific meeting on infectious diseases.

“Many urban HIV providers have an increased proportion of patients who are older long-term survivors of the epidemic. Many, but not all of the comorbidities (including cardiovascular, neurocognitive, renal, and malignancies) have been associated with age, long-term HIV infection, especially uncontrolled HIV infection, and low CD4 nadirs,” commented Harry Lampiris, MD, professor of clinical medicine at the University of California, San Francisco.

“An increasing number of patients are experiencing geriatric syndromes (especially problems with mobility, cognitive decline, food insecurity, polypharmacy, and social isolation) at younger ages than HIV-negative populations,” he added.

Dr. Lampiris, who moderated the session where Dr. Althoff presented her findings, commented on it in an interview, but was not involved in her research.
 

Pathways to comorbidity

The three primary pathways to comorbidities in people with HIV infections are as follows, according to Dr. Athloff:

• The virus itself, with its associated inflammation, immunosuppression, immune activation, and AIDS.
• HIV therapies, beginning with the notoriously toxic dideoxynucleoside analogues or “d-drugs,” and following with subsequent generations of newer, less toxic agents.
• Individual risk factors, including smoking, stress, diet, exercise, and environment.

Cardiovascular and renal complications

Persons with HIV have an approximately twofold higher risk for major adverse cardiovascular events (myocardial infarction, stroke) compared with persons without HIV. Conditions contributing to cardiovascular disease including hypertension, diabetes, and hyperlipidemia are also significantly higher among persons with HIV, Dr. Althoff said.

Hypertension among persons with HIV from the ages 60-69 years is especially high for Black men and to a lesser degree non-Black men, compared with either White or Black women, she noted.

Pathways to renal disease in persons with HIV include diabetes and hypertension, as well as therapies to treat them, hepatitis B and C coinfection, HIV-associated nephropathy, and immune complex kidney disease, as well as chronic kidney disease resulting from acute kidney injury related to therapy.

“Cardiovascular disease and kidney disease are excellent examples of why the life-course perspective is essential when caring for people with HIV. For those diagnosed with HIV at younger ages, there are points of intervention along the decades-long path, and the timing and implementation of the most effective intervention may preserve comorbidity-free years,” Dr. Althoff said.

Prevention and screening interventions to lower risk for future heart- and kidney-related comorbidities include smoking cessation and lifestyle optimization (diet, exercise, mental health), as well as lipid-lowering medications to lower risk for cardiovascular events.
 

Liver comorbidities

“Primary drivers of liver disease are social determinants of health and individual lifestyle risk factors that share the same pathways as HIV, resulting in this increased burden of liver disease in people with HIV,” she said.

Risk factors include alcoholic liver disease, nonalcoholic fatty liver disease, hepatitis B and C coinfection, drug use, autoimmune disease, and aging. These risk factors contribute to oxidative stress, mitochondrial injury, lipotoxicity, cytotoxicity, and other mechanisms that can lead to fibrosis, cirrhosis, hepatocellular carcinoma, and end-stage liver disease.

“I want to be sure to acknowledge the importance of liver disease as a comorbidity among people with HIV. Liver disease accounts for nearly 20% of mortality in persons with HIV,” she said.
 

Neurocognitive problems

HIV has been linked to neurocognitive decline since the beginning of the epidemic, Dr. Althoff noted. The term HIV-associated neurocognitive disorders encompasses the broad spectrum of cognitive effects of HIV, from asymptomatic illness to AIDS-related dementia. Estimates of cognitive impairment in people with HIV range from 14% to 64% across various study populations, but diagnosing and treating it in the community can be challenging.

“Routine monitoring of cognition is often just out of reach in the clinical setting, due to the time it takes to use validated tools. We need a deeper toolbox of quick and validated tools calibrated to people with HIV in order to accurately monitor cognition,” she said.

She noted that the average age of onset of Alzheimer’s disease in the general population is 80 years, and that relatively few people with HIV infection have reached that age.

“But before the population age distribution shifts to the older ages, we can do more to monitor cognition in people with HIV,” she added.

In addition to HIV, factors that can contribute to worse neurocognitive outcomes include major depressive disorder, occurring in and estimated 20%-40% of adults with HIV versus 8% of the U.S. population, generalized anxiety disorder (10%-25% vs. 3%), bipolar disorder (3%-9% vs. 3%), schizophrenia (4%-15% vs. 1%), and posttraumatic stress disorder (10%-30% vs. 8%).

Substance use and polypharmacy, common among adults with HIV, can also contribute to cognitive decline, she said.
 

Decreased mobility

The Multicenter AIDS Cohort Study (MACS) showed that decreased mobility, defined as a gait speed less than 1 m/sec, occurred earlier in life among HIV-positive men than in HIV-negative men.

In the general aging population, slow gait speed is a predictor for lower extremity limitations, hospitalization, and death, and in more recent MACS studies was associated with increased hemoglobin A_1C levels, as well as neurocognitive impairment.

“Hemoglobin A_1C is an intervenable target, and perhaps it will help to slow the decline in gait speed,” Dr. Althoff said.
 

Reduce ‘healthspan’ disparities

The goal for treating aging adults with HIV “is to reduce the disparity in healthspan between people with HIV compared to people without HIV by delaying or eliminating the onset of comorbidities among people with HIV,” she said.

The gerontological concept of extending “healthspan” – the duration of life without significant comorbidities – is to target common mechanisms of aging, thereby delaying the onset of more than one age-related disease at the same time.

“Crude translation of this concept to the population of aging with HIV includes reducing that gap in comorbidity-free survival in people with versus without HIV,” she said.

Modification of care models from geriatrics may help infectious disease specialists manage adults with HIV who have increasingly complex needs.

For example, the geriatric “5 M” model emphasizes focusing on issues of mind (mentation, dementia, delirium, depression), mobility (impaired gait and balance, as well as fall prevention), medications (reducing polypharmacy, optimal prescribing), multicomplexity (multiple morbidities and complex bio-psycho-social situations), and “matters most” (each patient’s individual meaningful health outcome goals and care preferences).

Changing exposures that may influence the pattern of comorbidities for patients with HIV in the future include earlier start on ART, shorter duration of uncontrolled viremia, compared with older populations, newer and less toxic ARTs, long-term viral suppression, and risk factor interventions, Dr. Althoff concluded.

Dr. Lampiris noted that “patients who have initiated therapy in the last 5-10 years are more likely to initiate antiretroviral therapy at higher CD4 counts, and less likely to experience long-term toxicities of antiretroviral therapy. However, African Americans, Hispanics and HIV-positive women continue to lag behind others with regard to timely initiation of treatment.

“In addition there are toxicities associated with the newer agents, particularly weight gain, which disproportionately affect African Americans and women and which may be made worse by poverty, food insecurity, and other health-related behaviors.”

Dr. Athloff’s work is supported by grants from the National Institutes for Health. She disclosed serving as a consultant to the NIH-funded All of US study and to MediQ, and as an adviser to TrioHealth. Dr. Lampiris reported having no disclosures.

A smartphone app that combines passively collected physiologic data from wearable devices, such as fitness trackers, and self-reported symptoms can discriminate between COVID-19–positive and –negative individuals among those who report symptoms, new data suggest.

LDProd/Getty Images

After analyzing data from more than 30,000 participants, researchers from the Digital Engagement and Tracking for Early Control and Treatment (DETECT) study concluded that adding individual changes in sensor data improves models based on symptoms alone for differentiating symptomatic persons who are COVID-19 positive and symptomatic persons who are COVID-19 negative.

The combination can potentially identify infection clusters before wider community spread occurs, Giorgio Quer, PhD, and colleagues report in an article published online Oct. 29 in Nature Medicine. DETECT investigators note that marrying participant-reported symptoms with personal sensor data, such as deviation from normal sleep duration and resting heart rate, resulted in an area under the curve (AUC) of 0.80 (interquartile range [IQR], 0.73-0.86) for differentiating between symptomatic individuals who were positive and those who were negative for COVID-19.

“By better characterizing each individual’s unique baseline, you can then identify changes that may indicate that someone has a viral illness,” said Dr. Quer, director of artificial intelligence at Scripps Research Translational Institute in La Jolla, Calif. “In previous research, we found that the proportion of individuals with elevated resting heart rate and sleep duration compared with their normal could significantly improve real-time detection of influenza-like illness rates at the state level,” he said in an interview.

Thus, continuous passively captured data may be a useful adjunct to bricks-and-mortar site testing, which is generally a one-off or infrequent sampling assay and is not always easily accessible, he added. Furthermore, traditional screening with temperature and symptom reporting is inadequate. An elevation in temperature is not as common as frequently believed for people who test positive for COVID-19, Dr. Quer continued. “Early identification via sensor variables of those who are presymptomatic or even asymptomatic would be especially valuable, as people may potentially be infectious during this period, and early detection is the ultimate goal,” Dr. Quer said.

According to his group, adding these physiologic changes from baseline values significantly outperformed detection (P < .01) using a British model described in an earlier study by by Cristina Menni, PhD, and associates. That method, in which symptoms were considered alone, yielded an AUC of 0.71 (IQR, 0.63-0.79).

According to Dr. Quer, one in five Americans currently wear an electronic device. “If we could enroll even a small percentage of these individuals, we’d be able to potentially identify clusters before they have the opportunity to spread,” he said.
 

DETECT study details

During the period March 15 to June 7, 2020, the study enrolled 30,529 participants from all 50 states. They ranged in age from younger than 35 years (23.1%) to older than 65 years (12.8%); the majority (63.5%) were aged 35-65 years, and 62% were women. Sensor devices in use by the cohort included Fitbit activity trackers (78.4%) and Apple HealthKit (31.2%).

Participants downloaded an app called MyDataHelps, which collects smartwatch and activity tracker information, including self-reported symptoms and diagnostic testing results. The app also monitors changes from baseline in resting heart rate, sleep duration, and physical activity, as measured by steps.

Overall, 3,811 participants reported having at least one symptom of some kind (e.g., fatigue, cough, dyspnea, loss of taste or smell). Of these, 54 reported testing positive for COVID-19, and 279 reported testing negative.

Sleep and activity were significantly different for the positive and negative groups, with an AUC of 0.68 (IQR, 0.57-0.79) for the sleep metric and 0.69 (IQR, 0.61-0.77) for the activity metric, suggesting that these parameters were more affected in COVID-19–positive participants.

When the investigators combined resting heart rate, sleep, and activity into a single metric, predictive performance improved to an AUC of 0.72 (IQR, 0.64-0.80).

The next step, Dr. Quer said, is to include an alert to notify users of possible infection.
 

Alerting users to possible COVID-19 infection

In a similar study, an alert feature was already incorporated. The study, led by Michael P. Snyder, PhD, director of the Center for Genomics and Personalized Medicine at Stanford (Calif.) University, will soon be published online in Nature Biomedical Engineering. In that study, presymptomatic detection of COVID-19 was achieved in more than 80% of participants using resting heart rate.

“The median is 4 days prior to symptom formation,” Dr. Snyder said in an interview. “We have an alarm system to notify people when their heart rate is elevated. So a positive signal from a smartwatch can be used to follow up by polymerase chain reaction [testing].”

Dr. Snyder said these approaches offer a roadmap to containing widespread infections. “Public health authorities need to be open to these technologies and begin incorporating them into their tracking,” he said. “Right now, people do temperature checks, which are of limited value. Resting heart rate is much better information.”

Although the DETECT researchers have not yet received feedback on their results, they believe public health authorities could recommend the use of such apps. “These are devices that people routinely wear for tracking their fitness and sleep, so it would be relatively easy to use the data for viral illness tracking,” said co–lead author Jennifer Radin, PhD, an epidemiologist at Scripps. “Testing resources are still limited and don’t allow for routine serial testing of individuals who may be asymptomatic or presymptomatic. Wearables can offer a different way to routinely monitor and screen people for changes in their data that may indicate COVID-19.”

The marshaling of data through consumer digital platforms to fight the coronavirus is gaining ground. New York State and New Jersey are already embracing smartphone apps to alert individuals to possible exposure to the virus.

More than 710,000 New Yorkers have downloaded the COVID NY Alert app, launched in October to help protect individuals and communities from COVID-19 by sending alerts without compromising privacy or personal information. “Upon receiving a notification about a potential exposure, users are then able to self-quarantine, get tested, and reduce the potential exposure risk to family, friends, coworkers, and others,” Jonah Bruno, a spokesperson for the New York State Department of Health, said in an interview.

And recently the Mayo Clinic and Safe Health Systems launched a platform to store COVID-19 testing and vaccination data.

Both the Scripps and Stanford platforms are part of a global technologic response to the COVID-19 pandemic. Prospective studies, led by device manufacturers and academic institutions, allow individuals to voluntarily share sensor and clinical data to address the crisis. Similar approaches have been used to track COVID-19 in large populations in Germany via the Corona Data Donation app.

The study by Dr. Quer and colleagues was funded by a grant from the National Center for Advancing Translational Sciences at the National Institutes of Health. One coauthor reported grants from Janssen and personal fees from Otsuka and Livongo outside of the submitted work. The other authors have disclosed no relevant financial relationships. Dr. Snyder has ties to Personalis, Qbio, January, SensOmics, Protos, Mirvie, and Oralome.
 

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

A smartphone app that combines passively collected physiologic data from wearable devices, such as fitness trackers, and self-reported symptoms can discriminate between COVID-19–positive and –negative individuals among those who report symptoms, new data suggest.

LDProd/Getty Images

After analyzing data from more than 30,000 participants, researchers from the Digital Engagement and Tracking for Early Control and Treatment (DETECT) study concluded that adding individual changes in sensor data improves models based on symptoms alone for differentiating symptomatic persons who are COVID-19 positive and symptomatic persons who are COVID-19 negative.

The combination can potentially identify infection clusters before wider community spread occurs, Giorgio Quer, PhD, and colleagues report in an article published online Oct. 29 in Nature Medicine. DETECT investigators note that marrying participant-reported symptoms with personal sensor data, such as deviation from normal sleep duration and resting heart rate, resulted in an area under the curve (AUC) of 0.80 (interquartile range [IQR], 0.73-0.86) for differentiating between symptomatic individuals who were positive and those who were negative for COVID-19.

“By better characterizing each individual’s unique baseline, you can then identify changes that may indicate that someone has a viral illness,” said Dr. Quer, director of artificial intelligence at Scripps Research Translational Institute in La Jolla, Calif. “In previous research, we found that the proportion of individuals with elevated resting heart rate and sleep duration compared with their normal could significantly improve real-time detection of influenza-like illness rates at the state level,” he said in an interview.

