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Vaccination reduces risk of flu-associated pediatric deaths
.
“These results support current recommendations for annual influenza vaccination for all children 6 months of age” and older, wrote Brendan Flannery, PhD, and his coauthors at the Centers for Disease Control and Prevention, Atlanta. “To our knowledge, this is the first study to use laboratory-confirmed outcomes to investigate influenza vaccine effectiveness against influenza-associated deaths.”
“Best estimates based on [National Health Interview Survey] data suggested that vaccination reduced the risk of influenza-associated death by half among children with high-risk conditions and by nearly two-thirds among children without high-risk conditions,” Dr. Flannery and his coauthors reported.
Of 358 cases of pediatric death (aged 6 months to 17 years) confirmed to be associated with influenza, 75 (26%) had been vaccinated prior to their disease onset. The case-cohort analysis compared the 358 cases against three cohorts of U.S. children and adolescents: a telephone survey, a household survey, and a health insurance claims database.
The researchers had examined cases that were reported to the U.S. Influenza-Associated Pediatric Mortality Surveillance System from July 2010 to June 2014. They excluded cases of children not yet eligible to be vaccinated or whose disease onset may have occurred before their vaccine had 14 days to take full effect (Pediatrics. 2017 Apr. doi: 10.1542/peds.2016-4244).
.
“These results support current recommendations for annual influenza vaccination for all children 6 months of age” and older, wrote Brendan Flannery, PhD, and his coauthors at the Centers for Disease Control and Prevention, Atlanta. “To our knowledge, this is the first study to use laboratory-confirmed outcomes to investigate influenza vaccine effectiveness against influenza-associated deaths.”
“Best estimates based on [National Health Interview Survey] data suggested that vaccination reduced the risk of influenza-associated death by half among children with high-risk conditions and by nearly two-thirds among children without high-risk conditions,” Dr. Flannery and his coauthors reported.
Of 358 cases of pediatric death (aged 6 months to 17 years) confirmed to be associated with influenza, 75 (26%) had been vaccinated prior to their disease onset. The case-cohort analysis compared the 358 cases against three cohorts of U.S. children and adolescents: a telephone survey, a household survey, and a health insurance claims database.
The researchers had examined cases that were reported to the U.S. Influenza-Associated Pediatric Mortality Surveillance System from July 2010 to June 2014. They excluded cases of children not yet eligible to be vaccinated or whose disease onset may have occurred before their vaccine had 14 days to take full effect (Pediatrics. 2017 Apr. doi: 10.1542/peds.2016-4244).
.
“These results support current recommendations for annual influenza vaccination for all children 6 months of age” and older, wrote Brendan Flannery, PhD, and his coauthors at the Centers for Disease Control and Prevention, Atlanta. “To our knowledge, this is the first study to use laboratory-confirmed outcomes to investigate influenza vaccine effectiveness against influenza-associated deaths.”
“Best estimates based on [National Health Interview Survey] data suggested that vaccination reduced the risk of influenza-associated death by half among children with high-risk conditions and by nearly two-thirds among children without high-risk conditions,” Dr. Flannery and his coauthors reported.
Of 358 cases of pediatric death (aged 6 months to 17 years) confirmed to be associated with influenza, 75 (26%) had been vaccinated prior to their disease onset. The case-cohort analysis compared the 358 cases against three cohorts of U.S. children and adolescents: a telephone survey, a household survey, and a health insurance claims database.
The researchers had examined cases that were reported to the U.S. Influenza-Associated Pediatric Mortality Surveillance System from July 2010 to June 2014. They excluded cases of children not yet eligible to be vaccinated or whose disease onset may have occurred before their vaccine had 14 days to take full effect (Pediatrics. 2017 Apr. doi: 10.1542/peds.2016-4244).
FROM PEDIATRICS
Partnering to optimize care of childhood cancer survivors
The number of childhood cancer survivors (CCSs) entering the adult health care system is increasing, a not-so-surprising trend when you consider that more than 80% of children and adolescents given a cancer diagnosis become long-term survivors.1 This patient population has a heightened risk for developing at least one chronic health problem, resulting from therapy. By the fourth decade of life, 88% of all CCSs will have a chronic condition,2 and about one-third develop a late effect that is either severe or life-threatening.3 In contrast to patients with many other pediatric chronic diseases that manifest at an early age and are progressive, CCSs are often physically well for many years, or decades, prior to their manifestation of late effects.4
Cancer survivorship has varying definitions; however, we define cancer survivorship as the phase of cancer care for individuals who have been diagnosed with cancer and have completed primary treatment for their disease.5 Cancer survivorship, which is becoming more widely acknowledged as a distinct and critically important phase of cancer care, includes:6
- “surveillance for recurrence,
- evaluation … and treatment of medical and psychosocial consequences of treatment,
- recommendations for screening for new primary cancers,
- health promotion recommendations, and
- provision of a written treatment summary and care plan to the patient and other health professionals.”
Although models of survivorship care vary, their common goal is to promote optimal health and well-being in cancer survivors, and to prevent and detect any health concerns that may be related to prior cancer diagnosis or treatment.
Some pediatric cancer survivors have not received recommended survivorship care because of a lack of insurance or limitations from pre-existing conditions.4,7 The Affordable Care Act may remove these barriers for many.8 Others, however, fail to receive such recommendations because national models of transition are lacking. Unique considerations for this population include their need to establish age appropriate, lifelong follow-up care (and education) from a primary care provider (PCP). Unfortunately, many CCSs become lost to follow-up and fail to receive recommended survivorship care when they discontinue the relationship with their pediatrician or family practitioner and their pediatric oncologist. Fewer than 25% of CCSs who have been successfully treated for cancer during childhood continue to be followed by a cancer center and are at risk for missing survivorship-focused care or recommended screening.4,9
PCPs are an invaluable link in helping CCSs to continue to receive recommended care and surveillance. However, PCPs experience barriers in providing cancer care because of a lack of timely and specific communication from oncologists and limited knowledge of guidelines and resources available to them.10 The purpose of this article is to share information with you, the family physician, about childhood cancer survivorship needs, available resources, and how partnering with pediatric oncologists may improve treatment and health outcomes for CCSs.
Providing for the future health of childhood cancer survivors
Numerous studies have outlined the myriad of potential late effects that CCSs may experience from disease and treatment.11,12 These effects can manifest at any time and can appear in virtually every body system from the central nervous system, to the lungs, heart, bones, and endocrine systems. CCSs' particular risk for late effects may result from many factors including cancer diagnosis, types of treatments (eg, surgery, chemotherapy, radiation, and stem-cell transplant), and dosages of medications, gender, and age at diagnosis.
Determining individual risk for late effects
The Children’s Oncology Group (COG) is the world’s largest organization devoted exclusively to childhood and adolescent cancer research, including the long-term health of cancer survivors. To help provide more individualized recommendations, COG has set forth risk-based, evidence-based, exposure-related clinical practice guidelines to offer recommendations for screening and management of late effects in survivors of childhood and adolescent cancers.13 (These guidelines, Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers, are available at http://www.survivorshipguidelines.org.) The purpose of the guidelines is to standardize and enhance follow-up care for CCSs throughout their lifespan.13 To remain current, a multidisciplinary task force reviews and incorporates findings from the medical literature—including evaluations of the cost-effectiveness of recommended testing—into guideline revisions at least every 5 years.
Some of the most severe or life-threatening late effects include cardiomyopathies, endocrine disorders, and secondary malignancies (TABLE).13 Ongoing follow-up care is based on a survivor’s individual risk level and the frequency of lifelong recommended screening. The majority of patients will require yearly follow-up with additional testing, such as echocardiograms occurring as infrequently as every 2 to 5 years. Patients who received more intense therapy, such as hematopoietic stem-cell transplants, will require follow-up (often including annual echocardiograms, blood work, and a thorough physical exam) every 6 months to one year. Common testing and surveillance include blood pressure checks, urinalyses, thyroid function tests, lipid panels, echocardiograms, and electrocardiograms.
After treatment, patients should receive survivorship care plans
For health care providers to use COG Guidelines effectively across medical disciplines, it is important to know critical pieces of the patient’s cancer diagnosis and treatment history. In 2006, the Institute of Medicine released a report14 recommending that all cancer survivors be given a comprehensive care summary and follow-up plan when they complete their primary cancer care. More recently, the Commission on Cancer of the American College of Surgeons has mandated that, in order to be a cancer program accredited by the Commission, all cancer patients must be given a survivorship care plan after completing treatment.15 Generated by the treating cancer center, these care plans are meant to concisely communicate a patient’s cancer diagnosis, treatment, and long-term risks to other health care providers (across disciplines and institutions).
What’s included in a survivorship care plan?
The survivorship care plan is a paper or electronic document created by the treating institution that contains 2 components: a treatment summary and a long-term care plan based on medical/treatment history. The treatment summary includes, at a minimum, general background information (eg, demographics, pertinent medical history, diagnostic details, and significant treatment complications) and a therapeutic summary (such as dates of treatment, protocol, and details of chemotherapy, radiation, hematopoietic stem-cell transplant, and/or surgery).
The second component, the long-term care plan, details potential long-term effects specific to the treatment received, and recommendations for ongoing follow-up related to long-term risk (FIGURE). The post-treatment plan is primarily based on COG Guideline recommendations. Many institutions are introducing an electronic-based survivorship care plan, either in addition to or in replacement of a paper-based care plan. Electronic-based care plans have several benefits for patients and providers, including increased accessibility, and some offer the ability to easily update follow-up recommendations, as guidelines change, without the need for manual entry.
Shared care for cancer survivors: Oncology and primary care
Numerous models of cancer survivorship care have been described, including care by the treating oncologist, a dedicated cancer survivorship program, or follow-up completed by PCPs. There is no consensus on the best model, although many have noted that shared care is a critically important component of successful cancer survivorship care,6,16–18 and appears to be the preferred model of PCPs.19
Shared care, as the name implies, involves care that is coordinated between 2 or more health providers across specialties or locations.20 This model has shown improved outcomes in other chronic disease-management models, such as those for diabetes21 and chronic renal disease.22 One study23 found that colorectal cancer survivors who were seen by both an oncologist and a PCP were significantly more likely to receive recommended testing and follow-up to promote overall health than when they were followed by either physician alone. Information sharing between oncology and PCPs is critical to maintaining and promoting optimal health and well-being in cancer survivors, and requires ongoing communication and a concerted effort to facilitate and maintain collaboration between oncology specialists and other health care providers.6,17
Role of the cancer center in survivorship care
Although every cancer center has a slightly different timeline and structure in terms of survivorship care, there are common themes across programs regarding the type of care provided. Immediately following treatment, care is focused on surveillance for recurrence, with appointments ranging from monthly to a few times a year. This care is most often provided by the primary oncologist.
The next phase of care is reached 2 to 5 years after treatment, when recurrence is no longer a significant risk, and care is focused on monitoring and treating late effects. Depending on the center, this care may be coordinated by a dedicated survivorship clinic, the primary oncologist, or the PCP. In some models,6 the survivorship team is integrated into the patient’s care from the beginning of treatment, while others do not become active in care until the patient is considered cured of disease. In all models, a survivorship care plan should be completed after treatment has ended and before transitioning care to a PCP.
In our institution’s model, we have a survivorship program that serves patients who are more than 5 years from the completion of their treatment. Our survivorship team is comprised of a pediatric oncologist, advanced practice practitioner (APP) coordinator, a project coordinator, a clinical social worker, and a research staff member. Patients are seen every one to 2 years, depending on their overall risk for late effects. For those who are seen every other year, we are available to the PCP for questions or concerns, and the survivorship team connects with the CCS by phone to screen for any change in health status that would alter recommendations for an earlier follow-up at the oncology center.
A typical visit to our survivorship clinic includes completion of an annual health questionnaire, which addresses current health issues, as well as screening for anxiety, depression, nicotine, alcohol, and drug use. This questionnaire is reviewed by the pediatric oncologist and is used to tailor screening, referrals, and patient education based on current complaints. The oncologist also performs a thorough physical exam with special attention to areas in which late effects may occur (eg, skin exam in areas of previous radiation). In addition, each patient receives an individualized treatment summary based on COG guidelines, which is updated before each visit by the APP coordinator. The APP coordinator reviews the document at each visit and offers patient education and health maintenance counseling.
Ensuring patients aren’t lost to follow-up. In our experience, numerous patients become lost to follow-up as they age, enter college or the workforce, or move away. So, rather than attempting to follow these patients for life, we work to transition patient care to a PCP of their choice, particularly if they are at least 21 years old and more than 10 years post-diagnosis. However, we will work to transition at any time at the request of the CCS. Even when a patient’s ongoing care is transitioned to a PCP, we will remain as a continuing resource to PCPs and CCSs on an as-needed basis.
Role of primary care providers in survivorship care
Every health care provider caring for a CCS should have a copy of the patient’s survivorship care plan. This document should be provided by the treating institution, but research has shown that as many as 86% of PCPs fail to receive this critical information.24 Any PCP who treats a patient with a history of cancer and has not received a survivorship care plan should contact the treating cancer center to request a copy. A properly prepared survivorship care plan summarizes the patient’s disease and treatment history, and provides a road map of the patient’s risk for long-term effects from disease and treatment.
