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Most Potentially Hepatotoxic Meds Revealed: Real-World Data Analysis
TOPLINE:
An analysis of real-world evidence identified 17 medications, many not previously regarded as potentially hepatotoxic, that have high incidence rates of patient hospitalization for acute liver injury (ALI), offering insights on how to better determine which drugs carry the most significant risk and warrant liver monitoring.
METHODOLOGY:
- Without a systematic approach to classifying medications’ hepatotoxic risk, researchers have used case reports published on the National Institutes of Health’s LiverTox, which doesn’t account for the number of people exposed, to categorize drugs’ likelihood of causing ALI. The objective was to identify the most potentially hepatotoxic medications using real-world incidence rates of severe ALI.
- Researchers analyzed US Department of Veterans Affairs electronic health record data for almost 7.9 million individuals (mean age, 64.4 years; 92.5% men) without preexisting liver or biliary disease who were initiated in an outpatient setting on any one of 194 medications with four or more published reports of hepatotoxicity. Drugs delivered by injection or intravenously, prescribed for alcohol use disorder or liver disease treatment, or used as an anticoagulant were not included in the study.
- The primary outcome measured was hospitalization for severe ALI, defined by alanine aminotransferase levels > 120 U/L and total bilirubin levels > 2.0 mg/dL or the international normalized ratio ≥ 1.5 and total bilirubin levels > 2.0 mg/dL within the first 2 days of admission.
- Researchers organized the medications into groups on the basis of observed rates of severe ALI per 10,000 person-years and classified drugs with 10 or more hospitalizations (group 1) and 5-9.9 hospitalizations (group 2) as the most potentially hepatotoxic. The study period was October 2000 through September 2021.
TAKEAWAY:
- Among the study population, 1739 hospitalizations for severe ALI were identified. Incidence rates of severe ALI varied widely by medication, from 0 to 86.4 events per 10,000 person-years.
- Seventeen medications were classified as the most potentially hepatotoxic (groups 1 and 2). Seven of them (stavudine, erlotinib, lenalidomide or thalidomide, chlorpromazine, metronidazole, prochlorperazine, and isoniazid) had incidence rates of ≥ 10 events per 10,000 person-years. The other 10 medications (moxifloxacin, azathioprine, levofloxacin, clarithromycin, ketoconazole, fluconazole, captopril, amoxicillin-clavulanate, sulfamethoxazole-trimethoprim, and ciprofloxacin) showed incidence rates of 5-9.9 events per 10,000 person-years.
- Of the 17 most hepatotoxic medications, 11 (64%) were not classified as highly hepatotoxic in the published case reports, suggesting a discrepancy between real-world data and case report categorizations.
- Similarly, several medications, including some statins, identified as low-risk in this study were classified as among the most hepatotoxic in the published case reports.
IN PRACTICE:
“Categorization of hepatotoxicity based on the number of published case reports did not accurately reflect observed rates of severe ALI (acute liver injury),” the researchers wrote. “This study represents a systematic, reproducible approach to using real-world data to measure rates of severe ALI following medication initiation among patients without liver or biliary disease…Patients initiating a medication with a high rate of severe ALI might require closer monitoring of liver-related laboratory tests to detect evolving hepatic dysfunction earlier, which might improve prognosis.”
The study illustrates the potential to use electronic health record data to “revolutionize how we characterize drug-related toxic effects,” not just on the liver but other organs, Grace Y. Zhang, MD, and Jessica B. Rubin, MD, MPH, of the University of California, San Francisco, wrote in an accompanying editorial. “If curated and disseminated effectively…such evidence will undoubtedly improve clinical decision-making and allow for more informed patient counseling regarding the true risks of starting or discontinuing medications.
SOURCE:
The study, led by Jessie Torgersen, MD, MHS, MSCE, of the Division of Infectious Diseases, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, was published online in JAMA Internal Medicine.
LIMITATIONS:
The researchers listed several limitations, including the possibility that reliance on laboratory tests for ascertainment of acute liver injuries could introduce surveillance bias. The study focused on a population predominantly consisting of men without preexisting liver or biliary disease, so the findings may not be generalizable to women or individuals with liver disease. Additionally, researchers did not perform a causality assessment of all outcomes, did not study medications with fewer than four published case reports, and did not evaluate the influence of dosage.
DISCLOSURES:
This study was partly funded by several grants from the National Institutes of Health. Some authors declared receiving grants and personal fees from some of the funding agencies and other sources outside of this work.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
An analysis of real-world evidence identified 17 medications, many not previously regarded as potentially hepatotoxic, that have high incidence rates of patient hospitalization for acute liver injury (ALI), offering insights on how to better determine which drugs carry the most significant risk and warrant liver monitoring.
METHODOLOGY:
- Without a systematic approach to classifying medications’ hepatotoxic risk, researchers have used case reports published on the National Institutes of Health’s LiverTox, which doesn’t account for the number of people exposed, to categorize drugs’ likelihood of causing ALI. The objective was to identify the most potentially hepatotoxic medications using real-world incidence rates of severe ALI.
- Researchers analyzed US Department of Veterans Affairs electronic health record data for almost 7.9 million individuals (mean age, 64.4 years; 92.5% men) without preexisting liver or biliary disease who were initiated in an outpatient setting on any one of 194 medications with four or more published reports of hepatotoxicity. Drugs delivered by injection or intravenously, prescribed for alcohol use disorder or liver disease treatment, or used as an anticoagulant were not included in the study.
- The primary outcome measured was hospitalization for severe ALI, defined by alanine aminotransferase levels > 120 U/L and total bilirubin levels > 2.0 mg/dL or the international normalized ratio ≥ 1.5 and total bilirubin levels > 2.0 mg/dL within the first 2 days of admission.
- Researchers organized the medications into groups on the basis of observed rates of severe ALI per 10,000 person-years and classified drugs with 10 or more hospitalizations (group 1) and 5-9.9 hospitalizations (group 2) as the most potentially hepatotoxic. The study period was October 2000 through September 2021.
TAKEAWAY:
- Among the study population, 1739 hospitalizations for severe ALI were identified. Incidence rates of severe ALI varied widely by medication, from 0 to 86.4 events per 10,000 person-years.
- Seventeen medications were classified as the most potentially hepatotoxic (groups 1 and 2). Seven of them (stavudine, erlotinib, lenalidomide or thalidomide, chlorpromazine, metronidazole, prochlorperazine, and isoniazid) had incidence rates of ≥ 10 events per 10,000 person-years. The other 10 medications (moxifloxacin, azathioprine, levofloxacin, clarithromycin, ketoconazole, fluconazole, captopril, amoxicillin-clavulanate, sulfamethoxazole-trimethoprim, and ciprofloxacin) showed incidence rates of 5-9.9 events per 10,000 person-years.
- Of the 17 most hepatotoxic medications, 11 (64%) were not classified as highly hepatotoxic in the published case reports, suggesting a discrepancy between real-world data and case report categorizations.
- Similarly, several medications, including some statins, identified as low-risk in this study were classified as among the most hepatotoxic in the published case reports.
IN PRACTICE:
“Categorization of hepatotoxicity based on the number of published case reports did not accurately reflect observed rates of severe ALI (acute liver injury),” the researchers wrote. “This study represents a systematic, reproducible approach to using real-world data to measure rates of severe ALI following medication initiation among patients without liver or biliary disease…Patients initiating a medication with a high rate of severe ALI might require closer monitoring of liver-related laboratory tests to detect evolving hepatic dysfunction earlier, which might improve prognosis.”
The study illustrates the potential to use electronic health record data to “revolutionize how we characterize drug-related toxic effects,” not just on the liver but other organs, Grace Y. Zhang, MD, and Jessica B. Rubin, MD, MPH, of the University of California, San Francisco, wrote in an accompanying editorial. “If curated and disseminated effectively…such evidence will undoubtedly improve clinical decision-making and allow for more informed patient counseling regarding the true risks of starting or discontinuing medications.
SOURCE:
The study, led by Jessie Torgersen, MD, MHS, MSCE, of the Division of Infectious Diseases, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, was published online in JAMA Internal Medicine.
LIMITATIONS:
The researchers listed several limitations, including the possibility that reliance on laboratory tests for ascertainment of acute liver injuries could introduce surveillance bias. The study focused on a population predominantly consisting of men without preexisting liver or biliary disease, so the findings may not be generalizable to women or individuals with liver disease. Additionally, researchers did not perform a causality assessment of all outcomes, did not study medications with fewer than four published case reports, and did not evaluate the influence of dosage.
DISCLOSURES:
This study was partly funded by several grants from the National Institutes of Health. Some authors declared receiving grants and personal fees from some of the funding agencies and other sources outside of this work.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
An analysis of real-world evidence identified 17 medications, many not previously regarded as potentially hepatotoxic, that have high incidence rates of patient hospitalization for acute liver injury (ALI), offering insights on how to better determine which drugs carry the most significant risk and warrant liver monitoring.
METHODOLOGY:
- Without a systematic approach to classifying medications’ hepatotoxic risk, researchers have used case reports published on the National Institutes of Health’s LiverTox, which doesn’t account for the number of people exposed, to categorize drugs’ likelihood of causing ALI. The objective was to identify the most potentially hepatotoxic medications using real-world incidence rates of severe ALI.
- Researchers analyzed US Department of Veterans Affairs electronic health record data for almost 7.9 million individuals (mean age, 64.4 years; 92.5% men) without preexisting liver or biliary disease who were initiated in an outpatient setting on any one of 194 medications with four or more published reports of hepatotoxicity. Drugs delivered by injection or intravenously, prescribed for alcohol use disorder or liver disease treatment, or used as an anticoagulant were not included in the study.
- The primary outcome measured was hospitalization for severe ALI, defined by alanine aminotransferase levels > 120 U/L and total bilirubin levels > 2.0 mg/dL or the international normalized ratio ≥ 1.5 and total bilirubin levels > 2.0 mg/dL within the first 2 days of admission.
- Researchers organized the medications into groups on the basis of observed rates of severe ALI per 10,000 person-years and classified drugs with 10 or more hospitalizations (group 1) and 5-9.9 hospitalizations (group 2) as the most potentially hepatotoxic. The study period was October 2000 through September 2021.
TAKEAWAY:
- Among the study population, 1739 hospitalizations for severe ALI were identified. Incidence rates of severe ALI varied widely by medication, from 0 to 86.4 events per 10,000 person-years.
- Seventeen medications were classified as the most potentially hepatotoxic (groups 1 and 2). Seven of them (stavudine, erlotinib, lenalidomide or thalidomide, chlorpromazine, metronidazole, prochlorperazine, and isoniazid) had incidence rates of ≥ 10 events per 10,000 person-years. The other 10 medications (moxifloxacin, azathioprine, levofloxacin, clarithromycin, ketoconazole, fluconazole, captopril, amoxicillin-clavulanate, sulfamethoxazole-trimethoprim, and ciprofloxacin) showed incidence rates of 5-9.9 events per 10,000 person-years.
- Of the 17 most hepatotoxic medications, 11 (64%) were not classified as highly hepatotoxic in the published case reports, suggesting a discrepancy between real-world data and case report categorizations.
- Similarly, several medications, including some statins, identified as low-risk in this study were classified as among the most hepatotoxic in the published case reports.
IN PRACTICE:
“Categorization of hepatotoxicity based on the number of published case reports did not accurately reflect observed rates of severe ALI (acute liver injury),” the researchers wrote. “This study represents a systematic, reproducible approach to using real-world data to measure rates of severe ALI following medication initiation among patients without liver or biliary disease…Patients initiating a medication with a high rate of severe ALI might require closer monitoring of liver-related laboratory tests to detect evolving hepatic dysfunction earlier, which might improve prognosis.”
The study illustrates the potential to use electronic health record data to “revolutionize how we characterize drug-related toxic effects,” not just on the liver but other organs, Grace Y. Zhang, MD, and Jessica B. Rubin, MD, MPH, of the University of California, San Francisco, wrote in an accompanying editorial. “If curated and disseminated effectively…such evidence will undoubtedly improve clinical decision-making and allow for more informed patient counseling regarding the true risks of starting or discontinuing medications.
SOURCE:
The study, led by Jessie Torgersen, MD, MHS, MSCE, of the Division of Infectious Diseases, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, was published online in JAMA Internal Medicine.
LIMITATIONS:
The researchers listed several limitations, including the possibility that reliance on laboratory tests for ascertainment of acute liver injuries could introduce surveillance bias. The study focused on a population predominantly consisting of men without preexisting liver or biliary disease, so the findings may not be generalizable to women or individuals with liver disease. Additionally, researchers did not perform a causality assessment of all outcomes, did not study medications with fewer than four published case reports, and did not evaluate the influence of dosage.
DISCLOSURES:
This study was partly funded by several grants from the National Institutes of Health. Some authors declared receiving grants and personal fees from some of the funding agencies and other sources outside of this work.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
Brazilian Peppertree: Watch Out for This Lesser-Known Relative of Poison Ivy
Brazilian peppertree (Schinus terebinthifolia), a member of the Anacardiaceae family, is an internationally invasive plant that causes allergic contact dermatitis (ACD) in susceptible individuals. This noxious weed has settled into the landscape of the southern United States and continues to expand. Its key identifying features include its year-round white flowers as well as a peppery and turpentinelike aroma created by cracking its bright red berries. The ACD associated with contact—primarily with the plant’s sap—stems from known alkenyl phenols, cardol and cardanol. Treatment of Brazilian peppertree–associated ACD parallels that for poison ivy. As this pest increases its range, dermatologists living in endemic areas should familiarize themselves with Brazilian peppertree and its potential for harm.
Brazilian Peppertree Morphology and Geography
Plants in the Anacardiaceae family contribute to more ACD than any other family, and its 80 genera include most of the urushiol-containing plants, such as Toxicodendron (poison ivy, poison oak, poison sumac, Japanese lacquer tree), Anacardium (cashew tree), Mangifera (mango fruit), Semecarpus (India marking nut tree), and Schinus (Brazilian peppertree). Deciduous and evergreen tree members of the Anacardiaceae family grow primarily in tropical and subtropical locations and produce thick resins, 5-petalled flowers, and small fruit known as drupes. The genus name for Brazilian peppertree, Schinus, derives from Latin and Greek words meaning “mastic tree,” a relative of the pistachio tree that the Brazilian peppertree resembles.1 Brazilian peppertree leaves look and smell similar to Pistacia terebinthus (turpentine tree or terebinth), from which the species name terebinthifolia derives.2
Brazilian peppertree originated in South America, particularly Brazil, Paraguay, and Argentina.3 Since the 1840s,4 it has been an invasive weed in the United States, notably in Florida, California, Hawaii, Alabama, Georgia,5 Arizona,6 Nevada,3 and Texas.5,7 The plant also grows throughout the world, including parts of Africa, Asia, Central America, Europe,6 New Zealand,8 Australia, and various islands.9 The plant expertly outcompetes neighboring plants and has prompted control and eradication efforts in many locations.3
Identifying Features and Allergenic Plant Parts
Brazilian peppertree can be either a shrub or tree up to 30 feet tall.4 As an evergreen, it retains its leaves year-round. During fruiting seasons (primarily December through March7), bright red or pink (depending on the variety3) berries appear (Figure 1A) and contribute to its nickname “Florida holly.” Although generally considered an unwelcome guest in Florida, it does display white flowers (Figure 1B) year-round, especially from September to November.9 It characteristically exhibits 3 to 13 leaflets per leaf.10 The leaflets’ ovoid and ridged edges, netlike vasculature, shiny hue, and aroma can help identify the plant (Figure 2A). For decades, the sap of the Brazilian peppertree has been associated with skin irritation (Figure 2B).6 Although the sap of the plant serves as the main culprit of Brazilian peppertree–associated ACD, it appears that other parts of the plant, including the fruit, can cause irritating effects to skin on contact.11,12 The leaves, trunk, and fruit can be harmful to both humans and animals.6 Chemicals from flowers and crushed fruit also can lead to irritating effects in the respiratory tract if aspirated.13
Urushiol, an oily resin present in most plants of the Anacardiaceae family,14 contains many chemicals, including allergenic phenols, catechols, and resorcinols.15 Urushiol-allergic individuals develop dermatitis upon exposure to Brazilian peppertree sap.6 Alkenyl phenols found in Brazilian peppertree lead to the cutaneous manifestations in sensitized patients.11,12 In 1983, Stahl et al11 identified a phenol, cardanol (chemical name 3-pentadecylphenol16) C15:1, in Brazilian peppertree fruit. The group further tested this compound’s effect on skin via patch testing, which showed an allergic response.11 Cashew nut shells (Anacardium occidentale) contain cardanol, anacardic acid (a phenolic acid), and cardol (a phenol with the chemical name 5-pentadecylresorcinol),15,16 though Stahl et al11 were unable to extract these 2 substances (if present) from Brazilian peppertree fruit. When exposed to cardol and anacardic acid, those allergic to poison ivy often develop ACD,15 and these 2 substances are more irritating than cardanol.11 A later study did identify cardol in addition to cardanol in Brazilian peppertree.12
Cutaneous Manifestations
Brazilian peppertree–induced ACD appears similar to other plant-induced ACD with linear streaks of erythema, juicy papules, vesicles, coalescing erythematous plaques, and/or occasional edema and bullae accompanied by intense pruritus.
Treatment
Avoiding contact with Brazilian peppertree is the first line of defense, and treatment for a reaction associated with exposure is similar to that of poison ivy.17 Application of cool compresses, calamine lotion, and topical astringents offer symptom alleviation, and topical steroids (eg, clobetasol propionate 0.05% twice daily) can improve mild localized ACD when given prior to formation of blisters. For more severe and diffuse ACD, oral steroids (eg, prednisone 1 mg/kg/d tapered over 2–3 weeks) likely are necessary, though intramuscular options greatly alleviate discomfort in more severe cases (eg, intramuscular triamcinolone acetonide 1 mg/kg combined with betamethasone 0.1 mg/kg). Physicians should monitor sites for any signs of superimposed bacterial infection and initiate antibiotics as necessary.17
- Zona S. The correct gender of Schinus (Anacardiaceae). Phytotaxa. 2015;222:075-077.
- Terebinth. Encyclopedia.com website. Updated May 17, 2018. Accessed July 9, 2024. https://www.encyclopedia.com/plants-and-animals/plants/plants/terebinth
- Brazilian pepper tree. iNaturalist website. Accessed July 1, 2024. https://www.inaturalist.org/guide_taxa/841531#:~:text=Throughout% 20South%20and%20Central%20America,and%20as%20a%20topical%20antiseptic
- Center for Aquatic and Invasive Plants. Schinus terebinthifolia. Brazilian peppertree. Accessed July 1, 2024. https://plants.ifas.ufl.edu/plant-directory/schinus-terebinthifolia/#:~:text=Species%20Overview&text=People%20sensitive%20to%20poison%20ivy,associated%20with%20its%20bloom%20period
- Brazilian peppertree (Schinus terebinthifolia). Early Detection & Distribution Mapping System. Accessed July 4, 2024. https://www.eddmaps.org/distribution/usstate.cfm?sub=78819
- Morton F. Brazilian pepper: its impact on people, animals, and the environment. Econ Bot. 1978;32:353-359.
- Fire Effects Information System. Schinus terebinthifolius. US Department of Agriculture website. Accessed July 4, 2024. https://www.fs.usda.gov/database/feis/plants/shrub/schter/all.html
- New Zealand Plant Conservation Network. Schinus terebinthifolius. Accessed July 1, 2024. https://www.nzpcn.org.nz/flora/species/schinus-terebinthifolius
- Rojas-Sandoval J, Acevedo-Rodriguez P. Schinus terebinthifolius (Brazilian pepper tree). CABI Compendium. July 23, 2014. Accessed July 1, 2024. https://www.cabidigitallibrary.org/doi/10.1079/cabicompendium.49031
- Patocka J, Diz de Almeida J. Brazilian peppertree: review of pharmacology. Mil Med Sci Lett. 2017;86:32-41.
- Stahl E, Keller K, Blinn C. Cardanol, a skin irritant in pink pepper. Plant Medica. 1983;48:5-9.
- Skopp G, Opferkuch H-J, Schqenker G. n-Alkylphenols from Schinus terebinthifolius Raddi (Anacardiaceae). In German. Zeitschrift für Naturforschung C. 1987;42:1-16. https://doi.org/10.1515/znc-1987-1-203.
- Lloyd HA, Jaouni TM, Evans SL, et al. Terpenes of Schinus terebinthifolius. Phytochemistry. 1977;16:1301-1302.
- Goon ATJ, Goh CL. Plant dermatitis: Asian perspective. Indian J Dermatol. 2011;56:707-710.
- Rozas-Muñoz E, Lepoittevin JP, Pujol RM, et al. Allergic contact dermatitis to plants: understanding the chemistry will help our diagnostic approach. Actas Dermosifiliogr. 2012;103:456-477.
- Caillol S. Cardanol: a promising building block for biobased polymers and additives. Curr Opin Green Sustain Chem. 2018;14: 26-32.