Thus, continuous passively captured data may be a useful adjunct to bricks-and-mortar site testing, which is generally a one-off or infrequent sampling assay and is not always easily accessible, he added. Furthermore, traditional screening with temperature and symptom reporting is inadequate. An elevation in temperature is not as common as frequently believed for people who test positive for COVID-19, Dr. Quer continued. “Early identification via sensor variables of those who are presymptomatic or even asymptomatic would be especially valuable, as people may potentially be infectious during this period, and early detection is the ultimate goal,” Dr. Quer said.

According to his group, adding these physiologic changes from baseline values significantly outperformed detection (P < .01) using a British model described in an earlier study by by Cristina Menni, PhD, and associates. That method, in which symptoms were considered alone, yielded an AUC of 0.71 (IQR, 0.63-0.79).

According to Dr. Quer, one in five Americans currently wear an electronic device. “If we could enroll even a small percentage of these individuals, we’d be able to potentially identify clusters before they have the opportunity to spread,” he said.
 

DETECT study details

During the period March 15 to June 7, 2020, the study enrolled 30,529 participants from all 50 states. They ranged in age from younger than 35 years (23.1%) to older than 65 years (12.8%); the majority (63.5%) were aged 35-65 years, and 62% were women. Sensor devices in use by the cohort included Fitbit activity trackers (78.4%) and Apple HealthKit (31.2%).

Participants downloaded an app called MyDataHelps, which collects smartwatch and activity tracker information, including self-reported symptoms and diagnostic testing results. The app also monitors changes from baseline in resting heart rate, sleep duration, and physical activity, as measured by steps.

Overall, 3,811 participants reported having at least one symptom of some kind (e.g., fatigue, cough, dyspnea, loss of taste or smell). Of these, 54 reported testing positive for COVID-19, and 279 reported testing negative.

Sleep and activity were significantly different for the positive and negative groups, with an AUC of 0.68 (IQR, 0.57-0.79) for the sleep metric and 0.69 (IQR, 0.61-0.77) for the activity metric, suggesting that these parameters were more affected in COVID-19–positive participants.

When the investigators combined resting heart rate, sleep, and activity into a single metric, predictive performance improved to an AUC of 0.72 (IQR, 0.64-0.80).

The next step, Dr. Quer said, is to include an alert to notify users of possible infection.
 

Alerting users to possible COVID-19 infection

In a similar study, an alert feature was already incorporated. The study, led by Michael P. Snyder, PhD, director of the Center for Genomics and Personalized Medicine at Stanford (Calif.) University, will soon be published online in Nature Biomedical Engineering. In that study, presymptomatic detection of COVID-19 was achieved in more than 80% of participants using resting heart rate.

“The median is 4 days prior to symptom formation,” Dr. Snyder said in an interview. “We have an alarm system to notify people when their heart rate is elevated. So a positive signal from a smartwatch can be used to follow up by polymerase chain reaction [testing].”

Dr. Snyder said these approaches offer a roadmap to containing widespread infections. “Public health authorities need to be open to these technologies and begin incorporating them into their tracking,” he said. “Right now, people do temperature checks, which are of limited value. Resting heart rate is much better information.”

Although the DETECT researchers have not yet received feedback on their results, they believe public health authorities could recommend the use of such apps. “These are devices that people routinely wear for tracking their fitness and sleep, so it would be relatively easy to use the data for viral illness tracking,” said co–lead author Jennifer Radin, PhD, an epidemiologist at Scripps. “Testing resources are still limited and don’t allow for routine serial testing of individuals who may be asymptomatic or presymptomatic. Wearables can offer a different way to routinely monitor and screen people for changes in their data that may indicate COVID-19.”

The marshaling of data through consumer digital platforms to fight the coronavirus is gaining ground. New York State and New Jersey are already embracing smartphone apps to alert individuals to possible exposure to the virus.

More than 710,000 New Yorkers have downloaded the COVID NY Alert app, launched in October to help protect individuals and communities from COVID-19 by sending alerts without compromising privacy or personal information. “Upon receiving a notification about a potential exposure, users are then able to self-quarantine, get tested, and reduce the potential exposure risk to family, friends, coworkers, and others,” Jonah Bruno, a spokesperson for the New York State Department of Health, said in an interview.

And recently the Mayo Clinic and Safe Health Systems launched a platform to store COVID-19 testing and vaccination data.

Both the Scripps and Stanford platforms are part of a global technologic response to the COVID-19 pandemic. Prospective studies, led by device manufacturers and academic institutions, allow individuals to voluntarily share sensor and clinical data to address the crisis. Similar approaches have been used to track COVID-19 in large populations in Germany via the Corona Data Donation app.

The study by Dr. Quer and colleagues was funded by a grant from the National Center for Advancing Translational Sciences at the National Institutes of Health. One coauthor reported grants from Janssen and personal fees from Otsuka and Livongo outside of the submitted work. The other authors have disclosed no relevant financial relationships. Dr. Snyder has ties to Personalis, Qbio, January, SensOmics, Protos, Mirvie, and Oralome.
 

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

A smartphone app that combines passively collected physiologic data from wearable devices, such as fitness trackers, and self-reported symptoms can discriminate between COVID-19–positive and –negative individuals among those who report symptoms, new data suggest.

LDProd/Getty Images

After analyzing data from more than 30,000 participants, researchers from the Digital Engagement and Tracking for Early Control and Treatment (DETECT) study concluded that adding individual changes in sensor data improves models based on symptoms alone for differentiating symptomatic persons who are COVID-19 positive and symptomatic persons who are COVID-19 negative.

The combination can potentially identify infection clusters before wider community spread occurs, Giorgio Quer, PhD, and colleagues report in an article published online Oct. 29 in Nature Medicine. DETECT investigators note that marrying participant-reported symptoms with personal sensor data, such as deviation from normal sleep duration and resting heart rate, resulted in an area under the curve (AUC) of 0.80 (interquartile range [IQR], 0.73-0.86) for differentiating between symptomatic individuals who were positive and those who were negative for COVID-19.

“By better characterizing each individual’s unique baseline, you can then identify changes that may indicate that someone has a viral illness,” said Dr. Quer, director of artificial intelligence at Scripps Research Translational Institute in La Jolla, Calif. “In previous research, we found that the proportion of individuals with elevated resting heart rate and sleep duration compared with their normal could significantly improve real-time detection of influenza-like illness rates at the state level,” he said in an interview.

Thus, continuous passively captured data may be a useful adjunct to bricks-and-mortar site testing, which is generally a one-off or infrequent sampling assay and is not always easily accessible, he added. Furthermore, traditional screening with temperature and symptom reporting is inadequate. An elevation in temperature is not as common as frequently believed for people who test positive for COVID-19, Dr. Quer continued. “Early identification via sensor variables of those who are presymptomatic or even asymptomatic would be especially valuable, as people may potentially be infectious during this period, and early detection is the ultimate goal,” Dr. Quer said.

According to his group, adding these physiologic changes from baseline values significantly outperformed detection (P < .01) using a British model described in an earlier study by by Cristina Menni, PhD, and associates. That method, in which symptoms were considered alone, yielded an AUC of 0.71 (IQR, 0.63-0.79).

According to Dr. Quer, one in five Americans currently wear an electronic device. “If we could enroll even a small percentage of these individuals, we’d be able to potentially identify clusters before they have the opportunity to spread,” he said.
 

DETECT study details

During the period March 15 to June 7, 2020, the study enrolled 30,529 participants from all 50 states. They ranged in age from younger than 35 years (23.1%) to older than 65 years (12.8%); the majority (63.5%) were aged 35-65 years, and 62% were women. Sensor devices in use by the cohort included Fitbit activity trackers (78.4%) and Apple HealthKit (31.2%).

Participants downloaded an app called MyDataHelps, which collects smartwatch and activity tracker information, including self-reported symptoms and diagnostic testing results. The app also monitors changes from baseline in resting heart rate, sleep duration, and physical activity, as measured by steps.

Overall, 3,811 participants reported having at least one symptom of some kind (e.g., fatigue, cough, dyspnea, loss of taste or smell). Of these, 54 reported testing positive for COVID-19, and 279 reported testing negative.

Sleep and activity were significantly different for the positive and negative groups, with an AUC of 0.68 (IQR, 0.57-0.79) for the sleep metric and 0.69 (IQR, 0.61-0.77) for the activity metric, suggesting that these parameters were more affected in COVID-19–positive participants.

When the investigators combined resting heart rate, sleep, and activity into a single metric, predictive performance improved to an AUC of 0.72 (IQR, 0.64-0.80).

The next step, Dr. Quer said, is to include an alert to notify users of possible infection.
 

Alerting users to possible COVID-19 infection

In a similar study, an alert feature was already incorporated. The study, led by Michael P. Snyder, PhD, director of the Center for Genomics and Personalized Medicine at Stanford (Calif.) University, will soon be published online in Nature Biomedical Engineering. In that study, presymptomatic detection of COVID-19 was achieved in more than 80% of participants using resting heart rate.

“The median is 4 days prior to symptom formation,” Dr. Snyder said in an interview. “We have an alarm system to notify people when their heart rate is elevated. So a positive signal from a smartwatch can be used to follow up by polymerase chain reaction [testing].”

Dr. Snyder said these approaches offer a roadmap to containing widespread infections. “Public health authorities need to be open to these technologies and begin incorporating them into their tracking,” he said. “Right now, people do temperature checks, which are of limited value. Resting heart rate is much better information.”

Although the DETECT researchers have not yet received feedback on their results, they believe public health authorities could recommend the use of such apps. “These are devices that people routinely wear for tracking their fitness and sleep, so it would be relatively easy to use the data for viral illness tracking,” said co–lead author Jennifer Radin, PhD, an epidemiologist at Scripps. “Testing resources are still limited and don’t allow for routine serial testing of individuals who may be asymptomatic or presymptomatic. Wearables can offer a different way to routinely monitor and screen people for changes in their data that may indicate COVID-19.”

The marshaling of data through consumer digital platforms to fight the coronavirus is gaining ground. New York State and New Jersey are already embracing smartphone apps to alert individuals to possible exposure to the virus.

More than 710,000 New Yorkers have downloaded the COVID NY Alert app, launched in October to help protect individuals and communities from COVID-19 by sending alerts without compromising privacy or personal information. “Upon receiving a notification about a potential exposure, users are then able to self-quarantine, get tested, and reduce the potential exposure risk to family, friends, coworkers, and others,” Jonah Bruno, a spokesperson for the New York State Department of Health, said in an interview.

And recently the Mayo Clinic and Safe Health Systems launched a platform to store COVID-19 testing and vaccination data.

Both the Scripps and Stanford platforms are part of a global technologic response to the COVID-19 pandemic. Prospective studies, led by device manufacturers and academic institutions, allow individuals to voluntarily share sensor and clinical data to address the crisis. Similar approaches have been used to track COVID-19 in large populations in Germany via the Corona Data Donation app.

The study by Dr. Quer and colleagues was funded by a grant from the National Center for Advancing Translational Sciences at the National Institutes of Health. One coauthor reported grants from Janssen and personal fees from Otsuka and Livongo outside of the submitted work. The other authors have disclosed no relevant financial relationships. Dr. Snyder has ties to Personalis, Qbio, January, SensOmics, Protos, Mirvie, and Oralome.
 

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

Combination afatinib and cetuximab did not improve progression-free survival (PFS) over afatinib alone in a phase 2 trial of treatment-naive patients with advanced EGFR-mutant non–small cell lung cancer (NSCLC).

In addition, toxicity was greater with the afatinib/cetuximab combination, according to study author Sarah S. Goldberg, MD, of Yale University, New Haven, Conn.

Dr. Goldberg and colleagues reported these results, from the SWOG S1403 trial, in the Journal of Clinical Oncology.

The authors noted that activating EGFR mutations are present in about 15% of patients with lung adenocarcinomas in Western populations and the mutations confer heightened sensitivity to EGFR tyrosine kinase inhibitors (TKIs). EGFR-TKIs have been shown to improve clinical outcomes, quality of life, and toxicity when compared with chemotherapy.

Based on better outcomes over chemotherapy, the third-generation EGFR-TKI osimertinib is now the standard treatment for patients with T790M-mediated resistance, but osimertinib is not effective in TKI-resistant T790M-negative disease, the authors pointed out.

In a phase 1b trial of patients with EGFR-mutant NSCLC with acquired resistance to first-generation agents, afatinib/cetuximab produced a response rate of 29% and comparable activity regardless of T790M status.

The aim of the SWOG S1403 study was to test whether adding cetuximab to afatinib would improve PFS over afatinib alone in patients with treatment-naive, EGFR-mutant NSCLC by preventing or delaying resistance.
 

Trial details

The phase 2, multicenter trial included 168 eligible patients with EGFR-mutant NSCLC without prior treatment of advanced disease. The patients’ median age was 66 years (range, 27-93 years), and 66% were women.

The most common histology was adenocarcinoma (96%). EGFR exon 19 deletions were detected in 64% of patients and L858R point mutations in 36%.

Patients were randomly assigned 2:1 to receive afatinib at 40 mg orally daily plus cetuximab at 500 mg/m² intravenously every 2 weeks or afatinib at 40 mg alone. Patients received diphenhydramine at 50 mg intravenously before the first dose of cetuximab to prevent hypersensitivity reaction, and it was recommended before subsequent doses.

Patients continued on treatment until disease progression, symptomatic deterioration, unacceptable toxicity, pregnancy, treatment delay greater than 28 days, or patient decision. The study’s primary endpoint was PFS.
 

Further accrual not supported

At the interim analysis, the SWOG data safety and monitoring committee decided there was insufficient evidence to support further accrual, and the trial was closed.

The primary endpoint analysis revealed a median PFS of 11.9 months in the afatinib/cetuximab group and 13.4 months in the afatinib-alone group (hazard ratio, 1.01; 95% confidence interval, 0.72-1.43; P = .94). A subset analysis showed no PFS differences based on clinical or tumor characteristics.

Overall survival, time to response, and overall response rate were not improved in the afatinib/cetuximab arm.

PFS and overall survival were longer in patients with tumors harboring exon 19 deletions than in patients with L858R mutations. However, there were no mutation subtype–based PFS and overall survival differences between the treatment arms.

Grade 3 or higher treatment-related adverse events were more common in the combination arm than in the monotherapy arm (72% and 40%, respectively; P < .0001).

The most common grade 3 or higher treatment-related adverse events (in the combination and monotherapy arms, respectively) were acneiform rash (27% and 2%), maculopapular rash (13% and 0%), and diarrhea (15% and 20%).

Patients receiving afatinib plus cetuximab required dose reductions more often (56.7% vs. 26.2%), and treatment discontinuation because of an adverse event was more frequent in the combination arm (14% vs. 11%).
 