The most important sections of the survivorship care plan for use in primary care will be the list of potential late effects and ongoing recommended testing. This list will help to guide the PCP’s differential and work-up for specific complaints. For example, knowing that a patient is at risk for a second malignancy because of radiation therapy may result in earlier diagnostic imaging, leading to a timelier diagnosis.
The COG screening recommendations that are generally included in a survivorship care plan are appropriate for survivors who are asymptomatic and presenting for routine, exposure-based medical follow-up. More extensive work-ups are presumed to be completed as clinically indicated. Consultation with a pediatric long-term follow-up clinic is also encouraged, particularly if a concern arises.
A complementary set of patient education materials, known as “Health Links,” accompany the COG guidelines to broaden their application and enhance patient follow-up visits. A survivorship care plan and the COG Guidelines help ensure that CCSs receive appropriate ongoing follow-up based on their history. A collaborative approach between Oncology and PCPs is essential to improve the quality of care for CCSs and to maintain the long-term health of this vulnerable population.
CORRESPONDENCE
Jean M. Tersak, Children’s Hospital of Pittsburgh of UPMC, 4401 Penn Avenue, 5th Floor Plaza Building, Pittsburgh, PA 15224; tersakjm@upmc.edu.
1. Ries LAG, Eisner MP, Kosary CL, et al, eds. SEER Cancer Statistics Review, 1975-2002. National Cancer Institute. Bethesda, MD. Available at: http://seer.cancer.gov/csr/1975_2002/. Accessed May 26, 2016.
2. Phillips SM, Padgett LS, Leisenring WM, et al. Survivors of childhood cancer in the United States: prevalence and burden of morbidity. Cancer Epidemiol Biomarkers Prev. 2015;24:653-663.
3. Oeffinger KC, Mertens AC, Sklar CA, et al. Chronic health conditions in adult survivors of childhood cancer. N Engl J Med. 2006;355:1572-1582.
4. Nathan PC, Greenberg ML, Ness KK, et al. Medical care in long-term survivors of childhood cancer: a report from the childhood cancer survivor study. J Clin Oncol. 2008;26:4401-4409.
5. Feuerstein M. Defining cancer survivorship. J Cancer Surviv. 2007;1:5-7.
6. McCabe MS, Jacobs LA. Clinical update: survivorship care—models and programs. Semin Oncol Nurs. 2012;28:e1-e8.
7. Oeffinger K, Mertens A, Hudson M, et al. Health care of young adult survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. Ann Fam Med. 2004;2:61-70.
8. Mueller EL, Park ER, Davis MM. What the affordable care act means for survivors of pediatric cancer. J Clin Oncol. 2014;32:615-617.
9. Oeffinger KC. Longitudinal risk-based health care for adult survivors of childhood cancer. Curr Probl Cancer. 2003;27:143-167.
10. Lawrence RA, McLoone JK, Wakefield CE, et al. Primary care physicians’ perspectives of their role in cancer care: a systematic review. J Gen Intern Med. 2016:1-15.
11. Schwartz CL. Long-term survivors of childhood cancer: the late effects of therapy. Oncologist. 1999;4:45-54.
12. Late Effects of Treatment for Childhood Cancer (PDQ(R)): Health Professional Version [Internet]. Bethesda, MD: National Cancer Institute. Updated March 31, 2016. Available at: www.cancer.gov/types/childhood-cancers/late-effects-hp-pdq. Accessed June 2, 2016.
13. Children’s Oncology Group. Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancer, Version 4.0. Monrovia CA: Children’s Oncology Group. 2013. Available at: www.survivorshipguidelines.org. Accessed June 2, 2016.
14. Hewitt M, Greenfield S, Stovall E, Committee on Cancer Survivorship: Improving Care and Quality of Life. National Cancer Policy Board, Institute of Medicine, National Research Council, eds. From cancer patient to cancer survivor: Lost in transition. Washington, DC: The National Academies Press; 2005.
15. Commission on Cancer [Internet]. Cancer Program Standards: Ensuring Patient-Centered Care. Chicago, IL: American College of Surgeons; 2015. Available at: https://www.facs.org/quality%20programs/cancer/coc/standards. Accessed June 2, 2016.
16. Askins MA, Moore BD. Preventing neurocognitive late effects in childhood cancer survivors. J Child Neurol. 2008;23:1160-1171.
17. McCabe MS, Jacobs L. Survivorship care: models and programs. Semin Oncol Nurs. 2008;24:202-207.
18. Oeffinger KC, McCabe MS. Models for delivering survivorship care. J Clin Oncol. 2006;24:5117-5124.
19. Potosky AL, Han PKJ, Rowland J, et al. Differences between primary care physicians’ and oncologists’ knowledge, attitudes and practices regarding the care of cancer survivors. J Gen Intern Med. 2011;26:1403-1410.
20. Gilbert SM, Miller DC, Hollenbeck BK, et al. Cancer survivorship: challenges and changing paradigms. J Urol. 2008;179:431-438.
21. Renders CM, Valk GD, de Sonnaville JJ, et al. Quality of care for patients with Type 2 diabetes mellitus—a long-term comparison of two quality improvement programmes in the Netherlands. Diabet Med. 2003;20:846-852.
22. Jones C, Roderick P, Harris S, et al. An evaluation of a shared primary and secondary care nephrology service for managing patients with moderate to advanced CKD. Am J Kidney Dis. 2006;47:103-114.
23. Earle CC, Neville BA. Under use of necessary care among cancer survivors. Cancer. 2004;101:1712-1719.
24. Sima JL, Perkins SM, Haggstrom DA. Primary care physician perceptions of adult survivors of childhood cancer. J Pediatr Hematol Oncol. 2014;36:118-124.
The number of childhood cancer survivors (CCSs) entering the adult health care system is increasing, a not-so-surprising trend when you consider that more than 80% of children and adolescents given a cancer diagnosis become long-term survivors.1 This patient population has a heightened risk for developing at least one chronic health problem, resulting from therapy. By the fourth decade of life, 88% of all CCSs will have a chronic condition,2 and about one-third develop a late effect that is either severe or life-threatening.3 In contrast to patients with many other pediatric chronic diseases that manifest at an early age and are progressive, CCSs are often physically well for many years, or decades, prior to their manifestation of late effects.4
Cancer survivorship has varying definitions; however, we define cancer survivorship as the phase of cancer care for individuals who have been diagnosed with cancer and have completed primary treatment for their disease.5 Cancer survivorship, which is becoming more widely acknowledged as a distinct and critically important phase of cancer care, includes:6
- “surveillance for recurrence,
- evaluation … and treatment of medical and psychosocial consequences of treatment,
- recommendations for screening for new primary cancers,
- health promotion recommendations, and
- provision of a written treatment summary and care plan to the patient and other health professionals.”
Although models of survivorship care vary, their common goal is to promote optimal health and well-being in cancer survivors, and to prevent and detect any health concerns that may be related to prior cancer diagnosis or treatment.
Some pediatric cancer survivors have not received recommended survivorship care because of a lack of insurance or limitations from pre-existing conditions.4,7 The Affordable Care Act may remove these barriers for many.8 Others, however, fail to receive such recommendations because national models of transition are lacking. Unique considerations for this population include their need to establish age appropriate, lifelong follow-up care (and education) from a primary care provider (PCP). Unfortunately, many CCSs become lost to follow-up and fail to receive recommended survivorship care when they discontinue the relationship with their pediatrician or family practitioner and their pediatric oncologist. Fewer than 25% of CCSs who have been successfully treated for cancer during childhood continue to be followed by a cancer center and are at risk for missing survivorship-focused care or recommended screening.4,9
PCPs are an invaluable link in helping CCSs to continue to receive recommended care and surveillance. However, PCPs experience barriers in providing cancer care because of a lack of timely and specific communication from oncologists and limited knowledge of guidelines and resources available to them.10 The purpose of this article is to share information with you, the family physician, about childhood cancer survivorship needs, available resources, and how partnering with pediatric oncologists may improve treatment and health outcomes for CCSs.
Providing for the future health of childhood cancer survivors
Numerous studies have outlined the myriad of potential late effects that CCSs may experience from disease and treatment.11,12 These effects can manifest at any time and can appear in virtually every body system from the central nervous system, to the lungs, heart, bones, and endocrine systems. CCSs' particular risk for late effects may result from many factors including cancer diagnosis, types of treatments (eg, surgery, chemotherapy, radiation, and stem-cell transplant), and dosages of medications, gender, and age at diagnosis.
Determining individual risk for late effects
The Children’s Oncology Group (COG) is the world’s largest organization devoted exclusively to childhood and adolescent cancer research, including the long-term health of cancer survivors. To help provide more individualized recommendations, COG has set forth risk-based, evidence-based, exposure-related clinical practice guidelines to offer recommendations for screening and management of late effects in survivors of childhood and adolescent cancers.13 (These guidelines, Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers, are available at http://www.survivorshipguidelines.org.) The purpose of the guidelines is to standardize and enhance follow-up care for CCSs throughout their lifespan.13 To remain current, a multidisciplinary task force reviews and incorporates findings from the medical literature—including evaluations of the cost-effectiveness of recommended testing—into guideline revisions at least every 5 years.
Some of the most severe or life-threatening late effects include cardiomyopathies, endocrine disorders, and secondary malignancies (TABLE).13 Ongoing follow-up care is based on a survivor’s individual risk level and the frequency of lifelong recommended screening. The majority of patients will require yearly follow-up with additional testing, such as echocardiograms occurring as infrequently as every 2 to 5 years. Patients who received more intense therapy, such as hematopoietic stem-cell transplants, will require follow-up (often including annual echocardiograms, blood work, and a thorough physical exam) every 6 months to one year. Common testing and surveillance include blood pressure checks, urinalyses, thyroid function tests, lipid panels, echocardiograms, and electrocardiograms.
After treatment, patients should receive survivorship care plans
For health care providers to use COG Guidelines effectively across medical disciplines, it is important to know critical pieces of the patient’s cancer diagnosis and treatment history. In 2006, the Institute of Medicine released a report14 recommending that all cancer survivors be given a comprehensive care summary and follow-up plan when they complete their primary cancer care. More recently, the Commission on Cancer of the American College of Surgeons has mandated that, in order to be a cancer program accredited by the Commission, all cancer patients must be given a survivorship care plan after completing treatment.15 Generated by the treating cancer center, these care plans are meant to concisely communicate a patient’s cancer diagnosis, treatment, and long-term risks to other health care providers (across disciplines and institutions).
What’s included in a survivorship care plan?
The survivorship care plan is a paper or electronic document created by the treating institution that contains 2 components: a treatment summary and a long-term care plan based on medical/treatment history. The treatment summary includes, at a minimum, general background information (eg, demographics, pertinent medical history, diagnostic details, and significant treatment complications) and a therapeutic summary (such as dates of treatment, protocol, and details of chemotherapy, radiation, hematopoietic stem-cell transplant, and/or surgery).
The second component, the long-term care plan, details potential long-term effects specific to the treatment received, and recommendations for ongoing follow-up related to long-term risk (FIGURE). The post-treatment plan is primarily based on COG Guideline recommendations. Many institutions are introducing an electronic-based survivorship care plan, either in addition to or in replacement of a paper-based care plan. Electronic-based care plans have several benefits for patients and providers, including increased accessibility, and some offer the ability to easily update follow-up recommendations, as guidelines change, without the need for manual entry.
Shared care for cancer survivors: Oncology and primary care
Numerous models of cancer survivorship care have been described, including care by the treating oncologist, a dedicated cancer survivorship program, or follow-up completed by PCPs. There is no consensus on the best model, although many have noted that shared care is a critically important component of successful cancer survivorship care,6,16–18 and appears to be the preferred model of PCPs.19
Shared care, as the name implies, involves care that is coordinated between 2 or more health providers across specialties or locations.20 This model has shown improved outcomes in other chronic disease-management models, such as those for diabetes21 and chronic renal disease.22 One study23 found that colorectal cancer survivors who were seen by both an oncologist and a PCP were significantly more likely to receive recommended testing and follow-up to promote overall health than when they were followed by either physician alone. Information sharing between oncology and PCPs is critical to maintaining and promoting optimal health and well-being in cancer survivors, and requires ongoing communication and a concerted effort to facilitate and maintain collaboration between oncology specialists and other health care providers.6,17
Role of the cancer center in survivorship care
Although every cancer center has a slightly different timeline and structure in terms of survivorship care, there are common themes across programs regarding the type of care provided. Immediately following treatment, care is focused on surveillance for recurrence, with appointments ranging from monthly to a few times a year. This care is most often provided by the primary oncologist.
The next phase of care is reached 2 to 5 years after treatment, when recurrence is no longer a significant risk, and care is focused on monitoring and treating late effects. Depending on the center, this care may be coordinated by a dedicated survivorship clinic, the primary oncologist, or the PCP. In some models,6 the survivorship team is integrated into the patient’s care from the beginning of treatment, while others do not become active in care until the patient is considered cured of disease. In all models, a survivorship care plan should be completed after treatment has ended and before transitioning care to a PCP.
In our institution’s model, we have a survivorship program that serves patients who are more than 5 years from the completion of their treatment. Our survivorship team is comprised of a pediatric oncologist, advanced practice practitioner (APP) coordinator, a project coordinator, a clinical social worker, and a research staff member. Patients are seen every one to 2 years, depending on their overall risk for late effects. For those who are seen every other year, we are available to the PCP for questions or concerns, and the survivorship team connects with the CCS by phone to screen for any change in health status that would alter recommendations for an earlier follow-up at the oncology center.