- Prok L, McGovern T. Poison ivy (Toxicodendron) dermatitis. UpToDate. Updated June 21, 2024. Accessed July 7, 2024. https://www.uptodate.com/contents/poison-ivy-toxicodendron-dermatitis#
Brazilian peppertree (Schinus terebinthifolia), a member of the Anacardiaceae family, is an internationally invasive plant that causes allergic contact dermatitis (ACD) in susceptible individuals. This noxious weed has settled into the landscape of the southern United States and continues to expand. Its key identifying features include its year-round white flowers as well as a peppery and turpentinelike aroma created by cracking its bright red berries. The ACD associated with contact—primarily with the plant’s sap—stems from known alkenyl phenols, cardol and cardanol. Treatment of Brazilian peppertree–associated ACD parallels that for poison ivy. As this pest increases its range, dermatologists living in endemic areas should familiarize themselves with Brazilian peppertree and its potential for harm.
Brazilian Peppertree Morphology and Geography
Plants in the Anacardiaceae family contribute to more ACD than any other family, and its 80 genera include most of the urushiol-containing plants, such as Toxicodendron (poison ivy, poison oak, poison sumac, Japanese lacquer tree), Anacardium (cashew tree), Mangifera (mango fruit), Semecarpus (India marking nut tree), and Schinus (Brazilian peppertree). Deciduous and evergreen tree members of the Anacardiaceae family grow primarily in tropical and subtropical locations and produce thick resins, 5-petalled flowers, and small fruit known as drupes. The genus name for Brazilian peppertree, Schinus, derives from Latin and Greek words meaning “mastic tree,” a relative of the pistachio tree that the Brazilian peppertree resembles.1 Brazilian peppertree leaves look and smell similar to Pistacia terebinthus (turpentine tree or terebinth), from which the species name terebinthifolia derives.2
Brazilian peppertree originated in South America, particularly Brazil, Paraguay, and Argentina.3 Since the 1840s,4 it has been an invasive weed in the United States, notably in Florida, California, Hawaii, Alabama, Georgia,5 Arizona,6 Nevada,3 and Texas.5,7 The plant also grows throughout the world, including parts of Africa, Asia, Central America, Europe,6 New Zealand,8 Australia, and various islands.9 The plant expertly outcompetes neighboring plants and has prompted control and eradication efforts in many locations.3
Identifying Features and Allergenic Plant Parts
Brazilian peppertree can be either a shrub or tree up to 30 feet tall.4 As an evergreen, it retains its leaves year-round. During fruiting seasons (primarily December through March7), bright red or pink (depending on the variety3) berries appear (Figure 1A) and contribute to its nickname “Florida holly.” Although generally considered an unwelcome guest in Florida, it does display white flowers (Figure 1B) year-round, especially from September to November.9 It characteristically exhibits 3 to 13 leaflets per leaf.10 The leaflets’ ovoid and ridged edges, netlike vasculature, shiny hue, and aroma can help identify the plant (Figure 2A). For decades, the sap of the Brazilian peppertree has been associated with skin irritation (Figure 2B).6 Although the sap of the plant serves as the main culprit of Brazilian peppertree–associated ACD, it appears that other parts of the plant, including the fruit, can cause irritating effects to skin on contact.11,12 The leaves, trunk, and fruit can be harmful to both humans and animals.6 Chemicals from flowers and crushed fruit also can lead to irritating effects in the respiratory tract if aspirated.13
Urushiol, an oily resin present in most plants of the Anacardiaceae family,14 contains many chemicals, including allergenic phenols, catechols, and resorcinols.15 Urushiol-allergic individuals develop dermatitis upon exposure to Brazilian peppertree sap.6 Alkenyl phenols found in Brazilian peppertree lead to the cutaneous manifestations in sensitized patients.11,12 In 1983, Stahl et al11 identified a phenol, cardanol (chemical name 3-pentadecylphenol16) C15:1, in Brazilian peppertree fruit. The group further tested this compound’s effect on skin via patch testing, which showed an allergic response.11 Cashew nut shells (Anacardium occidentale) contain cardanol, anacardic acid (a phenolic acid), and cardol (a phenol with the chemical name 5-pentadecylresorcinol),15,16 though Stahl et al11 were unable to extract these 2 substances (if present) from Brazilian peppertree fruit. When exposed to cardol and anacardic acid, those allergic to poison ivy often develop ACD,15 and these 2 substances are more irritating than cardanol.11 A later study did identify cardol in addition to cardanol in Brazilian peppertree.12
Cutaneous Manifestations
Brazilian peppertree–induced ACD appears similar to other plant-induced ACD with linear streaks of erythema, juicy papules, vesicles, coalescing erythematous plaques, and/or occasional edema and bullae accompanied by intense pruritus.
Treatment
Avoiding contact with Brazilian peppertree is the first line of defense, and treatment for a reaction associated with exposure is similar to that of poison ivy.17 Application of cool compresses, calamine lotion, and topical astringents offer symptom alleviation, and topical steroids (eg, clobetasol propionate 0.05% twice daily) can improve mild localized ACD when given prior to formation of blisters. For more severe and diffuse ACD, oral steroids (eg, prednisone 1 mg/kg/d tapered over 2–3 weeks) likely are necessary, though intramuscular options greatly alleviate discomfort in more severe cases (eg, intramuscular triamcinolone acetonide 1 mg/kg combined with betamethasone 0.1 mg/kg). Physicians should monitor sites for any signs of superimposed bacterial infection and initiate antibiotics as necessary.17
Brazilian peppertree (Schinus terebinthifolia), a member of the Anacardiaceae family, is an internationally invasive plant that causes allergic contact dermatitis (ACD) in susceptible individuals. This noxious weed has settled into the landscape of the southern United States and continues to expand. Its key identifying features include its year-round white flowers as well as a peppery and turpentinelike aroma created by cracking its bright red berries. The ACD associated with contact—primarily with the plant’s sap—stems from known alkenyl phenols, cardol and cardanol. Treatment of Brazilian peppertree–associated ACD parallels that for poison ivy. As this pest increases its range, dermatologists living in endemic areas should familiarize themselves with Brazilian peppertree and its potential for harm.
Brazilian Peppertree Morphology and Geography
Plants in the Anacardiaceae family contribute to more ACD than any other family, and its 80 genera include most of the urushiol-containing plants, such as Toxicodendron (poison ivy, poison oak, poison sumac, Japanese lacquer tree), Anacardium (cashew tree), Mangifera (mango fruit), Semecarpus (India marking nut tree), and Schinus (Brazilian peppertree). Deciduous and evergreen tree members of the Anacardiaceae family grow primarily in tropical and subtropical locations and produce thick resins, 5-petalled flowers, and small fruit known as drupes. The genus name for Brazilian peppertree, Schinus, derives from Latin and Greek words meaning “mastic tree,” a relative of the pistachio tree that the Brazilian peppertree resembles.1 Brazilian peppertree leaves look and smell similar to Pistacia terebinthus (turpentine tree or terebinth), from which the species name terebinthifolia derives.2
Brazilian peppertree originated in South America, particularly Brazil, Paraguay, and Argentina.3 Since the 1840s,4 it has been an invasive weed in the United States, notably in Florida, California, Hawaii, Alabama, Georgia,5 Arizona,6 Nevada,3 and Texas.5,7 The plant also grows throughout the world, including parts of Africa, Asia, Central America, Europe,6 New Zealand,8 Australia, and various islands.9 The plant expertly outcompetes neighboring plants and has prompted control and eradication efforts in many locations.3
Identifying Features and Allergenic Plant Parts
Brazilian peppertree can be either a shrub or tree up to 30 feet tall.4 As an evergreen, it retains its leaves year-round. During fruiting seasons (primarily December through March7), bright red or pink (depending on the variety3) berries appear (Figure 1A) and contribute to its nickname “Florida holly.” Although generally considered an unwelcome guest in Florida, it does display white flowers (Figure 1B) year-round, especially from September to November.9 It characteristically exhibits 3 to 13 leaflets per leaf.10 The leaflets’ ovoid and ridged edges, netlike vasculature, shiny hue, and aroma can help identify the plant (Figure 2A). For decades, the sap of the Brazilian peppertree has been associated with skin irritation (Figure 2B).6 Although the sap of the plant serves as the main culprit of Brazilian peppertree–associated ACD, it appears that other parts of the plant, including the fruit, can cause irritating effects to skin on contact.11,12 The leaves, trunk, and fruit can be harmful to both humans and animals.6 Chemicals from flowers and crushed fruit also can lead to irritating effects in the respiratory tract if aspirated.13
Urushiol, an oily resin present in most plants of the Anacardiaceae family,14 contains many chemicals, including allergenic phenols, catechols, and resorcinols.15 Urushiol-allergic individuals develop dermatitis upon exposure to Brazilian peppertree sap.6 Alkenyl phenols found in Brazilian peppertree lead to the cutaneous manifestations in sensitized patients.11,12 In 1983, Stahl et al11 identified a phenol, cardanol (chemical name 3-pentadecylphenol16) C15:1, in Brazilian peppertree fruit. The group further tested this compound’s effect on skin via patch testing, which showed an allergic response.11 Cashew nut shells (Anacardium occidentale) contain cardanol, anacardic acid (a phenolic acid), and cardol (a phenol with the chemical name 5-pentadecylresorcinol),15,16 though Stahl et al11 were unable to extract these 2 substances (if present) from Brazilian peppertree fruit. When exposed to cardol and anacardic acid, those allergic to poison ivy often develop ACD,15 and these 2 substances are more irritating than cardanol.11 A later study did identify cardol in addition to cardanol in Brazilian peppertree.12
Cutaneous Manifestations
Brazilian peppertree–induced ACD appears similar to other plant-induced ACD with linear streaks of erythema, juicy papules, vesicles, coalescing erythematous plaques, and/or occasional edema and bullae accompanied by intense pruritus.
Treatment
Avoiding contact with Brazilian peppertree is the first line of defense, and treatment for a reaction associated with exposure is similar to that of poison ivy.17 Application of cool compresses, calamine lotion, and topical astringents offer symptom alleviation, and topical steroids (eg, clobetasol propionate 0.05% twice daily) can improve mild localized ACD when given prior to formation of blisters. For more severe and diffuse ACD, oral steroids (eg, prednisone 1 mg/kg/d tapered over 2–3 weeks) likely are necessary, though intramuscular options greatly alleviate discomfort in more severe cases (eg, intramuscular triamcinolone acetonide 1 mg/kg combined with betamethasone 0.1 mg/kg). Physicians should monitor sites for any signs of superimposed bacterial infection and initiate antibiotics as necessary.17
- Zona S. The correct gender of Schinus (Anacardiaceae). Phytotaxa. 2015;222:075-077.
- Terebinth. Encyclopedia.com website. Updated May 17, 2018. Accessed July 9, 2024. https://www.encyclopedia.com/plants-and-animals/plants/plants/terebinth
- Brazilian pepper tree. iNaturalist website. Accessed July 1, 2024. https://www.inaturalist.org/guide_taxa/841531#:~:text=Throughout% 20South%20and%20Central%20America,and%20as%20a%20topical%20antiseptic
- Center for Aquatic and Invasive Plants. Schinus terebinthifolia. Brazilian peppertree. Accessed July 1, 2024. https://plants.ifas.ufl.edu/plant-directory/schinus-terebinthifolia/#:~:text=Species%20Overview&text=People%20sensitive%20to%20poison%20ivy,associated%20with%20its%20bloom%20period
- Brazilian peppertree (Schinus terebinthifolia). Early Detection & Distribution Mapping System. Accessed July 4, 2024. https://www.eddmaps.org/distribution/usstate.cfm?sub=78819
- Morton F. Brazilian pepper: its impact on people, animals, and the environment. Econ Bot. 1978;32:353-359.
- Fire Effects Information System. Schinus terebinthifolius. US Department of Agriculture website. Accessed July 4, 2024. https://www.fs.usda.gov/database/feis/plants/shrub/schter/all.html
- New Zealand Plant Conservation Network. Schinus terebinthifolius. Accessed July 1, 2024. https://www.nzpcn.org.nz/flora/species/schinus-terebinthifolius
- Rojas-Sandoval J, Acevedo-Rodriguez P. Schinus terebinthifolius (Brazilian pepper tree). CABI Compendium. July 23, 2014. Accessed July 1, 2024. https://www.cabidigitallibrary.org/doi/10.1079/cabicompendium.49031
- Patocka J, Diz de Almeida J. Brazilian peppertree: review of pharmacology. Mil Med Sci Lett. 2017;86:32-41.
- Stahl E, Keller K, Blinn C. Cardanol, a skin irritant in pink pepper. Plant Medica. 1983;48:5-9.
- Skopp G, Opferkuch H-J, Schqenker G. n-Alkylphenols from Schinus terebinthifolius Raddi (Anacardiaceae). In German. Zeitschrift für Naturforschung C. 1987;42:1-16. https://doi.org/10.1515/znc-1987-1-203.
- Lloyd HA, Jaouni TM, Evans SL, et al. Terpenes of Schinus terebinthifolius. Phytochemistry. 1977;16:1301-1302.
- Goon ATJ, Goh CL. Plant dermatitis: Asian perspective. Indian J Dermatol. 2011;56:707-710.
- Rozas-Muñoz E, Lepoittevin JP, Pujol RM, et al. Allergic contact dermatitis to plants: understanding the chemistry will help our diagnostic approach. Actas Dermosifiliogr. 2012;103:456-477.
- Caillol S. Cardanol: a promising building block for biobased polymers and additives. Curr Opin Green Sustain Chem. 2018;14: 26-32.
- Prok L, McGovern T. Poison ivy (Toxicodendron) dermatitis. UpToDate. Updated June 21, 2024. Accessed July 7, 2024. https://www.uptodate.com/contents/poison-ivy-toxicodendron-dermatitis#
- Zona S. The correct gender of Schinus (Anacardiaceae). Phytotaxa. 2015;222:075-077.
- Terebinth. Encyclopedia.com website. Updated May 17, 2018. Accessed July 9, 2024. https://www.encyclopedia.com/plants-and-animals/plants/plants/terebinth
- Brazilian pepper tree. iNaturalist website. Accessed July 1, 2024. https://www.inaturalist.org/guide_taxa/841531#:~:text=Throughout% 20South%20and%20Central%20America,and%20as%20a%20topical%20antiseptic
- Center for Aquatic and Invasive Plants. Schinus terebinthifolia. Brazilian peppertree. Accessed July 1, 2024. https://plants.ifas.ufl.edu/plant-directory/schinus-terebinthifolia/#:~:text=Species%20Overview&text=People%20sensitive%20to%20poison%20ivy,associated%20with%20its%20bloom%20period
- Brazilian peppertree (Schinus terebinthifolia). Early Detection & Distribution Mapping System. Accessed July 4, 2024. https://www.eddmaps.org/distribution/usstate.cfm?sub=78819
- Morton F. Brazilian pepper: its impact on people, animals, and the environment. Econ Bot. 1978;32:353-359.
- Fire Effects Information System. Schinus terebinthifolius. US Department of Agriculture website. Accessed July 4, 2024. https://www.fs.usda.gov/database/feis/plants/shrub/schter/all.html
- New Zealand Plant Conservation Network. Schinus terebinthifolius. Accessed July 1, 2024. https://www.nzpcn.org.nz/flora/species/schinus-terebinthifolius
- Rojas-Sandoval J, Acevedo-Rodriguez P. Schinus terebinthifolius (Brazilian pepper tree). CABI Compendium. July 23, 2014. Accessed July 1, 2024. https://www.cabidigitallibrary.org/doi/10.1079/cabicompendium.49031
- Patocka J, Diz de Almeida J. Brazilian peppertree: review of pharmacology. Mil Med Sci Lett. 2017;86:32-41.
- Stahl E, Keller K, Blinn C. Cardanol, a skin irritant in pink pepper. Plant Medica. 1983;48:5-9.
- Skopp G, Opferkuch H-J, Schqenker G. n-Alkylphenols from Schinus terebinthifolius Raddi (Anacardiaceae). In German. Zeitschrift für Naturforschung C. 1987;42:1-16. https://doi.org/10.1515/znc-1987-1-203.
- Lloyd HA, Jaouni TM, Evans SL, et al. Terpenes of Schinus terebinthifolius. Phytochemistry. 1977;16:1301-1302.
- Goon ATJ, Goh CL. Plant dermatitis: Asian perspective. Indian J Dermatol. 2011;56:707-710.
- Rozas-Muñoz E, Lepoittevin JP, Pujol RM, et al. Allergic contact dermatitis to plants: understanding the chemistry will help our diagnostic approach. Actas Dermosifiliogr. 2012;103:456-477.
- Caillol S. Cardanol: a promising building block for biobased polymers and additives. Curr Opin Green Sustain Chem. 2018;14: 26-32.
- Prok L, McGovern T. Poison ivy (Toxicodendron) dermatitis. UpToDate. Updated June 21, 2024. Accessed July 7, 2024. https://www.uptodate.com/contents/poison-ivy-toxicodendron-dermatitis#
Practice Points
- The Anacardiaceae family contains several plants, including Brazilian peppertree and poison ivy, that have the potential to cause allergic contact dermatitis (ACD).
- Hot spots for Brazilian peppertree include Florida and California, though it also has been reported in Texas, Hawaii, Georgia, Alabama, Arkansas, Nevada, and Arizona.
- Alkenyl phenols (eg, cardol, cardanol) are the key sensitizers found in Brazilian peppertree.
- Treatment consists of supportive care and either topical, oral, or intramuscular steroids depending on the extent and severity of the ACD.
Meet the Pregnancy Challenges of Women With Chronic Conditions
Preconception and prenatal care are more complicated in women with chronic health conditions but attention to disease management and promoting the adoption of a healthier lifestyle can improve outcomes for mothers and infants, according to a growing body of research.
The latest version of the International Federation of Gynecology and Obstetrics Preconception Checklist, published in the International Journal of Gynecology & Obstetrics, highlights preexisting chronic medical conditions such as diabetes, lupus, and obesity as key factors to address in preconception care through disease management. A growing number of studies support the impact of these strategies on short- and long-term outcomes for mothers and babies, according to the authors.
Meet Glycemic Control Goals Prior to Pregnancy
“Women with diabetes can have healthy pregnancies but need to prepare for pregnancy in advance,” Ellen W. Seely, MD, professor of medicine at Harvard Medical School and director of clinical research in the endocrinology, diabetes, and hypertension division of Brigham and Women’s Hospital, Boston, said in an interview.
“If glucose levels are running high in the first trimester, this is associated with an increased risk of birth defects, some of which are very serious,” said Dr. Seely. Getting glucose levels under control reduces the risk of birth defects in women with diabetes close to that of the general population, she said.
The American Diabetes Association has set a goal for women to attain an HbA1c of less than 6.5% before conception, Dr. Seely said. “In addition, some women with diabetes may be on medications that should be changed to another class prior to pregnancy,” she noted. Women with type 1 or type 2 diabetes often have hypertension as well, but ACE inhibitors are associated with an increased risk of fetal renal damage that can result in neonatal death; therefore, these medications should be stopped prior to pregnancy, Dr. Seely emphasized.
“If a woman with type 2 diabetes is on medications other than insulin, recommendations from the ADA are to change to insulin prior to pregnancy, since we have the most data on the safety profile of insulin use in pregnancy,” she said.
To help women with diabetes improve glycemic control prior to pregnancy, Dr. Seely recommends home glucose monitoring, with checks of glucose four times a day, fasting, and 2 hours after each meal, and adjustment of insulin accordingly.
A healthy diet and physical activity remain important components of glycemic control as well. A barrier to proper preconception and prenatal care for women with diabetes is not knowing that a pregnancy should be planned, Dr. Seely said. Discussions about pregnancy should start at puberty for women with diabetes, according to the ADA, and the topic should be raised yearly so women can optimize their health and adjust medications prior to conception.
Although studies of drugs have been done to inform preconception care for women with diabetes, research is lacking in several areas, notably the safety of GLP-1 agonists in pregnancy, said Dr. Seely. “This class of drug is commonly used in type 2 diabetes and the current recommendation is to stop these agents 2 months prior to conception,” she said.
Conceive in Times of Lupus Remission
Advance planning also is important for a healthy pregnancy in women with systemic lupus erythematosus (SLE), Sayna Norouzi, MD, director of the glomerular disease clinic and polycystic kidney disease clinic of Loma Linda University Medical Center, California, said in an interview.
“Lupus mostly affects women of childbearing age and can create many challenges during pregnancy,” said Dr. Norouzi, the corresponding author of a recent review on managing lupus nephritis during pregnancy.
“Women with lupus face an increased risk of pregnancy complications such as preeclampsia, problems with fetal growth, stillbirth, and premature birth, and these risks increase based on factors such as disease activity, certain antibodies in the body, and other baseline existing conditions such as high blood pressure,” she said.
“It can be difficult to distinguish between a lupus flare and pregnancy-related issues, so proper management is important,” she noted. The Predictors of Pregnancy Outcome: Biomarkers in Antiphospholipid Syndrome and Systemic Lupus Erythematosus (PROMISSE) study findings indicated a lupus nephritis relapse rate of 7.8% of patients in complete remission and 21% of those in partial remission during pregnancy, said Dr. Norouzi. “Current evidence has shown that SLE patients without lupus nephritis flare in the preconception period have a small risk of relapse during pregnancy,” she said.
Before and during pregnancy, women with lupus should work with their treating physicians to adjust medications for safety, watch for signs of flare, and aim to conceive during a period of lupus remission.
Preconception care for women with lupus nephritis involves a careful review of the medications used to control the disease and protect the kidneys and other organs, said Dr. Norouzi.