Turn toward third-generation drug

“Treatment with a single-agent EGFR-TKI remains the standard of care for patients with EGFR-mutant NSCLC,” Dr. Goldberg and colleagues wrote.

Why the combination of afatinib and cetuximab, which has demonstrated activity in the resistance setting, failed in the first-line setting remains unclear, Dr. Goldberg observed in an interview.

She noted that about one-quarter of patients receiving the afatinib/cetuximab combination discontinued cetuximab because of toxicity.

“That’s a good amount. It could be part of the explanation,” Dr. Goldberg said.

Investigators are currently analyzing collected tissue and blood samples in an effort to identify biomarkers that could potentially predict subgroups receiving benefit.

“That’s our next step: looking at specific EGFR mutation types, comutation types, and amplification of other genes and of EGFR,” Dr. Goldberg said.

She noted that, because of a superior side-effect profile and possibly greater efficacy, osimertinib is being used in the first-line setting.

“So now the idea of combining an EGFR-TKI with an EGFR antibody is still an active area of research, but with osimertinib rather than a first- or second-generation drug,” she said.

This research was supported by Boehringer Ingelheim, Eli Lilly, grants from the National Institutes of Health/National Cancer Institute, The Hope Foundation Career Development Award, and the SWOG and NIH Yale SPORE in Lung Cancer Grant. Dr. Goldberg and colleagues disclosed relationships with many pharmaceutical companies.

SOURCE: Goldberg SB et al. J Clin Oncol. 2020 Oct 6. doi: 10.1200/JCO.20.01149.

Combination afatinib and cetuximab did not improve progression-free survival (PFS) over afatinib alone in a phase 2 trial of treatment-naive patients with advanced EGFR-mutant non–small cell lung cancer (NSCLC).

In addition, toxicity was greater with the afatinib/cetuximab combination, according to study author Sarah S. Goldberg, MD, of Yale University, New Haven, Conn.

Dr. Goldberg and colleagues reported these results, from the SWOG S1403 trial, in the Journal of Clinical Oncology.

The authors noted that activating EGFR mutations are present in about 15% of patients with lung adenocarcinomas in Western populations and the mutations confer heightened sensitivity to EGFR tyrosine kinase inhibitors (TKIs). EGFR-TKIs have been shown to improve clinical outcomes, quality of life, and toxicity when compared with chemotherapy.

Based on better outcomes over chemotherapy, the third-generation EGFR-TKI osimertinib is now the standard treatment for patients with T790M-mediated resistance, but osimertinib is not effective in TKI-resistant T790M-negative disease, the authors pointed out.

In a phase 1b trial of patients with EGFR-mutant NSCLC with acquired resistance to first-generation agents, afatinib/cetuximab produced a response rate of 29% and comparable activity regardless of T790M status.

The aim of the SWOG S1403 study was to test whether adding cetuximab to afatinib would improve PFS over afatinib alone in patients with treatment-naive, EGFR-mutant NSCLC by preventing or delaying resistance.
 

Trial details

The phase 2, multicenter trial included 168 eligible patients with EGFR-mutant NSCLC without prior treatment of advanced disease. The patients’ median age was 66 years (range, 27-93 years), and 66% were women.

The most common histology was adenocarcinoma (96%). EGFR exon 19 deletions were detected in 64% of patients and L858R point mutations in 36%.

Patients were randomly assigned 2:1 to receive afatinib at 40 mg orally daily plus cetuximab at 500 mg/m² intravenously every 2 weeks or afatinib at 40 mg alone. Patients received diphenhydramine at 50 mg intravenously before the first dose of cetuximab to prevent hypersensitivity reaction, and it was recommended before subsequent doses.

Patients continued on treatment until disease progression, symptomatic deterioration, unacceptable toxicity, pregnancy, treatment delay greater than 28 days, or patient decision. The study’s primary endpoint was PFS.
 

Further accrual not supported

At the interim analysis, the SWOG data safety and monitoring committee decided there was insufficient evidence to support further accrual, and the trial was closed.

The primary endpoint analysis revealed a median PFS of 11.9 months in the afatinib/cetuximab group and 13.4 months in the afatinib-alone group (hazard ratio, 1.01; 95% confidence interval, 0.72-1.43; P = .94). A subset analysis showed no PFS differences based on clinical or tumor characteristics.

Overall survival, time to response, and overall response rate were not improved in the afatinib/cetuximab arm.

PFS and overall survival were longer in patients with tumors harboring exon 19 deletions than in patients with L858R mutations. However, there were no mutation subtype–based PFS and overall survival differences between the treatment arms.

Grade 3 or higher treatment-related adverse events were more common in the combination arm than in the monotherapy arm (72% and 40%, respectively; P < .0001).

The most common grade 3 or higher treatment-related adverse events (in the combination and monotherapy arms, respectively) were acneiform rash (27% and 2%), maculopapular rash (13% and 0%), and diarrhea (15% and 20%).

Patients receiving afatinib plus cetuximab required dose reductions more often (56.7% vs. 26.2%), and treatment discontinuation because of an adverse event was more frequent in the combination arm (14% vs. 11%).
 

Turn toward third-generation drug

“Treatment with a single-agent EGFR-TKI remains the standard of care for patients with EGFR-mutant NSCLC,” Dr. Goldberg and colleagues wrote.

Why the combination of afatinib and cetuximab, which has demonstrated activity in the resistance setting, failed in the first-line setting remains unclear, Dr. Goldberg observed in an interview.

She noted that about one-quarter of patients receiving the afatinib/cetuximab combination discontinued cetuximab because of toxicity.

“That’s a good amount. It could be part of the explanation,” Dr. Goldberg said.

Investigators are currently analyzing collected tissue and blood samples in an effort to identify biomarkers that could potentially predict subgroups receiving benefit.

“That’s our next step: looking at specific EGFR mutation types, comutation types, and amplification of other genes and of EGFR,” Dr. Goldberg said.

She noted that, because of a superior side-effect profile and possibly greater efficacy, osimertinib is being used in the first-line setting.

“So now the idea of combining an EGFR-TKI with an EGFR antibody is still an active area of research, but with osimertinib rather than a first- or second-generation drug,” she said.

This research was supported by Boehringer Ingelheim, Eli Lilly, grants from the National Institutes of Health/National Cancer Institute, The Hope Foundation Career Development Award, and the SWOG and NIH Yale SPORE in Lung Cancer Grant. Dr. Goldberg and colleagues disclosed relationships with many pharmaceutical companies.

SOURCE: Goldberg SB et al. J Clin Oncol. 2020 Oct 6. doi: 10.1200/JCO.20.01149.

Combination afatinib and cetuximab did not improve progression-free survival (PFS) over afatinib alone in a phase 2 trial of treatment-naive patients with advanced EGFR-mutant non–small cell lung cancer (NSCLC).

In addition, toxicity was greater with the afatinib/cetuximab combination, according to study author Sarah S. Goldberg, MD, of Yale University, New Haven, Conn.

Dr. Goldberg and colleagues reported these results, from the SWOG S1403 trial, in the Journal of Clinical Oncology.

The authors noted that activating EGFR mutations are present in about 15% of patients with lung adenocarcinomas in Western populations and the mutations confer heightened sensitivity to EGFR tyrosine kinase inhibitors (TKIs). EGFR-TKIs have been shown to improve clinical outcomes, quality of life, and toxicity when compared with chemotherapy.

Based on better outcomes over chemotherapy, the third-generation EGFR-TKI osimertinib is now the standard treatment for patients with T790M-mediated resistance, but osimertinib is not effective in TKI-resistant T790M-negative disease, the authors pointed out.

In a phase 1b trial of patients with EGFR-mutant NSCLC with acquired resistance to first-generation agents, afatinib/cetuximab produced a response rate of 29% and comparable activity regardless of T790M status.

The aim of the SWOG S1403 study was to test whether adding cetuximab to afatinib would improve PFS over afatinib alone in patients with treatment-naive, EGFR-mutant NSCLC by preventing or delaying resistance.
 

Trial details

The phase 2, multicenter trial included 168 eligible patients with EGFR-mutant NSCLC without prior treatment of advanced disease. The patients’ median age was 66 years (range, 27-93 years), and 66% were women.

The most common histology was adenocarcinoma (96%). EGFR exon 19 deletions were detected in 64% of patients and L858R point mutations in 36%.

Patients were randomly assigned 2:1 to receive afatinib at 40 mg orally daily plus cetuximab at 500 mg/m² intravenously every 2 weeks or afatinib at 40 mg alone. Patients received diphenhydramine at 50 mg intravenously before the first dose of cetuximab to prevent hypersensitivity reaction, and it was recommended before subsequent doses.

Patients continued on treatment until disease progression, symptomatic deterioration, unacceptable toxicity, pregnancy, treatment delay greater than 28 days, or patient decision. The study’s primary endpoint was PFS.
 

Further accrual not supported

At the interim analysis, the SWOG data safety and monitoring committee decided there was insufficient evidence to support further accrual, and the trial was closed.

The primary endpoint analysis revealed a median PFS of 11.9 months in the afatinib/cetuximab group and 13.4 months in the afatinib-alone group (hazard ratio, 1.01; 95% confidence interval, 0.72-1.43; P = .94). A subset analysis showed no PFS differences based on clinical or tumor characteristics.

Overall survival, time to response, and overall response rate were not improved in the afatinib/cetuximab arm.

PFS and overall survival were longer in patients with tumors harboring exon 19 deletions than in patients with L858R mutations. However, there were no mutation subtype–based PFS and overall survival differences between the treatment arms.

Grade 3 or higher treatment-related adverse events were more common in the combination arm than in the monotherapy arm (72% and 40%, respectively; P < .0001).

The most common grade 3 or higher treatment-related adverse events (in the combination and monotherapy arms, respectively) were acneiform rash (27% and 2%), maculopapular rash (13% and 0%), and diarrhea (15% and 20%).

Patients receiving afatinib plus cetuximab required dose reductions more often (56.7% vs. 26.2%), and treatment discontinuation because of an adverse event was more frequent in the combination arm (14% vs. 11%).
 

Turn toward third-generation drug

“Treatment with a single-agent EGFR-TKI remains the standard of care for patients with EGFR-mutant NSCLC,” Dr. Goldberg and colleagues wrote.

Why the combination of afatinib and cetuximab, which has demonstrated activity in the resistance setting, failed in the first-line setting remains unclear, Dr. Goldberg observed in an interview.

She noted that about one-quarter of patients receiving the afatinib/cetuximab combination discontinued cetuximab because of toxicity.

“That’s a good amount. It could be part of the explanation,” Dr. Goldberg said.

Investigators are currently analyzing collected tissue and blood samples in an effort to identify biomarkers that could potentially predict subgroups receiving benefit.

“That’s our next step: looking at specific EGFR mutation types, comutation types, and amplification of other genes and of EGFR,” Dr. Goldberg said.

She noted that, because of a superior side-effect profile and possibly greater efficacy, osimertinib is being used in the first-line setting.

“So now the idea of combining an EGFR-TKI with an EGFR antibody is still an active area of research, but with osimertinib rather than a first- or second-generation drug,” she said.

This research was supported by Boehringer Ingelheim, Eli Lilly, grants from the National Institutes of Health/National Cancer Institute, The Hope Foundation Career Development Award, and the SWOG and NIH Yale SPORE in Lung Cancer Grant. Dr. Goldberg and colleagues disclosed relationships with many pharmaceutical companies.

SOURCE: Goldberg SB et al. J Clin Oncol. 2020 Oct 6. doi: 10.1200/JCO.20.01149.

The number of primary care providers is increasing per capita in the United States, but they are still disproportionately concentrated in urban centers, researchers say.

The finding may provide some reassurance for those who have worried about a shortage of health care workers and whether they will be able to meet the nation’s growing burden of chronic diseases.

“Access to primary care doctors is critical to population health and to reduce health care disparities in this country,” said Donglan Zhang, PhD, an assistant professor of public health at the University of Georgia, Athens.

However, many counties remain underserved, Dr. Zhang said in an interview. The need for primary care in the United States is increasing not only with population growth but because the population is aging.

Dr. Zhang and colleagues published the finding in JAMA Network Open.

Many previous reports have warned of a shortage in primary care providers. To examine recent trends in the primary care workforce, Dr. Zhang and colleagues obtained data on all the primary care clinicians registered with the Centers for Medicare & Medicaid Services from 2009 to 2017.

For the study, the researchers included general practitioners, family physicians and internists without subspecialties, nurse practitioners, and physician assistants. They then compared the number of providers with the number of residents in each county as recorded by the US Census, using urban or rural classifications for each county from the Centers for Disease Control and Prevention.

Because the U.S. Health Resources and Services Administration defines a primary care “shortage” as fewer than 1 primary care practitioner per 3,500 people, the researchers focused on this ratio. They found that the number of nurse practitioners and physician assistants was increasing much faster than the number of primary care physicians. This was true especially in rural areas, but the percentage increase for both nurse practitioners and physician assistants was lower in rural areas versus urban.

The researchers also found that there were more primary care physicians per capita in counties with higher household incomes, a higher proportion of Asian residents, and a higher proportion of college graduates.

They didn’t find a significant association between the median household income and per capita number of nurse practitioners.

They found that counties with a higher proportion of Black and Asian residents had a higher number of nurse practitioners per capita. But they found an opposite association between the proportion of Black residents and the number of physician assistants per capita.

The authors hypothesized that health care reform, particularly the passage of the Affordable Care Act in 2010, may explain the recent increase in the primary care workforce. The legislation expanded the number of people with health insurance and provided incentives for primary and preventive care.

Another factor behind the increase in the primary care workforce could be state laws that have expanded the scope of practice for nurse practitioners and primary care providers, she said.
 

Numbers may overestimate available care

The gap between rural and urban areas could be even wider than this study suggests, Ada D. Stewart, MD, president of the American Academy of Family Physicians, said in an interview. Many nurse practitioners and physician assistants don’t actually practice primary care, but instead assist physicians in other specialties such as orthopedics or general surgery.

“They are part of a team and I don’t want to diminish that at all, but especially when we talk about infant and maternal mortality, family physicians need to be there themselves providing primary care,” she said. “We’re there in hospitals and emergency rooms, and not just taking care of diabetes and hypertension.”

In addition, the primary care workforce may have been reduced since the conclusion of the study period (Dec. 31, 2017) as a result of the COVID-19 pandemic forcing some primary care physicians into retirement, Dr. Stewart said.

Measures that could help reduce the disparity include a more robust system of teaching health centers in rural counties, higher reimbursement for primary care, a lower cost of medical education, and recruiting more people from rural areas to become physicians, Dr. Stewart said.