A typical visit to our survivorship clinic includes completion of an annual health questionnaire, which addresses current health issues, as well as screening for anxiety, depression, nicotine, alcohol, and drug use. This questionnaire is reviewed by the pediatric oncologist and is used to tailor screening, referrals, and patient education based on current complaints. The oncologist also performs a thorough physical exam with special attention to areas in which late effects may occur (eg, skin exam in areas of previous radiation). In addition, each patient receives an individualized treatment summary based on COG guidelines, which is updated before each visit by the APP coordinator. The APP coordinator reviews the document at each visit and offers patient education and health maintenance counseling.
Ensuring patients aren’t lost to follow-up. In our experience, numerous patients become lost to follow-up as they age, enter college or the workforce, or move away. So, rather than attempting to follow these patients for life, we work to transition patient care to a PCP of their choice, particularly if they are at least 21 years old and more than 10 years post-diagnosis. However, we will work to transition at any time at the request of the CCS. Even when a patient’s ongoing care is transitioned to a PCP, we will remain as a continuing resource to PCPs and CCSs on an as-needed basis.
Role of primary care providers in survivorship care
Every health care provider caring for a CCS should have a copy of the patient’s survivorship care plan. This document should be provided by the treating institution, but research has shown that as many as 86% of PCPs fail to receive this critical information.24 Any PCP who treats a patient with a history of cancer and has not received a survivorship care plan should contact the treating cancer center to request a copy. A properly prepared survivorship care plan summarizes the patient’s disease and treatment history, and provides a road map of the patient’s risk for long-term effects from disease and treatment.
The most important sections of the survivorship care plan for use in primary care will be the list of potential late effects and ongoing recommended testing. This list will help to guide the PCP’s differential and work-up for specific complaints. For example, knowing that a patient is at risk for a second malignancy because of radiation therapy may result in earlier diagnostic imaging, leading to a timelier diagnosis.
The COG screening recommendations that are generally included in a survivorship care plan are appropriate for survivors who are asymptomatic and presenting for routine, exposure-based medical follow-up. More extensive work-ups are presumed to be completed as clinically indicated. Consultation with a pediatric long-term follow-up clinic is also encouraged, particularly if a concern arises.
A complementary set of patient education materials, known as “Health Links,” accompany the COG guidelines to broaden their application and enhance patient follow-up visits. A survivorship care plan and the COG Guidelines help ensure that CCSs receive appropriate ongoing follow-up based on their history. A collaborative approach between Oncology and PCPs is essential to improve the quality of care for CCSs and to maintain the long-term health of this vulnerable population.
CORRESPONDENCE
Jean M. Tersak, Children’s Hospital of Pittsburgh of UPMC, 4401 Penn Avenue, 5th Floor Plaza Building, Pittsburgh, PA 15224; tersakjm@upmc.edu.
The number of childhood cancer survivors (CCSs) entering the adult health care system is increasing, a not-so-surprising trend when you consider that more than 80% of children and adolescents given a cancer diagnosis become long-term survivors.1 This patient population has a heightened risk for developing at least one chronic health problem, resulting from therapy. By the fourth decade of life, 88% of all CCSs will have a chronic condition,2 and about one-third develop a late effect that is either severe or life-threatening.3 In contrast to patients with many other pediatric chronic diseases that manifest at an early age and are progressive, CCSs are often physically well for many years, or decades, prior to their manifestation of late effects.4
Cancer survivorship has varying definitions; however, we define cancer survivorship as the phase of cancer care for individuals who have been diagnosed with cancer and have completed primary treatment for their disease.5 Cancer survivorship, which is becoming more widely acknowledged as a distinct and critically important phase of cancer care, includes:6
- “surveillance for recurrence,
- evaluation … and treatment of medical and psychosocial consequences of treatment,
- recommendations for screening for new primary cancers,
- health promotion recommendations, and
- provision of a written treatment summary and care plan to the patient and other health professionals.”
Although models of survivorship care vary, their common goal is to promote optimal health and well-being in cancer survivors, and to prevent and detect any health concerns that may be related to prior cancer diagnosis or treatment.
Some pediatric cancer survivors have not received recommended survivorship care because of a lack of insurance or limitations from pre-existing conditions.4,7 The Affordable Care Act may remove these barriers for many.8 Others, however, fail to receive such recommendations because national models of transition are lacking. Unique considerations for this population include their need to establish age appropriate, lifelong follow-up care (and education) from a primary care provider (PCP). Unfortunately, many CCSs become lost to follow-up and fail to receive recommended survivorship care when they discontinue the relationship with their pediatrician or family practitioner and their pediatric oncologist. Fewer than 25% of CCSs who have been successfully treated for cancer during childhood continue to be followed by a cancer center and are at risk for missing survivorship-focused care or recommended screening.4,9
PCPs are an invaluable link in helping CCSs to continue to receive recommended care and surveillance. However, PCPs experience barriers in providing cancer care because of a lack of timely and specific communication from oncologists and limited knowledge of guidelines and resources available to them.10 The purpose of this article is to share information with you, the family physician, about childhood cancer survivorship needs, available resources, and how partnering with pediatric oncologists may improve treatment and health outcomes for CCSs.
Providing for the future health of childhood cancer survivors
Numerous studies have outlined the myriad of potential late effects that CCSs may experience from disease and treatment.11,12 These effects can manifest at any time and can appear in virtually every body system from the central nervous system, to the lungs, heart, bones, and endocrine systems. CCSs' particular risk for late effects may result from many factors including cancer diagnosis, types of treatments (eg, surgery, chemotherapy, radiation, and stem-cell transplant), and dosages of medications, gender, and age at diagnosis.
Determining individual risk for late effects
The Children’s Oncology Group (COG) is the world’s largest organization devoted exclusively to childhood and adolescent cancer research, including the long-term health of cancer survivors. To help provide more individualized recommendations, COG has set forth risk-based, evidence-based, exposure-related clinical practice guidelines to offer recommendations for screening and management of late effects in survivors of childhood and adolescent cancers.13 (These guidelines, Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers, are available at http://www.survivorshipguidelines.org.) The purpose of the guidelines is to standardize and enhance follow-up care for CCSs throughout their lifespan.13 To remain current, a multidisciplinary task force reviews and incorporates findings from the medical literature—including evaluations of the cost-effectiveness of recommended testing—into guideline revisions at least every 5 years.
Some of the most severe or life-threatening late effects include cardiomyopathies, endocrine disorders, and secondary malignancies (TABLE).13 Ongoing follow-up care is based on a survivor’s individual risk level and the frequency of lifelong recommended screening. The majority of patients will require yearly follow-up with additional testing, such as echocardiograms occurring as infrequently as every 2 to 5 years. Patients who received more intense therapy, such as hematopoietic stem-cell transplants, will require follow-up (often including annual echocardiograms, blood work, and a thorough physical exam) every 6 months to one year. Common testing and surveillance include blood pressure checks, urinalyses, thyroid function tests, lipid panels, echocardiograms, and electrocardiograms.
After treatment, patients should receive survivorship care plans
For health care providers to use COG Guidelines effectively across medical disciplines, it is important to know critical pieces of the patient’s cancer diagnosis and treatment history. In 2006, the Institute of Medicine released a report14 recommending that all cancer survivors be given a comprehensive care summary and follow-up plan when they complete their primary cancer care. More recently, the Commission on Cancer of the American College of Surgeons has mandated that, in order to be a cancer program accredited by the Commission, all cancer patients must be given a survivorship care plan after completing treatment.15 Generated by the treating cancer center, these care plans are meant to concisely communicate a patient’s cancer diagnosis, treatment, and long-term risks to other health care providers (across disciplines and institutions).
What’s included in a survivorship care plan?
The survivorship care plan is a paper or electronic document created by the treating institution that contains 2 components: a treatment summary and a long-term care plan based on medical/treatment history. The treatment summary includes, at a minimum, general background information (eg, demographics, pertinent medical history, diagnostic details, and significant treatment complications) and a therapeutic summary (such as dates of treatment, protocol, and details of chemotherapy, radiation, hematopoietic stem-cell transplant, and/or surgery).
The second component, the long-term care plan, details potential long-term effects specific to the treatment received, and recommendations for ongoing follow-up related to long-term risk (FIGURE). The post-treatment plan is primarily based on COG Guideline recommendations. Many institutions are introducing an electronic-based survivorship care plan, either in addition to or in replacement of a paper-based care plan. Electronic-based care plans have several benefits for patients and providers, including increased accessibility, and some offer the ability to easily update follow-up recommendations, as guidelines change, without the need for manual entry.
Shared care for cancer survivors: Oncology and primary care
Numerous models of cancer survivorship care have been described, including care by the treating oncologist, a dedicated cancer survivorship program, or follow-up completed by PCPs. There is no consensus on the best model, although many have noted that shared care is a critically important component of successful cancer survivorship care,6,16–18 and appears to be the preferred model of PCPs.19
Shared care, as the name implies, involves care that is coordinated between 2 or more health providers across specialties or locations.20 This model has shown improved outcomes in other chronic disease-management models, such as those for diabetes21 and chronic renal disease.22 One study23 found that colorectal cancer survivors who were seen by both an oncologist and a PCP were significantly more likely to receive recommended testing and follow-up to promote overall health than when they were followed by either physician alone. Information sharing between oncology and PCPs is critical to maintaining and promoting optimal health and well-being in cancer survivors, and requires ongoing communication and a concerted effort to facilitate and maintain collaboration between oncology specialists and other health care providers.6,17
Role of the cancer center in survivorship care
Although every cancer center has a slightly different timeline and structure in terms of survivorship care, there are common themes across programs regarding the type of care provided. Immediately following treatment, care is focused on surveillance for recurrence, with appointments ranging from monthly to a few times a year. This care is most often provided by the primary oncologist.
The next phase of care is reached 2 to 5 years after treatment, when recurrence is no longer a significant risk, and care is focused on monitoring and treating late effects. Depending on the center, this care may be coordinated by a dedicated survivorship clinic, the primary oncologist, or the PCP. In some models,6 the survivorship team is integrated into the patient’s care from the beginning of treatment, while others do not become active in care until the patient is considered cured of disease. In all models, a survivorship care plan should be completed after treatment has ended and before transitioning care to a PCP.
In our institution’s model, we have a survivorship program that serves patients who are more than 5 years from the completion of their treatment. Our survivorship team is comprised of a pediatric oncologist, advanced practice practitioner (APP) coordinator, a project coordinator, a clinical social worker, and a research staff member. Patients are seen every one to 2 years, depending on their overall risk for late effects. For those who are seen every other year, we are available to the PCP for questions or concerns, and the survivorship team connects with the CCS by phone to screen for any change in health status that would alter recommendations for an earlier follow-up at the oncology center.
A typical visit to our survivorship clinic includes completion of an annual health questionnaire, which addresses current health issues, as well as screening for anxiety, depression, nicotine, alcohol, and drug use. This questionnaire is reviewed by the pediatric oncologist and is used to tailor screening, referrals, and patient education based on current complaints. The oncologist also performs a thorough physical exam with special attention to areas in which late effects may occur (eg, skin exam in areas of previous radiation). In addition, each patient receives an individualized treatment summary based on COG guidelines, which is updated before each visit by the APP coordinator. The APP coordinator reviews the document at each visit and offers patient education and health maintenance counseling.
Ensuring patients aren’t lost to follow-up. In our experience, numerous patients become lost to follow-up as they age, enter college or the workforce, or move away. So, rather than attempting to follow these patients for life, we work to transition patient care to a PCP of their choice, particularly if they are at least 21 years old and more than 10 years post-diagnosis. However, we will work to transition at any time at the request of the CCS. Even when a patient’s ongoing care is transitioned to a PCP, we will remain as a continuing resource to PCPs and CCSs on an as-needed basis.
Role of primary care providers in survivorship care
Every health care provider caring for a CCS should have a copy of the patient’s survivorship care plan. This document should be provided by the treating institution, but research has shown that as many as 86% of PCPs fail to receive this critical information.24 Any PCP who treats a patient with a history of cancer and has not received a survivorship care plan should contact the treating cancer center to request a copy. A properly prepared survivorship care plan summarizes the patient’s disease and treatment history, and provides a road map of the patient’s risk for long-term effects from disease and treatment.
The most important sections of the survivorship care plan for use in primary care will be the list of potential late effects and ongoing recommended testing. This list will help to guide the PCP’s differential and work-up for specific complaints. For example, knowing that a patient is at risk for a second malignancy because of radiation therapy may result in earlier diagnostic imaging, leading to a timelier diagnosis.
The COG screening recommendations that are generally included in a survivorship care plan are appropriate for survivors who are asymptomatic and presenting for routine, exposure-based medical follow-up. More extensive work-ups are presumed to be completed as clinically indicated. Consultation with a pediatric long-term follow-up clinic is also encouraged, particularly if a concern arises.
A complementary set of patient education materials, known as “Health Links,” accompany the COG guidelines to broaden their application and enhance patient follow-up visits. A survivorship care plan and the COG Guidelines help ensure that CCSs receive appropriate ongoing follow-up based on their history. A collaborative approach between Oncology and PCPs is essential to improve the quality of care for CCSs and to maintain the long-term health of this vulnerable population.