“Adjustments,” she said, “should be personalized, taking into account the mother’s health and the safety of the baby. Managing the disease actively during pregnancy may require changes to the treatment plan while minimizing risks,” she noted. However, changing medications can cause challenges for patients, as medications that are safer for pregnancy may lead to new symptoms and side effects, and patients will need to work closely with their healthcare providers to overcome new issues that arise, she added.
Preconception lifestyle changes such as increasing exercise and adopting a healthier diet can help with blood pressure control for kidney disease patients, said Dr. Norouzi.
In the review article, Dr. Norouzi and colleagues noted that preconception counseling for patients with lupus should address common comorbidities such as hypertension, diabetes, obesity, and dyslipidemia, and the risk for immediate and long-term cardiovascular complications.
Benefits of Preconception Obesity Care Extend to Infants
Current guidelines from the American College of Obstetricians and Gynecologists and the Institute of Medicine advise lifestyle interventions to reduce excessive weight gain during pregnancy and reduce the risk of inflammation, oxidative stress, insulin resistance, and lipotoxicity that can promote complications in the mother and fetus during pregnancy.
In addition, a growing number of studies suggest that women with obesity who make healthy lifestyle changes prior to conception can reduce obesity-associated risks to their infants.
Adults born to women with obesity are at increased risk of cardiovascular disease and early signs of heart remodeling are identifiable in newborns, Samuel J. Burden, PhD, a research associate in the department of women and children’s health, Kings’ College, London, said in an interview. “It is therefore important to investigate whether intervening either before or during pregnancy by promoting a healthy lifestyle can reduce this adverse impact on the heart and blood vessels,” he said.
In a recent study published in the International Journal of Obesity, Dr. Burden and colleagues examined data from eight studies based on data from five randomized, controlled trials including children of mothers with obesity who engaged in healthy lifestyle interventions of improved diet and increased physical activity prior to and during pregnancy. The study population included children ranging in age from less than 2 months to 3-7 years.
Lifestyle interventions for mothers both before conception and during pregnancy were associated with significant changes in cardiac remodeling in the children, notably reduced interventricular septal wall thickness. Additionally, five studies of cardiac systolic function and three studies of diastolic function showed improvement in blood pressure in children of mothers who took part in the interventions.
Dr. Burden acknowledged that lifestyle changes in women with obesity before conception and during pregnancy can be challenging, but should be encouraged. “During pregnancy, it may also seem unnatural to increase daily physical activity or change the way you are eating.” He emphasized that patients should consult their physicians and follow an established program. More randomized, controlled trials are needed from the preconception period to examine whether the health benefits are greater if the intervention begins prior to pregnancy, said Dr. Burden. However, “the current findings indeed indicate that women with obesity who lead a healthy lifestyle before and during their pregnancy can reduce the degree of unhealthy heart remodeling in their children,” he said.
Dr. Seely, Dr. Norouzi, and Dr. Burden had no financial conflicts to disclose.
Preconception and prenatal care are more complicated in women with chronic health conditions but attention to disease management and promoting the adoption of a healthier lifestyle can improve outcomes for mothers and infants, according to a growing body of research.
The latest version of the International Federation of Gynecology and Obstetrics Preconception Checklist, published in the International Journal of Gynecology & Obstetrics, highlights preexisting chronic medical conditions such as diabetes, lupus, and obesity as key factors to address in preconception care through disease management. A growing number of studies support the impact of these strategies on short- and long-term outcomes for mothers and babies, according to the authors.
Meet Glycemic Control Goals Prior to Pregnancy
“Women with diabetes can have healthy pregnancies but need to prepare for pregnancy in advance,” Ellen W. Seely, MD, professor of medicine at Harvard Medical School and director of clinical research in the endocrinology, diabetes, and hypertension division of Brigham and Women’s Hospital, Boston, said in an interview.
“If glucose levels are running high in the first trimester, this is associated with an increased risk of birth defects, some of which are very serious,” said Dr. Seely. Getting glucose levels under control reduces the risk of birth defects in women with diabetes close to that of the general population, she said.
The American Diabetes Association has set a goal for women to attain an HbA1c of less than 6.5% before conception, Dr. Seely said. “In addition, some women with diabetes may be on medications that should be changed to another class prior to pregnancy,” she noted. Women with type 1 or type 2 diabetes often have hypertension as well, but ACE inhibitors are associated with an increased risk of fetal renal damage that can result in neonatal death; therefore, these medications should be stopped prior to pregnancy, Dr. Seely emphasized.
“If a woman with type 2 diabetes is on medications other than insulin, recommendations from the ADA are to change to insulin prior to pregnancy, since we have the most data on the safety profile of insulin use in pregnancy,” she said.
To help women with diabetes improve glycemic control prior to pregnancy, Dr. Seely recommends home glucose monitoring, with checks of glucose four times a day, fasting, and 2 hours after each meal, and adjustment of insulin accordingly.
A healthy diet and physical activity remain important components of glycemic control as well. A barrier to proper preconception and prenatal care for women with diabetes is not knowing that a pregnancy should be planned, Dr. Seely said. Discussions about pregnancy should start at puberty for women with diabetes, according to the ADA, and the topic should be raised yearly so women can optimize their health and adjust medications prior to conception.
Although studies of drugs have been done to inform preconception care for women with diabetes, research is lacking in several areas, notably the safety of GLP-1 agonists in pregnancy, said Dr. Seely. “This class of drug is commonly used in type 2 diabetes and the current recommendation is to stop these agents 2 months prior to conception,” she said.
Conceive in Times of Lupus Remission
Advance planning also is important for a healthy pregnancy in women with systemic lupus erythematosus (SLE), Sayna Norouzi, MD, director of the glomerular disease clinic and polycystic kidney disease clinic of Loma Linda University Medical Center, California, said in an interview.
“Lupus mostly affects women of childbearing age and can create many challenges during pregnancy,” said Dr. Norouzi, the corresponding author of a recent review on managing lupus nephritis during pregnancy.
“Women with lupus face an increased risk of pregnancy complications such as preeclampsia, problems with fetal growth, stillbirth, and premature birth, and these risks increase based on factors such as disease activity, certain antibodies in the body, and other baseline existing conditions such as high blood pressure,” she said.
“It can be difficult to distinguish between a lupus flare and pregnancy-related issues, so proper management is important,” she noted. The Predictors of Pregnancy Outcome: Biomarkers in Antiphospholipid Syndrome and Systemic Lupus Erythematosus (PROMISSE) study findings indicated a lupus nephritis relapse rate of 7.8% of patients in complete remission and 21% of those in partial remission during pregnancy, said Dr. Norouzi. “Current evidence has shown that SLE patients without lupus nephritis flare in the preconception period have a small risk of relapse during pregnancy,” she said.
Before and during pregnancy, women with lupus should work with their treating physicians to adjust medications for safety, watch for signs of flare, and aim to conceive during a period of lupus remission.
Preconception care for women with lupus nephritis involves a careful review of the medications used to control the disease and protect the kidneys and other organs, said Dr. Norouzi.
“Adjustments,” she said, “should be personalized, taking into account the mother’s health and the safety of the baby. Managing the disease actively during pregnancy may require changes to the treatment plan while minimizing risks,” she noted. However, changing medications can cause challenges for patients, as medications that are safer for pregnancy may lead to new symptoms and side effects, and patients will need to work closely with their healthcare providers to overcome new issues that arise, she added.
Preconception lifestyle changes such as increasing exercise and adopting a healthier diet can help with blood pressure control for kidney disease patients, said Dr. Norouzi.
In the review article, Dr. Norouzi and colleagues noted that preconception counseling for patients with lupus should address common comorbidities such as hypertension, diabetes, obesity, and dyslipidemia, and the risk for immediate and long-term cardiovascular complications.
Benefits of Preconception Obesity Care Extend to Infants
Current guidelines from the American College of Obstetricians and Gynecologists and the Institute of Medicine advise lifestyle interventions to reduce excessive weight gain during pregnancy and reduce the risk of inflammation, oxidative stress, insulin resistance, and lipotoxicity that can promote complications in the mother and fetus during pregnancy.
In addition, a growing number of studies suggest that women with obesity who make healthy lifestyle changes prior to conception can reduce obesity-associated risks to their infants.
Adults born to women with obesity are at increased risk of cardiovascular disease and early signs of heart remodeling are identifiable in newborns, Samuel J. Burden, PhD, a research associate in the department of women and children’s health, Kings’ College, London, said in an interview. “It is therefore important to investigate whether intervening either before or during pregnancy by promoting a healthy lifestyle can reduce this adverse impact on the heart and blood vessels,” he said.
In a recent study published in the International Journal of Obesity, Dr. Burden and colleagues examined data from eight studies based on data from five randomized, controlled trials including children of mothers with obesity who engaged in healthy lifestyle interventions of improved diet and increased physical activity prior to and during pregnancy. The study population included children ranging in age from less than 2 months to 3-7 years.
Lifestyle interventions for mothers both before conception and during pregnancy were associated with significant changes in cardiac remodeling in the children, notably reduced interventricular septal wall thickness. Additionally, five studies of cardiac systolic function and three studies of diastolic function showed improvement in blood pressure in children of mothers who took part in the interventions.
Dr. Burden acknowledged that lifestyle changes in women with obesity before conception and during pregnancy can be challenging, but should be encouraged. “During pregnancy, it may also seem unnatural to increase daily physical activity or change the way you are eating.” He emphasized that patients should consult their physicians and follow an established program. More randomized, controlled trials are needed from the preconception period to examine whether the health benefits are greater if the intervention begins prior to pregnancy, said Dr. Burden. However, “the current findings indeed indicate that women with obesity who lead a healthy lifestyle before and during their pregnancy can reduce the degree of unhealthy heart remodeling in their children,” he said.
Dr. Seely, Dr. Norouzi, and Dr. Burden had no financial conflicts to disclose.
Preconception and prenatal care are more complicated in women with chronic health conditions but attention to disease management and promoting the adoption of a healthier lifestyle can improve outcomes for mothers and infants, according to a growing body of research.
The latest version of the International Federation of Gynecology and Obstetrics Preconception Checklist, published in the International Journal of Gynecology & Obstetrics, highlights preexisting chronic medical conditions such as diabetes, lupus, and obesity as key factors to address in preconception care through disease management. A growing number of studies support the impact of these strategies on short- and long-term outcomes for mothers and babies, according to the authors.
Meet Glycemic Control Goals Prior to Pregnancy
“Women with diabetes can have healthy pregnancies but need to prepare for pregnancy in advance,” Ellen W. Seely, MD, professor of medicine at Harvard Medical School and director of clinical research in the endocrinology, diabetes, and hypertension division of Brigham and Women’s Hospital, Boston, said in an interview.
“If glucose levels are running high in the first trimester, this is associated with an increased risk of birth defects, some of which are very serious,” said Dr. Seely. Getting glucose levels under control reduces the risk of birth defects in women with diabetes close to that of the general population, she said.
The American Diabetes Association has set a goal for women to attain an HbA1c of less than 6.5% before conception, Dr. Seely said. “In addition, some women with diabetes may be on medications that should be changed to another class prior to pregnancy,” she noted. Women with type 1 or type 2 diabetes often have hypertension as well, but ACE inhibitors are associated with an increased risk of fetal renal damage that can result in neonatal death; therefore, these medications should be stopped prior to pregnancy, Dr. Seely emphasized.
“If a woman with type 2 diabetes is on medications other than insulin, recommendations from the ADA are to change to insulin prior to pregnancy, since we have the most data on the safety profile of insulin use in pregnancy,” she said.
To help women with diabetes improve glycemic control prior to pregnancy, Dr. Seely recommends home glucose monitoring, with checks of glucose four times a day, fasting, and 2 hours after each meal, and adjustment of insulin accordingly.
A healthy diet and physical activity remain important components of glycemic control as well. A barrier to proper preconception and prenatal care for women with diabetes is not knowing that a pregnancy should be planned, Dr. Seely said. Discussions about pregnancy should start at puberty for women with diabetes, according to the ADA, and the topic should be raised yearly so women can optimize their health and adjust medications prior to conception.
Although studies of drugs have been done to inform preconception care for women with diabetes, research is lacking in several areas, notably the safety of GLP-1 agonists in pregnancy, said Dr. Seely. “This class of drug is commonly used in type 2 diabetes and the current recommendation is to stop these agents 2 months prior to conception,” she said.
Conceive in Times of Lupus Remission
Advance planning also is important for a healthy pregnancy in women with systemic lupus erythematosus (SLE), Sayna Norouzi, MD, director of the glomerular disease clinic and polycystic kidney disease clinic of Loma Linda University Medical Center, California, said in an interview.
“Lupus mostly affects women of childbearing age and can create many challenges during pregnancy,” said Dr. Norouzi, the corresponding author of a recent review on managing lupus nephritis during pregnancy.
“Women with lupus face an increased risk of pregnancy complications such as preeclampsia, problems with fetal growth, stillbirth, and premature birth, and these risks increase based on factors such as disease activity, certain antibodies in the body, and other baseline existing conditions such as high blood pressure,” she said.
“It can be difficult to distinguish between a lupus flare and pregnancy-related issues, so proper management is important,” she noted. The Predictors of Pregnancy Outcome: Biomarkers in Antiphospholipid Syndrome and Systemic Lupus Erythematosus (PROMISSE) study findings indicated a lupus nephritis relapse rate of 7.8% of patients in complete remission and 21% of those in partial remission during pregnancy, said Dr. Norouzi. “Current evidence has shown that SLE patients without lupus nephritis flare in the preconception period have a small risk of relapse during pregnancy,” she said.
Before and during pregnancy, women with lupus should work with their treating physicians to adjust medications for safety, watch for signs of flare, and aim to conceive during a period of lupus remission.
Preconception care for women with lupus nephritis involves a careful review of the medications used to control the disease and protect the kidneys and other organs, said Dr. Norouzi.
“Adjustments,” she said, “should be personalized, taking into account the mother’s health and the safety of the baby. Managing the disease actively during pregnancy may require changes to the treatment plan while minimizing risks,” she noted. However, changing medications can cause challenges for patients, as medications that are safer for pregnancy may lead to new symptoms and side effects, and patients will need to work closely with their healthcare providers to overcome new issues that arise, she added.
Preconception lifestyle changes such as increasing exercise and adopting a healthier diet can help with blood pressure control for kidney disease patients, said Dr. Norouzi.
In the review article, Dr. Norouzi and colleagues noted that preconception counseling for patients with lupus should address common comorbidities such as hypertension, diabetes, obesity, and dyslipidemia, and the risk for immediate and long-term cardiovascular complications.
Benefits of Preconception Obesity Care Extend to Infants
Current guidelines from the American College of Obstetricians and Gynecologists and the Institute of Medicine advise lifestyle interventions to reduce excessive weight gain during pregnancy and reduce the risk of inflammation, oxidative stress, insulin resistance, and lipotoxicity that can promote complications in the mother and fetus during pregnancy.
In addition, a growing number of studies suggest that women with obesity who make healthy lifestyle changes prior to conception can reduce obesity-associated risks to their infants.
Adults born to women with obesity are at increased risk of cardiovascular disease and early signs of heart remodeling are identifiable in newborns, Samuel J. Burden, PhD, a research associate in the department of women and children’s health, Kings’ College, London, said in an interview. “It is therefore important to investigate whether intervening either before or during pregnancy by promoting a healthy lifestyle can reduce this adverse impact on the heart and blood vessels,” he said.
In a recent study published in the International Journal of Obesity, Dr. Burden and colleagues examined data from eight studies based on data from five randomized, controlled trials including children of mothers with obesity who engaged in healthy lifestyle interventions of improved diet and increased physical activity prior to and during pregnancy. The study population included children ranging in age from less than 2 months to 3-7 years.
Lifestyle interventions for mothers both before conception and during pregnancy were associated with significant changes in cardiac remodeling in the children, notably reduced interventricular septal wall thickness. Additionally, five studies of cardiac systolic function and three studies of diastolic function showed improvement in blood pressure in children of mothers who took part in the interventions.
Dr. Burden acknowledged that lifestyle changes in women with obesity before conception and during pregnancy can be challenging, but should be encouraged. “During pregnancy, it may also seem unnatural to increase daily physical activity or change the way you are eating.” He emphasized that patients should consult their physicians and follow an established program. More randomized, controlled trials are needed from the preconception period to examine whether the health benefits are greater if the intervention begins prior to pregnancy, said Dr. Burden. However, “the current findings indeed indicate that women with obesity who lead a healthy lifestyle before and during their pregnancy can reduce the degree of unhealthy heart remodeling in their children,” he said.
Dr. Seely, Dr. Norouzi, and Dr. Burden had no financial conflicts to disclose.
What Are the Ethics of Sex and Romance for Older Adults in Nursing Homes?
This transcript has been edited for clarity.
I had a case a couple years ago in which I found myself completely at odds with the person complaining. A daughter came to me and said [paraphrasing], look, my dad is in a nursing home, and he’s just there for care that he needs, but he’s mentally competent. He’s enjoying watching television, playing games. He plays bridge and does many things. The nursing home is letting him have a romantic relationship with a woman who’s also in the nursing home. I think you, ethicist, should both intervene and try to stop that, and write more about the immorality of facilities like nursing homes or other long-term care settings permitting romance or sexual relations to take place.
I was reminded of that case because a report recently appeared that sexually transmitted diseases are on the rise among the elderly, both in nursing homes and in other settings. This obviously is linked up to another technological advance: the erectile dysfunction drugs.
I’m sure there are many men who, at one point in their lives, could not engage in sexual activity due to impotence. We have found a treatment for erectile dysfunction. Loads and loads of men are using it, and we forget that some of them are going to be older. The rate of impotence goes up directly with aging. If you’re in a nursing home, home care, or wherever you are, you may find yourself able to engage in sex in a way that your dad or your granddad may not have been.
We also know — and I found this out when I was tracking sales of erectile dysfunction drugs — that some of these older men are going to visit prostitutes. That’s another route, unsafe sex, for sexual diseases to be spreading into various older communities.
Morally, I think every individual who is competent and wishes to engage in a romantic or sexual relationship should be able to do so. If they’re within a marriage and they want to resume sexual activity because they get better or they can use these drugs, well, that’s great. If they’re single and they’re just living with others and they form an interesting romantic relationship, why shouldn’t they be allowed to engage in sex?
It is not only something that I didn’t agree with the complaining daughter about, but also I think some of these facilities should make more rooms for privacy and more opportunity for intimacy. It’s not like we should tell granddad that he’s living in a college dorm and try to make sure that his roommate doesn’t come in if he’s going to have his girlfriend over.
Are there ethical issues? Sure. Obviously, we should remember, if we have older patients, to talk to them about sexually transmitted diseases as part of a discussion of their sex life. We shouldn’t presume that they’re not doing something. We should presume that they might be, and then remind them about safe sex, particularly if they’re going to use third parties like prostitutes.
Competency becomes important. It’s one thing to have a mutually agreed upon romantic relationship. It’s another thing if somebody is taking advantage of someone who has Alzheimer’s or severe mental dysfunction and they’re not consenting.
How do we determine that and how do we manage that? I think people who are incompetent need to be protected from sexual advances unless they have a relative or someone who says they can engage if they enjoy it and it brings them pleasure. I wouldn’t just have people who are vulnerable, exploited, or acting in a predatory way toward others.
As I said, we need to rethink the design of where older people are living, whether it’s assisted living, nursing home living, or wherever, just to give them the opportunity to have a full life, as any individual would have once they’re past the age of majority, no matter who they want to have romance with and what they want to do in terms of how far that intimacy goes.
Sadly, I didn’t agree with the daughter who came to me and asked me to stop it. I wouldn’t stop it nor would I publish against it. There are risks that we ought to be aware of, including exploiting vulnerable people if they can’t consent, and the danger of transmission of disease, as would be true in any group that might engage in high-risk behavior.
Another risk may be injury if someone is frail and can’t physically sustain sexual intimacy because they’re just too frail to do it. We also need to be sure to address the issue of sexuality with patients to make sure they know what’s going on, what risks there are, what rights they have, and so on.
At the end of the day, I’m not in the camp that says, “Just say no” when it comes to sex among the elderly.
Dr. Caplan is director, Division of Medical Ethics, New York University Langone Medical Center, New York. He has served as a director, officer, partner, employee, advisor, consultant, or trustee for Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position); he also serves as a contributing author and advisor for Medscape.
A version of this article first appeared on Medscape.com.
This transcript has been edited for clarity.
I had a case a couple years ago in which I found myself completely at odds with the person complaining. A daughter came to me and said [paraphrasing], look, my dad is in a nursing home, and he’s just there for care that he needs, but he’s mentally competent. He’s enjoying watching television, playing games. He plays bridge and does many things. The nursing home is letting him have a romantic relationship with a woman who’s also in the nursing home. I think you, ethicist, should both intervene and try to stop that, and write more about the immorality of facilities like nursing homes or other long-term care settings permitting romance or sexual relations to take place.
I was reminded of that case because a report recently appeared that sexually transmitted diseases are on the rise among the elderly, both in nursing homes and in other settings. This obviously is linked up to another technological advance: the erectile dysfunction drugs.
I’m sure there are many men who, at one point in their lives, could not engage in sexual activity due to impotence. We have found a treatment for erectile dysfunction. Loads and loads of men are using it, and we forget that some of them are going to be older. The rate of impotence goes up directly with aging. If you’re in a nursing home, home care, or wherever you are, you may find yourself able to engage in sex in a way that your dad or your granddad may not have been.