Telehealth can enhance health care in rural areas, but many people in rural areas lack internet or cellular service, or don’t have access to computers. “We don’t want to create another healthcare disparity,” she said.

And physicians can get to know their patients’ needs better in a face-to-face visit, she said. “Telehealth does have a place, but it does not replace that person-to-person visit.”

This study was funded by National Institute on Minority Health and Health Disparities. Dr. Zhang and Dr. Stewart disclosed no relevant financial relationships.

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

The number of primary care providers is increasing per capita in the United States, but they are still disproportionately concentrated in urban centers, researchers say.

The finding may provide some reassurance for those who have worried about a shortage of health care workers and whether they will be able to meet the nation’s growing burden of chronic diseases.

“Access to primary care doctors is critical to population health and to reduce health care disparities in this country,” said Donglan Zhang, PhD, an assistant professor of public health at the University of Georgia, Athens.

However, many counties remain underserved, Dr. Zhang said in an interview. The need for primary care in the United States is increasing not only with population growth but because the population is aging.

Dr. Zhang and colleagues published the finding in JAMA Network Open.

Many previous reports have warned of a shortage in primary care providers. To examine recent trends in the primary care workforce, Dr. Zhang and colleagues obtained data on all the primary care clinicians registered with the Centers for Medicare & Medicaid Services from 2009 to 2017.

For the study, the researchers included general practitioners, family physicians and internists without subspecialties, nurse practitioners, and physician assistants. They then compared the number of providers with the number of residents in each county as recorded by the US Census, using urban or rural classifications for each county from the Centers for Disease Control and Prevention.

Because the U.S. Health Resources and Services Administration defines a primary care “shortage” as fewer than 1 primary care practitioner per 3,500 people, the researchers focused on this ratio. They found that the number of nurse practitioners and physician assistants was increasing much faster than the number of primary care physicians. This was true especially in rural areas, but the percentage increase for both nurse practitioners and physician assistants was lower in rural areas versus urban.

The researchers also found that there were more primary care physicians per capita in counties with higher household incomes, a higher proportion of Asian residents, and a higher proportion of college graduates.

They didn’t find a significant association between the median household income and per capita number of nurse practitioners.

They found that counties with a higher proportion of Black and Asian residents had a higher number of nurse practitioners per capita. But they found an opposite association between the proportion of Black residents and the number of physician assistants per capita.

The authors hypothesized that health care reform, particularly the passage of the Affordable Care Act in 2010, may explain the recent increase in the primary care workforce. The legislation expanded the number of people with health insurance and provided incentives for primary and preventive care.

Another factor behind the increase in the primary care workforce could be state laws that have expanded the scope of practice for nurse practitioners and primary care providers, she said.
 

Numbers may overestimate available care

The gap between rural and urban areas could be even wider than this study suggests, Ada D. Stewart, MD, president of the American Academy of Family Physicians, said in an interview. Many nurse practitioners and physician assistants don’t actually practice primary care, but instead assist physicians in other specialties such as orthopedics or general surgery.

“They are part of a team and I don’t want to diminish that at all, but especially when we talk about infant and maternal mortality, family physicians need to be there themselves providing primary care,” she said. “We’re there in hospitals and emergency rooms, and not just taking care of diabetes and hypertension.”

In addition, the primary care workforce may have been reduced since the conclusion of the study period (Dec. 31, 2017) as a result of the COVID-19 pandemic forcing some primary care physicians into retirement, Dr. Stewart said.

Measures that could help reduce the disparity include a more robust system of teaching health centers in rural counties, higher reimbursement for primary care, a lower cost of medical education, and recruiting more people from rural areas to become physicians, Dr. Stewart said.

Telehealth can enhance health care in rural areas, but many people in rural areas lack internet or cellular service, or don’t have access to computers. “We don’t want to create another healthcare disparity,” she said.

And physicians can get to know their patients’ needs better in a face-to-face visit, she said. “Telehealth does have a place, but it does not replace that person-to-person visit.”

This study was funded by National Institute on Minority Health and Health Disparities. Dr. Zhang and Dr. Stewart disclosed no relevant financial relationships.

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

The number of primary care providers is increasing per capita in the United States, but they are still disproportionately concentrated in urban centers, researchers say.

The finding may provide some reassurance for those who have worried about a shortage of health care workers and whether they will be able to meet the nation’s growing burden of chronic diseases.

“Access to primary care doctors is critical to population health and to reduce health care disparities in this country,” said Donglan Zhang, PhD, an assistant professor of public health at the University of Georgia, Athens.

However, many counties remain underserved, Dr. Zhang said in an interview. The need for primary care in the United States is increasing not only with population growth but because the population is aging.

Dr. Zhang and colleagues published the finding in JAMA Network Open.

Many previous reports have warned of a shortage in primary care providers. To examine recent trends in the primary care workforce, Dr. Zhang and colleagues obtained data on all the primary care clinicians registered with the Centers for Medicare & Medicaid Services from 2009 to 2017.

For the study, the researchers included general practitioners, family physicians and internists without subspecialties, nurse practitioners, and physician assistants. They then compared the number of providers with the number of residents in each county as recorded by the US Census, using urban or rural classifications for each county from the Centers for Disease Control and Prevention.

Because the U.S. Health Resources and Services Administration defines a primary care “shortage” as fewer than 1 primary care practitioner per 3,500 people, the researchers focused on this ratio. They found that the number of nurse practitioners and physician assistants was increasing much faster than the number of primary care physicians. This was true especially in rural areas, but the percentage increase for both nurse practitioners and physician assistants was lower in rural areas versus urban.

The researchers also found that there were more primary care physicians per capita in counties with higher household incomes, a higher proportion of Asian residents, and a higher proportion of college graduates.

They didn’t find a significant association between the median household income and per capita number of nurse practitioners.

They found that counties with a higher proportion of Black and Asian residents had a higher number of nurse practitioners per capita. But they found an opposite association between the proportion of Black residents and the number of physician assistants per capita.

The authors hypothesized that health care reform, particularly the passage of the Affordable Care Act in 2010, may explain the recent increase in the primary care workforce. The legislation expanded the number of people with health insurance and provided incentives for primary and preventive care.

Another factor behind the increase in the primary care workforce could be state laws that have expanded the scope of practice for nurse practitioners and primary care providers, she said.
 

Numbers may overestimate available care

The gap between rural and urban areas could be even wider than this study suggests, Ada D. Stewart, MD, president of the American Academy of Family Physicians, said in an interview. Many nurse practitioners and physician assistants don’t actually practice primary care, but instead assist physicians in other specialties such as orthopedics or general surgery.

“They are part of a team and I don’t want to diminish that at all, but especially when we talk about infant and maternal mortality, family physicians need to be there themselves providing primary care,” she said. “We’re there in hospitals and emergency rooms, and not just taking care of diabetes and hypertension.”

In addition, the primary care workforce may have been reduced since the conclusion of the study period (Dec. 31, 2017) as a result of the COVID-19 pandemic forcing some primary care physicians into retirement, Dr. Stewart said.

Measures that could help reduce the disparity include a more robust system of teaching health centers in rural counties, higher reimbursement for primary care, a lower cost of medical education, and recruiting more people from rural areas to become physicians, Dr. Stewart said.

Telehealth can enhance health care in rural areas, but many people in rural areas lack internet or cellular service, or don’t have access to computers. “We don’t want to create another healthcare disparity,” she said.

And physicians can get to know their patients’ needs better in a face-to-face visit, she said. “Telehealth does have a place, but it does not replace that person-to-person visit.”

This study was funded by National Institute on Minority Health and Health Disparities. Dr. Zhang and Dr. Stewart disclosed no relevant financial relationships.

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

A punch biopsy of the markedly erythematous lateral edge helped to confirm this as tumid lupus erythematosus (TLE), a rare subtype of chronic cutaneous lupus erythematosus. TLE occurs in men and women of all ages. Annular or arcuate patches and plaques most often arise on the face, trunk, extremities, and V of the neck after sun exposure. However, as in this case, plaques may appear in areas covered by clothing. Plaques generally do not itch or hurt, but their presence can be alarming.

Annular and arcuate plaques raise a complex differential diagnosis including common conditions such as urticaria and tinea corporis, as well as more uncommon disorders such as erythema annulare centrifugum and lymphoma cutis. Unlike tinea corporis and erythema annulare centrifugum, there is very little, if any, scaling of the superficial epidermis. Plaques heal without scarring or changes to skin pigmentation.

Multiple punch biopsies of affected areas are key to a proper diagnosis. Patients with confirmed TLE should undergo antinuclear antibody testing to rule out systemic lupus erythematosus, although the vast majority will have normal results.

Treatment includes potent or ultrapotent topical steroids for the trunk and extremities, and mid- to low-potency steroids for intertriginous areas or the face. Systemic immunomodulators with hydroxychloroquine are used as first-line treatment for more extensive disease.

In this case, the patient had a normal antinuclear antibody titer and was treated with topical betamethasone dipropionate augmented 0.05% cream bid for 2 weeks, which led to complete clearance. She experienced a flare-up a year later and was retreated with the same results.

‌

Text and photos courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. (Photo copyright retained.)

A punch biopsy of the markedly erythematous lateral edge helped to confirm this as tumid lupus erythematosus (TLE), a rare subtype of chronic cutaneous lupus erythematosus. TLE occurs in men and women of all ages. Annular or arcuate patches and plaques most often arise on the face, trunk, extremities, and V of the neck after sun exposure. However, as in this case, plaques may appear in areas covered by clothing. Plaques generally do not itch or hurt, but their presence can be alarming.

Annular and arcuate plaques raise a complex differential diagnosis including common conditions such as urticaria and tinea corporis, as well as more uncommon disorders such as erythema annulare centrifugum and lymphoma cutis. Unlike tinea corporis and erythema annulare centrifugum, there is very little, if any, scaling of the superficial epidermis. Plaques heal without scarring or changes to skin pigmentation.

Multiple punch biopsies of affected areas are key to a proper diagnosis. Patients with confirmed TLE should undergo antinuclear antibody testing to rule out systemic lupus erythematosus, although the vast majority will have normal results.

Treatment includes potent or ultrapotent topical steroids for the trunk and extremities, and mid- to low-potency steroids for intertriginous areas or the face. Systemic immunomodulators with hydroxychloroquine are used as first-line treatment for more extensive disease.

In this case, the patient had a normal antinuclear antibody titer and was treated with topical betamethasone dipropionate augmented 0.05% cream bid for 2 weeks, which led to complete clearance. She experienced a flare-up a year later and was retreated with the same results.

‌

Text and photos courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. (Photo copyright retained.)

A punch biopsy of the markedly erythematous lateral edge helped to confirm this as tumid lupus erythematosus (TLE), a rare subtype of chronic cutaneous lupus erythematosus. TLE occurs in men and women of all ages. Annular or arcuate patches and plaques most often arise on the face, trunk, extremities, and V of the neck after sun exposure. However, as in this case, plaques may appear in areas covered by clothing. Plaques generally do not itch or hurt, but their presence can be alarming.

Annular and arcuate plaques raise a complex differential diagnosis including common conditions such as urticaria and tinea corporis, as well as more uncommon disorders such as erythema annulare centrifugum and lymphoma cutis. Unlike tinea corporis and erythema annulare centrifugum, there is very little, if any, scaling of the superficial epidermis. Plaques heal without scarring or changes to skin pigmentation.

Multiple punch biopsies of affected areas are key to a proper diagnosis. Patients with confirmed TLE should undergo antinuclear antibody testing to rule out systemic lupus erythematosus, although the vast majority will have normal results.

Treatment includes potent or ultrapotent topical steroids for the trunk and extremities, and mid- to low-potency steroids for intertriginous areas or the face. Systemic immunomodulators with hydroxychloroquine are used as first-line treatment for more extensive disease.

In this case, the patient had a normal antinuclear antibody titer and was treated with topical betamethasone dipropionate augmented 0.05% cream bid for 2 weeks, which led to complete clearance. She experienced a flare-up a year later and was retreated with the same results.

‌

Text and photos courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. (Photo copyright retained.)

Black patients may be significantly less likely to receive eradication testing after treatment for Helicobacter pylori infection than patients of other races/ethnic groups, based on a retrospective analysis of more than 1,700 individuals.

Patho/Wikimedia Commons/CC BY-SA 3.0

This disparity may exacerbate the already increased burden of H. pylori infection and gastric cancer among Black individuals, according to principal author David A. Leiman, MD, MSHP, of Duke University Medical Center in Durham, N.C.

“H. pylori infection disproportionately affects racial/ethnic minorities and those of lower socioeconomic status,” Dr. Leiman, coauthor Julius Wilder, MD, PhD, of Duke University in Durham, and colleagues wrote in their abstract presented at the annual meeting of the American College of Gastroenterology. “ACG guidelines recommend treatment for H. pylori infection followed by confirmation of cure. Adherence to these recommendations varies and its impact on practice patterns is unclear. This study characterizes the management of H. pylori infection and predictors of guideline adherence.”

The investigators analyzed electronic medical records from 1,711 patients diagnosed with H. pylori infection through the Duke University Health System between June 2016 and June 2018, most often (71%) via serum antibody test. Approximately two-thirds of those diagnosed were non-White (66%) and female (63%). Out of 1,711 patients, 622 (36%) underwent eradication testing, of whom 559 (90%) were cured.

Despite publication of the ACG H. pylori guideline midway through the study (February 2017), testing rates dropped significantly from 43.1% in 2016 to 35.9% in 2017, and finally 25.5% in 2018 (P < .0001).

“These findings are consistent with other work that has shown low rates of testing to confirm cure in patients treated for H. pylori,” Dr. Leiman said. “There remains a disappointingly low number of patients who are tested for cure.”

Across the entire study period, patients were significantly more likely to undergo eradication testing if they were treated in the gastroenterology department (52.4%), compared with rates ranging from 33% to 34.6% for internal medicine, family medicine, and other departments (P < .001).

Across all departments, Black patients underwent eradication testing significantly less often than patients of other races/ethnicities, at a rate of 30.5% versus 32.2% for White patients, 35.1% for Asian patients, and 36.7% for patients who were of other backgrounds (P < .001). Compared with White patients, Black patients were 38% less likely to undergo eradication testing (odds ratio, 0.62; 95% confidence interval, 0.48-0.79).

Dr. Leiman noted that these findings contrast with a study by Dr. Shria Kumar and colleagues from earlier this year, which found no racial disparity in eradication testing within a Veterans Health Affairs cohort.