CORRESPONDENCE
Jean M. Tersak, Children’s Hospital of Pittsburgh of UPMC, 4401 Penn Avenue, 5th Floor Plaza Building, Pittsburgh, PA 15224; tersakjm@upmc.edu.
1. Ries LAG, Eisner MP, Kosary CL, et al, eds. SEER Cancer Statistics Review, 1975-2002. National Cancer Institute. Bethesda, MD. Available at: http://seer.cancer.gov/csr/1975_2002/. Accessed May 26, 2016.
2. Phillips SM, Padgett LS, Leisenring WM, et al. Survivors of childhood cancer in the United States: prevalence and burden of morbidity. Cancer Epidemiol Biomarkers Prev. 2015;24:653-663.
3. Oeffinger KC, Mertens AC, Sklar CA, et al. Chronic health conditions in adult survivors of childhood cancer. N Engl J Med. 2006;355:1572-1582.
4. Nathan PC, Greenberg ML, Ness KK, et al. Medical care in long-term survivors of childhood cancer: a report from the childhood cancer survivor study. J Clin Oncol. 2008;26:4401-4409.
5. Feuerstein M. Defining cancer survivorship. J Cancer Surviv. 2007;1:5-7.
6. McCabe MS, Jacobs LA. Clinical update: survivorship care—models and programs. Semin Oncol Nurs. 2012;28:e1-e8.
7. Oeffinger K, Mertens A, Hudson M, et al. Health care of young adult survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. Ann Fam Med. 2004;2:61-70.
8. Mueller EL, Park ER, Davis MM. What the affordable care act means for survivors of pediatric cancer. J Clin Oncol. 2014;32:615-617.
9. Oeffinger KC. Longitudinal risk-based health care for adult survivors of childhood cancer. Curr Probl Cancer. 2003;27:143-167.
10. Lawrence RA, McLoone JK, Wakefield CE, et al. Primary care physicians’ perspectives of their role in cancer care: a systematic review. J Gen Intern Med. 2016:1-15.
11. Schwartz CL. Long-term survivors of childhood cancer: the late effects of therapy. Oncologist. 1999;4:45-54.
12. Late Effects of Treatment for Childhood Cancer (PDQ(R)): Health Professional Version [Internet]. Bethesda, MD: National Cancer Institute. Updated March 31, 2016. Available at: www.cancer.gov/types/childhood-cancers/late-effects-hp-pdq. Accessed June 2, 2016.
13. Children’s Oncology Group. Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancer, Version 4.0. Monrovia CA: Children’s Oncology Group. 2013. Available at: www.survivorshipguidelines.org. Accessed June 2, 2016.
14. Hewitt M, Greenfield S, Stovall E, Committee on Cancer Survivorship: Improving Care and Quality of Life. National Cancer Policy Board, Institute of Medicine, National Research Council, eds. From cancer patient to cancer survivor: Lost in transition. Washington, DC: The National Academies Press; 2005.
15. Commission on Cancer [Internet]. Cancer Program Standards: Ensuring Patient-Centered Care. Chicago, IL: American College of Surgeons; 2015. Available at: https://www.facs.org/quality%20programs/cancer/coc/standards. Accessed June 2, 2016.
16. Askins MA, Moore BD. Preventing neurocognitive late effects in childhood cancer survivors. J Child Neurol. 2008;23:1160-1171.
17. McCabe MS, Jacobs L. Survivorship care: models and programs. Semin Oncol Nurs. 2008;24:202-207.
18. Oeffinger KC, McCabe MS. Models for delivering survivorship care. J Clin Oncol. 2006;24:5117-5124.
19. Potosky AL, Han PKJ, Rowland J, et al. Differences between primary care physicians’ and oncologists’ knowledge, attitudes and practices regarding the care of cancer survivors. J Gen Intern Med. 2011;26:1403-1410.
20. Gilbert SM, Miller DC, Hollenbeck BK, et al. Cancer survivorship: challenges and changing paradigms. J Urol. 2008;179:431-438.
21. Renders CM, Valk GD, de Sonnaville JJ, et al. Quality of care for patients with Type 2 diabetes mellitus—a long-term comparison of two quality improvement programmes in the Netherlands. Diabet Med. 2003;20:846-852.
22. Jones C, Roderick P, Harris S, et al. An evaluation of a shared primary and secondary care nephrology service for managing patients with moderate to advanced CKD. Am J Kidney Dis. 2006;47:103-114.
23. Earle CC, Neville BA. Under use of necessary care among cancer survivors. Cancer. 2004;101:1712-1719.
24. Sima JL, Perkins SM, Haggstrom DA. Primary care physician perceptions of adult survivors of childhood cancer. J Pediatr Hematol Oncol. 2014;36:118-124.
1. Ries LAG, Eisner MP, Kosary CL, et al, eds. SEER Cancer Statistics Review, 1975-2002. National Cancer Institute. Bethesda, MD. Available at: http://seer.cancer.gov/csr/1975_2002/. Accessed May 26, 2016.
2. Phillips SM, Padgett LS, Leisenring WM, et al. Survivors of childhood cancer in the United States: prevalence and burden of morbidity. Cancer Epidemiol Biomarkers Prev. 2015;24:653-663.
3. Oeffinger KC, Mertens AC, Sklar CA, et al. Chronic health conditions in adult survivors of childhood cancer. N Engl J Med. 2006;355:1572-1582.
4. Nathan PC, Greenberg ML, Ness KK, et al. Medical care in long-term survivors of childhood cancer: a report from the childhood cancer survivor study. J Clin Oncol. 2008;26:4401-4409.
5. Feuerstein M. Defining cancer survivorship. J Cancer Surviv. 2007;1:5-7.
6. McCabe MS, Jacobs LA. Clinical update: survivorship care—models and programs. Semin Oncol Nurs. 2012;28:e1-e8.
7. Oeffinger K, Mertens A, Hudson M, et al. Health care of young adult survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. Ann Fam Med. 2004;2:61-70.
8. Mueller EL, Park ER, Davis MM. What the affordable care act means for survivors of pediatric cancer. J Clin Oncol. 2014;32:615-617.
9. Oeffinger KC. Longitudinal risk-based health care for adult survivors of childhood cancer. Curr Probl Cancer. 2003;27:143-167.
10. Lawrence RA, McLoone JK, Wakefield CE, et al. Primary care physicians’ perspectives of their role in cancer care: a systematic review. J Gen Intern Med. 2016:1-15.
11. Schwartz CL. Long-term survivors of childhood cancer: the late effects of therapy. Oncologist. 1999;4:45-54.
12. Late Effects of Treatment for Childhood Cancer (PDQ(R)): Health Professional Version [Internet]. Bethesda, MD: National Cancer Institute. Updated March 31, 2016. Available at: www.cancer.gov/types/childhood-cancers/late-effects-hp-pdq. Accessed June 2, 2016.
13. Children’s Oncology Group. Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancer, Version 4.0. Monrovia CA: Children’s Oncology Group. 2013. Available at: www.survivorshipguidelines.org. Accessed June 2, 2016.
14. Hewitt M, Greenfield S, Stovall E, Committee on Cancer Survivorship: Improving Care and Quality of Life. National Cancer Policy Board, Institute of Medicine, National Research Council, eds. From cancer patient to cancer survivor: Lost in transition. Washington, DC: The National Academies Press; 2005.
15. Commission on Cancer [Internet]. Cancer Program Standards: Ensuring Patient-Centered Care. Chicago, IL: American College of Surgeons; 2015. Available at: https://www.facs.org/quality%20programs/cancer/coc/standards. Accessed June 2, 2016.
16. Askins MA, Moore BD. Preventing neurocognitive late effects in childhood cancer survivors. J Child Neurol. 2008;23:1160-1171.
17. McCabe MS, Jacobs L. Survivorship care: models and programs. Semin Oncol Nurs. 2008;24:202-207.
18. Oeffinger KC, McCabe MS. Models for delivering survivorship care. J Clin Oncol. 2006;24:5117-5124.
19. Potosky AL, Han PKJ, Rowland J, et al. Differences between primary care physicians’ and oncologists’ knowledge, attitudes and practices regarding the care of cancer survivors. J Gen Intern Med. 2011;26:1403-1410.
20. Gilbert SM, Miller DC, Hollenbeck BK, et al. Cancer survivorship: challenges and changing paradigms. J Urol. 2008;179:431-438.
21. Renders CM, Valk GD, de Sonnaville JJ, et al. Quality of care for patients with Type 2 diabetes mellitus—a long-term comparison of two quality improvement programmes in the Netherlands. Diabet Med. 2003;20:846-852.
22. Jones C, Roderick P, Harris S, et al. An evaluation of a shared primary and secondary care nephrology service for managing patients with moderate to advanced CKD. Am J Kidney Dis. 2006;47:103-114.
23. Earle CC, Neville BA. Under use of necessary care among cancer survivors. Cancer. 2004;101:1712-1719.
24. Sima JL, Perkins SM, Haggstrom DA. Primary care physician perceptions of adult survivors of childhood cancer. J Pediatr Hematol Oncol. 2014;36:118-124.
PRACTICE RECOMMENDATIONS
› Use the survivorship care plan from the patient’s primary oncologist to guide your screening and management of late effects. C
› Apply the Children’s Oncology Group Guidelines, which are risk-based, exposure-related, clinical practice guidelines, to direct screening and management of late effects in survivors of pediatric malignancies. B
Strength of recommendation (SOR)
A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series
Psyllium cut frequency of abdominal pain in pediatric IBS trial
Consuming psyllium fiber significantly reduced the frequency, but not the severity, of abdominal pain in children with irritable bowel syndrome in a randomized, double-blind, placebo-controlled trial reported in the May issue of Clinical Gastroenterology and Hepatology (2016 Nov;14[11]:1667).
Psyllium therapy did not reduce the self-reported severity of abdominal pain, Robert J. Shulman, MD, of Baylor College of Medicine in Houston reported with his associates in Clinical Gastroenterology and Hepatology. Psyllium was associated with shifts in intestinal microbiota, compared with baseline, although the changes did not reach statistical significance when compared with placebo, the researchers added. “Further studies are needed to investigate the potential mechanism whereby psyllium decreases abdominal pain frequency in children with irritable bowel syndrome [IBS],” they wrote.
IBS affects up to 20% of school-aged children. Consuming psyllium is thought to improve abdominal pain and stooling symptoms in adults with IBS, but data are inconclusive, and few randomized trials have evaluated fiber in childhood IBS. Therefore, the investigators randomly assigned 103 children (average age, 13 years; standard deviation, 3 years) with IBS who had responded inadequately to an 8-day carbohydrate elimination diet to receive a single daily dose of either psyllium or placebo maltodextrin for 6 weeks. Children aged 7-11 years received 6 g of fiber, while those aged 12-18 years received 12 g of fiber. Patients filled out a daily pain and stool diary during a 2-week baseline assessment period and again during the final 2 weeks of the trial. They also underwent breath hydrogen and methane testing, gut permeability testing, and a stool microbiota assessment during the final weekend of treatment.
At baseline, the trial arms resembled each other in terms of frequency and severity of abdominal pain, psychological characteristics, percentage of normal stools, baseline hydrogen production, and gastrointestinal permeability, the researchers said. During the final 2 weeks of treatment, the psyllium arm reported an average of 8.2 (standard deviation, 1.2) fewer episodes of abdominal pain, compared with baseline, while the control arm reported a mean reduction of 4.1 (SD, 1.3) episodes of abdominal pain (P = .03). At the end of treatment, the arms did not significantly differ in percentage of breath hydrogen or methane production, gastrointestinal permeability, or percentage of normal stools or diarrhea. However, controls had a significantly greater reduction in constipation compared with the psyllium group (P = .048).
Stool microbiome assessments of 33 children revealed a trend toward a greater increase in Bacteroidetes and a greater decrease in Firmicutes bacteria in the fiber group, compared with the control group (P = .068). The fiber group was also “marginally enriched” in bacteria of class Bacteroidia, while the placebo group was enriched in bacteria of class Clostridia (P = .094). However, the groups did not differ at narrower taxonomic levels, the researchers said. A larger sample size might have facilitated better detection of differences between groups, such as in breath hydrogen production or interactions between abdominal pain and psychological symptoms, they added.
The study was supported in part by the National Institutes of Health, the Daffy’s Foundation, and the USDA/ARS. The investigators reported having no conflicts of interest.
Consuming psyllium fiber significantly reduced the frequency, but not the severity, of abdominal pain in children with irritable bowel syndrome in a randomized, double-blind, placebo-controlled trial reported in the May issue of Clinical Gastroenterology and Hepatology (2016 Nov;14[11]:1667).
Psyllium therapy did not reduce the self-reported severity of abdominal pain, Robert J. Shulman, MD, of Baylor College of Medicine in Houston reported with his associates in Clinical Gastroenterology and Hepatology. Psyllium was associated with shifts in intestinal microbiota, compared with baseline, although the changes did not reach statistical significance when compared with placebo, the researchers added. “Further studies are needed to investigate the potential mechanism whereby psyllium decreases abdominal pain frequency in children with irritable bowel syndrome [IBS],” they wrote.