We also know — and I found this out when I was tracking sales of erectile dysfunction drugs — that some of these older men are going to visit prostitutes. That’s another route, unsafe sex, for sexual diseases to be spreading into various older communities.
Morally, I think every individual who is competent and wishes to engage in a romantic or sexual relationship should be able to do so. If they’re within a marriage and they want to resume sexual activity because they get better or they can use these drugs, well, that’s great. If they’re single and they’re just living with others and they form an interesting romantic relationship, why shouldn’t they be allowed to engage in sex?
It is not only something that I didn’t agree with the complaining daughter about, but also I think some of these facilities should make more rooms for privacy and more opportunity for intimacy. It’s not like we should tell granddad that he’s living in a college dorm and try to make sure that his roommate doesn’t come in if he’s going to have his girlfriend over.
Are there ethical issues? Sure. Obviously, we should remember, if we have older patients, to talk to them about sexually transmitted diseases as part of a discussion of their sex life. We shouldn’t presume that they’re not doing something. We should presume that they might be, and then remind them about safe sex, particularly if they’re going to use third parties like prostitutes.
Competency becomes important. It’s one thing to have a mutually agreed upon romantic relationship. It’s another thing if somebody is taking advantage of someone who has Alzheimer’s or severe mental dysfunction and they’re not consenting.
How do we determine that and how do we manage that? I think people who are incompetent need to be protected from sexual advances unless they have a relative or someone who says they can engage if they enjoy it and it brings them pleasure. I wouldn’t just have people who are vulnerable, exploited, or acting in a predatory way toward others.
As I said, we need to rethink the design of where older people are living, whether it’s assisted living, nursing home living, or wherever, just to give them the opportunity to have a full life, as any individual would have once they’re past the age of majority, no matter who they want to have romance with and what they want to do in terms of how far that intimacy goes.
Sadly, I didn’t agree with the daughter who came to me and asked me to stop it. I wouldn’t stop it nor would I publish against it. There are risks that we ought to be aware of, including exploiting vulnerable people if they can’t consent, and the danger of transmission of disease, as would be true in any group that might engage in high-risk behavior.
Another risk may be injury if someone is frail and can’t physically sustain sexual intimacy because they’re just too frail to do it. We also need to be sure to address the issue of sexuality with patients to make sure they know what’s going on, what risks there are, what rights they have, and so on.
At the end of the day, I’m not in the camp that says, “Just say no” when it comes to sex among the elderly.
Dr. Caplan is director, Division of Medical Ethics, New York University Langone Medical Center, New York. He has served as a director, officer, partner, employee, advisor, consultant, or trustee for Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position); he also serves as a contributing author and advisor for Medscape.
A version of this article first appeared on Medscape.com.
This transcript has been edited for clarity.
I had a case a couple years ago in which I found myself completely at odds with the person complaining. A daughter came to me and said [paraphrasing], look, my dad is in a nursing home, and he’s just there for care that he needs, but he’s mentally competent. He’s enjoying watching television, playing games. He plays bridge and does many things. The nursing home is letting him have a romantic relationship with a woman who’s also in the nursing home. I think you, ethicist, should both intervene and try to stop that, and write more about the immorality of facilities like nursing homes or other long-term care settings permitting romance or sexual relations to take place.
I was reminded of that case because a report recently appeared that sexually transmitted diseases are on the rise among the elderly, both in nursing homes and in other settings. This obviously is linked up to another technological advance: the erectile dysfunction drugs.
I’m sure there are many men who, at one point in their lives, could not engage in sexual activity due to impotence. We have found a treatment for erectile dysfunction. Loads and loads of men are using it, and we forget that some of them are going to be older. The rate of impotence goes up directly with aging. If you’re in a nursing home, home care, or wherever you are, you may find yourself able to engage in sex in a way that your dad or your granddad may not have been.
We also know — and I found this out when I was tracking sales of erectile dysfunction drugs — that some of these older men are going to visit prostitutes. That’s another route, unsafe sex, for sexual diseases to be spreading into various older communities.
Morally, I think every individual who is competent and wishes to engage in a romantic or sexual relationship should be able to do so. If they’re within a marriage and they want to resume sexual activity because they get better or they can use these drugs, well, that’s great. If they’re single and they’re just living with others and they form an interesting romantic relationship, why shouldn’t they be allowed to engage in sex?
It is not only something that I didn’t agree with the complaining daughter about, but also I think some of these facilities should make more rooms for privacy and more opportunity for intimacy. It’s not like we should tell granddad that he’s living in a college dorm and try to make sure that his roommate doesn’t come in if he’s going to have his girlfriend over.
Are there ethical issues? Sure. Obviously, we should remember, if we have older patients, to talk to them about sexually transmitted diseases as part of a discussion of their sex life. We shouldn’t presume that they’re not doing something. We should presume that they might be, and then remind them about safe sex, particularly if they’re going to use third parties like prostitutes.
Competency becomes important. It’s one thing to have a mutually agreed upon romantic relationship. It’s another thing if somebody is taking advantage of someone who has Alzheimer’s or severe mental dysfunction and they’re not consenting.
How do we determine that and how do we manage that? I think people who are incompetent need to be protected from sexual advances unless they have a relative or someone who says they can engage if they enjoy it and it brings them pleasure. I wouldn’t just have people who are vulnerable, exploited, or acting in a predatory way toward others.
As I said, we need to rethink the design of where older people are living, whether it’s assisted living, nursing home living, or wherever, just to give them the opportunity to have a full life, as any individual would have once they’re past the age of majority, no matter who they want to have romance with and what they want to do in terms of how far that intimacy goes.
Sadly, I didn’t agree with the daughter who came to me and asked me to stop it. I wouldn’t stop it nor would I publish against it. There are risks that we ought to be aware of, including exploiting vulnerable people if they can’t consent, and the danger of transmission of disease, as would be true in any group that might engage in high-risk behavior.
Another risk may be injury if someone is frail and can’t physically sustain sexual intimacy because they’re just too frail to do it. We also need to be sure to address the issue of sexuality with patients to make sure they know what’s going on, what risks there are, what rights they have, and so on.
At the end of the day, I’m not in the camp that says, “Just say no” when it comes to sex among the elderly.
Dr. Caplan is director, Division of Medical Ethics, New York University Langone Medical Center, New York. He has served as a director, officer, partner, employee, advisor, consultant, or trustee for Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position); he also serves as a contributing author and advisor for Medscape.
A version of this article first appeared on Medscape.com.
Strong Sibling Link With Autism Spectrum Disorder
a study published in Pediatrics.
according toWhen a baby had more than one older sibling with autism, the family recurrence rate rose to 36.9%, the study found.
The researchers, led by Sally Ozonoff, PhD, Department of Psychiatry and Behavioral Sciences at University of California Davis Health in Sacramento, analyzed data from 1,605 infants who had an older sibling with ASD using data from the global Baby Siblings Research Consortium.
They calculated that the rate of autism recurrence is seven times higher in families who already have one autistic child than in the general population, which points to the importance of close developmental observance in infants born in families with autistic children, particularly male infants in those families. This study replicated a 2011 study, also led by Dr. Ozonoff, which found a similar rate of familial recurrence.
Differences by Sex and Race
Dr. Ozonoff’s team found that sex and race played a part in likelihood of recurrence. Younger siblings of females with ASD were much more likely to develop the disorder (34.7%) than siblings of boys (22.5%). And male younger siblings were more likely to have ASD than girls (25.3% vs. 13.1%).
Additionally, ASD recurrence in White families was 17.8% while across other races collectively the recurrence rate was 25%.
Links with Maternal Education
Differences by maternal education were also striking. Recurrence was 32.6% when mothers had a high school or less education; 25.5% with some college; 19.7 with a college degree; and 16.9% with a graduate degree. The parental education revealed a significant effect only for mothers (P < .01); paternal education was not significant (P = .09).
Suzanne Rybczynski, MD, chief medical officer at East Tennessee Children’s Hospital in Knoxville, who was not part of the study, praised the study for following babies over time, “doing serial evaluation using two very standard tools in diagnosing autism and developmental delay.”
The babies were evaluated as early as 6 months of age, for up to seven visits. A final assessment was made at 36 months.
Dr. Rybczynski said it was interesting to see that, although ASD prevalence has increased substantially from the 2011 study (0.9%-2.8%), the findings regarding the sibling link have been consistent (18.7% in the 2011 study to 20.2% now).
Eliminating Biases
Dr. Rybczynski noted the current study also used diagnoses only from autism experts, which strengthened the findings, noting the potential for overdiagnosis when interviews are with the parents. “This really eliminates those biases.”
The authors explained the factors driving the need to update recurrence rate studies, including the growth in the prevalence of ASD in the last decade to 1 in 36. That may be caused partly by “greater awareness and identification of autistic females and cognitively able, verbal children.”
Also, new diagnostic criteria have been published, with different diagnostic thresholds since the last study. This study, they noted, had a sample size twice as large and more diverse than the 2011 sample.
The size and the diversity are particularly important, Dr. Rybczynski said, as it helps support more recent findings that ASD is not as heavily centered in White males as previously thought.
“We need to make sure we’re monitoring all children, especially from groups where there’s at least one older sibling or multiple siblings with autism or a sister with autism,” she said. The findings of this study are important not just for pediatricians but for families and all who have professional interactions with children.
Dr. Ozonoff reports travel reimbursements and honoraria from Autism Speaks and the Autism Science Foundation and book royalties from Guilford Press. One coauthor has served as a paid consultant to F. Hoffmann–La Roche and Servier and has received royalties from Sage Publications and Guilford Publications. Another is supported by the Stollery Children’s Hospital Foundation Chair in Autism. One coauthor reported a consulting agreement with EarliTec Diagnostics and book royalties from Wiley. A fourth coauthor has received funding from the Simons Foundation and consults for the Beasley Law Firm and Linus Technology. Dr. Rybczynski reported no relevant financial relationships.
a study published in Pediatrics.
according toWhen a baby had more than one older sibling with autism, the family recurrence rate rose to 36.9%, the study found.
The researchers, led by Sally Ozonoff, PhD, Department of Psychiatry and Behavioral Sciences at University of California Davis Health in Sacramento, analyzed data from 1,605 infants who had an older sibling with ASD using data from the global Baby Siblings Research Consortium.
They calculated that the rate of autism recurrence is seven times higher in families who already have one autistic child than in the general population, which points to the importance of close developmental observance in infants born in families with autistic children, particularly male infants in those families. This study replicated a 2011 study, also led by Dr. Ozonoff, which found a similar rate of familial recurrence.
Differences by Sex and Race
Dr. Ozonoff’s team found that sex and race played a part in likelihood of recurrence. Younger siblings of females with ASD were much more likely to develop the disorder (34.7%) than siblings of boys (22.5%). And male younger siblings were more likely to have ASD than girls (25.3% vs. 13.1%).
Additionally, ASD recurrence in White families was 17.8% while across other races collectively the recurrence rate was 25%.
Links with Maternal Education
Differences by maternal education were also striking. Recurrence was 32.6% when mothers had a high school or less education; 25.5% with some college; 19.7 with a college degree; and 16.9% with a graduate degree. The parental education revealed a significant effect only for mothers (P < .01); paternal education was not significant (P = .09).
Suzanne Rybczynski, MD, chief medical officer at East Tennessee Children’s Hospital in Knoxville, who was not part of the study, praised the study for following babies over time, “doing serial evaluation using two very standard tools in diagnosing autism and developmental delay.”
The babies were evaluated as early as 6 months of age, for up to seven visits. A final assessment was made at 36 months.
Dr. Rybczynski said it was interesting to see that, although ASD prevalence has increased substantially from the 2011 study (0.9%-2.8%), the findings regarding the sibling link have been consistent (18.7% in the 2011 study to 20.2% now).
Eliminating Biases
Dr. Rybczynski noted the current study also used diagnoses only from autism experts, which strengthened the findings, noting the potential for overdiagnosis when interviews are with the parents. “This really eliminates those biases.”
The authors explained the factors driving the need to update recurrence rate studies, including the growth in the prevalence of ASD in the last decade to 1 in 36. That may be caused partly by “greater awareness and identification of autistic females and cognitively able, verbal children.”
Also, new diagnostic criteria have been published, with different diagnostic thresholds since the last study. This study, they noted, had a sample size twice as large and more diverse than the 2011 sample.
The size and the diversity are particularly important, Dr. Rybczynski said, as it helps support more recent findings that ASD is not as heavily centered in White males as previously thought.
“We need to make sure we’re monitoring all children, especially from groups where there’s at least one older sibling or multiple siblings with autism or a sister with autism,” she said. The findings of this study are important not just for pediatricians but for families and all who have professional interactions with children.
Dr. Ozonoff reports travel reimbursements and honoraria from Autism Speaks and the Autism Science Foundation and book royalties from Guilford Press. One coauthor has served as a paid consultant to F. Hoffmann–La Roche and Servier and has received royalties from Sage Publications and Guilford Publications. Another is supported by the Stollery Children’s Hospital Foundation Chair in Autism. One coauthor reported a consulting agreement with EarliTec Diagnostics and book royalties from Wiley. A fourth coauthor has received funding from the Simons Foundation and consults for the Beasley Law Firm and Linus Technology. Dr. Rybczynski reported no relevant financial relationships.
a study published in Pediatrics.
according toWhen a baby had more than one older sibling with autism, the family recurrence rate rose to 36.9%, the study found.
The researchers, led by Sally Ozonoff, PhD, Department of Psychiatry and Behavioral Sciences at University of California Davis Health in Sacramento, analyzed data from 1,605 infants who had an older sibling with ASD using data from the global Baby Siblings Research Consortium.
They calculated that the rate of autism recurrence is seven times higher in families who already have one autistic child than in the general population, which points to the importance of close developmental observance in infants born in families with autistic children, particularly male infants in those families. This study replicated a 2011 study, also led by Dr. Ozonoff, which found a similar rate of familial recurrence.
Differences by Sex and Race
Dr. Ozonoff’s team found that sex and race played a part in likelihood of recurrence. Younger siblings of females with ASD were much more likely to develop the disorder (34.7%) than siblings of boys (22.5%). And male younger siblings were more likely to have ASD than girls (25.3% vs. 13.1%).
Additionally, ASD recurrence in White families was 17.8% while across other races collectively the recurrence rate was 25%.
Links with Maternal Education
Differences by maternal education were also striking. Recurrence was 32.6% when mothers had a high school or less education; 25.5% with some college; 19.7 with a college degree; and 16.9% with a graduate degree. The parental education revealed a significant effect only for mothers (P < .01); paternal education was not significant (P = .09).
Suzanne Rybczynski, MD, chief medical officer at East Tennessee Children’s Hospital in Knoxville, who was not part of the study, praised the study for following babies over time, “doing serial evaluation using two very standard tools in diagnosing autism and developmental delay.”
The babies were evaluated as early as 6 months of age, for up to seven visits. A final assessment was made at 36 months.
Dr. Rybczynski said it was interesting to see that, although ASD prevalence has increased substantially from the 2011 study (0.9%-2.8%), the findings regarding the sibling link have been consistent (18.7% in the 2011 study to 20.2% now).
Eliminating Biases
Dr. Rybczynski noted the current study also used diagnoses only from autism experts, which strengthened the findings, noting the potential for overdiagnosis when interviews are with the parents. “This really eliminates those biases.”
The authors explained the factors driving the need to update recurrence rate studies, including the growth in the prevalence of ASD in the last decade to 1 in 36. That may be caused partly by “greater awareness and identification of autistic females and cognitively able, verbal children.”
Also, new diagnostic criteria have been published, with different diagnostic thresholds since the last study. This study, they noted, had a sample size twice as large and more diverse than the 2011 sample.
The size and the diversity are particularly important, Dr. Rybczynski said, as it helps support more recent findings that ASD is not as heavily centered in White males as previously thought.
“We need to make sure we’re monitoring all children, especially from groups where there’s at least one older sibling or multiple siblings with autism or a sister with autism,” she said. The findings of this study are important not just for pediatricians but for families and all who have professional interactions with children.
Dr. Ozonoff reports travel reimbursements and honoraria from Autism Speaks and the Autism Science Foundation and book royalties from Guilford Press. One coauthor has served as a paid consultant to F. Hoffmann–La Roche and Servier and has received royalties from Sage Publications and Guilford Publications. Another is supported by the Stollery Children’s Hospital Foundation Chair in Autism. One coauthor reported a consulting agreement with EarliTec Diagnostics and book royalties from Wiley. A fourth coauthor has received funding from the Simons Foundation and consults for the Beasley Law Firm and Linus Technology. Dr. Rybczynski reported no relevant financial relationships.
FROM PEDIATRICS
Guidance on How Best to Manage Opioid Risks in Older Adults
Polypharmacy and slow metabolism of drugs create a high risk among older adults for substance use disorder, raising the odds of intentional and unintentional overdoses. However, screening, assessment, and treatment for substance use disorder occurs less often in younger adults.
Rates of overdose from opioids increased the most among people aged 65 years and older from 2021 to 2022, compared with among younger age groups. Meanwhile, recent data show less than half older adults with opioid use disorder (OUD) receive care for the condition.
“Nobody is immune to developing some kind of use disorder, so don’t just assume that because someone’s 80 years old that there’s no way that they have a problem,” said Sara Meyer, PharmD, a medication safety pharmacist at Novant Health in Winston-Salem, North Carolina. “You never know who’s going to potentially have an issue.”
in an effort to reduce addiction and overdoses.
Older Adults Have Unique Needs
A major challenge of treating older adults is their high incidence of chronic pain and multiple complex chronic conditions. As a result, some of the nonopioid medications clinicians might otherwise prescribe, like nonsteroidal anti-inflammatory drugs, cannot be used, according to Caroline Goldzweig, MD, chief medical officer of the Cedars-Sinai Medical Network in Los Angeles, California.
“Before you know it, the only thing left is an opiate, so you can sometimes be between a rock and a hard place,” she said.
But for adults older than 65 years, opioids can carry problematic side effects, including sedation, cognitive impairment, falls, and fractures.
With those factors in mind, part of a yearly checkup or wellness visit should include time to discuss how a patient is managing their chronic pain, according to Timothy Anderson, MD, an assistant professor of medicine at the University of Pittsburgh, Pittsburgh, Pennsylvania, and codirector of the Prescribing Wisely Lab, a research collaboration between that institution and Beth Israel Deaconess Medical Center in Boston.
When considering a prescription for pain medication, Dr. Anderson said he evaluates the potential worst, best, and average outcomes for a patient. Nonopioid options should always be considered first-line treatment. Patients and physicians often struggle with balancing an option that meets a patient’s goals for pain relief but does not put them at a risk for adverse outcomes, he said.
Greater Risk
Older adults experience neurophysiologic effects different from younger people, said Benjamin Han, MD, a geriatrician and addiction medicine specialist at the University of California, San Diego.
Seniors also absorb, metabolize, and excrete drugs differently, sometimes affected by decreased production of gastric acid, lean body mass, and renal function. Coupled with complications of other chronic conditions or medications, diagnosing problematic opioid use or OUD can be one of the most challenging experiences in geriatrics, Dr. Han said.
As a result, OUD is often underdiagnosed in these patients, he said. Single-item screening tools like the TAPS and OWLS can be used to assess if the benefits of an opioid outweigh a patient’s risk for addiction.
Dr. Han finds medications like buprenorphine to be relatively safe and effective, along with nonpharmacologic interventions like physical therapy. He also advised clinicians to provide patients with opioid-overdose reversal agents.
“Naloxone is only used for reversing opioid withdrawal, but it is important to ensure that any patient at risk for an overdose, including being on chronic opioids, is provided naloxone and educated on preventing opioid overdoses,” he said.
Steroid injections and medications that target specific pathways, such as neuropathic pain, can be helpful in primary care for these older patients, according to Pooja Lagisetty, MD, an internal medicine physician at Michigan Medicine and a research scientist at VA Ann Arbor Health Care, Ann Arbor, Michigan.
She often recommends to her patients online programs that help them maintain strength and mobility, as well as low-impact exercises like tai chi, for pain management.
“This will ensure a much more balanced, patient-centered conversation with whatever decisions you and your patient come to,” Dr. Lagisetty said.
New Protocols for Pain Management in Older Adults
At the health system level, clinicians can use treatment agreements for patients taking opioids. At Novant, patients must attest they agree to take the medications only as prescribed and from a specified pharmacy. They promise not to seek opioids from other sources, to submit to random drug screenings, and to communicate regularly with their clinician about any health issues.
If a patient violates any part of this agreement, their clinician can stop the treatment. The system encourages clinicians to help patients find additional care for substance abuse disorder or pain management if it occurs.
Over the past 2 years, Novant also developed an AI prediction model, which generates a score for the risk a patient has in developing substance use disorder or experiencing an overdose within a year of initial opioid prescription. The model was validated by an internal team at the system but has not been independently certified.
If a patient has a high-risk score, their clinician considers additional risk mitigation strategies, such as seeing the patient more frequently or using an abuse deterrent formulation of an opioid. They also have the option of referring the patient to specialists in addiction medicine or neurology. Opioids are not necessarily withheld, according to Dr. Meyer. The tool is now used by clinicians during Medicare annual wellness visits.
And coming later this year are new protocols for pain management in patients aged 80 years and older. Clinicians will target a 50% dose reduction, compared with what a younger patient might receive to account for physiologic differences.