“Black patients are significantly less likely to undergo testing for eradication than [patients of other races/ethnicities],” Dr. Leiman said. “More work is needed to understand the mechanisms driving this disparity.” He suggested a number of possible contributing factors, including provider knowledge gaps, fragmented care, and social determinants of health.

“It is clear that a greater emphasis on characterizing and addressing the social determinants of health, including poverty, education, and location, are needed,” Dr. Leiman said. “Although health systems are not solely responsible for the known and ongoing observations of disparities in care, interventions must be identified and implemented to mitigate these issues.” Such interventions would likely require broad participation, he said, including policy makers, health systems, and individual practitioners.

“We plan to perform a prospective mixed methods study to contextualize which social determinants are associated with a decreased likelihood of receiving appropriate eradication testing by exploring barriers at patient, practitioner, and health-system levels,” Dr. Leiman said. “Ultimately, we aim to leverage these findings to develop an evidence-based intervention to circumnavigate those identified barriers, thereby eliminating the observed disparities in H. pylori care.”

According to Gregory L. Hall, MD, of Northeast Ohio Medical University, Rootstown, and Case Western Reserve University, Cleveland, and codirector of the Partnership for Urban Health Research, Atlanta, the higher rate of H. pylori infection in Black individuals may stem partly from genetic factors.

“Studies have shown that African Americans with a higher proportion of African ancestry have higher rates of H. pylori, suggesting a genetic component to this increased risk,” he said.

Still, Dr. Hall, who is the author of the book Patient-Centered Clinical Care for African Americans, went on to emphasize appropriate H. pylori management and recognition of racial disparities in medicine.

“The ability to test for, treat, and confirm eradication of H. pylori infections represents a great opportunity to improve quality of life through decreased gastritis, gastric ulcers, and gastric cancer,” he said. “[The present findings] show yet another disparity in our clinical care of African Americans that needs increased awareness among providers to these communities.”

Rotonya Carr, MD, of the Hospital of the University of Pennsylvania, Philadelphia, and lead author of a recent publication addressing racism and health disparities in gastroenterology, said the findings of the present study add weight to a known equity gap.

“These data are concerning in view of the twofold higher prevalence of H. pylori seropositivity and twofold higher incidence of gastric cancer in Black patients, compared with White patients,” Dr. Carr said. “These and other data support a comprehensive approach to reduce GI disparities that includes targeted education of both GI specialists and referring providers.”

According to Dr. Leiman, individual practitioners may work toward more equitable outcomes through a comprehensive clinical approach, regardless of patient race or ethnicity.

“Clinicians should consider H. pylori therapy an episode of care that spans diagnosis, treatment, and confirmation of cure,” he said. “Closing the loop in that episode by ensuring eradication is vital to conforming with best practices, and to reduce patients’ long-term risks.”The investigators disclosed relationships with Exact Sciences, Guardant Health, and Phathom Pharmaceuticals. Dr. Hall and Dr. Carr reported no relevant conflicts of interest.

SOURCE: Reichstein J et al. ACG 2020. Abstract S1332.

Black patients may be significantly less likely to receive eradication testing after treatment for Helicobacter pylori infection than patients of other races/ethnic groups, based on a retrospective analysis of more than 1,700 individuals.

Patho/Wikimedia Commons/CC BY-SA 3.0

This disparity may exacerbate the already increased burden of H. pylori infection and gastric cancer among Black individuals, according to principal author David A. Leiman, MD, MSHP, of Duke University Medical Center in Durham, N.C.

“H. pylori infection disproportionately affects racial/ethnic minorities and those of lower socioeconomic status,” Dr. Leiman, coauthor Julius Wilder, MD, PhD, of Duke University in Durham, and colleagues wrote in their abstract presented at the annual meeting of the American College of Gastroenterology. “ACG guidelines recommend treatment for H. pylori infection followed by confirmation of cure. Adherence to these recommendations varies and its impact on practice patterns is unclear. This study characterizes the management of H. pylori infection and predictors of guideline adherence.”

The investigators analyzed electronic medical records from 1,711 patients diagnosed with H. pylori infection through the Duke University Health System between June 2016 and June 2018, most often (71%) via serum antibody test. Approximately two-thirds of those diagnosed were non-White (66%) and female (63%). Out of 1,711 patients, 622 (36%) underwent eradication testing, of whom 559 (90%) were cured.

Despite publication of the ACG H. pylori guideline midway through the study (February 2017), testing rates dropped significantly from 43.1% in 2016 to 35.9% in 2017, and finally 25.5% in 2018 (P < .0001).

“These findings are consistent with other work that has shown low rates of testing to confirm cure in patients treated for H. pylori,” Dr. Leiman said. “There remains a disappointingly low number of patients who are tested for cure.”

Across the entire study period, patients were significantly more likely to undergo eradication testing if they were treated in the gastroenterology department (52.4%), compared with rates ranging from 33% to 34.6% for internal medicine, family medicine, and other departments (P < .001).

Across all departments, Black patients underwent eradication testing significantly less often than patients of other races/ethnicities, at a rate of 30.5% versus 32.2% for White patients, 35.1% for Asian patients, and 36.7% for patients who were of other backgrounds (P < .001). Compared with White patients, Black patients were 38% less likely to undergo eradication testing (odds ratio, 0.62; 95% confidence interval, 0.48-0.79).

Dr. Leiman noted that these findings contrast with a study by Dr. Shria Kumar and colleagues from earlier this year, which found no racial disparity in eradication testing within a Veterans Health Affairs cohort.

“Black patients are significantly less likely to undergo testing for eradication than [patients of other races/ethnicities],” Dr. Leiman said. “More work is needed to understand the mechanisms driving this disparity.” He suggested a number of possible contributing factors, including provider knowledge gaps, fragmented care, and social determinants of health.

“It is clear that a greater emphasis on characterizing and addressing the social determinants of health, including poverty, education, and location, are needed,” Dr. Leiman said. “Although health systems are not solely responsible for the known and ongoing observations of disparities in care, interventions must be identified and implemented to mitigate these issues.” Such interventions would likely require broad participation, he said, including policy makers, health systems, and individual practitioners.

“We plan to perform a prospective mixed methods study to contextualize which social determinants are associated with a decreased likelihood of receiving appropriate eradication testing by exploring barriers at patient, practitioner, and health-system levels,” Dr. Leiman said. “Ultimately, we aim to leverage these findings to develop an evidence-based intervention to circumnavigate those identified barriers, thereby eliminating the observed disparities in H. pylori care.”

According to Gregory L. Hall, MD, of Northeast Ohio Medical University, Rootstown, and Case Western Reserve University, Cleveland, and codirector of the Partnership for Urban Health Research, Atlanta, the higher rate of H. pylori infection in Black individuals may stem partly from genetic factors.

“Studies have shown that African Americans with a higher proportion of African ancestry have higher rates of H. pylori, suggesting a genetic component to this increased risk,” he said.

Still, Dr. Hall, who is the author of the book Patient-Centered Clinical Care for African Americans, went on to emphasize appropriate H. pylori management and recognition of racial disparities in medicine.

“The ability to test for, treat, and confirm eradication of H. pylori infections represents a great opportunity to improve quality of life through decreased gastritis, gastric ulcers, and gastric cancer,” he said. “[The present findings] show yet another disparity in our clinical care of African Americans that needs increased awareness among providers to these communities.”

Rotonya Carr, MD, of the Hospital of the University of Pennsylvania, Philadelphia, and lead author of a recent publication addressing racism and health disparities in gastroenterology, said the findings of the present study add weight to a known equity gap.

“These data are concerning in view of the twofold higher prevalence of H. pylori seropositivity and twofold higher incidence of gastric cancer in Black patients, compared with White patients,” Dr. Carr said. “These and other data support a comprehensive approach to reduce GI disparities that includes targeted education of both GI specialists and referring providers.”

According to Dr. Leiman, individual practitioners may work toward more equitable outcomes through a comprehensive clinical approach, regardless of patient race or ethnicity.

“Clinicians should consider H. pylori therapy an episode of care that spans diagnosis, treatment, and confirmation of cure,” he said. “Closing the loop in that episode by ensuring eradication is vital to conforming with best practices, and to reduce patients’ long-term risks.”The investigators disclosed relationships with Exact Sciences, Guardant Health, and Phathom Pharmaceuticals. Dr. Hall and Dr. Carr reported no relevant conflicts of interest.

SOURCE: Reichstein J et al. ACG 2020. Abstract S1332.

Black patients may be significantly less likely to receive eradication testing after treatment for Helicobacter pylori infection than patients of other races/ethnic groups, based on a retrospective analysis of more than 1,700 individuals.

Patho/Wikimedia Commons/CC BY-SA 3.0

This disparity may exacerbate the already increased burden of H. pylori infection and gastric cancer among Black individuals, according to principal author David A. Leiman, MD, MSHP, of Duke University Medical Center in Durham, N.C.

“H. pylori infection disproportionately affects racial/ethnic minorities and those of lower socioeconomic status,” Dr. Leiman, coauthor Julius Wilder, MD, PhD, of Duke University in Durham, and colleagues wrote in their abstract presented at the annual meeting of the American College of Gastroenterology. “ACG guidelines recommend treatment for H. pylori infection followed by confirmation of cure. Adherence to these recommendations varies and its impact on practice patterns is unclear. This study characterizes the management of H. pylori infection and predictors of guideline adherence.”

The investigators analyzed electronic medical records from 1,711 patients diagnosed with H. pylori infection through the Duke University Health System between June 2016 and June 2018, most often (71%) via serum antibody test. Approximately two-thirds of those diagnosed were non-White (66%) and female (63%). Out of 1,711 patients, 622 (36%) underwent eradication testing, of whom 559 (90%) were cured.

Despite publication of the ACG H. pylori guideline midway through the study (February 2017), testing rates dropped significantly from 43.1% in 2016 to 35.9% in 2017, and finally 25.5% in 2018 (P < .0001).

“These findings are consistent with other work that has shown low rates of testing to confirm cure in patients treated for H. pylori,” Dr. Leiman said. “There remains a disappointingly low number of patients who are tested for cure.”

Across the entire study period, patients were significantly more likely to undergo eradication testing if they were treated in the gastroenterology department (52.4%), compared with rates ranging from 33% to 34.6% for internal medicine, family medicine, and other departments (P < .001).

Across all departments, Black patients underwent eradication testing significantly less often than patients of other races/ethnicities, at a rate of 30.5% versus 32.2% for White patients, 35.1% for Asian patients, and 36.7% for patients who were of other backgrounds (P < .001). Compared with White patients, Black patients were 38% less likely to undergo eradication testing (odds ratio, 0.62; 95% confidence interval, 0.48-0.79).

Dr. Leiman noted that these findings contrast with a study by Dr. Shria Kumar and colleagues from earlier this year, which found no racial disparity in eradication testing within a Veterans Health Affairs cohort.

“Black patients are significantly less likely to undergo testing for eradication than [patients of other races/ethnicities],” Dr. Leiman said. “More work is needed to understand the mechanisms driving this disparity.” He suggested a number of possible contributing factors, including provider knowledge gaps, fragmented care, and social determinants of health.

“It is clear that a greater emphasis on characterizing and addressing the social determinants of health, including poverty, education, and location, are needed,” Dr. Leiman said. “Although health systems are not solely responsible for the known and ongoing observations of disparities in care, interventions must be identified and implemented to mitigate these issues.” Such interventions would likely require broad participation, he said, including policy makers, health systems, and individual practitioners.

“We plan to perform a prospective mixed methods study to contextualize which social determinants are associated with a decreased likelihood of receiving appropriate eradication testing by exploring barriers at patient, practitioner, and health-system levels,” Dr. Leiman said. “Ultimately, we aim to leverage these findings to develop an evidence-based intervention to circumnavigate those identified barriers, thereby eliminating the observed disparities in H. pylori care.”

According to Gregory L. Hall, MD, of Northeast Ohio Medical University, Rootstown, and Case Western Reserve University, Cleveland, and codirector of the Partnership for Urban Health Research, Atlanta, the higher rate of H. pylori infection in Black individuals may stem partly from genetic factors.

“Studies have shown that African Americans with a higher proportion of African ancestry have higher rates of H. pylori, suggesting a genetic component to this increased risk,” he said.

Still, Dr. Hall, who is the author of the book Patient-Centered Clinical Care for African Americans, went on to emphasize appropriate H. pylori management and recognition of racial disparities in medicine.

“The ability to test for, treat, and confirm eradication of H. pylori infections represents a great opportunity to improve quality of life through decreased gastritis, gastric ulcers, and gastric cancer,” he said. “[The present findings] show yet another disparity in our clinical care of African Americans that needs increased awareness among providers to these communities.”

Rotonya Carr, MD, of the Hospital of the University of Pennsylvania, Philadelphia, and lead author of a recent publication addressing racism and health disparities in gastroenterology, said the findings of the present study add weight to a known equity gap.

“These data are concerning in view of the twofold higher prevalence of H. pylori seropositivity and twofold higher incidence of gastric cancer in Black patients, compared with White patients,” Dr. Carr said. “These and other data support a comprehensive approach to reduce GI disparities that includes targeted education of both GI specialists and referring providers.”

According to Dr. Leiman, individual practitioners may work toward more equitable outcomes through a comprehensive clinical approach, regardless of patient race or ethnicity.

“Clinicians should consider H. pylori therapy an episode of care that spans diagnosis, treatment, and confirmation of cure,” he said. “Closing the loop in that episode by ensuring eradication is vital to conforming with best practices, and to reduce patients’ long-term risks.”The investigators disclosed relationships with Exact Sciences, Guardant Health, and Phathom Pharmaceuticals. Dr. Hall and Dr. Carr reported no relevant conflicts of interest.

SOURCE: Reichstein J et al. ACG 2020. Abstract S1332.

The Oct. 5, 2020 move by the Food and Drug Administration’s Center for Drug Evaluation and Research (CDER) suggesting the withdrawal of the approval of Makena incited some opposition.

herjua/Thinkstock

Amag Pharmaceuticals’ 17 alpha-hydroxyprogesterone caproate (17OHP) injection received accelerated approval in 2011 to reduce the risk of recurrent preterm birth in women with previous unexplained preterm birth. Makena is the only drug approved for preventing recurrent preterm birth.
 

The back story

The approval was based on findings from a randomized, placebo-controlled trial that demonstrated a 34% relative risk reduction in births before 37 weeks – from 55% in the placebo arm to 36% in the 17OHP-treated arm.

The trial was not designed to measure neonatal outcomes, with the surrogate outcome of recurrent preterm birth being determined as “reasonably likely” to predict benefit to the neonate.

Subsequently, results of the required postapproval confirmatory PROLONG trialproduced conflicting results, failing to show a benefit of 17OHP on either preterm birth or neonatal outcome, which prompted the proposed withdrawal of the drug’s approval.