IBS affects up to 20% of school-aged children. Consuming psyllium is thought to improve abdominal pain and stooling symptoms in adults with IBS, but data are inconclusive, and few randomized trials have evaluated fiber in childhood IBS. Therefore, the investigators randomly assigned 103 children (average age, 13 years; standard deviation, 3 years) with IBS who had responded inadequately to an 8-day carbohydrate elimination diet to receive a single daily dose of either psyllium or placebo maltodextrin for 6 weeks. Children aged 7-11 years received 6 g of fiber, while those aged 12-18 years received 12 g of fiber. Patients filled out a daily pain and stool diary during a 2-week baseline assessment period and again during the final 2 weeks of the trial. They also underwent breath hydrogen and methane testing, gut permeability testing, and a stool microbiota assessment during the final weekend of treatment.
At baseline, the trial arms resembled each other in terms of frequency and severity of abdominal pain, psychological characteristics, percentage of normal stools, baseline hydrogen production, and gastrointestinal permeability, the researchers said. During the final 2 weeks of treatment, the psyllium arm reported an average of 8.2 (standard deviation, 1.2) fewer episodes of abdominal pain, compared with baseline, while the control arm reported a mean reduction of 4.1 (SD, 1.3) episodes of abdominal pain (P = .03). At the end of treatment, the arms did not significantly differ in percentage of breath hydrogen or methane production, gastrointestinal permeability, or percentage of normal stools or diarrhea. However, controls had a significantly greater reduction in constipation compared with the psyllium group (P = .048).
Stool microbiome assessments of 33 children revealed a trend toward a greater increase in Bacteroidetes and a greater decrease in Firmicutes bacteria in the fiber group, compared with the control group (P = .068). The fiber group was also “marginally enriched” in bacteria of class Bacteroidia, while the placebo group was enriched in bacteria of class Clostridia (P = .094). However, the groups did not differ at narrower taxonomic levels, the researchers said. A larger sample size might have facilitated better detection of differences between groups, such as in breath hydrogen production or interactions between abdominal pain and psychological symptoms, they added.
The study was supported in part by the National Institutes of Health, the Daffy’s Foundation, and the USDA/ARS. The investigators reported having no conflicts of interest.
Consuming psyllium fiber significantly reduced the frequency, but not the severity, of abdominal pain in children with irritable bowel syndrome in a randomized, double-blind, placebo-controlled trial reported in the May issue of Clinical Gastroenterology and Hepatology (2016 Nov;14[11]:1667).
Psyllium therapy did not reduce the self-reported severity of abdominal pain, Robert J. Shulman, MD, of Baylor College of Medicine in Houston reported with his associates in Clinical Gastroenterology and Hepatology. Psyllium was associated with shifts in intestinal microbiota, compared with baseline, although the changes did not reach statistical significance when compared with placebo, the researchers added. “Further studies are needed to investigate the potential mechanism whereby psyllium decreases abdominal pain frequency in children with irritable bowel syndrome [IBS],” they wrote.
IBS affects up to 20% of school-aged children. Consuming psyllium is thought to improve abdominal pain and stooling symptoms in adults with IBS, but data are inconclusive, and few randomized trials have evaluated fiber in childhood IBS. Therefore, the investigators randomly assigned 103 children (average age, 13 years; standard deviation, 3 years) with IBS who had responded inadequately to an 8-day carbohydrate elimination diet to receive a single daily dose of either psyllium or placebo maltodextrin for 6 weeks. Children aged 7-11 years received 6 g of fiber, while those aged 12-18 years received 12 g of fiber. Patients filled out a daily pain and stool diary during a 2-week baseline assessment period and again during the final 2 weeks of the trial. They also underwent breath hydrogen and methane testing, gut permeability testing, and a stool microbiota assessment during the final weekend of treatment.
At baseline, the trial arms resembled each other in terms of frequency and severity of abdominal pain, psychological characteristics, percentage of normal stools, baseline hydrogen production, and gastrointestinal permeability, the researchers said. During the final 2 weeks of treatment, the psyllium arm reported an average of 8.2 (standard deviation, 1.2) fewer episodes of abdominal pain, compared with baseline, while the control arm reported a mean reduction of 4.1 (SD, 1.3) episodes of abdominal pain (P = .03). At the end of treatment, the arms did not significantly differ in percentage of breath hydrogen or methane production, gastrointestinal permeability, or percentage of normal stools or diarrhea. However, controls had a significantly greater reduction in constipation compared with the psyllium group (P = .048).
Stool microbiome assessments of 33 children revealed a trend toward a greater increase in Bacteroidetes and a greater decrease in Firmicutes bacteria in the fiber group, compared with the control group (P = .068). The fiber group was also “marginally enriched” in bacteria of class Bacteroidia, while the placebo group was enriched in bacteria of class Clostridia (P = .094). However, the groups did not differ at narrower taxonomic levels, the researchers said. A larger sample size might have facilitated better detection of differences between groups, such as in breath hydrogen production or interactions between abdominal pain and psychological symptoms, they added.
The study was supported in part by the National Institutes of Health, the Daffy’s Foundation, and the USDA/ARS. The investigators reported having no conflicts of interest.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Key clinical point: Compared with placebo maltodextrin, consuming psyllium fiber significantly reduced the self-reported frequency of abdominal pain in children with irritable bowel syndrome.
Major finding: Children who received psyllium reported an average of 8.2 fewer pain episodes, compared with baseline, while controls reported a mean reduction of 4.1 pain episodes (P = .03).
Data source: A randomized, double-blind trial of 103 children aged 12-18 years of age with irritable bowel syndrome.
Disclosures: The study was supported in part by the National Institutes of Health, the Daffy’s Foundation, and the USDA/ARS. The investigators reported having no conflicts of interest.
Drops, Ointments, Gels, and Patches: The Dangers of Topical Medications
The anxiety of caring for a child in imminent peril may cause even an experienced clinician to forget to ask important questions about ingestions and exposures that can be critical to the patient’s management. Though emergency physicians (EPs) routinely ask about household medications when obtaining a history from family members, they occasionally gloss over a detail of utmost importance: topical medications.
The use of topical medications is extremely prevalent in the United States, in turn resulting in accidental ingestion—particularly in the pediatric population. In 2015, there were 56,455 calls to US Poison Control Centers for pediatric (children ≤5 years) exposures to topical preparations.1 Topical drug-delivery-system formulations include drops, ointments, gels, and patches. Intentional and unintentional misuse or overdose of any of these formulations can cause toxicity. Unintentional overdose of these drugs can occur secondary to exploratory ingestions, therapeutic errors, or medication overuse due to the perception of safety associated with topical preparations.
Drops
Topical liquid medications such as ophthalmic and otologic drops can be fatal when ingested or used inappropriately. The following sections review commonly used prescription and nonprescription formulations, associated toxicological manifestations, and appropriate management.
Ophthalmic Drops
A common class of ophthalmic drops includes imidazoline-derived agents such as tetrahydrozoline (eg, Opti-Clear, Visine). Te
Treatment. Management of overdose of imidazoline agents depends greatly on the patient’s presentation and is largely supportive. Overdoses of these agents and clonidine are similar: Patients can be extremely somnolent, but may transiently improve when a painful stimulus is applied. Activated charcoal may be useful for recent ingestions,3 but it should only be considered in patients whose airway is patent or protected. Intravenous fluids are indicated if the patient is hypotensive. Atropine may be considered for symptomatic bradycardia,3 and transcutaneous pacing should be considered if the patient is hemodynamically unstable. Intubation may be required if there is concern for airway compromise, though such compromise is a rare occurrence in ophthalmic ingestion of imidazoline-derived agents.
Although not well studied due to a lack of data, some sources recommend naloxone administration, given the similarities of imidazoline agents to clonidine in the overdose scenario.3,4 Although the optimal dose is unknown, high doses of naloxone (ie, pediatric patients, 0.4 mg, followed by 2 mg, then 10 mg, if no response) are typically required and should be considered in symptomatic patients after an ingestion. After successful supportive management, most patients continue to do well during their hospital course and have a full recovery.
Methyl Salicylate
Methyl salicylate (oil of wintergreen) is a common ingredient in muscular pain-relieving creams and ointments that can have devastating consequences in overdose. Significant toxicity from these compounds is rare, as large exposures are needed to reach a toxic threshold. However, oil of wintergreen is also available as a liquid preparation with 98% methyl salicylate.5 At this concentration, 1 teaspoon (5 mL) is roughly equivalent to 7 g of acetylsalicylate,5 and this amount of oil of wintergreen is severely toxic and may be lethal to a child. Because it is a liquid, oil of wintergreen is more rapidly absorbed than creams and ointments and can cause rapid toxicity in small quantities.
Methyl salicylate overdose initially causes stimulation of the brain’s respiratory center, which leads to a respiratory alkalosis. Uncoupling of oxidative phosphorylation later causes an anion gap metabolic acidosis. The combination of these two processes leads to a mixed acid-base disturbance. Common signs and symptoms of toxicity include tinnitus, hyperpnea, tachypnea, hyperthermia, nausea, vomiting, multisystem organ dysfunction, altered mental status, and death.
Treatment. Supportive care is critically important. Clinicians must be sure the patient’s airway is patent, particularly in those with altered sensorium or in patients who are becoming fatigued secondary to work of breathing. Extreme caution should be used when intubating these patients, as the patient’s respiratory rate (RR) must be matched if placed on a ventilator. If the RR is too low, the patient will become increasingly acidotic and may become hemodynamically unstable. Activated charcoal should be considered if the patient is mentating well or if the airway is protected.5,6 Adequate fluid resuscitation is essential.
Serum alkalinization is critical in helping to prevent central nervous system (CNS) toxicity. Urinary alkalinization with sodium bicarbonate will augment the salicylate excretion rate and may also help correct the patient’s acidemia.
Current guidelines recommend hemodialysis in asymptomatic patients whose serum salicylate concentration is greater than 100 mg/dL, or in patients with consequential findings, such as altered mental status.7
In infants with severe salicylate toxicity, exchange transfusion can be considered, given the limitations of hemodialysis at this age.8 Clinical outcomes are generally good if managed appropriately, though oil of wintergreen ingestion can be fatal.
Liquids
Liquid nicotine also poses a major threat to the pediatric population. Since the early 2000s, electronic cigarettes (e-cigarettes) have gained popularity. E-cigarette cartridges contain highly concentrated liquid nicotine, and, until May 2016, were not regulated by the US Food and Drug Administration (FDA).9 Since then, the FDA’s updated rule now extends to all tobacco products, including e-cigarettes.10
Some of the recent literature suggest oral lethal doses of nicotine occur at levels as low as 0.8 mg/kg,11 though this is likely an overly conservative level. At this dose, even relatively diluted products with a 1.8% nicotine solution could be fatal.12
Liquid nicotine comes in thousands of flavors,13 and while this may make its use more enjoyable for adults, it poses a significant risk to small children. Children may be enticed to ingest liquid nicotine products due to their flavor-enhanced scents.12
At relatively low serum levels, nicotine acts as a nicotinic acetylcholine receptor agonist. Symptoms such as nausea, vomiting, diarrhea, abdominal discomfort, increased salivation, and weakness can occur early on in toxicity.13 Once nicotine concentrations reach higher levels, patients develop altered mental status, hemodynamic instability, seizure, muscle weakness, and respiratory compromise.
Treatment. Supportive therapy should be initiated when caring for patients with nicotine ingestion. Airway management is paramount, particularly if the patient has altered mental status. In some cases, intubation may be necessary, especially in patients with altered mental status and excessive salivation/bronchorrhea. Intravenous fluid administration is pivotal in patients with hypotension, particularly for those at risk for dehydration secondary to vomiting and diarrhea. Although there is no definitive antidote, atropine can be used to treat patients who are symptomatic from excessive muscarinic cholinergic stimulation.13,14 If seizures occur, they can be treated with benzodiazepines as needed.
The use of activated charcoal has little mention in the current literature. Because of its liquid formulation, nicotine will likely be absorbed quickly. If ingestion occurred shortly prior to presentation and the patient’s airway is patent or secured, a dose of activated charcoal may be cautiously administered.15 The prognosis is poor if large amounts of liquid nicotine have been consumed.
Topical Ointments
Ointments are semisolid preparations, typically for topical application. Topical anesthetics are available in a variety of prescription and nonprescription ointments. Of the local prescription and nonprescription anesthetics currently available, amide-type local anesthetics have become especially popular for their rapid and reliable onset of local anesthesia and low occurrence of hypersensitive reactions. Increased popularity raises the likelihood of accidental ingestion—especially in pediatric patients.
Dibucaine, an amide anesthetic, is available as a nonprescription medication. Its uses include treating pain associated with external hemorrhoids and pain after episiotomy. Compared with lidocaine, dibucaine is significantly more potent, and toxicity can occur at much lower levels.16
Therapeutically, local anesthetics act by binding to sodium channels, which are necessary for propagation of action potentials17; this blocks signal transduction in local sensory nerves. Toxicity occurs when these agents exert systemic effects, especially on the CNS and heart. Patients with toxic ingestion typically exhibit CNS effects, such as gait disturbances, visual changes, agitation, altered mental status, and seizure; mortality can occur in severe cases. At higher doses, cardiovascular effects may manifest and lead to vasodilation, hemodynamic instability, and dysrhythmias. QRS prolongation, which likely results from sodium channel blockade, can precipitate dysrhythmias; wide-complex bradycardia, ventricular tachycardia, ventricular fibrillation, and asystole have all been reported.16,17Treatment. Supportive care, including airway management and fluid resuscitation, should be initiated as early as possible. Although not well documented in the literature, activated charcoal may be administered if there is no concern for the patency of the patient’s airway or if the airway has been secured.16,17
Patients with clinically significant dibucaine ingestions typically exhibit the CNS findings previously described. Seizures require aggressive management because they can cause a metabolic acidosis that potentiates the toxicity of dibucaine. Benzodiazepines are good first-line agents, though pentobarbital, phenobarbital, or propofol can be used if the patient continues to seize.17
Fluid resuscitation should be maximized in hemodynamically unstable patients prior to administering vasopressors, which are often warranted if blood pressure does not respond to fluids. Evidence supports the use of lipid emulsion therapy in hemodynamically unstable patients18; several authors have reported successful resuscitation after administrating lipid emulsion to treat amide anesthetic toxicity (generally bupivacaine toxicity). Fatalities associated with dibucaine ingestion have been reported16; therefore, ingestion of any topical anesthetic must be recognized and treated promptly.