“We know that especially with some opioids like morphine, they’re not going to metabolize that the same way a young person with a young kidney will, so we’re trying to set the clinician up to select a lower starting dose for patients that are older,” Dr. Meyer said.
In 2017, the system implemented a program to reduce prescription of opioids to less than 350 morphine milligram equivalents (MME) per order following any kind of surgery. The health system compared numbers of prescriptions written among surgical colleagues and met with them to discuss alternative approaches. Novant said it continues to monitor the data and follow-up with surgeons who are not in alignment with the goal.
Between 2017 and 2019, patients switching to lower doses after surgeries rose by 20%.
Across the country at Cedars-Sinai Medical Network, leadership in 2016 made the move to deprescribe opioids or lower doses of the drugs to less than 90 MME per day, in accordance with Centers for Disease Control and Prevention guidelines established that year. Patients were referred to their pain program for support and for nonopioid interventions. Pharmacists worked closely with clinicians on safely tapering these medications in patients taking high doses.
The program worked, according to Dr. Goldzweig. Dr. Goldzweig could only find two patients currently taking high-dose opioids in the system’s database out of more than 7000 patients with Medicare Advantage insurance coverage.
“There will always be some patients who have no alternative than opioids, but we established some discipline with urine tox screens and pain agreements, and over time, we’ve been able to reduce the number of high-risk opioid prescriptions,” she said.
A version of this article first appeared on Medscape.com.
Polypharmacy and slow metabolism of drugs create a high risk among older adults for substance use disorder, raising the odds of intentional and unintentional overdoses. However, screening, assessment, and treatment for substance use disorder occurs less often in younger adults.
Rates of overdose from opioids increased the most among people aged 65 years and older from 2021 to 2022, compared with among younger age groups. Meanwhile, recent data show less than half older adults with opioid use disorder (OUD) receive care for the condition.
“Nobody is immune to developing some kind of use disorder, so don’t just assume that because someone’s 80 years old that there’s no way that they have a problem,” said Sara Meyer, PharmD, a medication safety pharmacist at Novant Health in Winston-Salem, North Carolina. “You never know who’s going to potentially have an issue.”
in an effort to reduce addiction and overdoses.
Older Adults Have Unique Needs
A major challenge of treating older adults is their high incidence of chronic pain and multiple complex chronic conditions. As a result, some of the nonopioid medications clinicians might otherwise prescribe, like nonsteroidal anti-inflammatory drugs, cannot be used, according to Caroline Goldzweig, MD, chief medical officer of the Cedars-Sinai Medical Network in Los Angeles, California.
“Before you know it, the only thing left is an opiate, so you can sometimes be between a rock and a hard place,” she said.
But for adults older than 65 years, opioids can carry problematic side effects, including sedation, cognitive impairment, falls, and fractures.
With those factors in mind, part of a yearly checkup or wellness visit should include time to discuss how a patient is managing their chronic pain, according to Timothy Anderson, MD, an assistant professor of medicine at the University of Pittsburgh, Pittsburgh, Pennsylvania, and codirector of the Prescribing Wisely Lab, a research collaboration between that institution and Beth Israel Deaconess Medical Center in Boston.
When considering a prescription for pain medication, Dr. Anderson said he evaluates the potential worst, best, and average outcomes for a patient. Nonopioid options should always be considered first-line treatment. Patients and physicians often struggle with balancing an option that meets a patient’s goals for pain relief but does not put them at a risk for adverse outcomes, he said.
Greater Risk
Older adults experience neurophysiologic effects different from younger people, said Benjamin Han, MD, a geriatrician and addiction medicine specialist at the University of California, San Diego.
Seniors also absorb, metabolize, and excrete drugs differently, sometimes affected by decreased production of gastric acid, lean body mass, and renal function. Coupled with complications of other chronic conditions or medications, diagnosing problematic opioid use or OUD can be one of the most challenging experiences in geriatrics, Dr. Han said.
As a result, OUD is often underdiagnosed in these patients, he said. Single-item screening tools like the TAPS and OWLS can be used to assess if the benefits of an opioid outweigh a patient’s risk for addiction.
Dr. Han finds medications like buprenorphine to be relatively safe and effective, along with nonpharmacologic interventions like physical therapy. He also advised clinicians to provide patients with opioid-overdose reversal agents.
“Naloxone is only used for reversing opioid withdrawal, but it is important to ensure that any patient at risk for an overdose, including being on chronic opioids, is provided naloxone and educated on preventing opioid overdoses,” he said.
Steroid injections and medications that target specific pathways, such as neuropathic pain, can be helpful in primary care for these older patients, according to Pooja Lagisetty, MD, an internal medicine physician at Michigan Medicine and a research scientist at VA Ann Arbor Health Care, Ann Arbor, Michigan.
She often recommends to her patients online programs that help them maintain strength and mobility, as well as low-impact exercises like tai chi, for pain management.
“This will ensure a much more balanced, patient-centered conversation with whatever decisions you and your patient come to,” Dr. Lagisetty said.
New Protocols for Pain Management in Older Adults
At the health system level, clinicians can use treatment agreements for patients taking opioids. At Novant, patients must attest they agree to take the medications only as prescribed and from a specified pharmacy. They promise not to seek opioids from other sources, to submit to random drug screenings, and to communicate regularly with their clinician about any health issues.
If a patient violates any part of this agreement, their clinician can stop the treatment. The system encourages clinicians to help patients find additional care for substance abuse disorder or pain management if it occurs.
Over the past 2 years, Novant also developed an AI prediction model, which generates a score for the risk a patient has in developing substance use disorder or experiencing an overdose within a year of initial opioid prescription. The model was validated by an internal team at the system but has not been independently certified.
If a patient has a high-risk score, their clinician considers additional risk mitigation strategies, such as seeing the patient more frequently or using an abuse deterrent formulation of an opioid. They also have the option of referring the patient to specialists in addiction medicine or neurology. Opioids are not necessarily withheld, according to Dr. Meyer. The tool is now used by clinicians during Medicare annual wellness visits.
And coming later this year are new protocols for pain management in patients aged 80 years and older. Clinicians will target a 50% dose reduction, compared with what a younger patient might receive to account for physiologic differences.
“We know that especially with some opioids like morphine, they’re not going to metabolize that the same way a young person with a young kidney will, so we’re trying to set the clinician up to select a lower starting dose for patients that are older,” Dr. Meyer said.
In 2017, the system implemented a program to reduce prescription of opioids to less than 350 morphine milligram equivalents (MME) per order following any kind of surgery. The health system compared numbers of prescriptions written among surgical colleagues and met with them to discuss alternative approaches. Novant said it continues to monitor the data and follow-up with surgeons who are not in alignment with the goal.
Between 2017 and 2019, patients switching to lower doses after surgeries rose by 20%.
Across the country at Cedars-Sinai Medical Network, leadership in 2016 made the move to deprescribe opioids or lower doses of the drugs to less than 90 MME per day, in accordance with Centers for Disease Control and Prevention guidelines established that year. Patients were referred to their pain program for support and for nonopioid interventions. Pharmacists worked closely with clinicians on safely tapering these medications in patients taking high doses.
The program worked, according to Dr. Goldzweig. Dr. Goldzweig could only find two patients currently taking high-dose opioids in the system’s database out of more than 7000 patients with Medicare Advantage insurance coverage.
“There will always be some patients who have no alternative than opioids, but we established some discipline with urine tox screens and pain agreements, and over time, we’ve been able to reduce the number of high-risk opioid prescriptions,” she said.
A version of this article first appeared on Medscape.com.
Polypharmacy and slow metabolism of drugs create a high risk among older adults for substance use disorder, raising the odds of intentional and unintentional overdoses. However, screening, assessment, and treatment for substance use disorder occurs less often in younger adults.
Rates of overdose from opioids increased the most among people aged 65 years and older from 2021 to 2022, compared with among younger age groups. Meanwhile, recent data show less than half older adults with opioid use disorder (OUD) receive care for the condition.
“Nobody is immune to developing some kind of use disorder, so don’t just assume that because someone’s 80 years old that there’s no way that they have a problem,” said Sara Meyer, PharmD, a medication safety pharmacist at Novant Health in Winston-Salem, North Carolina. “You never know who’s going to potentially have an issue.”
in an effort to reduce addiction and overdoses.
Older Adults Have Unique Needs
A major challenge of treating older adults is their high incidence of chronic pain and multiple complex chronic conditions. As a result, some of the nonopioid medications clinicians might otherwise prescribe, like nonsteroidal anti-inflammatory drugs, cannot be used, according to Caroline Goldzweig, MD, chief medical officer of the Cedars-Sinai Medical Network in Los Angeles, California.
“Before you know it, the only thing left is an opiate, so you can sometimes be between a rock and a hard place,” she said.
But for adults older than 65 years, opioids can carry problematic side effects, including sedation, cognitive impairment, falls, and fractures.
With those factors in mind, part of a yearly checkup or wellness visit should include time to discuss how a patient is managing their chronic pain, according to Timothy Anderson, MD, an assistant professor of medicine at the University of Pittsburgh, Pittsburgh, Pennsylvania, and codirector of the Prescribing Wisely Lab, a research collaboration between that institution and Beth Israel Deaconess Medical Center in Boston.
When considering a prescription for pain medication, Dr. Anderson said he evaluates the potential worst, best, and average outcomes for a patient. Nonopioid options should always be considered first-line treatment. Patients and physicians often struggle with balancing an option that meets a patient’s goals for pain relief but does not put them at a risk for adverse outcomes, he said.
Greater Risk
Older adults experience neurophysiologic effects different from younger people, said Benjamin Han, MD, a geriatrician and addiction medicine specialist at the University of California, San Diego.
Seniors also absorb, metabolize, and excrete drugs differently, sometimes affected by decreased production of gastric acid, lean body mass, and renal function. Coupled with complications of other chronic conditions or medications, diagnosing problematic opioid use or OUD can be one of the most challenging experiences in geriatrics, Dr. Han said.
As a result, OUD is often underdiagnosed in these patients, he said. Single-item screening tools like the TAPS and OWLS can be used to assess if the benefits of an opioid outweigh a patient’s risk for addiction.
Dr. Han finds medications like buprenorphine to be relatively safe and effective, along with nonpharmacologic interventions like physical therapy. He also advised clinicians to provide patients with opioid-overdose reversal agents.
“Naloxone is only used for reversing opioid withdrawal, but it is important to ensure that any patient at risk for an overdose, including being on chronic opioids, is provided naloxone and educated on preventing opioid overdoses,” he said.
Steroid injections and medications that target specific pathways, such as neuropathic pain, can be helpful in primary care for these older patients, according to Pooja Lagisetty, MD, an internal medicine physician at Michigan Medicine and a research scientist at VA Ann Arbor Health Care, Ann Arbor, Michigan.
She often recommends to her patients online programs that help them maintain strength and mobility, as well as low-impact exercises like tai chi, for pain management.
“This will ensure a much more balanced, patient-centered conversation with whatever decisions you and your patient come to,” Dr. Lagisetty said.
New Protocols for Pain Management in Older Adults
At the health system level, clinicians can use treatment agreements for patients taking opioids. At Novant, patients must attest they agree to take the medications only as prescribed and from a specified pharmacy. They promise not to seek opioids from other sources, to submit to random drug screenings, and to communicate regularly with their clinician about any health issues.
If a patient violates any part of this agreement, their clinician can stop the treatment. The system encourages clinicians to help patients find additional care for substance abuse disorder or pain management if it occurs.
Over the past 2 years, Novant also developed an AI prediction model, which generates a score for the risk a patient has in developing substance use disorder or experiencing an overdose within a year of initial opioid prescription. The model was validated by an internal team at the system but has not been independently certified.
If a patient has a high-risk score, their clinician considers additional risk mitigation strategies, such as seeing the patient more frequently or using an abuse deterrent formulation of an opioid. They also have the option of referring the patient to specialists in addiction medicine or neurology. Opioids are not necessarily withheld, according to Dr. Meyer. The tool is now used by clinicians during Medicare annual wellness visits.
And coming later this year are new protocols for pain management in patients aged 80 years and older. Clinicians will target a 50% dose reduction, compared with what a younger patient might receive to account for physiologic differences.
“We know that especially with some opioids like morphine, they’re not going to metabolize that the same way a young person with a young kidney will, so we’re trying to set the clinician up to select a lower starting dose for patients that are older,” Dr. Meyer said.
In 2017, the system implemented a program to reduce prescription of opioids to less than 350 morphine milligram equivalents (MME) per order following any kind of surgery. The health system compared numbers of prescriptions written among surgical colleagues and met with them to discuss alternative approaches. Novant said it continues to monitor the data and follow-up with surgeons who are not in alignment with the goal.
Between 2017 and 2019, patients switching to lower doses after surgeries rose by 20%.
Across the country at Cedars-Sinai Medical Network, leadership in 2016 made the move to deprescribe opioids or lower doses of the drugs to less than 90 MME per day, in accordance with Centers for Disease Control and Prevention guidelines established that year. Patients were referred to their pain program for support and for nonopioid interventions. Pharmacists worked closely with clinicians on safely tapering these medications in patients taking high doses.
The program worked, according to Dr. Goldzweig. Dr. Goldzweig could only find two patients currently taking high-dose opioids in the system’s database out of more than 7000 patients with Medicare Advantage insurance coverage.
“There will always be some patients who have no alternative than opioids, but we established some discipline with urine tox screens and pain agreements, and over time, we’ve been able to reduce the number of high-risk opioid prescriptions,” she said.
A version of this article first appeared on Medscape.com.
School Avoidance
The start of the school year is a time that is always full of anticipation and even anxiety. Who will my teachers be? Will I be in classes with friends? Have some of my friends changed over the summer? Will the work be too hard? For some children this anxiety will be so intense that they will resist going back to school. School avoidance is very important to identify and address quickly, as it can intensify and threaten development. Each day of school missed due to accommodating to a child’s anxiety makes a return to school more difficult and less likely. Days can easily become weeks and even months of missed school. A child who misses a substantial amount of school is inevitably going to face developmental delays: academic, social, behavioral and emotional. The pediatrician is often brought into these situations early, as when a child complains of vague physical symptoms that are keeping him or her from school or when a previously calm child becomes inconsolable about going to school in the mornings. With a thoughtful assessment of the potential causes of school avoidance, you can help almost all children return to school successfully.
School Refusal
Sustained school avoidance is now called “school refusal,” a term coined in the late 1990s to describe a school attendance problem driven by emotional distress, as opposed to truancy. It affects up to 15% of children (depending on the operational definition) and seems to peak in the earliest years of elementary school and again in early high school. These are not occasional absences, but missing over 80% of classroom time in a 2-week period. It is also marked by the presence of an anxiety disorder and the absence of conduct disorder. Often in such cases the parents are aware of their child’s whereabouts and motivated to return them to school. Youth with school refusal experience social and academic consequences in the short term and, over the long term, have shown problems with social, family, and professional performance, along with higher rates of major depressive disorder than is seen in the general population. Early identification of these children can make addressing the underlying distress and return to school much easier than attempts to treat after weeks or months out of school.
Identifying the Problem
With younger children, school avoidance is most commonly associated with an anxious temperament or an underlying anxiety disorder, such as separation anxiety disorder or social phobia. A family history of anxiety may contribute or impact a parent’s approach to the issue. Children often present with vague somatic concerns that are genuine symptoms of anxiety (upset stomach, headache). A screening instrument such as the Screen for Child Anxiety Related Disorders (SCARED) can be helpful, but so is inquiring about sleep and other anxiety symptoms. Do the symptoms remit on weekends or in after-school hours? Are there other environmental factors that may be stressing younger children: Are they being teased or bullied at school? Are they struggling to find friends in a new classroom? Might they be having trouble with reading or other new tasks? Perhaps they are afraid of walking to school alone. Has there been a recent change or stress at home, such as a move or parental illness? Younger children may feel more anxious about separating from parents in the face of stress. But when parents accommodate a child’s wish to avoid school, the child’s anxiety, briefly relieved, grows more persistent, gets rewarded by parental attention, and reinforces their reluctance to try new things.
Adolescents may be facing more complex challenges that lead to school avoidance. They may have an undiagnosed anxiety or mood disorder, perhaps complicated by substance abuse that is presenting as an inability to perform at school or to manage the challenge of keeping up with higher workloads. They may be facing complex situations with friends, bullying, or rejection. Those adolescents who are prone to procrastination may avoid school to manage their workload and their distress, which can then become tangled up with symptoms of anxiety and dysphoria. Missing school compounds this problem rather than solving it. Adolescents outside of the structure of school, hungry for socializing and new experiences, often turn to social media for entertainment. Days without exercise and nights without adequate sleep can make mood, attention, and anxiety symptoms worse while overdue work grows. Parents often fear that setting limits or “pushing” their stuck and miserable child may make them more depressed or even suicidal.
Accommodating the Problem Will Likely Make It Worse
It is worth noting that children with a genuine medical illness can also experience school avoidance. Temperamentally anxious children who stay home for several days with a febrile illness may find it overwhelming to return to school as they have become so comfortable at home. Adolescents may have fallen behind with work and find themselves unable to set a schedule and return to more structure. Youth who are managing a known mood or anxiety disorder often have low motivation or high anxiety and want to wait to feel entirely better before returning to school. Youth with a chronic condition such as severe allergies or a sustained viral infection may be anxious about managing symptoms at school. Their parents may have kept them home to be safe or until they feel better, unwittingly making the school avoidance worse.
Formulating a Management Plan
When you suspect school avoidance is present, the critical first step is to engage the parents alongside their child. Without their understanding of the nature of this behavior, it will continue. Start by acknowledging the real physical and emotional symptoms their child is experiencing; it is important that parents and patients not feel that they are being told this is “just” a psychological problem. Children rarely feign illness or manipulate; they genuinely feel bad enough to stay home. It is important that they understand this is a common problem that will get worse unless it is addressed directly. If you believe they are suffering from a mood or anxiety disorder, talk about treatment options and consider getting started with treatment while finding a therapist to participate in their care. Help everyone listen to the child or teenager to understand any realistic basis for anxiety and attempt to address it (e.g. address bullying, provide a tutor, support a parent dependent on the child, etc.)
You can partner with parents and the school to provide the child with structure and support to make the return to school manageable. Frame the challenge of “demagnetizing” home and “remagnetizing” school. When they are at home, there should be no screen time except to catch up or keep up with homework. The child should not be in bed all day unless he or she has a fever. There needs to be close attention paid to maintaining a regular routine, with bedtime and wake time, meals with family, and regular exercise. This may mean turning off the Wi-Fi while a child is at home and parents are at work and providing them with books.
Work with the school to make getting into school and staying there as easy as possible. If a child has very high distress or has been out of school for a long time, he or she may need to return gradually; perhaps aim for the child to spend an hour at school for the first few days and then gradually work up to half and full days. Younger children may benefit from having a “buddy” who meets them outside and enters school with them. This can help avoid intense emotional scenes with parents that heighten distress and lead to accommodation. The child can identify a preferred teacher (or librarian, coach, or school nurse). When they feel overwhelmed, they can have a “break” with that teacher to avoid leaving school altogether. If they enjoy sports, music, or art, emphasize these classes or practices as part of their return to school.
Remind parents and your patients that it is not a matter of making the distress better first and then returning to school. They can be in treatment for an illness and manage returning to school at the same time. Indeed, the distress around school will only get better by getting back to school. This is hard! Ask about previous challenges they have managed or mastered and remind them that this is no different. Providing parents with knowledge and support will help them to be validating of their children without accommodating their wish to avoid discomfort. This support of your patient and the parents is the first step in helping them manage a difficult period and stay on their healthiest developmental trajectory.
Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at [email protected].
The start of the school year is a time that is always full of anticipation and even anxiety. Who will my teachers be? Will I be in classes with friends? Have some of my friends changed over the summer? Will the work be too hard? For some children this anxiety will be so intense that they will resist going back to school. School avoidance is very important to identify and address quickly, as it can intensify and threaten development. Each day of school missed due to accommodating to a child’s anxiety makes a return to school more difficult and less likely. Days can easily become weeks and even months of missed school. A child who misses a substantial amount of school is inevitably going to face developmental delays: academic, social, behavioral and emotional. The pediatrician is often brought into these situations early, as when a child complains of vague physical symptoms that are keeping him or her from school or when a previously calm child becomes inconsolable about going to school in the mornings. With a thoughtful assessment of the potential causes of school avoidance, you can help almost all children return to school successfully.
School Refusal
Sustained school avoidance is now called “school refusal,” a term coined in the late 1990s to describe a school attendance problem driven by emotional distress, as opposed to truancy. It affects up to 15% of children (depending on the operational definition) and seems to peak in the earliest years of elementary school and again in early high school. These are not occasional absences, but missing over 80% of classroom time in a 2-week period. It is also marked by the presence of an anxiety disorder and the absence of conduct disorder. Often in such cases the parents are aware of their child’s whereabouts and motivated to return them to school. Youth with school refusal experience social and academic consequences in the short term and, over the long term, have shown problems with social, family, and professional performance, along with higher rates of major depressive disorder than is seen in the general population. Early identification of these children can make addressing the underlying distress and return to school much easier than attempts to treat after weeks or months out of school.