The CDER advisory committee agreed unanimously that the PROLONG trial did not support the clinical benefit of 17OHP, but the committee was not unanimous in deciding what to do. Of the 16 members, 9 voted to withdraw the drug’s approval, while seven voted to retain it and require another confirmatory trial.

When CDER recommends withdrawal, the company can request a public hearing, which it has done. The FDA commissioner will recommend whether to grant this request.

In the meantime, the New England Journal of Medicine has published opposing views on withdrawal of FDA approval of 170HP: one from a group of three doctors who are against it and the other from the CDER.
 

Arguments from the opposing views

“We sympathize with women who are at risk for recurrent preterm birth that could result in death or significant lifelong health effects in neonates, but retaining on the market a drug not shown to be effective for this use does not protect or promote their health,” wrote Christina Chang, MD, MPH and associates from CDER.

On the other hand, “the widespread use of 17OHP after accelerated approval has not uncovered important safety signals,” countered Michael F. Greene, MD, from Massachusetts General Hospital, Boston; David Harrington, PhD, from the Harvard T. Chan School of Public Health, Boston; and Mark A. Klebanoff, MD, MPH, who was coauthor on the original preapproval study and is with Nationwide Children’s Hospital, the Ohio State University College of Medicine, and Ohio State University College of Public Health, all in Columbus. “Withdrawal of the approval for 17OHP, as imperfect as it may be, will leave a very vulnerable demographic group of U.S. women at high risk for this complication of pregnancy with absolutely no available therapeutic option.”

While both the preapproval study and postapproval PROLONG trial had the same enrollment criteria – namely women with a singleton pregnancy and previous singleton spontaneous preterm birth – all parties acknowledged that the studies ended up with very different cohorts. Approval of the drug in the United States made it difficult to recruit U.S. participants for the second trial “because of a lack of equipoise perceived by health care providers and patients,” noted Dr. Greene and associates, resulting in 75% of the PROLONG study’s cohort coming from Europe. This meant that 59% of those in the first study were non-Hispanic black compared with just 6.6% in the PROLONG study, a difference that is important because of the increased risk of preterm birth in Black women.

“Black women are generally underrepresented in U.S. clinical trials, and they are clearly underrepresented in the PROLONG study,” noted Dr. Greene and colleagues, adding that “the total number of qualifying composite neonatal outcome events among Blacks or African Americans in the entire PROLONG study population of 1,700 participants was 9 (6 of 69 in the 17OHP group and 3 of 40 in the placebo group). This is not a robust database from which to conclude that there is no effect in Black women.”

But, Dr. Chang and the CDER group argued, while the first study showed 17OHP “reduced the risk of recurrent preterm birth in both Black and non-Black participants, the lack of even a trend toward efficacy among either Black or non-Black women in [the PROLONG study] argues that the smaller proportion of Black women [in the PROLONG study] does not explain the lack of efficacy.”

In addition to race, there were other risk factors for preterm birth, such as tobacco, alcohol, and street drug use; marital status; and age that differed between the two study cohorts. Even after subcategorizing PROLONG trial participants into higher or lower risk for preterm birth based on these risk factors, Dr. Chang and associates still found no evidence of benefit to 17OHP treatment in any risk group.

Withdrawing approval of 17OHP for a recurrent preterm indication would still allow off-label prescribing, but would most likely end insurance coverage and eventually manufacturing of the drug, noted Dr. Greene and associates.

“When the majority of a population achieves little benefit from a drug, but a minority demographic group at greatest risk for a serious medical problem appears to obtain significant benefit, any decision that will ultimately make it impossible to obtain the drug should be undertaken cautiously,” they warned. “This issue is particularly pressing when that minority group may be the least able to find and financially afford work-arounds to obtain the needed medication in our complex medical system that has a history of failing to serve them well.”

Dr. Chang and associates reported they had no relevant financial disclosures. Dr. Greene and associates reported that they had no relevant conflicts of interest or financial disclosures. Dr. Greene reported he is employed by the New England Journal of Medicine as associate editor. Dr. Harrington reported being employed by the journal as statistical consultant. Dr. Klebanoff reported he was an author of the original article about 17OHP published in the journal and referenced in this article.
 

The Oct. 5, 2020 move by the Food and Drug Administration’s Center for Drug Evaluation and Research (CDER) suggesting the withdrawal of the approval of Makena incited some opposition.

herjua/Thinkstock

Amag Pharmaceuticals’ 17 alpha-hydroxyprogesterone caproate (17OHP) injection received accelerated approval in 2011 to reduce the risk of recurrent preterm birth in women with previous unexplained preterm birth. Makena is the only drug approved for preventing recurrent preterm birth.
 

The back story

The approval was based on findings from a randomized, placebo-controlled trial that demonstrated a 34% relative risk reduction in births before 37 weeks – from 55% in the placebo arm to 36% in the 17OHP-treated arm.

The trial was not designed to measure neonatal outcomes, with the surrogate outcome of recurrent preterm birth being determined as “reasonably likely” to predict benefit to the neonate.

Subsequently, results of the required postapproval confirmatory PROLONG trialproduced conflicting results, failing to show a benefit of 17OHP on either preterm birth or neonatal outcome, which prompted the proposed withdrawal of the drug’s approval.

The CDER advisory committee agreed unanimously that the PROLONG trial did not support the clinical benefit of 17OHP, but the committee was not unanimous in deciding what to do. Of the 16 members, 9 voted to withdraw the drug’s approval, while seven voted to retain it and require another confirmatory trial.

When CDER recommends withdrawal, the company can request a public hearing, which it has done. The FDA commissioner will recommend whether to grant this request.

In the meantime, the New England Journal of Medicine has published opposing views on withdrawal of FDA approval of 170HP: one from a group of three doctors who are against it and the other from the CDER.
 

Arguments from the opposing views

“We sympathize with women who are at risk for recurrent preterm birth that could result in death or significant lifelong health effects in neonates, but retaining on the market a drug not shown to be effective for this use does not protect or promote their health,” wrote Christina Chang, MD, MPH and associates from CDER.

On the other hand, “the widespread use of 17OHP after accelerated approval has not uncovered important safety signals,” countered Michael F. Greene, MD, from Massachusetts General Hospital, Boston; David Harrington, PhD, from the Harvard T. Chan School of Public Health, Boston; and Mark A. Klebanoff, MD, MPH, who was coauthor on the original preapproval study and is with Nationwide Children’s Hospital, the Ohio State University College of Medicine, and Ohio State University College of Public Health, all in Columbus. “Withdrawal of the approval for 17OHP, as imperfect as it may be, will leave a very vulnerable demographic group of U.S. women at high risk for this complication of pregnancy with absolutely no available therapeutic option.”

While both the preapproval study and postapproval PROLONG trial had the same enrollment criteria – namely women with a singleton pregnancy and previous singleton spontaneous preterm birth – all parties acknowledged that the studies ended up with very different cohorts. Approval of the drug in the United States made it difficult to recruit U.S. participants for the second trial “because of a lack of equipoise perceived by health care providers and patients,” noted Dr. Greene and associates, resulting in 75% of the PROLONG study’s cohort coming from Europe. This meant that 59% of those in the first study were non-Hispanic black compared with just 6.6% in the PROLONG study, a difference that is important because of the increased risk of preterm birth in Black women.

“Black women are generally underrepresented in U.S. clinical trials, and they are clearly underrepresented in the PROLONG study,” noted Dr. Greene and colleagues, adding that “the total number of qualifying composite neonatal outcome events among Blacks or African Americans in the entire PROLONG study population of 1,700 participants was 9 (6 of 69 in the 17OHP group and 3 of 40 in the placebo group). This is not a robust database from which to conclude that there is no effect in Black women.”

But, Dr. Chang and the CDER group argued, while the first study showed 17OHP “reduced the risk of recurrent preterm birth in both Black and non-Black participants, the lack of even a trend toward efficacy among either Black or non-Black women in [the PROLONG study] argues that the smaller proportion of Black women [in the PROLONG study] does not explain the lack of efficacy.”

In addition to race, there were other risk factors for preterm birth, such as tobacco, alcohol, and street drug use; marital status; and age that differed between the two study cohorts. Even after subcategorizing PROLONG trial participants into higher or lower risk for preterm birth based on these risk factors, Dr. Chang and associates still found no evidence of benefit to 17OHP treatment in any risk group.

Withdrawing approval of 17OHP for a recurrent preterm indication would still allow off-label prescribing, but would most likely end insurance coverage and eventually manufacturing of the drug, noted Dr. Greene and associates.

“When the majority of a population achieves little benefit from a drug, but a minority demographic group at greatest risk for a serious medical problem appears to obtain significant benefit, any decision that will ultimately make it impossible to obtain the drug should be undertaken cautiously,” they warned. “This issue is particularly pressing when that minority group may be the least able to find and financially afford work-arounds to obtain the needed medication in our complex medical system that has a history of failing to serve them well.”

Dr. Chang and associates reported they had no relevant financial disclosures. Dr. Greene and associates reported that they had no relevant conflicts of interest or financial disclosures. Dr. Greene reported he is employed by the New England Journal of Medicine as associate editor. Dr. Harrington reported being employed by the journal as statistical consultant. Dr. Klebanoff reported he was an author of the original article about 17OHP published in the journal and referenced in this article.
 

The Oct. 5, 2020 move by the Food and Drug Administration’s Center for Drug Evaluation and Research (CDER) suggesting the withdrawal of the approval of Makena incited some opposition.

herjua/Thinkstock

Amag Pharmaceuticals’ 17 alpha-hydroxyprogesterone caproate (17OHP) injection received accelerated approval in 2011 to reduce the risk of recurrent preterm birth in women with previous unexplained preterm birth. Makena is the only drug approved for preventing recurrent preterm birth.
 

The back story

The approval was based on findings from a randomized, placebo-controlled trial that demonstrated a 34% relative risk reduction in births before 37 weeks – from 55% in the placebo arm to 36% in the 17OHP-treated arm.

The trial was not designed to measure neonatal outcomes, with the surrogate outcome of recurrent preterm birth being determined as “reasonably likely” to predict benefit to the neonate.

Subsequently, results of the required postapproval confirmatory PROLONG trialproduced conflicting results, failing to show a benefit of 17OHP on either preterm birth or neonatal outcome, which prompted the proposed withdrawal of the drug’s approval.

The CDER advisory committee agreed unanimously that the PROLONG trial did not support the clinical benefit of 17OHP, but the committee was not unanimous in deciding what to do. Of the 16 members, 9 voted to withdraw the drug’s approval, while seven voted to retain it and require another confirmatory trial.

When CDER recommends withdrawal, the company can request a public hearing, which it has done. The FDA commissioner will recommend whether to grant this request.

In the meantime, the New England Journal of Medicine has published opposing views on withdrawal of FDA approval of 170HP: one from a group of three doctors who are against it and the other from the CDER.
 

Arguments from the opposing views

“We sympathize with women who are at risk for recurrent preterm birth that could result in death or significant lifelong health effects in neonates, but retaining on the market a drug not shown to be effective for this use does not protect or promote their health,” wrote Christina Chang, MD, MPH and associates from CDER.

On the other hand, “the widespread use of 17OHP after accelerated approval has not uncovered important safety signals,” countered Michael F. Greene, MD, from Massachusetts General Hospital, Boston; David Harrington, PhD, from the Harvard T. Chan School of Public Health, Boston; and Mark A. Klebanoff, MD, MPH, who was coauthor on the original preapproval study and is with Nationwide Children’s Hospital, the Ohio State University College of Medicine, and Ohio State University College of Public Health, all in Columbus. “Withdrawal of the approval for 17OHP, as imperfect as it may be, will leave a very vulnerable demographic group of U.S. women at high risk for this complication of pregnancy with absolutely no available therapeutic option.”

While both the preapproval study and postapproval PROLONG trial had the same enrollment criteria – namely women with a singleton pregnancy and previous singleton spontaneous preterm birth – all parties acknowledged that the studies ended up with very different cohorts. Approval of the drug in the United States made it difficult to recruit U.S. participants for the second trial “because of a lack of equipoise perceived by health care providers and patients,” noted Dr. Greene and associates, resulting in 75% of the PROLONG study’s cohort coming from Europe. This meant that 59% of those in the first study were non-Hispanic black compared with just 6.6% in the PROLONG study, a difference that is important because of the increased risk of preterm birth in Black women.

“Black women are generally underrepresented in U.S. clinical trials, and they are clearly underrepresented in the PROLONG study,” noted Dr. Greene and colleagues, adding that “the total number of qualifying composite neonatal outcome events among Blacks or African Americans in the entire PROLONG study population of 1,700 participants was 9 (6 of 69 in the 17OHP group and 3 of 40 in the placebo group). This is not a robust database from which to conclude that there is no effect in Black women.”

But, Dr. Chang and the CDER group argued, while the first study showed 17OHP “reduced the risk of recurrent preterm birth in both Black and non-Black participants, the lack of even a trend toward efficacy among either Black or non-Black women in [the PROLONG study] argues that the smaller proportion of Black women [in the PROLONG study] does not explain the lack of efficacy.”

In addition to race, there were other risk factors for preterm birth, such as tobacco, alcohol, and street drug use; marital status; and age that differed between the two study cohorts. Even after subcategorizing PROLONG trial participants into higher or lower risk for preterm birth based on these risk factors, Dr. Chang and associates still found no evidence of benefit to 17OHP treatment in any risk group.

Withdrawing approval of 17OHP for a recurrent preterm indication would still allow off-label prescribing, but would most likely end insurance coverage and eventually manufacturing of the drug, noted Dr. Greene and associates.

“When the majority of a population achieves little benefit from a drug, but a minority demographic group at greatest risk for a serious medical problem appears to obtain significant benefit, any decision that will ultimately make it impossible to obtain the drug should be undertaken cautiously,” they warned. “This issue is particularly pressing when that minority group may be the least able to find and financially afford work-arounds to obtain the needed medication in our complex medical system that has a history of failing to serve them well.”

Dr. Chang and associates reported they had no relevant financial disclosures. Dr. Greene and associates reported that they had no relevant conflicts of interest or financial disclosures. Dr. Greene reported he is employed by the New England Journal of Medicine as associate editor. Dr. Harrington reported being employed by the journal as statistical consultant. Dr. Klebanoff reported he was an author of the original article about 17OHP published in the journal and referenced in this article.
 

Editors in chief at 10 leading family medicine journals have banded together to address systemic racism in research, health care, and the medical profession.