Gels
Gels are a common topical drug-delivery system. In pediatric patients, these medications are typically used to help decrease teething pain.19
Benzocaine
Benzocaine (eg, Anbesol, Oragel), an ester anesthetic, is one of the most common medications used to alleviate teething pain in infants. Though benzocaine gels possess analgesic properties at therapeutic dosing, severe toxicity can develop in cases of overdose.
Benzocaine is metabolized into oxidizing compounds that lead to methemoglobin formation. Humans normally reduce methemoglobin to hemoglobin through the cytochrome b5 reductase pathway20; however, when an oxidizing agent overwhelms the reducing system, concentrations of methemoglobin begin to rise. Methemoglobin has a decreased oxygen-carrying capacity, and also has a higher subunit binding affinity that leads to a leftward shift of the oxygen dissociation curve.
Findings of benzocaine toxicity range greatly and depend on the amount of methemoglobin formed. Patients can develop asymptomatic cyanosis with low-methemoglobin concentrations (around 15%). At levels of 30% to 40%, neurological complaints may manifest, including weakness, disturbances in coordination, and headaches. High concentrations of methemoglobin (55% to 70%) can cause altered mental status, unresponsiveness, and seizures. When levels are extremely high (>70%), patients are at risk for life-threatening hemodynamic instability and death.21Treatment. For patients with methemoglobinemia, treatment depends upon the serum concentration of methemoglobin. Supportive care, including airway and circulatory management, is critical. If methemoglobin concentrations are low (<15%), close observation can be considered, as healthy individuals can reduce methemoglobin quickly.20 In patients with severe methemoglobinemia (a level above 25%, or clinical findings such as shortness of breath or altered mental status), treatment with methylene blue should be initiated. Methylene blue, an oxidizing agent, initiates a series of events that culminates with the reduction of methemoglobin into hemoglobin.22 Methylene blue is typically dosed 1 to 2 mg/kg17,21,22; dosing can be repeated to a maximum of 4 mg/kg in infants and 7 mg/kg in children.20-22 One should use caution when dosing methylene blue: As an oxidizing agent, when given in excess, methylene blue can worsen methemoglobinemia. Furthermore, methylene blue should not be given to patients with glucose-6-phosphate dehydrogenase deficiency, as this combination can cause massive hemolysis.17,20-22
Though rare, if patients are hemodynamically unstable or have life-threatening methemoglobinemia, hyperbaric oxygen therapy, exchange transfusion, or hemodialysis can be attempted—if these are readily available.17,20-22
Recognizing methemoglobinemia early is essential, and when a patient receives prompt treatment, mortality from methemoglobinemia secondary to benzocaine overdose is extremely low.
Transdermal Patches
Transdermal drug delivery is a relatively new route of administration—one that has gained increasingly in popularity. Patches are being used more frequently because they are easy to administer, have improved compliance due to decreased dosing frequency, allow concealment, and avoid first-pass metabolism, which increases the concentration of the parent compound.23
Although patches have several clinical advantages, they can pose a significant threat, particularly to pediatric patients, for several reasons. Patches, which work by delivering medication transdermally through a concentration gradient, are often impregnated with high concentrations of medication. If the patch is heated or damaged, this can significantly increase the amount of medication released onto the skin, leading to an overdose. Patches also normally contain high concentrations of medication even after they are worn for the prescribed time, though retained quantities vary depending on the drug and device.23,24 One study using fentanyl patches found 28% to 84.4% of the original drug remained in the patch after its clinical use.25 Toxicity from patches normally occurs from transdermal exposure as well as oral exposure/ingestion.
Fentanyl Patch
Fentanyl, a powerful synthetic opioid, has been available via transdermal delivery route since the early 1990s. Use of fentanyl patches has proven to be popular and efficacious in pain management. Unintentional exposure in pediatric patients is especially dangerous because children are often opioid-naive, and even small doses of fentanyl can be toxic.
Several cases of pediatric fentanyl toxicity secondary to transdermal exposure have been described in the literature. Though fewer in number, cases involving toxicity from patch ingestion have also been reported in adult patients26; to the best of our knowledge, no cases have been published on pediatric fentanyl-patch ingestions, though this should be considered when evaluating a patient with an opioid toxidrome.
Fentanyl, a mu-opioid agonist, can lead to significant morbidity and mortality. Findings from fentanyl toxicity are dose-dependent but include miosis, altered mental status, bradypnea, respiratory arrest, coma, and death, if left untreated.
Treatment. Airway protection is essential, and once opioid toxicity is suspected, patients who lack spontaneous respiration should receive immediate noninvasive respiratory support followed by naloxone administration; mechanical ventilation is sometimes required in patients with severe overdose. A thorough physical examination is crucial, and transdermal patches must be immediately identified and removed to prevent further drug absorption.
If a patch is found, the area should be thoroughly cleansed to remove any residual drug from the affected area. Removal of the patch does not result in an immediate reversal of toxicity. Due to the reservoir in the skin, spontaneous reversal may take up to 1 day. Oral ingestion can lead to a fatal outcome, so if ingestion is suspected, providers must examine the oral cavity to ensure that no piece of the patch is present.27Naloxone, a competitive opioid receptor antagonist, is used to reverse opioid overdose. It is typically dosed at 0.001 mg/kg28 and can be increased incrementally up to 0.01 mg/kg, or even higher if findings do not improve. Many patients require sequential doses of naloxone due to its relatively short half-life compared to the prolonged elimination of transdermal or ingested fentanyl.28,29
Naloxone infusions are commonly needed for these patients, and are typically dosed at about two-thirds of the dose required for initial opioid reversal.28 Given the prolonged duration of possible toxicity, any patient who presents to the ED with signs of opioid overdose from transdermal exposure or oral ingestion of a patch should be admitted to the hospital30 and monitored for 24 hours28,31 to ensure that symptoms do not rebound, especially once the naloxone drip is weaned. Patients should be monitored for 4 to 6 hours after cessation of a naloxone infusion. Fortunately, timely and adequate management can result in positive clinical outcomes in most of these situations.
Conclusion
Ingestions of topical products are relatively common occurrences, particularly in pediatric patients. During the history taking, clinicians should be vigilant and always inquire about any topical medications within the home any time a pediatric patient presents with signs and symptoms indicative of a toxic ingestion. Family members should also be counseled on the dangers of accidental topical medication ingestion or misuse. Providers should give recommendations for proper storage and disposal of all prescription and nonprescription medications, which may help not only save a repeat visit to the ED, but may in fact save a life.
1. Mowry JB, Spyker DA, Brooks DE, Zimmerman A, Schauben JL. 2015 annual report of the American Association of Poison Control Centers’ National Poison Data System (NPDS): 33rd annual report. Clin Toxicol. 2016;54(10):924-1109. doi:10.1080/15563650.2016.1245421.
2. Tobias JD. Central nervous system depression following accidental ingestion of visine eye drops. Clin Pediatr (Phila). 1996;35(10):539-540. doi:10.1177/000992289603501010.
3. Lev R, Clark RF. Visine overdose: case report of an adult with hemodynamic compromise. J Emerg Med. 1995;13(5):649-652.
4. Jensen P, Edgren B, Hall L, Ring JC. Hemodynamic effects following ingestion of an imidazoline-containing product. Pediatr Emerg Care. 1989;5(2):110-112.
5. Davis JE. Are one or two dangerous? Methyl salicylate exposure in toddlers. J Emerg Med. 2007;32(1):63-69. doi:10.1016/j.jemermed.2006.08.009.
6. Chan TY. The risk of severe salicylate poisoning following the ingestion of topical medicaments or aspirin. Postgrad Med J. 1996;72(844):109-112.
7. Juurlink DN, Gosselin S, Kielstein JT, et al. Extracorporeal treatment for salicylate poisoning: Systematic review and recommendations from the EXTRIP workgroup. Ann Emerg Med. 2015;66(2):165-181.
8. Manikian A, Stone S, Hamilton R, Foltin G, Howland MA, Hoffman RS. Exchange transfusion in severe infant salicylism. Vet Hum Toxicol. 2002;44(4):224-227.
9. Davis B, Dang M, Kim J, Talbot P. Nicotine concentrations in electronic cigarette refill and do-it-yourself fluids. Nicotine Tob Res. 2015;17(2):134-141. doi:10.1093/ntr/ntu080.
10. US Food & Drug Administration. Tobacco Products. Rules & Regulations. https://www.fda.gov/TobaccoProducts/Labeling/RulesRegulationsGuidance/ucm283974.htm. Updated February 16, 2017. Accessed March 7, 2017.
11. Mayer B. How much nicotine kills a human? Tracing back the generally accepted lethal dose to dubious self-experiments in the nineteenth century. Arch Toxicol. 2014;88(1):5-7. doi:10.1007/s00204-013-1127-0.
12. Bassett RA, Osterhoudt K, Brabazon T. Nicotine poisoning in an infant. N Engl J Med. 2014;370(23):2249-2250. doi:10.1056/NEJMc1403843.
13. Kim JW, Baum CR. Liquid nicotine toxicity. Pediatr Emerg Care. 2015;31(7):517-521; quiz 522-524. doi:10.1097/PEC.0000000000000486.
14. Wain AA, Martin J. Can transdermal nicotine patch cause acute intoxication in a child? A case report and review of literature. Ulster Med J. 2004;73(1):65-66.
15. Gill N, Sangha G, Poonai N, Lim R. E-Cigarette liquid nicotine ingestion in a child: case report and discussion. CJEM. 2015;17(6):699-703. doi:10.1017/cem.2015.10.
16. Dayan PS, Litovitz TL, Crouch BI, Scalzo AJ, Klein BL. Fatal accidental dibucaine poisoning in children. Ann Emerg Med. 1996;28(4):442-445.
17. Curtis LA, Dolan TS, Seibert HE. Are one or two dangerous? Lidocaine and topical anesthetic exposures in children. J Emerg Med. 2009;37(1):32-39. doi:10.1016/j.jemermed.2007.11.005.
18. Ciechanowicz S, Patil V. Lipid emulsion for local anesthetic systemic toxicity. Anesthesiol Res Pract. 2012;2012:131784. doi:10.1155/2012/131784.
19. Bong CL, Hilliard J, Seefelder C. Severe methemoglobinemia from topical benzocaine 7.5% (baby orajel) use for teething pain in a toddler. Clin Pediatr (Phila). 2009;48(2):209-211.
20. Chung N, Batra R, Itzkevitch M, Boruchov D, Baldauf M. Severe methemoglobinemia linked to gel-type topical benzocaine use: A case report. J Emerg Med. 2010;38(5):601-606. doi:10.1016/j.jemermed.2008.06.025.
21. Liebelt EL, Shannon MW. Small doses, big problems: A selected review of highly toxic common medications. Pediatr Emerg Care. 1993;9(5):292-297.
22. So TY, Farrington E. Topical benzocaine-induced methemoglobinemia in the pediatric population. J Pediatr Health Care. 2008;22(6):335-339; quiz 340-341. doi:10.1016/j.pedhc.2008.08.008.
23. Parekh D, Miller MA, Borys D, Patel PR, Levsky ME. Transdermal patch medication delivery systems and pediatric poisonings, 2002-2006. Clin Pediatr (Phila). 2008;47(7):659-663. doi:10.1177/0009922808315211.
24. Teske J, Weller JP, Larsch K, Tröger HD, Karst M. Fatal outcome in a child after ingestion of a transdermal fentanyl patch. Int J Legal Med. 2007;121(2):147-151. doi:10.1007/s00414-006-0137-3.
25. Marquardt KA, Tharratt RS, Musallam NA. Fentanyl remaining in a transdermal system following three days of continuous use. Ann Pharmacother. 1995;29(10):969-971. doi:10.1177/106002809502901001.
26. Faust AC, Terpolilli R, Hughes DW. Management of an oral ingestion of transdermal fentanyl patches: a case report and literature review. Case Rep Med. 2011;2011:495938. doi:10.1155/2011/495938.
27. Prosser JM, Jones BE, Nelson L. Complications of oral exposure to fentanyl transdermal delivery system patches. J Med Toxicol. 2010;6(4):443-447. doi:10.1007/s13181-010-0092-8.
28. Kim HK, Nelson LS. Reducing the harm of opioid overdose with the safe use of naloxone: a pharmacologic review. Expert Opin Drug Saf. 2015;14 (7 ):1137-1146. doi:10.1517/14740338.2015.1037274.