Identifying the Problem
With younger children, school avoidance is most commonly associated with an anxious temperament or an underlying anxiety disorder, such as separation anxiety disorder or social phobia. A family history of anxiety may contribute or impact a parent’s approach to the issue. Children often present with vague somatic concerns that are genuine symptoms of anxiety (upset stomach, headache). A screening instrument such as the Screen for Child Anxiety Related Disorders (SCARED) can be helpful, but so is inquiring about sleep and other anxiety symptoms. Do the symptoms remit on weekends or in after-school hours? Are there other environmental factors that may be stressing younger children: Are they being teased or bullied at school? Are they struggling to find friends in a new classroom? Might they be having trouble with reading or other new tasks? Perhaps they are afraid of walking to school alone. Has there been a recent change or stress at home, such as a move or parental illness? Younger children may feel more anxious about separating from parents in the face of stress. But when parents accommodate a child’s wish to avoid school, the child’s anxiety, briefly relieved, grows more persistent, gets rewarded by parental attention, and reinforces their reluctance to try new things.
Adolescents may be facing more complex challenges that lead to school avoidance. They may have an undiagnosed anxiety or mood disorder, perhaps complicated by substance abuse that is presenting as an inability to perform at school or to manage the challenge of keeping up with higher workloads. They may be facing complex situations with friends, bullying, or rejection. Those adolescents who are prone to procrastination may avoid school to manage their workload and their distress, which can then become tangled up with symptoms of anxiety and dysphoria. Missing school compounds this problem rather than solving it. Adolescents outside of the structure of school, hungry for socializing and new experiences, often turn to social media for entertainment. Days without exercise and nights without adequate sleep can make mood, attention, and anxiety symptoms worse while overdue work grows. Parents often fear that setting limits or “pushing” their stuck and miserable child may make them more depressed or even suicidal.
Accommodating the Problem Will Likely Make It Worse
It is worth noting that children with a genuine medical illness can also experience school avoidance. Temperamentally anxious children who stay home for several days with a febrile illness may find it overwhelming to return to school as they have become so comfortable at home. Adolescents may have fallen behind with work and find themselves unable to set a schedule and return to more structure. Youth who are managing a known mood or anxiety disorder often have low motivation or high anxiety and want to wait to feel entirely better before returning to school. Youth with a chronic condition such as severe allergies or a sustained viral infection may be anxious about managing symptoms at school. Their parents may have kept them home to be safe or until they feel better, unwittingly making the school avoidance worse.
Formulating a Management Plan
When you suspect school avoidance is present, the critical first step is to engage the parents alongside their child. Without their understanding of the nature of this behavior, it will continue. Start by acknowledging the real physical and emotional symptoms their child is experiencing; it is important that parents and patients not feel that they are being told this is “just” a psychological problem. Children rarely feign illness or manipulate; they genuinely feel bad enough to stay home. It is important that they understand this is a common problem that will get worse unless it is addressed directly. If you believe they are suffering from a mood or anxiety disorder, talk about treatment options and consider getting started with treatment while finding a therapist to participate in their care. Help everyone listen to the child or teenager to understand any realistic basis for anxiety and attempt to address it (e.g. address bullying, provide a tutor, support a parent dependent on the child, etc.)
You can partner with parents and the school to provide the child with structure and support to make the return to school manageable. Frame the challenge of “demagnetizing” home and “remagnetizing” school. When they are at home, there should be no screen time except to catch up or keep up with homework. The child should not be in bed all day unless he or she has a fever. There needs to be close attention paid to maintaining a regular routine, with bedtime and wake time, meals with family, and regular exercise. This may mean turning off the Wi-Fi while a child is at home and parents are at work and providing them with books.
Work with the school to make getting into school and staying there as easy as possible. If a child has very high distress or has been out of school for a long time, he or she may need to return gradually; perhaps aim for the child to spend an hour at school for the first few days and then gradually work up to half and full days. Younger children may benefit from having a “buddy” who meets them outside and enters school with them. This can help avoid intense emotional scenes with parents that heighten distress and lead to accommodation. The child can identify a preferred teacher (or librarian, coach, or school nurse). When they feel overwhelmed, they can have a “break” with that teacher to avoid leaving school altogether. If they enjoy sports, music, or art, emphasize these classes or practices as part of their return to school.
Remind parents and your patients that it is not a matter of making the distress better first and then returning to school. They can be in treatment for an illness and manage returning to school at the same time. Indeed, the distress around school will only get better by getting back to school. This is hard! Ask about previous challenges they have managed or mastered and remind them that this is no different. Providing parents with knowledge and support will help them to be validating of their children without accommodating their wish to avoid discomfort. This support of your patient and the parents is the first step in helping them manage a difficult period and stay on their healthiest developmental trajectory.
Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at [email protected].
The start of the school year is a time that is always full of anticipation and even anxiety. Who will my teachers be? Will I be in classes with friends? Have some of my friends changed over the summer? Will the work be too hard? For some children this anxiety will be so intense that they will resist going back to school. School avoidance is very important to identify and address quickly, as it can intensify and threaten development. Each day of school missed due to accommodating to a child’s anxiety makes a return to school more difficult and less likely. Days can easily become weeks and even months of missed school. A child who misses a substantial amount of school is inevitably going to face developmental delays: academic, social, behavioral and emotional. The pediatrician is often brought into these situations early, as when a child complains of vague physical symptoms that are keeping him or her from school or when a previously calm child becomes inconsolable about going to school in the mornings. With a thoughtful assessment of the potential causes of school avoidance, you can help almost all children return to school successfully.
School Refusal
Sustained school avoidance is now called “school refusal,” a term coined in the late 1990s to describe a school attendance problem driven by emotional distress, as opposed to truancy. It affects up to 15% of children (depending on the operational definition) and seems to peak in the earliest years of elementary school and again in early high school. These are not occasional absences, but missing over 80% of classroom time in a 2-week period. It is also marked by the presence of an anxiety disorder and the absence of conduct disorder. Often in such cases the parents are aware of their child’s whereabouts and motivated to return them to school. Youth with school refusal experience social and academic consequences in the short term and, over the long term, have shown problems with social, family, and professional performance, along with higher rates of major depressive disorder than is seen in the general population. Early identification of these children can make addressing the underlying distress and return to school much easier than attempts to treat after weeks or months out of school.
Identifying the Problem
With younger children, school avoidance is most commonly associated with an anxious temperament or an underlying anxiety disorder, such as separation anxiety disorder or social phobia. A family history of anxiety may contribute or impact a parent’s approach to the issue. Children often present with vague somatic concerns that are genuine symptoms of anxiety (upset stomach, headache). A screening instrument such as the Screen for Child Anxiety Related Disorders (SCARED) can be helpful, but so is inquiring about sleep and other anxiety symptoms. Do the symptoms remit on weekends or in after-school hours? Are there other environmental factors that may be stressing younger children: Are they being teased or bullied at school? Are they struggling to find friends in a new classroom? Might they be having trouble with reading or other new tasks? Perhaps they are afraid of walking to school alone. Has there been a recent change or stress at home, such as a move or parental illness? Younger children may feel more anxious about separating from parents in the face of stress. But when parents accommodate a child’s wish to avoid school, the child’s anxiety, briefly relieved, grows more persistent, gets rewarded by parental attention, and reinforces their reluctance to try new things.
Adolescents may be facing more complex challenges that lead to school avoidance. They may have an undiagnosed anxiety or mood disorder, perhaps complicated by substance abuse that is presenting as an inability to perform at school or to manage the challenge of keeping up with higher workloads. They may be facing complex situations with friends, bullying, or rejection. Those adolescents who are prone to procrastination may avoid school to manage their workload and their distress, which can then become tangled up with symptoms of anxiety and dysphoria. Missing school compounds this problem rather than solving it. Adolescents outside of the structure of school, hungry for socializing and new experiences, often turn to social media for entertainment. Days without exercise and nights without adequate sleep can make mood, attention, and anxiety symptoms worse while overdue work grows. Parents often fear that setting limits or “pushing” their stuck and miserable child may make them more depressed or even suicidal.
Accommodating the Problem Will Likely Make It Worse
It is worth noting that children with a genuine medical illness can also experience school avoidance. Temperamentally anxious children who stay home for several days with a febrile illness may find it overwhelming to return to school as they have become so comfortable at home. Adolescents may have fallen behind with work and find themselves unable to set a schedule and return to more structure. Youth who are managing a known mood or anxiety disorder often have low motivation or high anxiety and want to wait to feel entirely better before returning to school. Youth with a chronic condition such as severe allergies or a sustained viral infection may be anxious about managing symptoms at school. Their parents may have kept them home to be safe or until they feel better, unwittingly making the school avoidance worse.
Formulating a Management Plan
When you suspect school avoidance is present, the critical first step is to engage the parents alongside their child. Without their understanding of the nature of this behavior, it will continue. Start by acknowledging the real physical and emotional symptoms their child is experiencing; it is important that parents and patients not feel that they are being told this is “just” a psychological problem. Children rarely feign illness or manipulate; they genuinely feel bad enough to stay home. It is important that they understand this is a common problem that will get worse unless it is addressed directly. If you believe they are suffering from a mood or anxiety disorder, talk about treatment options and consider getting started with treatment while finding a therapist to participate in their care. Help everyone listen to the child or teenager to understand any realistic basis for anxiety and attempt to address it (e.g. address bullying, provide a tutor, support a parent dependent on the child, etc.)
You can partner with parents and the school to provide the child with structure and support to make the return to school manageable. Frame the challenge of “demagnetizing” home and “remagnetizing” school. When they are at home, there should be no screen time except to catch up or keep up with homework. The child should not be in bed all day unless he or she has a fever. There needs to be close attention paid to maintaining a regular routine, with bedtime and wake time, meals with family, and regular exercise. This may mean turning off the Wi-Fi while a child is at home and parents are at work and providing them with books.
Work with the school to make getting into school and staying there as easy as possible. If a child has very high distress or has been out of school for a long time, he or she may need to return gradually; perhaps aim for the child to spend an hour at school for the first few days and then gradually work up to half and full days. Younger children may benefit from having a “buddy” who meets them outside and enters school with them. This can help avoid intense emotional scenes with parents that heighten distress and lead to accommodation. The child can identify a preferred teacher (or librarian, coach, or school nurse). When they feel overwhelmed, they can have a “break” with that teacher to avoid leaving school altogether. If they enjoy sports, music, or art, emphasize these classes or practices as part of their return to school.
Remind parents and your patients that it is not a matter of making the distress better first and then returning to school. They can be in treatment for an illness and manage returning to school at the same time. Indeed, the distress around school will only get better by getting back to school. This is hard! Ask about previous challenges they have managed or mastered and remind them that this is no different. Providing parents with knowledge and support will help them to be validating of their children without accommodating their wish to avoid discomfort. This support of your patient and the parents is the first step in helping them manage a difficult period and stay on their healthiest developmental trajectory.
Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at [email protected].
New Mid-Year Vaccine Recommendations From ACIP
This transcript has been edited for clarity.
ACIP, the CDC’s Advisory Committee on Immunization Practices, met for 3 days in June. New vaccines and new recommendations for respiratory syncytial virus (RSV), flu, COVID, and a new pneumococcal vaccine were revealed.
RSV Protection
We’ll begin with RSV vaccines for adults aged 60 or older. For this group, shared clinical decision-making is out; it no longer applies. New, more specific recommendations from ACIP for RSV vaccines are both age based and risk based. The age-based recommendation applies to those aged 75 or older, who should receive a single RSV vaccine dose. If they have already received a dose under the old recommendation, they don’t need another one, at least for now.
The risk-based recommendation applies to adults from age 60 up to 75, but only for those with risk factors for severe RSV. These risk factors include lung disease, heart disease, immunocompromise, diabetes, obesity with a BMI of 40 or more, neurologic conditions, neuromuscular conditions, chronic kidney disease, liver disorders, hematologic disorders, frailty, and living in a nursing home or other long-term care facility. Those aged 60-75 with these risk factors should receive the RSV vaccine, and those without them should not receive it. The best time to get the RSV vaccine is late summer, but early fall administration with other adult vaccines is allowed and is acceptable.
Vaccine safety concerns were top of mind as ACIP members began their deliberations. Possible safety concerns for RSV vaccines have been detected for Guillain-Barré syndrome, atrial fibrillation, and idiopathic thrombocytopenic purpura. Safety surveillance updates are still interim and inconclusive. These signals still need further study and clarification.
Two RSV vaccines have been on the market: one by Pfizer, called Abrysvo, which does not contain an adjuvant; and another one by GSK, called Arexvy, which does contain an adjuvant. With the recent FDA approval of Moderna’s new mRNA RSV vaccine, mRESVIA, there are now three RSV vaccines licensed for those 60 or older. Arexvy is now FDA approved for adults in their 50s. That just happened in early June, but ACIP doesn’t currently recommend it for this fifty-something age group, even for those at high risk for severe RSV disease. This may change with greater clarification of potential vaccine safety concerns.
There is also news about protecting babies from RSV. RSV is the most common cause of hospitalization for infants in the United States, and most hospitalizations for RSV are in healthy, full-term infants. We now have two ways to protect babies: a dose of RSV vaccine given to mom, or a dose of the long-acting monoclonal antibody nirsevimab given to the baby. ACIP clarified that those who received a dose of maternal RSV vaccine during a previous pregnancy are not recommended to receive additional doses during future pregnancies, but infants born to those who were vaccinated for RSV during a prior pregnancy can receive nirsevimab, which is recommended for infants up to 8 months of age during their first RSV season, and for high-risk infants and toddlers aged 8-19 months during their second RSV season.
Last RSV season, supplies of nirsevimab were limited and doses had to be prioritized. No supply problems are anticipated for the upcoming season. A study published in March showed that nirsevimab was 90% effective at preventing RSV-associated hospitalization for infants in their first RSV season.
COVID
Here’s what’s new for COVID vaccines. A new-formula COVID vaccine will be ready for fall. ACIP voted unanimously to recommend a dose of the updated 2024-2025 COVID vaccine for everyone aged 6 months or older. This is a universal recommendation, just like the one we have for flu. But understand that even though COVID has waned, it’s still more deadly than flu. Most Americans now have some immunity against COVID, but this immunity wanes with time, and it also wanes as the virus keeps changing. These updated vaccines provide an incremental boost to our immunity for the new formula for fall. FDA has directed manufacturers to use a monovalent JN.1 lineage formula, with a preference for the KP.2 strain.
Older adults (aged 75 or older) and children under 6 months old are hit hardest by COVID. The littlest ones are too young to be vaccinated, but they can get protection from maternal vaccination. The uptake for last year’s COVID vaccine has been disappointing. Only 22.5% of adults and 14% of children received a dose of the updated shot. Focus-group discussions highlight the importance of a physician recommendation. Adults and children who receive a healthcare provider’s recommendation to get the COVID vaccine are more likely to get vaccinated.
Pneumococcal Vaccines
On June 17, 2024, a new pneumococcal vaccine, PCV21, was FDA approved for those aged 18 or older under an accelerated-approval pathway. ACIP voted to keep it simple and recommends PCV21 as an option for adults aged 19 or older who currently have an indication to receive a dose of PCV. This new PCV21 vaccine is indicated for prevention of both invasive pneumococcal disease (IPD) and pneumococcal pneumonia. Its brand name is Capvaxive and it’s made by Merck. IPD includes bacteremia, pneumonia, pneumococcal bacteremia, and meningitis.
There are two basic types of pneumococcal vaccines: polysaccharide vaccines (PPSV), which do not produce memory B cells; and PCV conjugate vaccines, which do trigger memory B-cell production and therefore induce greater long-term immunity. PCV21 covers 11 unique serotypes not in PCV20. This is important because many cases of adult disease are caused by subtypes not covered by other FDA-approved pneumococcal vaccines. PCV21 has greater coverage of the serotypes that cause invasive disease in adults as compared with PCV20. PCV20 covers up to 58% of those strains, while PCV21 covers up to 84% of strains responsible for invasive disease in adults. But there’s one serotype missing in PCV21, which may limit the groups who receive it. PCV21 does not cover serotype 4, a major cause of IPD in certain populations. Adults experiencing homelessness are 100-300 times more likely to develop IPD due to serotype 4. So are adults in Alaska, especially Alaska Natives. They have an 88-fold increase in serotype 4 invasive disease. Serotype 4 is covered by other pneumococcal vaccines, so for these patients, PCV20 is likely a better high-valent conjugate vaccine option than PCV21.
Flu Vaccines
What’s new for flu? Everyone aged 6 months or older needs a seasonal flu vaccination every year. That’s not new, but there are two new things coming this fall: (1) The seasonal flu vaccine is going trivalent. FDA has removed the Yamagata flu B strain because it no longer appears to be circulating. (2) ACIP made a special off-label recommendation to boost flu protection for solid organ transplant recipients ages 18-64 who are on immunosuppressive medications. These high-risk patients now have the off-label option of receiving one of the higher-dose flu vaccines, including high-dose and adjuvanted flu vaccines, which are FDA approved only for those 65 or older.
Sandra Adamson Fryhofer, Adjunct Clinical Associate Professor of Medicine, Emory University School of Medicine, Atlanta, Georgia, has disclosed the following relevant financial relationships: Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for American Medical Association; Medical Association of Atlanta; ACIP liaison. Received income in an amount equal to or greater than $250 from American College of Physicians; Medscape; American Medical Association.
A version of this article first appeared on Medscape.com.
This transcript has been edited for clarity.
ACIP, the CDC’s Advisory Committee on Immunization Practices, met for 3 days in June. New vaccines and new recommendations for respiratory syncytial virus (RSV), flu, COVID, and a new pneumococcal vaccine were revealed.
RSV Protection
We’ll begin with RSV vaccines for adults aged 60 or older. For this group, shared clinical decision-making is out; it no longer applies. New, more specific recommendations from ACIP for RSV vaccines are both age based and risk based. The age-based recommendation applies to those aged 75 or older, who should receive a single RSV vaccine dose. If they have already received a dose under the old recommendation, they don’t need another one, at least for now.
The risk-based recommendation applies to adults from age 60 up to 75, but only for those with risk factors for severe RSV. These risk factors include lung disease, heart disease, immunocompromise, diabetes, obesity with a BMI of 40 or more, neurologic conditions, neuromuscular conditions, chronic kidney disease, liver disorders, hematologic disorders, frailty, and living in a nursing home or other long-term care facility. Those aged 60-75 with these risk factors should receive the RSV vaccine, and those without them should not receive it. The best time to get the RSV vaccine is late summer, but early fall administration with other adult vaccines is allowed and is acceptable.
Vaccine safety concerns were top of mind as ACIP members began their deliberations. Possible safety concerns for RSV vaccines have been detected for Guillain-Barré syndrome, atrial fibrillation, and idiopathic thrombocytopenic purpura. Safety surveillance updates are still interim and inconclusive. These signals still need further study and clarification.
Two RSV vaccines have been on the market: one by Pfizer, called Abrysvo, which does not contain an adjuvant; and another one by GSK, called Arexvy, which does contain an adjuvant. With the recent FDA approval of Moderna’s new mRNA RSV vaccine, mRESVIA, there are now three RSV vaccines licensed for those 60 or older. Arexvy is now FDA approved for adults in their 50s. That just happened in early June, but ACIP doesn’t currently recommend it for this fifty-something age group, even for those at high risk for severe RSV disease. This may change with greater clarification of potential vaccine safety concerns.
There is also news about protecting babies from RSV. RSV is the most common cause of hospitalization for infants in the United States, and most hospitalizations for RSV are in healthy, full-term infants. We now have two ways to protect babies: a dose of RSV vaccine given to mom, or a dose of the long-acting monoclonal antibody nirsevimab given to the baby. ACIP clarified that those who received a dose of maternal RSV vaccine during a previous pregnancy are not recommended to receive additional doses during future pregnancies, but infants born to those who were vaccinated for RSV during a prior pregnancy can receive nirsevimab, which is recommended for infants up to 8 months of age during their first RSV season, and for high-risk infants and toddlers aged 8-19 months during their second RSV season.
Last RSV season, supplies of nirsevimab were limited and doses had to be prioritized. No supply problems are anticipated for the upcoming season. A study published in March showed that nirsevimab was 90% effective at preventing RSV-associated hospitalization for infants in their first RSV season.
COVID
Here’s what’s new for COVID vaccines. A new-formula COVID vaccine will be ready for fall. ACIP voted unanimously to recommend a dose of the updated 2024-2025 COVID vaccine for everyone aged 6 months or older. This is a universal recommendation, just like the one we have for flu. But understand that even though COVID has waned, it’s still more deadly than flu. Most Americans now have some immunity against COVID, but this immunity wanes with time, and it also wanes as the virus keeps changing. These updated vaccines provide an incremental boost to our immunity for the new formula for fall. FDA has directed manufacturers to use a monovalent JN.1 lineage formula, with a preference for the KP.2 strain.
Older adults (aged 75 or older) and children under 6 months old are hit hardest by COVID. The littlest ones are too young to be vaccinated, but they can get protection from maternal vaccination. The uptake for last year’s COVID vaccine has been disappointing. Only 22.5% of adults and 14% of children received a dose of the updated shot. Focus-group discussions highlight the importance of a physician recommendation. Adults and children who receive a healthcare provider’s recommendation to get the COVID vaccine are more likely to get vaccinated.