Sumi Sexton, MD, editor in chief of American Family Physician (AFP), said in an interview she had been working on changes at her journal that would answer the need for action that was made clear by this summer’s Black Lives Matter protests and realized the issue was much bigger than one journal. She proposed the collaboration with the other editors.

The editors wrote a joint statement explaining what they plan to do collectively. It was published online Oct. 15 ahead of print and will be published in all 10 journals at the beginning of the year.

Following the action by family medicine editors, the American College of Physicians issued a statement expressing commitment to being an antiracist organization. It calls on all doctors to speak out against hate and discrimination and to act against institutional and systemic racism. The statement also apologizes for the organization’s own past actions: “ACP acknowledges and regrets its own historical organizational injustices and inequities, and past racism, discrimination and exclusionary practices throughout its history, whether intentional or unintentional, by act or omission.”


 

Family medicine journals plan changes

Changes will differ at each family medicine publication, according to Sexton and other interviewees. Some specific changes at AFP, for example, include creating a medical editor role dedicated to diversity, equity, and inclusion to ensure that content is not only accurate but also that more content addresses racism, Dr. Sexton said.

AFP is creating a Web page dedicated to diversity and will now capitalize the word “Black” in racial and cultural references. Recent calls for papers have included emphasis on finding authors from underrepresented groups and on mentoring new authors.

“We really need to enable our colleagues,” Dr. Sexton said.

The journals are also pooling their published research on topics of racism and inclusion and have established a joint bibliography.

The steps are important, Dr. Sexton said, because reform in research will start a “cascade of action” that will result in better patient care.

“Our mission is to care for the individual as a whole person,” Dr. Sexton said. “This is part of that mission.”
 

Increasing diversity on editorial boards

Family physician Kameron Leigh Matthews, MD, chief medical officer for the Veterans Health Administration, praised the journals’ plan.

She noted that the groups are addressing diversity on their editorial boards, as well as evaluating content. Effective change must also happen regarding the people reviewing the content, she said in an interview. “It has to be both.

“I’m very proud as a family physician that our editors came together and are giving the right response. It’s not enough to say we stand against racism. They’re actually offering concrete actions that they will take as editors, and that will influence health care,” she said.

Dr. Matthews pointed to an example of what can happen when the editorial process fails and racism is introduced in research.

She cited the retraction of an article in the Journal of the American Heart Association entitled, “Evolution of Race and Ethnicity Considerations for the Cardiology Workforce.” The article advocated for ending racial and ethnic preferences in undergraduate and medical school admissions.

The American Heart Association said the article concluded “incorrectly that Black and Hispanic trainees in medicine are less qualified than White and Asian trainees.” The article had “rightfully drawn criticism for its misrepresentations and conclusions,” the AHA said, adding that it would launch an investigation into how the article came to be published.

Dr. Matthews says that’s why it’s so important that, in their statement, the family medicine editors vow to address not only the content but also the editing process to avoid similar systemic lapses.

Dr. Matthews added that, because the proportion of physicians from underrepresented groups is small – only 5% of physicians are Black and 6% are Hispanic – it is vital, as recommended in the editors’ statement, to mentor researchers from underrepresented groups and to reach out to students and residents to be coauthors.

“To sit back and say there’s not enough to recruit from is not sufficient,” Dr. Matthews said. “You need to recognize that you need to assist with expanding the pool.”

She also said she would like to see the journals focus more heavily on solutions to racial disparities in health care rather than on pointing them out.

At the Journal of Family Practice (JFP), Editor in Chief John Hickner, MD, said adding diversity to the editorial board is a top priority. He also reiterated that diversity in top leadership is a concern across all the journals, inasmuch as only 1 of the 10 editors in chief is a person of color.

As an editor, he said, he will personally, as well as through family medicine department chairs, be seeking authors who are members of underrepresented groups and that he will be assisting those who need help.

“I’m committed to giving them special attention in the editorial process,” he said.

Dr. Hickner said the 10 journals have also committed to periodically evaluate whether their approaches are making substantial changes. He said the editors have vowed to meet at least once a year to review progress “and hold each other accountable.”

Statement authors, in addition to Dr. Sexton and Dr. Hickner, include these editors in chief: Caroline R. Richardson, MD, Annals of Family Medicine; Sarina B. Schrager, MD, FPM; Marjorie A. Bowman, MD, The Journal of the American Board of Family Medicine; Christopher P. Morley, PhD, PRiMER; Nicholas Pimlott, MD, PhD, Canadian Family Physician; John W. Saultz, MD, Family Medicine; and Barry D. Weiss, MD, FP Essentials.

The authors have disclosed no relevant financial relationships. The Journal of Family Practice is owned by the same news organization as this publication.
 

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

Editors in chief at 10 leading family medicine journals have banded together to address systemic racism in research, health care, and the medical profession.

Sumi Sexton, MD, editor in chief of American Family Physician (AFP), said in an interview she had been working on changes at her journal that would answer the need for action that was made clear by this summer’s Black Lives Matter protests and realized the issue was much bigger than one journal. She proposed the collaboration with the other editors.

The editors wrote a joint statement explaining what they plan to do collectively. It was published online Oct. 15 ahead of print and will be published in all 10 journals at the beginning of the year.

Following the action by family medicine editors, the American College of Physicians issued a statement expressing commitment to being an antiracist organization. It calls on all doctors to speak out against hate and discrimination and to act against institutional and systemic racism. The statement also apologizes for the organization’s own past actions: “ACP acknowledges and regrets its own historical organizational injustices and inequities, and past racism, discrimination and exclusionary practices throughout its history, whether intentional or unintentional, by act or omission.”


 

Family medicine journals plan changes

Changes will differ at each family medicine publication, according to Sexton and other interviewees. Some specific changes at AFP, for example, include creating a medical editor role dedicated to diversity, equity, and inclusion to ensure that content is not only accurate but also that more content addresses racism, Dr. Sexton said.

AFP is creating a Web page dedicated to diversity and will now capitalize the word “Black” in racial and cultural references. Recent calls for papers have included emphasis on finding authors from underrepresented groups and on mentoring new authors.

“We really need to enable our colleagues,” Dr. Sexton said.

The journals are also pooling their published research on topics of racism and inclusion and have established a joint bibliography.

The steps are important, Dr. Sexton said, because reform in research will start a “cascade of action” that will result in better patient care.

“Our mission is to care for the individual as a whole person,” Dr. Sexton said. “This is part of that mission.”
 

Increasing diversity on editorial boards

Family physician Kameron Leigh Matthews, MD, chief medical officer for the Veterans Health Administration, praised the journals’ plan.

She noted that the groups are addressing diversity on their editorial boards, as well as evaluating content. Effective change must also happen regarding the people reviewing the content, she said in an interview. “It has to be both.

“I’m very proud as a family physician that our editors came together and are giving the right response. It’s not enough to say we stand against racism. They’re actually offering concrete actions that they will take as editors, and that will influence health care,” she said.

Dr. Matthews pointed to an example of what can happen when the editorial process fails and racism is introduced in research.

She cited the retraction of an article in the Journal of the American Heart Association entitled, “Evolution of Race and Ethnicity Considerations for the Cardiology Workforce.” The article advocated for ending racial and ethnic preferences in undergraduate and medical school admissions.

The American Heart Association said the article concluded “incorrectly that Black and Hispanic trainees in medicine are less qualified than White and Asian trainees.” The article had “rightfully drawn criticism for its misrepresentations and conclusions,” the AHA said, adding that it would launch an investigation into how the article came to be published.

Dr. Matthews says that’s why it’s so important that, in their statement, the family medicine editors vow to address not only the content but also the editing process to avoid similar systemic lapses.

Dr. Matthews added that, because the proportion of physicians from underrepresented groups is small – only 5% of physicians are Black and 6% are Hispanic – it is vital, as recommended in the editors’ statement, to mentor researchers from underrepresented groups and to reach out to students and residents to be coauthors.

“To sit back and say there’s not enough to recruit from is not sufficient,” Dr. Matthews said. “You need to recognize that you need to assist with expanding the pool.”

She also said she would like to see the journals focus more heavily on solutions to racial disparities in health care rather than on pointing them out.

At the Journal of Family Practice (JFP), Editor in Chief John Hickner, MD, said adding diversity to the editorial board is a top priority. He also reiterated that diversity in top leadership is a concern across all the journals, inasmuch as only 1 of the 10 editors in chief is a person of color.

As an editor, he said, he will personally, as well as through family medicine department chairs, be seeking authors who are members of underrepresented groups and that he will be assisting those who need help.

“I’m committed to giving them special attention in the editorial process,” he said.

Dr. Hickner said the 10 journals have also committed to periodically evaluate whether their approaches are making substantial changes. He said the editors have vowed to meet at least once a year to review progress “and hold each other accountable.”

Statement authors, in addition to Dr. Sexton and Dr. Hickner, include these editors in chief: Caroline R. Richardson, MD, Annals of Family Medicine; Sarina B. Schrager, MD, FPM; Marjorie A. Bowman, MD, The Journal of the American Board of Family Medicine; Christopher P. Morley, PhD, PRiMER; Nicholas Pimlott, MD, PhD, Canadian Family Physician; John W. Saultz, MD, Family Medicine; and Barry D. Weiss, MD, FP Essentials.

The authors have disclosed no relevant financial relationships. The Journal of Family Practice is owned by the same news organization as this publication.
 

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

Editors in chief at 10 leading family medicine journals have banded together to address systemic racism in research, health care, and the medical profession.

Sumi Sexton, MD, editor in chief of American Family Physician (AFP), said in an interview she had been working on changes at her journal that would answer the need for action that was made clear by this summer’s Black Lives Matter protests and realized the issue was much bigger than one journal. She proposed the collaboration with the other editors.

The editors wrote a joint statement explaining what they plan to do collectively. It was published online Oct. 15 ahead of print and will be published in all 10 journals at the beginning of the year.

Following the action by family medicine editors, the American College of Physicians issued a statement expressing commitment to being an antiracist organization. It calls on all doctors to speak out against hate and discrimination and to act against institutional and systemic racism. The statement also apologizes for the organization’s own past actions: “ACP acknowledges and regrets its own historical organizational injustices and inequities, and past racism, discrimination and exclusionary practices throughout its history, whether intentional or unintentional, by act or omission.”


 

Family medicine journals plan changes

Changes will differ at each family medicine publication, according to Sexton and other interviewees. Some specific changes at AFP, for example, include creating a medical editor role dedicated to diversity, equity, and inclusion to ensure that content is not only accurate but also that more content addresses racism, Dr. Sexton said.

AFP is creating a Web page dedicated to diversity and will now capitalize the word “Black” in racial and cultural references. Recent calls for papers have included emphasis on finding authors from underrepresented groups and on mentoring new authors.

“We really need to enable our colleagues,” Dr. Sexton said.

The journals are also pooling their published research on topics of racism and inclusion and have established a joint bibliography.

The steps are important, Dr. Sexton said, because reform in research will start a “cascade of action” that will result in better patient care.

“Our mission is to care for the individual as a whole person,” Dr. Sexton said. “This is part of that mission.”
 

Increasing diversity on editorial boards

Family physician Kameron Leigh Matthews, MD, chief medical officer for the Veterans Health Administration, praised the journals’ plan.

She noted that the groups are addressing diversity on their editorial boards, as well as evaluating content. Effective change must also happen regarding the people reviewing the content, she said in an interview. “It has to be both.

“I’m very proud as a family physician that our editors came together and are giving the right response. It’s not enough to say we stand against racism. They’re actually offering concrete actions that they will take as editors, and that will influence health care,” she said.

Dr. Matthews pointed to an example of what can happen when the editorial process fails and racism is introduced in research.

She cited the retraction of an article in the Journal of the American Heart Association entitled, “Evolution of Race and Ethnicity Considerations for the Cardiology Workforce.” The article advocated for ending racial and ethnic preferences in undergraduate and medical school admissions.

The American Heart Association said the article concluded “incorrectly that Black and Hispanic trainees in medicine are less qualified than White and Asian trainees.” The article had “rightfully drawn criticism for its misrepresentations and conclusions,” the AHA said, adding that it would launch an investigation into how the article came to be published.

Dr. Matthews says that’s why it’s so important that, in their statement, the family medicine editors vow to address not only the content but also the editing process to avoid similar systemic lapses.

Dr. Matthews added that, because the proportion of physicians from underrepresented groups is small – only 5% of physicians are Black and 6% are Hispanic – it is vital, as recommended in the editors’ statement, to mentor researchers from underrepresented groups and to reach out to students and residents to be coauthors.

“To sit back and say there’s not enough to recruit from is not sufficient,” Dr. Matthews said. “You need to recognize that you need to assist with expanding the pool.”

She also said she would like to see the journals focus more heavily on solutions to racial disparities in health care rather than on pointing them out.

At the Journal of Family Practice (JFP), Editor in Chief John Hickner, MD, said adding diversity to the editorial board is a top priority. He also reiterated that diversity in top leadership is a concern across all the journals, inasmuch as only 1 of the 10 editors in chief is a person of color.

As an editor, he said, he will personally, as well as through family medicine department chairs, be seeking authors who are members of underrepresented groups and that he will be assisting those who need help.

“I’m committed to giving them special attention in the editorial process,” he said.

Dr. Hickner said the 10 journals have also committed to periodically evaluate whether their approaches are making substantial changes. He said the editors have vowed to meet at least once a year to review progress “and hold each other accountable.”

Statement authors, in addition to Dr. Sexton and Dr. Hickner, include these editors in chief: Caroline R. Richardson, MD, Annals of Family Medicine; Sarina B. Schrager, MD, FPM; Marjorie A. Bowman, MD, The Journal of the American Board of Family Medicine; Christopher P. Morley, PhD, PRiMER; Nicholas Pimlott, MD, PhD, Canadian Family Physician; John W. Saultz, MD, Family Medicine; and Barry D. Weiss, MD, FP Essentials.

The authors have disclosed no relevant financial relationships. The Journal of Family Practice is owned by the same news organization as this publication.
 

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

Wildfires burned millions of acres in California, Oregon, and Washington this year. Record numbers of tropical storms and hurricanes formed in the Atlantic. “Climate change is here. Disasters are here. They are going to be increasing, which is why we want to talk about this and talk about how pediatricians can help and respond to these events,” Scott Needle, MD, said at the annual meeting American Academy of Pediatrics, held virtually this year.

SounderBruce/flickr.com/CC BY-SA 2.0

“We have seen from past disasters that people look to us ... as a trusted source of information,” said Dr. Needle, chief medical officer of Elica Health Centers in Sacramento, California. “We can be a positive influence in terms of getting out proactive messaging and keeping people informed.”