29 Mrvos R, Feuchter AC, Katz KD, Duback-Morris LF, Brooks DE, Krenzelok EP. Whole fentanyl patch ingestion: A multi-center case series. J Emerg Med. 2012;42(5):549-552. doi:10.1016/j.jemermed.2011.05.017.
30. Sachdeva DK, Stadnyk JM. Are one or two dangerous? Opioid exposure in toddlers. J Emerg Med. 2005;29(1):77-84. doi:10.1016/j.jemermed.2004.12.015.
31. Behrman A, Goertemoeller S. A sticky situation: toxicity of clonidine and fentanyl transdermal patches in pediatrics. J Emerg Nurs. 2007;33(3):290-293.doi: 10.1016/j.jen.2007.02.004.
The anxiety of caring for a child in imminent peril may cause even an experienced clinician to forget to ask important questions about ingestions and exposures that can be critical to the patient’s management. Though emergency physicians (EPs) routinely ask about household medications when obtaining a history from family members, they occasionally gloss over a detail of utmost importance: topical medications.
The use of topical medications is extremely prevalent in the United States, in turn resulting in accidental ingestion—particularly in the pediatric population. In 2015, there were 56,455 calls to US Poison Control Centers for pediatric (children ≤5 years) exposures to topical preparations.1 Topical drug-delivery-system formulations include drops, ointments, gels, and patches. Intentional and unintentional misuse or overdose of any of these formulations can cause toxicity. Unintentional overdose of these drugs can occur secondary to exploratory ingestions, therapeutic errors, or medication overuse due to the perception of safety associated with topical preparations.
Drops
Topical liquid medications such as ophthalmic and otologic drops can be fatal when ingested or used inappropriately. The following sections review commonly used prescription and nonprescription formulations, associated toxicological manifestations, and appropriate management.
Ophthalmic Drops
A common class of ophthalmic drops includes imidazoline-derived agents such as tetrahydrozoline (eg, Opti-Clear, Visine). Te
Treatment. Management of overdose of imidazoline agents depends greatly on the patient’s presentation and is largely supportive. Overdoses of these agents and clonidine are similar: Patients can be extremely somnolent, but may transiently improve when a painful stimulus is applied. Activated charcoal may be useful for recent ingestions,3 but it should only be considered in patients whose airway is patent or protected. Intravenous fluids are indicated if the patient is hypotensive. Atropine may be considered for symptomatic bradycardia,3 and transcutaneous pacing should be considered if the patient is hemodynamically unstable. Intubation may be required if there is concern for airway compromise, though such compromise is a rare occurrence in ophthalmic ingestion of imidazoline-derived agents.
Although not well studied due to a lack of data, some sources recommend naloxone administration, given the similarities of imidazoline agents to clonidine in the overdose scenario.3,4 Although the optimal dose is unknown, high doses of naloxone (ie, pediatric patients, 0.4 mg, followed by 2 mg, then 10 mg, if no response) are typically required and should be considered in symptomatic patients after an ingestion. After successful supportive management, most patients continue to do well during their hospital course and have a full recovery.
Methyl Salicylate
Methyl salicylate (oil of wintergreen) is a common ingredient in muscular pain-relieving creams and ointments that can have devastating consequences in overdose. Significant toxicity from these compounds is rare, as large exposures are needed to reach a toxic threshold. However, oil of wintergreen is also available as a liquid preparation with 98% methyl salicylate.5 At this concentration, 1 teaspoon (5 mL) is roughly equivalent to 7 g of acetylsalicylate,5 and this amount of oil of wintergreen is severely toxic and may be lethal to a child. Because it is a liquid, oil of wintergreen is more rapidly absorbed than creams and ointments and can cause rapid toxicity in small quantities.
Methyl salicylate overdose initially causes stimulation of the brain’s respiratory center, which leads to a respiratory alkalosis. Uncoupling of oxidative phosphorylation later causes an anion gap metabolic acidosis. The combination of these two processes leads to a mixed acid-base disturbance. Common signs and symptoms of toxicity include tinnitus, hyperpnea, tachypnea, hyperthermia, nausea, vomiting, multisystem organ dysfunction, altered mental status, and death.
Treatment. Supportive care is critically important. Clinicians must be sure the patient’s airway is patent, particularly in those with altered sensorium or in patients who are becoming fatigued secondary to work of breathing. Extreme caution should be used when intubating these patients, as the patient’s respiratory rate (RR) must be matched if placed on a ventilator. If the RR is too low, the patient will become increasingly acidotic and may become hemodynamically unstable. Activated charcoal should be considered if the patient is mentating well or if the airway is protected.5,6 Adequate fluid resuscitation is essential.
Serum alkalinization is critical in helping to prevent central nervous system (CNS) toxicity. Urinary alkalinization with sodium bicarbonate will augment the salicylate excretion rate and may also help correct the patient’s acidemia.
Current guidelines recommend hemodialysis in asymptomatic patients whose serum salicylate concentration is greater than 100 mg/dL, or in patients with consequential findings, such as altered mental status.7
In infants with severe salicylate toxicity, exchange transfusion can be considered, given the limitations of hemodialysis at this age.8 Clinical outcomes are generally good if managed appropriately, though oil of wintergreen ingestion can be fatal.
Liquids
Liquid nicotine also poses a major threat to the pediatric population. Since the early 2000s, electronic cigarettes (e-cigarettes) have gained popularity. E-cigarette cartridges contain highly concentrated liquid nicotine, and, until May 2016, were not regulated by the US Food and Drug Administration (FDA).9 Since then, the FDA’s updated rule now extends to all tobacco products, including e-cigarettes.10
Some of the recent literature suggest oral lethal doses of nicotine occur at levels as low as 0.8 mg/kg,11 though this is likely an overly conservative level. At this dose, even relatively diluted products with a 1.8% nicotine solution could be fatal.12
Liquid nicotine comes in thousands of flavors,13 and while this may make its use more enjoyable for adults, it poses a significant risk to small children. Children may be enticed to ingest liquid nicotine products due to their flavor-enhanced scents.12
At relatively low serum levels, nicotine acts as a nicotinic acetylcholine receptor agonist. Symptoms such as nausea, vomiting, diarrhea, abdominal discomfort, increased salivation, and weakness can occur early on in toxicity.13 Once nicotine concentrations reach higher levels, patients develop altered mental status, hemodynamic instability, seizure, muscle weakness, and respiratory compromise.
Treatment. Supportive therapy should be initiated when caring for patients with nicotine ingestion. Airway management is paramount, particularly if the patient has altered mental status. In some cases, intubation may be necessary, especially in patients with altered mental status and excessive salivation/bronchorrhea. Intravenous fluid administration is pivotal in patients with hypotension, particularly for those at risk for dehydration secondary to vomiting and diarrhea. Although there is no definitive antidote, atropine can be used to treat patients who are symptomatic from excessive muscarinic cholinergic stimulation.13,14 If seizures occur, they can be treated with benzodiazepines as needed.
The use of activated charcoal has little mention in the current literature. Because of its liquid formulation, nicotine will likely be absorbed quickly. If ingestion occurred shortly prior to presentation and the patient’s airway is patent or secured, a dose of activated charcoal may be cautiously administered.15 The prognosis is poor if large amounts of liquid nicotine have been consumed.
Topical Ointments
Ointments are semisolid preparations, typically for topical application. Topical anesthetics are available in a variety of prescription and nonprescription ointments. Of the local prescription and nonprescription anesthetics currently available, amide-type local anesthetics have become especially popular for their rapid and reliable onset of local anesthesia and low occurrence of hypersensitive reactions. Increased popularity raises the likelihood of accidental ingestion—especially in pediatric patients.
Dibucaine, an amide anesthetic, is available as a nonprescription medication. Its uses include treating pain associated with external hemorrhoids and pain after episiotomy. Compared with lidocaine, dibucaine is significantly more potent, and toxicity can occur at much lower levels.16
Therapeutically, local anesthetics act by binding to sodium channels, which are necessary for propagation of action potentials17; this blocks signal transduction in local sensory nerves. Toxicity occurs when these agents exert systemic effects, especially on the CNS and heart. Patients with toxic ingestion typically exhibit CNS effects, such as gait disturbances, visual changes, agitation, altered mental status, and seizure; mortality can occur in severe cases. At higher doses, cardiovascular effects may manifest and lead to vasodilation, hemodynamic instability, and dysrhythmias. QRS prolongation, which likely results from sodium channel blockade, can precipitate dysrhythmias; wide-complex bradycardia, ventricular tachycardia, ventricular fibrillation, and asystole have all been reported.16,17Treatment. Supportive care, including airway management and fluid resuscitation, should be initiated as early as possible. Although not well documented in the literature, activated charcoal may be administered if there is no concern for the patency of the patient’s airway or if the airway has been secured.16,17
Patients with clinically significant dibucaine ingestions typically exhibit the CNS findings previously described. Seizures require aggressive management because they can cause a metabolic acidosis that potentiates the toxicity of dibucaine. Benzodiazepines are good first-line agents, though pentobarbital, phenobarbital, or propofol can be used if the patient continues to seize.17
Fluid resuscitation should be maximized in hemodynamically unstable patients prior to administering vasopressors, which are often warranted if blood pressure does not respond to fluids. Evidence supports the use of lipid emulsion therapy in hemodynamically unstable patients18; several authors have reported successful resuscitation after administrating lipid emulsion to treat amide anesthetic toxicity (generally bupivacaine toxicity). Fatalities associated with dibucaine ingestion have been reported16; therefore, ingestion of any topical anesthetic must be recognized and treated promptly.
Gels
Gels are a common topical drug-delivery system. In pediatric patients, these medications are typically used to help decrease teething pain.19
Benzocaine
Benzocaine (eg, Anbesol, Oragel), an ester anesthetic, is one of the most common medications used to alleviate teething pain in infants. Though benzocaine gels possess analgesic properties at therapeutic dosing, severe toxicity can develop in cases of overdose.
Benzocaine is metabolized into oxidizing compounds that lead to methemoglobin formation. Humans normally reduce methemoglobin to hemoglobin through the cytochrome b5 reductase pathway20; however, when an oxidizing agent overwhelms the reducing system, concentrations of methemoglobin begin to rise. Methemoglobin has a decreased oxygen-carrying capacity, and also has a higher subunit binding affinity that leads to a leftward shift of the oxygen dissociation curve.
Findings of benzocaine toxicity range greatly and depend on the amount of methemoglobin formed. Patients can develop asymptomatic cyanosis with low-methemoglobin concentrations (around 15%). At levels of 30% to 40%, neurological complaints may manifest, including weakness, disturbances in coordination, and headaches. High concentrations of methemoglobin (55% to 70%) can cause altered mental status, unresponsiveness, and seizures. When levels are extremely high (>70%), patients are at risk for life-threatening hemodynamic instability and death.21Treatment. For patients with methemoglobinemia, treatment depends upon the serum concentration of methemoglobin. Supportive care, including airway and circulatory management, is critical. If methemoglobin concentrations are low (<15%), close observation can be considered, as healthy individuals can reduce methemoglobin quickly.20 In patients with severe methemoglobinemia (a level above 25%, or clinical findings such as shortness of breath or altered mental status), treatment with methylene blue should be initiated. Methylene blue, an oxidizing agent, initiates a series of events that culminates with the reduction of methemoglobin into hemoglobin.22 Methylene blue is typically dosed 1 to 2 mg/kg17,21,22; dosing can be repeated to a maximum of 4 mg/kg in infants and 7 mg/kg in children.20-22 One should use caution when dosing methylene blue: As an oxidizing agent, when given in excess, methylene blue can worsen methemoglobinemia. Furthermore, methylene blue should not be given to patients with glucose-6-phosphate dehydrogenase deficiency, as this combination can cause massive hemolysis.17,20-22
Though rare, if patients are hemodynamically unstable or have life-threatening methemoglobinemia, hyperbaric oxygen therapy, exchange transfusion, or hemodialysis can be attempted—if these are readily available.17,20-22
Recognizing methemoglobinemia early is essential, and when a patient receives prompt treatment, mortality from methemoglobinemia secondary to benzocaine overdose is extremely low.
Transdermal Patches
Transdermal drug delivery is a relatively new route of administration—one that has gained increasingly in popularity. Patches are being used more frequently because they are easy to administer, have improved compliance due to decreased dosing frequency, allow concealment, and avoid first-pass metabolism, which increases the concentration of the parent compound.23
Although patches have several clinical advantages, they can pose a significant threat, particularly to pediatric patients, for several reasons. Patches, which work by delivering medication transdermally through a concentration gradient, are often impregnated with high concentrations of medication. If the patch is heated or damaged, this can significantly increase the amount of medication released onto the skin, leading to an overdose. Patches also normally contain high concentrations of medication even after they are worn for the prescribed time, though retained quantities vary depending on the drug and device.23,24 One study using fentanyl patches found 28% to 84.4% of the original drug remained in the patch after its clinical use.25 Toxicity from patches normally occurs from transdermal exposure as well as oral exposure/ingestion.
Fentanyl Patch
Fentanyl, a powerful synthetic opioid, has been available via transdermal delivery route since the early 1990s. Use of fentanyl patches has proven to be popular and efficacious in pain management. Unintentional exposure in pediatric patients is especially dangerous because children are often opioid-naive, and even small doses of fentanyl can be toxic.
Several cases of pediatric fentanyl toxicity secondary to transdermal exposure have been described in the literature. Though fewer in number, cases involving toxicity from patch ingestion have also been reported in adult patients26; to the best of our knowledge, no cases have been published on pediatric fentanyl-patch ingestions, though this should be considered when evaluating a patient with an opioid toxidrome.