Pneumococcal Vaccines
On June 17, 2024, a new pneumococcal vaccine, PCV21, was FDA approved for those aged 18 or older under an accelerated-approval pathway. ACIP voted to keep it simple and recommends PCV21 as an option for adults aged 19 or older who currently have an indication to receive a dose of PCV. This new PCV21 vaccine is indicated for prevention of both invasive pneumococcal disease (IPD) and pneumococcal pneumonia. Its brand name is Capvaxive and it’s made by Merck. IPD includes bacteremia, pneumonia, pneumococcal bacteremia, and meningitis.
There are two basic types of pneumococcal vaccines: polysaccharide vaccines (PPSV), which do not produce memory B cells; and PCV conjugate vaccines, which do trigger memory B-cell production and therefore induce greater long-term immunity. PCV21 covers 11 unique serotypes not in PCV20. This is important because many cases of adult disease are caused by subtypes not covered by other FDA-approved pneumococcal vaccines. PCV21 has greater coverage of the serotypes that cause invasive disease in adults as compared with PCV20. PCV20 covers up to 58% of those strains, while PCV21 covers up to 84% of strains responsible for invasive disease in adults. But there’s one serotype missing in PCV21, which may limit the groups who receive it. PCV21 does not cover serotype 4, a major cause of IPD in certain populations. Adults experiencing homelessness are 100-300 times more likely to develop IPD due to serotype 4. So are adults in Alaska, especially Alaska Natives. They have an 88-fold increase in serotype 4 invasive disease. Serotype 4 is covered by other pneumococcal vaccines, so for these patients, PCV20 is likely a better high-valent conjugate vaccine option than PCV21.
Flu Vaccines
What’s new for flu? Everyone aged 6 months or older needs a seasonal flu vaccination every year. That’s not new, but there are two new things coming this fall: (1) The seasonal flu vaccine is going trivalent. FDA has removed the Yamagata flu B strain because it no longer appears to be circulating. (2) ACIP made a special off-label recommendation to boost flu protection for solid organ transplant recipients ages 18-64 who are on immunosuppressive medications. These high-risk patients now have the off-label option of receiving one of the higher-dose flu vaccines, including high-dose and adjuvanted flu vaccines, which are FDA approved only for those 65 or older.
Sandra Adamson Fryhofer, Adjunct Clinical Associate Professor of Medicine, Emory University School of Medicine, Atlanta, Georgia, has disclosed the following relevant financial relationships: Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for American Medical Association; Medical Association of Atlanta; ACIP liaison. Received income in an amount equal to or greater than $250 from American College of Physicians; Medscape; American Medical Association.
A version of this article first appeared on Medscape.com.
This transcript has been edited for clarity.
ACIP, the CDC’s Advisory Committee on Immunization Practices, met for 3 days in June. New vaccines and new recommendations for respiratory syncytial virus (RSV), flu, COVID, and a new pneumococcal vaccine were revealed.
RSV Protection
We’ll begin with RSV vaccines for adults aged 60 or older. For this group, shared clinical decision-making is out; it no longer applies. New, more specific recommendations from ACIP for RSV vaccines are both age based and risk based. The age-based recommendation applies to those aged 75 or older, who should receive a single RSV vaccine dose. If they have already received a dose under the old recommendation, they don’t need another one, at least for now.
The risk-based recommendation applies to adults from age 60 up to 75, but only for those with risk factors for severe RSV. These risk factors include lung disease, heart disease, immunocompromise, diabetes, obesity with a BMI of 40 or more, neurologic conditions, neuromuscular conditions, chronic kidney disease, liver disorders, hematologic disorders, frailty, and living in a nursing home or other long-term care facility. Those aged 60-75 with these risk factors should receive the RSV vaccine, and those without them should not receive it. The best time to get the RSV vaccine is late summer, but early fall administration with other adult vaccines is allowed and is acceptable.
Vaccine safety concerns were top of mind as ACIP members began their deliberations. Possible safety concerns for RSV vaccines have been detected for Guillain-Barré syndrome, atrial fibrillation, and idiopathic thrombocytopenic purpura. Safety surveillance updates are still interim and inconclusive. These signals still need further study and clarification.
Two RSV vaccines have been on the market: one by Pfizer, called Abrysvo, which does not contain an adjuvant; and another one by GSK, called Arexvy, which does contain an adjuvant. With the recent FDA approval of Moderna’s new mRNA RSV vaccine, mRESVIA, there are now three RSV vaccines licensed for those 60 or older. Arexvy is now FDA approved for adults in their 50s. That just happened in early June, but ACIP doesn’t currently recommend it for this fifty-something age group, even for those at high risk for severe RSV disease. This may change with greater clarification of potential vaccine safety concerns.
There is also news about protecting babies from RSV. RSV is the most common cause of hospitalization for infants in the United States, and most hospitalizations for RSV are in healthy, full-term infants. We now have two ways to protect babies: a dose of RSV vaccine given to mom, or a dose of the long-acting monoclonal antibody nirsevimab given to the baby. ACIP clarified that those who received a dose of maternal RSV vaccine during a previous pregnancy are not recommended to receive additional doses during future pregnancies, but infants born to those who were vaccinated for RSV during a prior pregnancy can receive nirsevimab, which is recommended for infants up to 8 months of age during their first RSV season, and for high-risk infants and toddlers aged 8-19 months during their second RSV season.
Last RSV season, supplies of nirsevimab were limited and doses had to be prioritized. No supply problems are anticipated for the upcoming season. A study published in March showed that nirsevimab was 90% effective at preventing RSV-associated hospitalization for infants in their first RSV season.
COVID
Here’s what’s new for COVID vaccines. A new-formula COVID vaccine will be ready for fall. ACIP voted unanimously to recommend a dose of the updated 2024-2025 COVID vaccine for everyone aged 6 months or older. This is a universal recommendation, just like the one we have for flu. But understand that even though COVID has waned, it’s still more deadly than flu. Most Americans now have some immunity against COVID, but this immunity wanes with time, and it also wanes as the virus keeps changing. These updated vaccines provide an incremental boost to our immunity for the new formula for fall. FDA has directed manufacturers to use a monovalent JN.1 lineage formula, with a preference for the KP.2 strain.
Older adults (aged 75 or older) and children under 6 months old are hit hardest by COVID. The littlest ones are too young to be vaccinated, but they can get protection from maternal vaccination. The uptake for last year’s COVID vaccine has been disappointing. Only 22.5% of adults and 14% of children received a dose of the updated shot. Focus-group discussions highlight the importance of a physician recommendation. Adults and children who receive a healthcare provider’s recommendation to get the COVID vaccine are more likely to get vaccinated.
Pneumococcal Vaccines
On June 17, 2024, a new pneumococcal vaccine, PCV21, was FDA approved for those aged 18 or older under an accelerated-approval pathway. ACIP voted to keep it simple and recommends PCV21 as an option for adults aged 19 or older who currently have an indication to receive a dose of PCV. This new PCV21 vaccine is indicated for prevention of both invasive pneumococcal disease (IPD) and pneumococcal pneumonia. Its brand name is Capvaxive and it’s made by Merck. IPD includes bacteremia, pneumonia, pneumococcal bacteremia, and meningitis.
There are two basic types of pneumococcal vaccines: polysaccharide vaccines (PPSV), which do not produce memory B cells; and PCV conjugate vaccines, which do trigger memory B-cell production and therefore induce greater long-term immunity. PCV21 covers 11 unique serotypes not in PCV20. This is important because many cases of adult disease are caused by subtypes not covered by other FDA-approved pneumococcal vaccines. PCV21 has greater coverage of the serotypes that cause invasive disease in adults as compared with PCV20. PCV20 covers up to 58% of those strains, while PCV21 covers up to 84% of strains responsible for invasive disease in adults. But there’s one serotype missing in PCV21, which may limit the groups who receive it. PCV21 does not cover serotype 4, a major cause of IPD in certain populations. Adults experiencing homelessness are 100-300 times more likely to develop IPD due to serotype 4. So are adults in Alaska, especially Alaska Natives. They have an 88-fold increase in serotype 4 invasive disease. Serotype 4 is covered by other pneumococcal vaccines, so for these patients, PCV20 is likely a better high-valent conjugate vaccine option than PCV21.
Flu Vaccines
What’s new for flu? Everyone aged 6 months or older needs a seasonal flu vaccination every year. That’s not new, but there are two new things coming this fall: (1) The seasonal flu vaccine is going trivalent. FDA has removed the Yamagata flu B strain because it no longer appears to be circulating. (2) ACIP made a special off-label recommendation to boost flu protection for solid organ transplant recipients ages 18-64 who are on immunosuppressive medications. These high-risk patients now have the off-label option of receiving one of the higher-dose flu vaccines, including high-dose and adjuvanted flu vaccines, which are FDA approved only for those 65 or older.
Sandra Adamson Fryhofer, Adjunct Clinical Associate Professor of Medicine, Emory University School of Medicine, Atlanta, Georgia, has disclosed the following relevant financial relationships: Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for American Medical Association; Medical Association of Atlanta; ACIP liaison. Received income in an amount equal to or greater than $250 from American College of Physicians; Medscape; American Medical Association.
A version of this article first appeared on Medscape.com.
Prescribing Epilepsy Meds in Pregnancy: ‘We Can Do Better,’ Experts Say
HELSINKI, FINLAND — When it comes to caring for women with epilepsy who become pregnant, there is a great deal of room for improvement, experts say.
“Too many women with epilepsy receive information about epilepsy and pregnancy only after pregnancy. We can do better,” Torbjörn Tomson, MD, PhD, senior professor of neurology and epileptology, Karolinska Institutet, Stockholm, Sweden, told delegates attending the Congress of the European Academy of Neurology 2024.
The goal in epilepsy is to maintain seizure control while minimizing exposure to potentially teratogenic medications, Dr. Tomson said. He added that pregnancy planning in women with epilepsy is important but also conceded that most pregnancies in this patient population are unplanned.
Overall, it’s important to tell patients that “there is a high likelihood of an uneventful pregnancy and a healthy offspring,” he said.
In recent years, new data have emerged on the risks to the fetus with exposure to different antiseizure medications (ASMs), said Dr. Tomson. This has led regulators, such as the US Food and Drug Administration and the European Medicines Agency, to issue restrictions on the use of some ASMs, particularly valproate and topiramate, in females of childbearing age.
Session chair Marte Bjørk, MD, PhD, of the Department of Neurology of Haukeland University Hospital, Bergen, Norway, questioned whether the latest recommendations from regulatory authorities have “sacrificed seizure control at the expense of teratogenic safety.”
To an extent, this is true, said Dr. Tomson, “as the regulations prioritize fetal health over women’s health.” However, “we have not seen poorer seizure control with newer medications” in recent datasets.
It’s about good planning, said Dr. Bjork, who is responsible for the clinical guidelines for treatment of epilepsy in pregnancy in Norway.
Start With Folic Acid
One simple measure is to ensure that all women with epilepsy of childbearing age are prescribed low-dose folic acid, Dr. Tomson said — even those who report that they are not considering pregnancy.
When it comes to folic acid, recently published guidelines on ASM use during pregnancy are relatively straightforward, he said.
The data do not show that folic acid reduces the risk for major congenital malformations, but they do show that it improves neurocognitive outcomes in children of mothers who received folic acid supplements prior to and throughout pregnancy.
Dr. Tomson said the new American Academy of Neurology (AAN) guidelines recommend a dosage of 0.4 mg/d, which balances the demonstrated benefits of supplementation and potential negative consequences of high doses of folic acid.
“Consider 0.4 mg of folic acid for all women on ASMs that are of childbearing potential, whether they become pregnant or not,” he said. However, well-designed, preferably randomized, studies are needed to better define the optimal folic acid dosing for pregnancy in women with epilepsy.
Choosing the Right ASM
The choice of the most appropriate ASM in pregnancy is based on the potential for an individual drug to cause major congenital malformations and, in more recent years, the likelihood that a woman with epilepsy is using any other medications associated with neurodevelopmental disorders in offspring.
Balanced against this must be the effect of pregnancy on seizure control, and the maternal and fetal risks associated with seizures during pregnancy.
“There are ways to optimize seizure control and to reduce teratogenic risks,” said Dr. Tomson, adding that the new AAN guidelines provide updated evidence-based conclusions on this topic.
The good news is that “there has been almost a 40% decline in the rate of major congenital malformations associated with ASM use in pregnancy, in parallel with a shift from use of ASMs such as carbamazepine and valproate to lamotrigine and levetiracetam.” The latter two medications are associated with a much lower risk for such birth defects, he added.
This is based on the average rate of major congenital malformations in the EURAP registry that tracks the comparative risk for major fetal malformations after ASM use during pregnancy in over 40 countries. The latest reporting from the registry shows that this risk has decreased from 6.1% in 1998-2004 to 3.7% in 2015-2022.
Taking valproate during pregnancy is associated with a significantly increased risk for neurodevelopmental outcomes, including autism spectrum disorder. However, the jury is still out on whether topiramate escalates the risk for neurodevelopmental disorders, because findings across studies have been inconsistent.
Overall, the AAN guidance, and similar advice from European regulatory authorities, is that valproate is associated with high risk for major congenital malformations and neurodevelopmental disorders. Topiramate has also been shown to increase the risk for major congenital malformations. Consequently, these two anticonvulsants are generally contraindicated in pregnancy, Dr. Tomson noted.
On the other hand, levetiracetam, lamotrigine, and oxcarbazepine seem to be the safest ASMs with respect to congenital malformation risk, and lamotrigine has the best documented safety profile when it comes to the risk for neurodevelopmental disorders.
Although there are newer ASMs on the market, including brivaracetam, cannabidiol, cenobamate, eslicarbazepine acetate, fenfluramine, lacosamide, perampanel, and zonisamide, at this juncture data on the risk potential of these agents are insufficient.
“For some of these newer meds, we don’t even have a single exposure in our large databases, even if you combine them all. We need to collect more data, and that will take time,” Dr. Tomson said.
Dose Optimization
Dose optimization of ASMs is also important — and for this to be accurate, it’s important to document an individual’s optimal ASM serum levels before pregnancy that can be used as a baseline target during pregnancy. However, Dr. Tomson noted, this information is not always available.
He pointed out that, with many ASMs, there can be a significant decline in serum concentration levels during pregnancy, which can increase seizure risk.
To address the uncertainty surrounding this issue, Dr. Tomson recommended that physicians consider future pregnancy when prescribing ASMs to women of childbearing age. He also advised discussing contraception with these patients, even if they indicate they are not currently planning to conceive.
The data clearly show the importance of planning a pregnancy so that the most appropriate and safest medications are prescribed, he said.
Dr. Tomson reported receiving research support, on behalf of EURAP, from Accord, Angelini, Bial, EcuPharma, Eisai, GlaxoSmithKline, Glenmark, GW Pharma, Hazz, Sanofi, Teva, USB, Zentiva, and SF Group. He has received speakers’ honoraria from Angelini, Eisai, and UCB. Dr. Bjørk reports receiving speakers’ honoraria from Pfizer, Eisai, AbbVie, Best Practice, Lilly, Novartis, and Teva. She has received unrestricted educational grants from The Research Council of Norway, the Research Council of the Nordic Countries (NordForsk), and the Norwegian Epilepsy Association. She has received consulting honoraria from Novartis and is on the advisory board of Eisai, Lundbeck, Angelini Pharma, and Jazz Pharmaceuticals. Dr. Bjørk also received institutional grants from marked authorization holders of valproate.
A version of this article first appeared on Medscape.com.
HELSINKI, FINLAND — When it comes to caring for women with epilepsy who become pregnant, there is a great deal of room for improvement, experts say.
“Too many women with epilepsy receive information about epilepsy and pregnancy only after pregnancy. We can do better,” Torbjörn Tomson, MD, PhD, senior professor of neurology and epileptology, Karolinska Institutet, Stockholm, Sweden, told delegates attending the Congress of the European Academy of Neurology 2024.
The goal in epilepsy is to maintain seizure control while minimizing exposure to potentially teratogenic medications, Dr. Tomson said. He added that pregnancy planning in women with epilepsy is important but also conceded that most pregnancies in this patient population are unplanned.
Overall, it’s important to tell patients that “there is a high likelihood of an uneventful pregnancy and a healthy offspring,” he said.
In recent years, new data have emerged on the risks to the fetus with exposure to different antiseizure medications (ASMs), said Dr. Tomson. This has led regulators, such as the US Food and Drug Administration and the European Medicines Agency, to issue restrictions on the use of some ASMs, particularly valproate and topiramate, in females of childbearing age.
Session chair Marte Bjørk, MD, PhD, of the Department of Neurology of Haukeland University Hospital, Bergen, Norway, questioned whether the latest recommendations from regulatory authorities have “sacrificed seizure control at the expense of teratogenic safety.”
To an extent, this is true, said Dr. Tomson, “as the regulations prioritize fetal health over women’s health.” However, “we have not seen poorer seizure control with newer medications” in recent datasets.
It’s about good planning, said Dr. Bjork, who is responsible for the clinical guidelines for treatment of epilepsy in pregnancy in Norway.
Start With Folic Acid
One simple measure is to ensure that all women with epilepsy of childbearing age are prescribed low-dose folic acid, Dr. Tomson said — even those who report that they are not considering pregnancy.
When it comes to folic acid, recently published guidelines on ASM use during pregnancy are relatively straightforward, he said.
The data do not show that folic acid reduces the risk for major congenital malformations, but they do show that it improves neurocognitive outcomes in children of mothers who received folic acid supplements prior to and throughout pregnancy.
Dr. Tomson said the new American Academy of Neurology (AAN) guidelines recommend a dosage of 0.4 mg/d, which balances the demonstrated benefits of supplementation and potential negative consequences of high doses of folic acid.
“Consider 0.4 mg of folic acid for all women on ASMs that are of childbearing potential, whether they become pregnant or not,” he said. However, well-designed, preferably randomized, studies are needed to better define the optimal folic acid dosing for pregnancy in women with epilepsy.
Choosing the Right ASM
The choice of the most appropriate ASM in pregnancy is based on the potential for an individual drug to cause major congenital malformations and, in more recent years, the likelihood that a woman with epilepsy is using any other medications associated with neurodevelopmental disorders in offspring.
Balanced against this must be the effect of pregnancy on seizure control, and the maternal and fetal risks associated with seizures during pregnancy.
“There are ways to optimize seizure control and to reduce teratogenic risks,” said Dr. Tomson, adding that the new AAN guidelines provide updated evidence-based conclusions on this topic.
The good news is that “there has been almost a 40% decline in the rate of major congenital malformations associated with ASM use in pregnancy, in parallel with a shift from use of ASMs such as carbamazepine and valproate to lamotrigine and levetiracetam.” The latter two medications are associated with a much lower risk for such birth defects, he added.
This is based on the average rate of major congenital malformations in the EURAP registry that tracks the comparative risk for major fetal malformations after ASM use during pregnancy in over 40 countries. The latest reporting from the registry shows that this risk has decreased from 6.1% in 1998-2004 to 3.7% in 2015-2022.
Taking valproate during pregnancy is associated with a significantly increased risk for neurodevelopmental outcomes, including autism spectrum disorder. However, the jury is still out on whether topiramate escalates the risk for neurodevelopmental disorders, because findings across studies have been inconsistent.
Overall, the AAN guidance, and similar advice from European regulatory authorities, is that valproate is associated with high risk for major congenital malformations and neurodevelopmental disorders. Topiramate has also been shown to increase the risk for major congenital malformations. Consequently, these two anticonvulsants are generally contraindicated in pregnancy, Dr. Tomson noted.
On the other hand, levetiracetam, lamotrigine, and oxcarbazepine seem to be the safest ASMs with respect to congenital malformation risk, and lamotrigine has the best documented safety profile when it comes to the risk for neurodevelopmental disorders.
Although there are newer ASMs on the market, including brivaracetam, cannabidiol, cenobamate, eslicarbazepine acetate, fenfluramine, lacosamide, perampanel, and zonisamide, at this juncture data on the risk potential of these agents are insufficient.
“For some of these newer meds, we don’t even have a single exposure in our large databases, even if you combine them all. We need to collect more data, and that will take time,” Dr. Tomson said.
Dose Optimization
Dose optimization of ASMs is also important — and for this to be accurate, it’s important to document an individual’s optimal ASM serum levels before pregnancy that can be used as a baseline target during pregnancy. However, Dr. Tomson noted, this information is not always available.
He pointed out that, with many ASMs, there can be a significant decline in serum concentration levels during pregnancy, which can increase seizure risk.
To address the uncertainty surrounding this issue, Dr. Tomson recommended that physicians consider future pregnancy when prescribing ASMs to women of childbearing age. He also advised discussing contraception with these patients, even if they indicate they are not currently planning to conceive.
The data clearly show the importance of planning a pregnancy so that the most appropriate and safest medications are prescribed, he said.
Dr. Tomson reported receiving research support, on behalf of EURAP, from Accord, Angelini, Bial, EcuPharma, Eisai, GlaxoSmithKline, Glenmark, GW Pharma, Hazz, Sanofi, Teva, USB, Zentiva, and SF Group. He has received speakers’ honoraria from Angelini, Eisai, and UCB. Dr. Bjørk reports receiving speakers’ honoraria from Pfizer, Eisai, AbbVie, Best Practice, Lilly, Novartis, and Teva. She has received unrestricted educational grants from The Research Council of Norway, the Research Council of the Nordic Countries (NordForsk), and the Norwegian Epilepsy Association. She has received consulting honoraria from Novartis and is on the advisory board of Eisai, Lundbeck, Angelini Pharma, and Jazz Pharmaceuticals. Dr. Bjørk also received institutional grants from marked authorization holders of valproate.