The Federal Emergency Management Agency (FEMA) 2019 National Household Survey found that about half of households had an emergency plan. A theme across surveys is that, although households take some steps to get ready for disasters, the public generally “is not as prepared for these events as they really need to be,” Dr. Needle said.

The AAP, the Red Cross, and FEMA are among the organizations that offer planning guides, most of which emphasize three simple things: have a kit, have a plan, and be informed, he said.

To prepare for a disaster, parents might refill a child’s medications ahead of time if possible, Dr. Needle suggested. And during the COVID-19 pandemic, families should add masks, sanitizers, and wipes to their go-bags.

Physicians also can help families by asking how they are coping.
 

Wildfire smoke

“Smoke from wildfires can blanket large, large areas,” Mark Miller, MD, MPH, said during the presentation at the AAP meeting. “This year, we have seen wildfire smoke from the western states reach all the way to the East Coast. So this impacts your patients and your own families sometimes, regardless of wherever you live.”

Children may be more vulnerable to wildfire smoke because they often spend more time outdoors and tend to be more active. In addition, their ongoing development means exposure to air pollutants could have lifelong consequences, said Dr. Miller, who recently reviewed the effects of wildfire smoke on children.

“Children with asthma should have some information about wildfires built into their asthma management plan,” said Dr. Miller, who is affiliated with Western States Pediatric Environmental Health Specialty Unit (PEHSU) and University of California, San Francisco. Pollutants are associated with respiratory visits and admissions, asthma exacerbations, decreased lung function, and neurocognitive effects. They also may be carcinogenic.

A study in monkeys found that smoke exposure during California wildfires in 2008 was associated with immune dysregulation and compromised lung function in adolescence.

Another study of three cohorts of children in southern California found that air pollutant levels were associated with children’s lung function.

Organizations have provided resources on creating cleaner air spaces during wildfires, including guides to build DIY air filter fans. AirNow.gov provides air quality and fire maps that can inform decisions about school closures and outdoor activities. Communities should prioritize establishing schools as clean air shelters, Dr. Miller suggested.

Studies have found that respirators and medical masks may decrease children’s exposure to smoke. Children should not use face coverings, however, if they are younger than 2 years, if they are not able to remove the face covering on their own or tell an adult that they need help, or if they have difficulty breathing with a face covering. Younger children should be observed by an adult.

During the pandemic, families should be aware that some types of masks are sold only for health care use, many foreign respirators are counterfeit, and cloth masks used for COVID-19 are not suitable for reducing wildfire smoke exposure, Dr. Miller said.
 

Hazards may linger

Long-term mental health issues may be the disaster consequence that pediatricians encounter most often, Dr. Needle said.

Eighteen months after a major wildfire in Canada, more than one-third of middle and high school students in one community had probable posttraumatic stress disorder (that is, intrusive thoughts, avoidance, and increased arousal). In addition, 31% of students had probable depression. Rates were elevated relative to a control group of students in another community that was not affected by the fire.

Findings indicate that a patient’s degree of exposure to a disaster affects the likelihood of adverse outcomes. On the other hand, resiliency may help mitigate adverse effects. “The hope is that if we can find ways to encourage resiliency before or in the aftermath of an event, we may be able to, in a sense, reduce some of these mental health sequelae,” Dr. Needle said.

Posttraumatic reactions in kids are likely after a disaster. “They may not rise to the level of a diagnosable condition, but they are very common in kids,” he said. “It is important to at least be able to counsel parents to recognize some of the common reactions,” such as acting withdrawn or aggressive, somatic complaints, and having trouble sleeping.

The AAP has a policy statement that encourages talking to children about their concerns with honest and age-appropriate responses, he noted.

When returning to an area after a disaster, many hazards may remain, such as floodwaters, ash pits, mold, and carbon monoxide from generators. “Generally speaking, you don’t want to have kids return to these areas until it is safe,” Dr. Needle said.

Exacerbation of existing conditions – perhaps because of lost medications, smoke exposure, or stress – may be another common problem. Other problems after a disaster could include domestic violence (direct or witnessed) and substance abuse.

“We have a responsibility to take care of our own health as well,” Dr. Needle added. “You can’t take care of others if you’re not taking care of yourself. It’s not being selfish. As a matter of fact, it’s being prudent. It’s survival.”

Dr. Needle and Dr. Miller had no relevant financial disclosures. Dr. Miller’s presentation was supported by the AAP and funded in part by the Agency for Toxic Substances and Disease Registry. The U.S. Environmental Protection Agency (EPA) provides funding support for the Pediatric Environmental Health Specialty Unit.

[email protected]

Wildfires burned millions of acres in California, Oregon, and Washington this year. Record numbers of tropical storms and hurricanes formed in the Atlantic. “Climate change is here. Disasters are here. They are going to be increasing, which is why we want to talk about this and talk about how pediatricians can help and respond to these events,” Scott Needle, MD, said at the annual meeting American Academy of Pediatrics, held virtually this year.

SounderBruce/flickr.com/CC BY-SA 2.0

“We have seen from past disasters that people look to us ... as a trusted source of information,” said Dr. Needle, chief medical officer of Elica Health Centers in Sacramento, California. “We can be a positive influence in terms of getting out proactive messaging and keeping people informed.”

The Federal Emergency Management Agency (FEMA) 2019 National Household Survey found that about half of households had an emergency plan. A theme across surveys is that, although households take some steps to get ready for disasters, the public generally “is not as prepared for these events as they really need to be,” Dr. Needle said.

The AAP, the Red Cross, and FEMA are among the organizations that offer planning guides, most of which emphasize three simple things: have a kit, have a plan, and be informed, he said.

To prepare for a disaster, parents might refill a child’s medications ahead of time if possible, Dr. Needle suggested. And during the COVID-19 pandemic, families should add masks, sanitizers, and wipes to their go-bags.

Physicians also can help families by asking how they are coping.
 

Wildfire smoke

“Smoke from wildfires can blanket large, large areas,” Mark Miller, MD, MPH, said during the presentation at the AAP meeting. “This year, we have seen wildfire smoke from the western states reach all the way to the East Coast. So this impacts your patients and your own families sometimes, regardless of wherever you live.”

Children may be more vulnerable to wildfire smoke because they often spend more time outdoors and tend to be more active. In addition, their ongoing development means exposure to air pollutants could have lifelong consequences, said Dr. Miller, who recently reviewed the effects of wildfire smoke on children.

“Children with asthma should have some information about wildfires built into their asthma management plan,” said Dr. Miller, who is affiliated with Western States Pediatric Environmental Health Specialty Unit (PEHSU) and University of California, San Francisco. Pollutants are associated with respiratory visits and admissions, asthma exacerbations, decreased lung function, and neurocognitive effects. They also may be carcinogenic.

A study in monkeys found that smoke exposure during California wildfires in 2008 was associated with immune dysregulation and compromised lung function in adolescence.

Another study of three cohorts of children in southern California found that air pollutant levels were associated with children’s lung function.

Organizations have provided resources on creating cleaner air spaces during wildfires, including guides to build DIY air filter fans. AirNow.gov provides air quality and fire maps that can inform decisions about school closures and outdoor activities. Communities should prioritize establishing schools as clean air shelters, Dr. Miller suggested.

Studies have found that respirators and medical masks may decrease children’s exposure to smoke. Children should not use face coverings, however, if they are younger than 2 years, if they are not able to remove the face covering on their own or tell an adult that they need help, or if they have difficulty breathing with a face covering. Younger children should be observed by an adult.

During the pandemic, families should be aware that some types of masks are sold only for health care use, many foreign respirators are counterfeit, and cloth masks used for COVID-19 are not suitable for reducing wildfire smoke exposure, Dr. Miller said.
 

Hazards may linger

Long-term mental health issues may be the disaster consequence that pediatricians encounter most often, Dr. Needle said.

Eighteen months after a major wildfire in Canada, more than one-third of middle and high school students in one community had probable posttraumatic stress disorder (that is, intrusive thoughts, avoidance, and increased arousal). In addition, 31% of students had probable depression. Rates were elevated relative to a control group of students in another community that was not affected by the fire.

Findings indicate that a patient’s degree of exposure to a disaster affects the likelihood of adverse outcomes. On the other hand, resiliency may help mitigate adverse effects. “The hope is that if we can find ways to encourage resiliency before or in the aftermath of an event, we may be able to, in a sense, reduce some of these mental health sequelae,” Dr. Needle said.

Posttraumatic reactions in kids are likely after a disaster. “They may not rise to the level of a diagnosable condition, but they are very common in kids,” he said. “It is important to at least be able to counsel parents to recognize some of the common reactions,” such as acting withdrawn or aggressive, somatic complaints, and having trouble sleeping.

The AAP has a policy statement that encourages talking to children about their concerns with honest and age-appropriate responses, he noted.

When returning to an area after a disaster, many hazards may remain, such as floodwaters, ash pits, mold, and carbon monoxide from generators. “Generally speaking, you don’t want to have kids return to these areas until it is safe,” Dr. Needle said.

Exacerbation of existing conditions – perhaps because of lost medications, smoke exposure, or stress – may be another common problem. Other problems after a disaster could include domestic violence (direct or witnessed) and substance abuse.

“We have a responsibility to take care of our own health as well,” Dr. Needle added. “You can’t take care of others if you’re not taking care of yourself. It’s not being selfish. As a matter of fact, it’s being prudent. It’s survival.”

Dr. Needle and Dr. Miller had no relevant financial disclosures. Dr. Miller’s presentation was supported by the AAP and funded in part by the Agency for Toxic Substances and Disease Registry. The U.S. Environmental Protection Agency (EPA) provides funding support for the Pediatric Environmental Health Specialty Unit.

[email protected]

Wildfires burned millions of acres in California, Oregon, and Washington this year. Record numbers of tropical storms and hurricanes formed in the Atlantic. “Climate change is here. Disasters are here. They are going to be increasing, which is why we want to talk about this and talk about how pediatricians can help and respond to these events,” Scott Needle, MD, said at the annual meeting American Academy of Pediatrics, held virtually this year.

SounderBruce/flickr.com/CC BY-SA 2.0

“We have seen from past disasters that people look to us ... as a trusted source of information,” said Dr. Needle, chief medical officer of Elica Health Centers in Sacramento, California. “We can be a positive influence in terms of getting out proactive messaging and keeping people informed.”

The Federal Emergency Management Agency (FEMA) 2019 National Household Survey found that about half of households had an emergency plan. A theme across surveys is that, although households take some steps to get ready for disasters, the public generally “is not as prepared for these events as they really need to be,” Dr. Needle said.

The AAP, the Red Cross, and FEMA are among the organizations that offer planning guides, most of which emphasize three simple things: have a kit, have a plan, and be informed, he said.

To prepare for a disaster, parents might refill a child’s medications ahead of time if possible, Dr. Needle suggested. And during the COVID-19 pandemic, families should add masks, sanitizers, and wipes to their go-bags.

Physicians also can help families by asking how they are coping.
 

Wildfire smoke

“Smoke from wildfires can blanket large, large areas,” Mark Miller, MD, MPH, said during the presentation at the AAP meeting. “This year, we have seen wildfire smoke from the western states reach all the way to the East Coast. So this impacts your patients and your own families sometimes, regardless of wherever you live.”

Children may be more vulnerable to wildfire smoke because they often spend more time outdoors and tend to be more active. In addition, their ongoing development means exposure to air pollutants could have lifelong consequences, said Dr. Miller, who recently reviewed the effects of wildfire smoke on children.

“Children with asthma should have some information about wildfires built into their asthma management plan,” said Dr. Miller, who is affiliated with Western States Pediatric Environmental Health Specialty Unit (PEHSU) and University of California, San Francisco. Pollutants are associated with respiratory visits and admissions, asthma exacerbations, decreased lung function, and neurocognitive effects. They also may be carcinogenic.

A study in monkeys found that smoke exposure during California wildfires in 2008 was associated with immune dysregulation and compromised lung function in adolescence.

Another study of three cohorts of children in southern California found that air pollutant levels were associated with children’s lung function.

Organizations have provided resources on creating cleaner air spaces during wildfires, including guides to build DIY air filter fans. AirNow.gov provides air quality and fire maps that can inform decisions about school closures and outdoor activities. Communities should prioritize establishing schools as clean air shelters, Dr. Miller suggested.

Studies have found that respirators and medical masks may decrease children’s exposure to smoke. Children should not use face coverings, however, if they are younger than 2 years, if they are not able to remove the face covering on their own or tell an adult that they need help, or if they have difficulty breathing with a face covering. Younger children should be observed by an adult.

During the pandemic, families should be aware that some types of masks are sold only for health care use, many foreign respirators are counterfeit, and cloth masks used for COVID-19 are not suitable for reducing wildfire smoke exposure, Dr. Miller said.
 

Hazards may linger

Long-term mental health issues may be the disaster consequence that pediatricians encounter most often, Dr. Needle said.

Eighteen months after a major wildfire in Canada, more than one-third of middle and high school students in one community had probable posttraumatic stress disorder (that is, intrusive thoughts, avoidance, and increased arousal). In addition, 31% of students had probable depression. Rates were elevated relative to a control group of students in another community that was not affected by the fire.

Findings indicate that a patient’s degree of exposure to a disaster affects the likelihood of adverse outcomes. On the other hand, resiliency may help mitigate adverse effects. “The hope is that if we can find ways to encourage resiliency before or in the aftermath of an event, we may be able to, in a sense, reduce some of these mental health sequelae,” Dr. Needle said.

Posttraumatic reactions in kids are likely after a disaster. “They may not rise to the level of a diagnosable condition, but they are very common in kids,” he said. “It is important to at least be able to counsel parents to recognize some of the common reactions,” such as acting withdrawn or aggressive, somatic complaints, and having trouble sleeping.

The AAP has a policy statement that encourages talking to children about their concerns with honest and age-appropriate responses, he noted.

When returning to an area after a disaster, many hazards may remain, such as floodwaters, ash pits, mold, and carbon monoxide from generators. “Generally speaking, you don’t want to have kids return to these areas until it is safe,” Dr. Needle said.

Exacerbation of existing conditions – perhaps because of lost medications, smoke exposure, or stress – may be another common problem. Other problems after a disaster could include domestic violence (direct or witnessed) and substance abuse.

“We have a responsibility to take care of our own health as well,” Dr. Needle added. “You can’t take care of others if you’re not taking care of yourself. It’s not being selfish. As a matter of fact, it’s being prudent. It’s survival.”

Dr. Needle and Dr. Miller had no relevant financial disclosures. Dr. Miller’s presentation was supported by the AAP and funded in part by the Agency for Toxic Substances and Disease Registry. The U.S. Environmental Protection Agency (EPA) provides funding support for the Pediatric Environmental Health Specialty Unit.

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