A version of this article first appeared on Medscape.com.
HELSINKI, FINLAND — When it comes to caring for women with epilepsy who become pregnant, there is a great deal of room for improvement, experts say.
“Too many women with epilepsy receive information about epilepsy and pregnancy only after pregnancy. We can do better,” Torbjörn Tomson, MD, PhD, senior professor of neurology and epileptology, Karolinska Institutet, Stockholm, Sweden, told delegates attending the Congress of the European Academy of Neurology 2024.
The goal in epilepsy is to maintain seizure control while minimizing exposure to potentially teratogenic medications, Dr. Tomson said. He added that pregnancy planning in women with epilepsy is important but also conceded that most pregnancies in this patient population are unplanned.
Overall, it’s important to tell patients that “there is a high likelihood of an uneventful pregnancy and a healthy offspring,” he said.
In recent years, new data have emerged on the risks to the fetus with exposure to different antiseizure medications (ASMs), said Dr. Tomson. This has led regulators, such as the US Food and Drug Administration and the European Medicines Agency, to issue restrictions on the use of some ASMs, particularly valproate and topiramate, in females of childbearing age.
Session chair Marte Bjørk, MD, PhD, of the Department of Neurology of Haukeland University Hospital, Bergen, Norway, questioned whether the latest recommendations from regulatory authorities have “sacrificed seizure control at the expense of teratogenic safety.”
To an extent, this is true, said Dr. Tomson, “as the regulations prioritize fetal health over women’s health.” However, “we have not seen poorer seizure control with newer medications” in recent datasets.
It’s about good planning, said Dr. Bjork, who is responsible for the clinical guidelines for treatment of epilepsy in pregnancy in Norway.
Start With Folic Acid
One simple measure is to ensure that all women with epilepsy of childbearing age are prescribed low-dose folic acid, Dr. Tomson said — even those who report that they are not considering pregnancy.
When it comes to folic acid, recently published guidelines on ASM use during pregnancy are relatively straightforward, he said.
The data do not show that folic acid reduces the risk for major congenital malformations, but they do show that it improves neurocognitive outcomes in children of mothers who received folic acid supplements prior to and throughout pregnancy.
Dr. Tomson said the new American Academy of Neurology (AAN) guidelines recommend a dosage of 0.4 mg/d, which balances the demonstrated benefits of supplementation and potential negative consequences of high doses of folic acid.
“Consider 0.4 mg of folic acid for all women on ASMs that are of childbearing potential, whether they become pregnant or not,” he said. However, well-designed, preferably randomized, studies are needed to better define the optimal folic acid dosing for pregnancy in women with epilepsy.
Choosing the Right ASM
The choice of the most appropriate ASM in pregnancy is based on the potential for an individual drug to cause major congenital malformations and, in more recent years, the likelihood that a woman with epilepsy is using any other medications associated with neurodevelopmental disorders in offspring.
Balanced against this must be the effect of pregnancy on seizure control, and the maternal and fetal risks associated with seizures during pregnancy.
“There are ways to optimize seizure control and to reduce teratogenic risks,” said Dr. Tomson, adding that the new AAN guidelines provide updated evidence-based conclusions on this topic.
The good news is that “there has been almost a 40% decline in the rate of major congenital malformations associated with ASM use in pregnancy, in parallel with a shift from use of ASMs such as carbamazepine and valproate to lamotrigine and levetiracetam.” The latter two medications are associated with a much lower risk for such birth defects, he added.
This is based on the average rate of major congenital malformations in the EURAP registry that tracks the comparative risk for major fetal malformations after ASM use during pregnancy in over 40 countries. The latest reporting from the registry shows that this risk has decreased from 6.1% in 1998-2004 to 3.7% in 2015-2022.
Taking valproate during pregnancy is associated with a significantly increased risk for neurodevelopmental outcomes, including autism spectrum disorder. However, the jury is still out on whether topiramate escalates the risk for neurodevelopmental disorders, because findings across studies have been inconsistent.
Overall, the AAN guidance, and similar advice from European regulatory authorities, is that valproate is associated with high risk for major congenital malformations and neurodevelopmental disorders. Topiramate has also been shown to increase the risk for major congenital malformations. Consequently, these two anticonvulsants are generally contraindicated in pregnancy, Dr. Tomson noted.
On the other hand, levetiracetam, lamotrigine, and oxcarbazepine seem to be the safest ASMs with respect to congenital malformation risk, and lamotrigine has the best documented safety profile when it comes to the risk for neurodevelopmental disorders.
Although there are newer ASMs on the market, including brivaracetam, cannabidiol, cenobamate, eslicarbazepine acetate, fenfluramine, lacosamide, perampanel, and zonisamide, at this juncture data on the risk potential of these agents are insufficient.
“For some of these newer meds, we don’t even have a single exposure in our large databases, even if you combine them all. We need to collect more data, and that will take time,” Dr. Tomson said.
Dose Optimization
Dose optimization of ASMs is also important — and for this to be accurate, it’s important to document an individual’s optimal ASM serum levels before pregnancy that can be used as a baseline target during pregnancy. However, Dr. Tomson noted, this information is not always available.
He pointed out that, with many ASMs, there can be a significant decline in serum concentration levels during pregnancy, which can increase seizure risk.
To address the uncertainty surrounding this issue, Dr. Tomson recommended that physicians consider future pregnancy when prescribing ASMs to women of childbearing age. He also advised discussing contraception with these patients, even if they indicate they are not currently planning to conceive.
The data clearly show the importance of planning a pregnancy so that the most appropriate and safest medications are prescribed, he said.
Dr. Tomson reported receiving research support, on behalf of EURAP, from Accord, Angelini, Bial, EcuPharma, Eisai, GlaxoSmithKline, Glenmark, GW Pharma, Hazz, Sanofi, Teva, USB, Zentiva, and SF Group. He has received speakers’ honoraria from Angelini, Eisai, and UCB. Dr. Bjørk reports receiving speakers’ honoraria from Pfizer, Eisai, AbbVie, Best Practice, Lilly, Novartis, and Teva. She has received unrestricted educational grants from The Research Council of Norway, the Research Council of the Nordic Countries (NordForsk), and the Norwegian Epilepsy Association. She has received consulting honoraria from Novartis and is on the advisory board of Eisai, Lundbeck, Angelini Pharma, and Jazz Pharmaceuticals. Dr. Bjørk also received institutional grants from marked authorization holders of valproate.
A version of this article first appeared on Medscape.com.
FROM EAN 2024
Buprenorphine One of Many Options For Pain Relief In Oldest Adults
Some degree of pain is inevitable in older individuals, and as people pass 80 years of age, the harms of medications used to control chronic pain increase. Pain-reducing medication use in this age group may cause inflammation, gastric bleeding, kidney damage, or constipation.
These risks may lead some clinicians to avoid aggressive pain treatment in their eldest patients, resulting in unnecessary suffering.
“Pain causes harm beyond just the physical suffering associated with it,” said Diane Meier, MD, a geriatrician and palliative care specialist at Mount Sinai Medicine in New York City who treats many people in their 80s and 90s.
Downstream effects of untreated pain could include a loss of mobility and isolation, Dr. Meier said. And, as these harms are mounting, some clinicians may avoid using an analgesic that could bring great relief: buprenorphine.
“People think about buprenorphine like they think about methadone,” Dr. Meier said, as something prescribed to treat substance use disorder. In reality, it is an effective analgesic in other situations.
Buprenorphine is better at treating chronic pain than other opioids that carry a higher addiction risk and often cause constipation in elderly patients. Buprenorphine is easier on the kidneys and has a lower addiction risk than opioids like oxycodone.
The transdermal patch form of buprenorphine (Butrans, PurduePharma) is changed weekly and starts at low doses.
“There’s an adage in geriatrics: start low and go slow,” said Jessica Merlin, MD, PhD, a palliative care and addiction medicine physician at the University of Pittsburgh Medical Center in Pittsburgh, Pennsylvania.
Dr. Merlin recommends beginning elderly patients with chronic pain on a 10-microgram/hour dose of Butrans, among the lowest doses available. Physicians could monitor side effects, which will generally be mild, with the aim of never increasing the dose if pain is managed.
Nonpharmacologic Remedies, Drug Considerations
“Nonpharmacologic therapy is very underutilized,” Dr. Merlin said, even though multiple alternatives to medications can improve chronic pain symptoms at any age.
Cognitive-behavioral therapy or acceptance and commitment therapy can both help people reduce the impact of pain, Dr. Merlin said. And for people who can do so, physical therapy programs, yoga, or tai chi are all ways to strengthen the body’s defenses against pain, Dr. Merlin added.
Sometimes medication is necessary, however.
“You can’t get an older person to participate in rehab if they are in severe pain,” Dr. Meier said, adding that judicious use of medications should go hand in hand with nonpharmacologic treatment.
When medications are unavoidable, internist Douglas S. Paauw, MD, starts with topical injections at the site of the pain — a troublesome joint, for example — rather than systemic medications that affect multiple organs and the brain.
“We try not to flood their body with meds” for localized problems, Dr. Paauw said, whose goal when treating elderly patients with pain is to improve their daily functioning and quality of life.
Dr. Paauw works at the University of Washington in Seattle and treats people who are approaching 100 years old. As some of his patients have grown older, Dr. Paauw’s interest in effective pain management has grown; he thinks that all internists and family medicine physician need to know how to manage chronic pain in their eldest patients.
“Were you able to play with your grandkid? Were you able to go grocery shopping? Were you able to take a walk outside?” These are the kinds of improvements Dr. Paauw hopes to see in older patients, recognizing that the wear and tear of life — orthopedic stresses or healed fractures that cause lingering pain — make it impossible for many older people to be pain free.
Pain is often spread throughout the body rather than focusing at one point, which requires systemic medications if physical therapy and similar approaches have not reduced pain. Per American Geriatrics Society (AGS) guidelines, in this situation Dr. Paauw starts with acetaminophen (Tylenol) as the lowest-risk systemic pain treatment.
Dr. Pauuw often counsels older patients to begin with 2 grams/day of acetaminophen and then progress to 3 grams if the lower dose has manageable side effects, rather than the standard dose of 4 grams that he feels is geared toward younger patients.
When acetaminophen doesn’t reduce pain sufficiently, or aggravates inflammation, Dr. Paauw may use the nerve pain medication pregabalin, or the antidepressant duloxetine — especially if the pain appears to be neuropathic.
Tricyclic antidepressants used to be recommended for neuropathic pain in older adults, but are now on the AGS’s Beers Criteria of drugs to avoid in elderly patients due to risk of causing dizziness or cardiac stress. Dr. Paauw might still use a tricyclic, but only after a careful risk-benefit analysis.
Nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen (Motrin) or naproxen (Aleve) could work in short bursts, Dr. Paauw said, although they may cause stomach bleeding or kidney damage in older patients.
This is why NSAIDs are not recommended by the AGS for chronic pain management. And opioids like oxycodone don’t work long at low doses, often leading to dose escalation and addiction.
“The American Geriatrics Society really puts opioids down at the bottom of the list,” Dr. Paauw said, to be used “judiciously and rarely.”
Opioids may interact with other drugs to increase risk of a fall, Dr. Meier added, making them inadvisable for older patients who live alone.
“That’s why knowing something about buprenorphine is so important,” Dr. Meier said.
Dr. Meier and Dr. Paauw are on the editorial board for Internal Medicine News. Dr. Merlin is a trainer for the Center to Advance Palliative Care, which Dr. Meier founded.
Some degree of pain is inevitable in older individuals, and as people pass 80 years of age, the harms of medications used to control chronic pain increase. Pain-reducing medication use in this age group may cause inflammation, gastric bleeding, kidney damage, or constipation.
These risks may lead some clinicians to avoid aggressive pain treatment in their eldest patients, resulting in unnecessary suffering.
“Pain causes harm beyond just the physical suffering associated with it,” said Diane Meier, MD, a geriatrician and palliative care specialist at Mount Sinai Medicine in New York City who treats many people in their 80s and 90s.
Downstream effects of untreated pain could include a loss of mobility and isolation, Dr. Meier said. And, as these harms are mounting, some clinicians may avoid using an analgesic that could bring great relief: buprenorphine.
“People think about buprenorphine like they think about methadone,” Dr. Meier said, as something prescribed to treat substance use disorder. In reality, it is an effective analgesic in other situations.
Buprenorphine is better at treating chronic pain than other opioids that carry a higher addiction risk and often cause constipation in elderly patients. Buprenorphine is easier on the kidneys and has a lower addiction risk than opioids like oxycodone.
The transdermal patch form of buprenorphine (Butrans, PurduePharma) is changed weekly and starts at low doses.
“There’s an adage in geriatrics: start low and go slow,” said Jessica Merlin, MD, PhD, a palliative care and addiction medicine physician at the University of Pittsburgh Medical Center in Pittsburgh, Pennsylvania.
Dr. Merlin recommends beginning elderly patients with chronic pain on a 10-microgram/hour dose of Butrans, among the lowest doses available. Physicians could monitor side effects, which will generally be mild, with the aim of never increasing the dose if pain is managed.
Nonpharmacologic Remedies, Drug Considerations
“Nonpharmacologic therapy is very underutilized,” Dr. Merlin said, even though multiple alternatives to medications can improve chronic pain symptoms at any age.
Cognitive-behavioral therapy or acceptance and commitment therapy can both help people reduce the impact of pain, Dr. Merlin said. And for people who can do so, physical therapy programs, yoga, or tai chi are all ways to strengthen the body’s defenses against pain, Dr. Merlin added.
Sometimes medication is necessary, however.
“You can’t get an older person to participate in rehab if they are in severe pain,” Dr. Meier said, adding that judicious use of medications should go hand in hand with nonpharmacologic treatment.
When medications are unavoidable, internist Douglas S. Paauw, MD, starts with topical injections at the site of the pain — a troublesome joint, for example — rather than systemic medications that affect multiple organs and the brain.
“We try not to flood their body with meds” for localized problems, Dr. Paauw said, whose goal when treating elderly patients with pain is to improve their daily functioning and quality of life.
Dr. Paauw works at the University of Washington in Seattle and treats people who are approaching 100 years old. As some of his patients have grown older, Dr. Paauw’s interest in effective pain management has grown; he thinks that all internists and family medicine physician need to know how to manage chronic pain in their eldest patients.
“Were you able to play with your grandkid? Were you able to go grocery shopping? Were you able to take a walk outside?” These are the kinds of improvements Dr. Paauw hopes to see in older patients, recognizing that the wear and tear of life — orthopedic stresses or healed fractures that cause lingering pain — make it impossible for many older people to be pain free.
Pain is often spread throughout the body rather than focusing at one point, which requires systemic medications if physical therapy and similar approaches have not reduced pain. Per American Geriatrics Society (AGS) guidelines, in this situation Dr. Paauw starts with acetaminophen (Tylenol) as the lowest-risk systemic pain treatment.
Dr. Pauuw often counsels older patients to begin with 2 grams/day of acetaminophen and then progress to 3 grams if the lower dose has manageable side effects, rather than the standard dose of 4 grams that he feels is geared toward younger patients.
When acetaminophen doesn’t reduce pain sufficiently, or aggravates inflammation, Dr. Paauw may use the nerve pain medication pregabalin, or the antidepressant duloxetine — especially if the pain appears to be neuropathic.
Tricyclic antidepressants used to be recommended for neuropathic pain in older adults, but are now on the AGS’s Beers Criteria of drugs to avoid in elderly patients due to risk of causing dizziness or cardiac stress. Dr. Paauw might still use a tricyclic, but only after a careful risk-benefit analysis.
Nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen (Motrin) or naproxen (Aleve) could work in short bursts, Dr. Paauw said, although they may cause stomach bleeding or kidney damage in older patients.
This is why NSAIDs are not recommended by the AGS for chronic pain management. And opioids like oxycodone don’t work long at low doses, often leading to dose escalation and addiction.
“The American Geriatrics Society really puts opioids down at the bottom of the list,” Dr. Paauw said, to be used “judiciously and rarely.”
Opioids may interact with other drugs to increase risk of a fall, Dr. Meier added, making them inadvisable for older patients who live alone.
“That’s why knowing something about buprenorphine is so important,” Dr. Meier said.
Dr. Meier and Dr. Paauw are on the editorial board for Internal Medicine News. Dr. Merlin is a trainer for the Center to Advance Palliative Care, which Dr. Meier founded.
Some degree of pain is inevitable in older individuals, and as people pass 80 years of age, the harms of medications used to control chronic pain increase. Pain-reducing medication use in this age group may cause inflammation, gastric bleeding, kidney damage, or constipation.
These risks may lead some clinicians to avoid aggressive pain treatment in their eldest patients, resulting in unnecessary suffering.
“Pain causes harm beyond just the physical suffering associated with it,” said Diane Meier, MD, a geriatrician and palliative care specialist at Mount Sinai Medicine in New York City who treats many people in their 80s and 90s.
Downstream effects of untreated pain could include a loss of mobility and isolation, Dr. Meier said. And, as these harms are mounting, some clinicians may avoid using an analgesic that could bring great relief: buprenorphine.
“People think about buprenorphine like they think about methadone,” Dr. Meier said, as something prescribed to treat substance use disorder. In reality, it is an effective analgesic in other situations.
Buprenorphine is better at treating chronic pain than other opioids that carry a higher addiction risk and often cause constipation in elderly patients. Buprenorphine is easier on the kidneys and has a lower addiction risk than opioids like oxycodone.
The transdermal patch form of buprenorphine (Butrans, PurduePharma) is changed weekly and starts at low doses.
“There’s an adage in geriatrics: start low and go slow,” said Jessica Merlin, MD, PhD, a palliative care and addiction medicine physician at the University of Pittsburgh Medical Center in Pittsburgh, Pennsylvania.
Dr. Merlin recommends beginning elderly patients with chronic pain on a 10-microgram/hour dose of Butrans, among the lowest doses available. Physicians could monitor side effects, which will generally be mild, with the aim of never increasing the dose if pain is managed.
Nonpharmacologic Remedies, Drug Considerations
“Nonpharmacologic therapy is very underutilized,” Dr. Merlin said, even though multiple alternatives to medications can improve chronic pain symptoms at any age.
Cognitive-behavioral therapy or acceptance and commitment therapy can both help people reduce the impact of pain, Dr. Merlin said. And for people who can do so, physical therapy programs, yoga, or tai chi are all ways to strengthen the body’s defenses against pain, Dr. Merlin added.
Sometimes medication is necessary, however.
“You can’t get an older person to participate in rehab if they are in severe pain,” Dr. Meier said, adding that judicious use of medications should go hand in hand with nonpharmacologic treatment.
When medications are unavoidable, internist Douglas S. Paauw, MD, starts with topical injections at the site of the pain — a troublesome joint, for example — rather than systemic medications that affect multiple organs and the brain.
“We try not to flood their body with meds” for localized problems, Dr. Paauw said, whose goal when treating elderly patients with pain is to improve their daily functioning and quality of life.
Dr. Paauw works at the University of Washington in Seattle and treats people who are approaching 100 years old. As some of his patients have grown older, Dr. Paauw’s interest in effective pain management has grown; he thinks that all internists and family medicine physician need to know how to manage chronic pain in their eldest patients.
“Were you able to play with your grandkid? Were you able to go grocery shopping? Were you able to take a walk outside?” These are the kinds of improvements Dr. Paauw hopes to see in older patients, recognizing that the wear and tear of life — orthopedic stresses or healed fractures that cause lingering pain — make it impossible for many older people to be pain free.
Pain is often spread throughout the body rather than focusing at one point, which requires systemic medications if physical therapy and similar approaches have not reduced pain. Per American Geriatrics Society (AGS) guidelines, in this situation Dr. Paauw starts with acetaminophen (Tylenol) as the lowest-risk systemic pain treatment.
Dr. Pauuw often counsels older patients to begin with 2 grams/day of acetaminophen and then progress to 3 grams if the lower dose has manageable side effects, rather than the standard dose of 4 grams that he feels is geared toward younger patients.
When acetaminophen doesn’t reduce pain sufficiently, or aggravates inflammation, Dr. Paauw may use the nerve pain medication pregabalin, or the antidepressant duloxetine — especially if the pain appears to be neuropathic.
Tricyclic antidepressants used to be recommended for neuropathic pain in older adults, but are now on the AGS’s Beers Criteria of drugs to avoid in elderly patients due to risk of causing dizziness or cardiac stress. Dr. Paauw might still use a tricyclic, but only after a careful risk-benefit analysis.
Nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen (Motrin) or naproxen (Aleve) could work in short bursts, Dr. Paauw said, although they may cause stomach bleeding or kidney damage in older patients.
This is why NSAIDs are not recommended by the AGS for chronic pain management. And opioids like oxycodone don’t work long at low doses, often leading to dose escalation and addiction.
“The American Geriatrics Society really puts opioids down at the bottom of the list,” Dr. Paauw said, to be used “judiciously and rarely.”
Opioids may interact with other drugs to increase risk of a fall, Dr. Meier added, making them inadvisable for older patients who live alone.
“That’s why knowing something about buprenorphine is so important,” Dr. Meier said.
Dr. Meier and Dr. Paauw are on the editorial board for Internal Medicine News. Dr. Merlin is a trainer for the Center to Advance Palliative Care, which Dr. Meier founded.