Fentanyl, a mu-opioid agonist, can lead to significant morbidity and mortality. Findings from fentanyl toxicity are dose-dependent but include miosis, altered mental status, bradypnea, respiratory arrest, coma, and death, if left untreated.
Treatment. Airway protection is essential, and once opioid toxicity is suspected, patients who lack spontaneous respiration should receive immediate noninvasive respiratory support followed by naloxone administration; mechanical ventilation is sometimes required in patients with severe overdose. A thorough physical examination is crucial, and transdermal patches must be immediately identified and removed to prevent further drug absorption.
If a patch is found, the area should be thoroughly cleansed to remove any residual drug from the affected area. Removal of the patch does not result in an immediate reversal of toxicity. Due to the reservoir in the skin, spontaneous reversal may take up to 1 day. Oral ingestion can lead to a fatal outcome, so if ingestion is suspected, providers must examine the oral cavity to ensure that no piece of the patch is present.27Naloxone, a competitive opioid receptor antagonist, is used to reverse opioid overdose. It is typically dosed at 0.001 mg/kg28 and can be increased incrementally up to 0.01 mg/kg, or even higher if findings do not improve. Many patients require sequential doses of naloxone due to its relatively short half-life compared to the prolonged elimination of transdermal or ingested fentanyl.28,29
Naloxone infusions are commonly needed for these patients, and are typically dosed at about two-thirds of the dose required for initial opioid reversal.28 Given the prolonged duration of possible toxicity, any patient who presents to the ED with signs of opioid overdose from transdermal exposure or oral ingestion of a patch should be admitted to the hospital30 and monitored for 24 hours28,31 to ensure that symptoms do not rebound, especially once the naloxone drip is weaned. Patients should be monitored for 4 to 6 hours after cessation of a naloxone infusion. Fortunately, timely and adequate management can result in positive clinical outcomes in most of these situations.
Conclusion
Ingestions of topical products are relatively common occurrences, particularly in pediatric patients. During the history taking, clinicians should be vigilant and always inquire about any topical medications within the home any time a pediatric patient presents with signs and symptoms indicative of a toxic ingestion. Family members should also be counseled on the dangers of accidental topical medication ingestion or misuse. Providers should give recommendations for proper storage and disposal of all prescription and nonprescription medications, which may help not only save a repeat visit to the ED, but may in fact save a life.
The anxiety of caring for a child in imminent peril may cause even an experienced clinician to forget to ask important questions about ingestions and exposures that can be critical to the patient’s management. Though emergency physicians (EPs) routinely ask about household medications when obtaining a history from family members, they occasionally gloss over a detail of utmost importance: topical medications.
The use of topical medications is extremely prevalent in the United States, in turn resulting in accidental ingestion—particularly in the pediatric population. In 2015, there were 56,455 calls to US Poison Control Centers for pediatric (children ≤5 years) exposures to topical preparations.1 Topical drug-delivery-system formulations include drops, ointments, gels, and patches. Intentional and unintentional misuse or overdose of any of these formulations can cause toxicity. Unintentional overdose of these drugs can occur secondary to exploratory ingestions, therapeutic errors, or medication overuse due to the perception of safety associated with topical preparations.
Drops
Topical liquid medications such as ophthalmic and otologic drops can be fatal when ingested or used inappropriately. The following sections review commonly used prescription and nonprescription formulations, associated toxicological manifestations, and appropriate management.
Ophthalmic Drops
A common class of ophthalmic drops includes imidazoline-derived agents such as tetrahydrozoline (eg, Opti-Clear, Visine). Te
Treatment. Management of overdose of imidazoline agents depends greatly on the patient’s presentation and is largely supportive. Overdoses of these agents and clonidine are similar: Patients can be extremely somnolent, but may transiently improve when a painful stimulus is applied. Activated charcoal may be useful for recent ingestions,3 but it should only be considered in patients whose airway is patent or protected. Intravenous fluids are indicated if the patient is hypotensive. Atropine may be considered for symptomatic bradycardia,3 and transcutaneous pacing should be considered if the patient is hemodynamically unstable. Intubation may be required if there is concern for airway compromise, though such compromise is a rare occurrence in ophthalmic ingestion of imidazoline-derived agents.
Although not well studied due to a lack of data, some sources recommend naloxone administration, given the similarities of imidazoline agents to clonidine in the overdose scenario.3,4 Although the optimal dose is unknown, high doses of naloxone (ie, pediatric patients, 0.4 mg, followed by 2 mg, then 10 mg, if no response) are typically required and should be considered in symptomatic patients after an ingestion. After successful supportive management, most patients continue to do well during their hospital course and have a full recovery.
Methyl Salicylate
Methyl salicylate (oil of wintergreen) is a common ingredient in muscular pain-relieving creams and ointments that can have devastating consequences in overdose. Significant toxicity from these compounds is rare, as large exposures are needed to reach a toxic threshold. However, oil of wintergreen is also available as a liquid preparation with 98% methyl salicylate.5 At this concentration, 1 teaspoon (5 mL) is roughly equivalent to 7 g of acetylsalicylate,5 and this amount of oil of wintergreen is severely toxic and may be lethal to a child. Because it is a liquid, oil of wintergreen is more rapidly absorbed than creams and ointments and can cause rapid toxicity in small quantities.
Methyl salicylate overdose initially causes stimulation of the brain’s respiratory center, which leads to a respiratory alkalosis. Uncoupling of oxidative phosphorylation later causes an anion gap metabolic acidosis. The combination of these two processes leads to a mixed acid-base disturbance. Common signs and symptoms of toxicity include tinnitus, hyperpnea, tachypnea, hyperthermia, nausea, vomiting, multisystem organ dysfunction, altered mental status, and death.
Treatment. Supportive care is critically important. Clinicians must be sure the patient’s airway is patent, particularly in those with altered sensorium or in patients who are becoming fatigued secondary to work of breathing. Extreme caution should be used when intubating these patients, as the patient’s respiratory rate (RR) must be matched if placed on a ventilator. If the RR is too low, the patient will become increasingly acidotic and may become hemodynamically unstable. Activated charcoal should be considered if the patient is mentating well or if the airway is protected.5,6 Adequate fluid resuscitation is essential.
Serum alkalinization is critical in helping to prevent central nervous system (CNS) toxicity. Urinary alkalinization with sodium bicarbonate will augment the salicylate excretion rate and may also help correct the patient’s acidemia.
Current guidelines recommend hemodialysis in asymptomatic patients whose serum salicylate concentration is greater than 100 mg/dL, or in patients with consequential findings, such as altered mental status.7
In infants with severe salicylate toxicity, exchange transfusion can be considered, given the limitations of hemodialysis at this age.8 Clinical outcomes are generally good if managed appropriately, though oil of wintergreen ingestion can be fatal.
Liquids
Liquid nicotine also poses a major threat to the pediatric population. Since the early 2000s, electronic cigarettes (e-cigarettes) have gained popularity. E-cigarette cartridges contain highly concentrated liquid nicotine, and, until May 2016, were not regulated by the US Food and Drug Administration (FDA).9 Since then, the FDA’s updated rule now extends to all tobacco products, including e-cigarettes.10
Some of the recent literature suggest oral lethal doses of nicotine occur at levels as low as 0.8 mg/kg,11 though this is likely an overly conservative level. At this dose, even relatively diluted products with a 1.8% nicotine solution could be fatal.12
Liquid nicotine comes in thousands of flavors,13 and while this may make its use more enjoyable for adults, it poses a significant risk to small children. Children may be enticed to ingest liquid nicotine products due to their flavor-enhanced scents.12
At relatively low serum levels, nicotine acts as a nicotinic acetylcholine receptor agonist. Symptoms such as nausea, vomiting, diarrhea, abdominal discomfort, increased salivation, and weakness can occur early on in toxicity.13 Once nicotine concentrations reach higher levels, patients develop altered mental status, hemodynamic instability, seizure, muscle weakness, and respiratory compromise.
Treatment. Supportive therapy should be initiated when caring for patients with nicotine ingestion. Airway management is paramount, particularly if the patient has altered mental status. In some cases, intubation may be necessary, especially in patients with altered mental status and excessive salivation/bronchorrhea. Intravenous fluid administration is pivotal in patients with hypotension, particularly for those at risk for dehydration secondary to vomiting and diarrhea. Although there is no definitive antidote, atropine can be used to treat patients who are symptomatic from excessive muscarinic cholinergic stimulation.13,14 If seizures occur, they can be treated with benzodiazepines as needed.
The use of activated charcoal has little mention in the current literature. Because of its liquid formulation, nicotine will likely be absorbed quickly. If ingestion occurred shortly prior to presentation and the patient’s airway is patent or secured, a dose of activated charcoal may be cautiously administered.15 The prognosis is poor if large amounts of liquid nicotine have been consumed.
Topical Ointments
Ointments are semisolid preparations, typically for topical application. Topical anesthetics are available in a variety of prescription and nonprescription ointments. Of the local prescription and nonprescription anesthetics currently available, amide-type local anesthetics have become especially popular for their rapid and reliable onset of local anesthesia and low occurrence of hypersensitive reactions. Increased popularity raises the likelihood of accidental ingestion—especially in pediatric patients.
Dibucaine, an amide anesthetic, is available as a nonprescription medication. Its uses include treating pain associated with external hemorrhoids and pain after episiotomy. Compared with lidocaine, dibucaine is significantly more potent, and toxicity can occur at much lower levels.16
Therapeutically, local anesthetics act by binding to sodium channels, which are necessary for propagation of action potentials17; this blocks signal transduction in local sensory nerves. Toxicity occurs when these agents exert systemic effects, especially on the CNS and heart. Patients with toxic ingestion typically exhibit CNS effects, such as gait disturbances, visual changes, agitation, altered mental status, and seizure; mortality can occur in severe cases. At higher doses, cardiovascular effects may manifest and lead to vasodilation, hemodynamic instability, and dysrhythmias. QRS prolongation, which likely results from sodium channel blockade, can precipitate dysrhythmias; wide-complex bradycardia, ventricular tachycardia, ventricular fibrillation, and asystole have all been reported.16,17Treatment. Supportive care, including airway management and fluid resuscitation, should be initiated as early as possible. Although not well documented in the literature, activated charcoal may be administered if there is no concern for the patency of the patient’s airway or if the airway has been secured.16,17
Patients with clinically significant dibucaine ingestions typically exhibit the CNS findings previously described. Seizures require aggressive management because they can cause a metabolic acidosis that potentiates the toxicity of dibucaine. Benzodiazepines are good first-line agents, though pentobarbital, phenobarbital, or propofol can be used if the patient continues to seize.17
Fluid resuscitation should be maximized in hemodynamically unstable patients prior to administering vasopressors, which are often warranted if blood pressure does not respond to fluids. Evidence supports the use of lipid emulsion therapy in hemodynamically unstable patients18; several authors have reported successful resuscitation after administrating lipid emulsion to treat amide anesthetic toxicity (generally bupivacaine toxicity). Fatalities associated with dibucaine ingestion have been reported16; therefore, ingestion of any topical anesthetic must be recognized and treated promptly.
Gels
Gels are a common topical drug-delivery system. In pediatric patients, these medications are typically used to help decrease teething pain.19
Benzocaine
Benzocaine (eg, Anbesol, Oragel), an ester anesthetic, is one of the most common medications used to alleviate teething pain in infants. Though benzocaine gels possess analgesic properties at therapeutic dosing, severe toxicity can develop in cases of overdose.
Benzocaine is metabolized into oxidizing compounds that lead to methemoglobin formation. Humans normally reduce methemoglobin to hemoglobin through the cytochrome b5 reductase pathway20; however, when an oxidizing agent overwhelms the reducing system, concentrations of methemoglobin begin to rise. Methemoglobin has a decreased oxygen-carrying capacity, and also has a higher subunit binding affinity that leads to a leftward shift of the oxygen dissociation curve.
Findings of benzocaine toxicity range greatly and depend on the amount of methemoglobin formed. Patients can develop asymptomatic cyanosis with low-methemoglobin concentrations (around 15%). At levels of 30% to 40%, neurological complaints may manifest, including weakness, disturbances in coordination, and headaches. High concentrations of methemoglobin (55% to 70%) can cause altered mental status, unresponsiveness, and seizures. When levels are extremely high (>70%), patients are at risk for life-threatening hemodynamic instability and death.21Treatment. For patients with methemoglobinemia, treatment depends upon the serum concentration of methemoglobin. Supportive care, including airway and circulatory management, is critical. If methemoglobin concentrations are low (<15%), close observation can be considered, as healthy individuals can reduce methemoglobin quickly.20 In patients with severe methemoglobinemia (a level above 25%, or clinical findings such as shortness of breath or altered mental status), treatment with methylene blue should be initiated. Methylene blue, an oxidizing agent, initiates a series of events that culminates with the reduction of methemoglobin into hemoglobin.22 Methylene blue is typically dosed 1 to 2 mg/kg17,21,22; dosing can be repeated to a maximum of 4 mg/kg in infants and 7 mg/kg in children.20-22 One should use caution when dosing methylene blue: As an oxidizing agent, when given in excess, methylene blue can worsen methemoglobinemia. Furthermore, methylene blue should not be given to patients with glucose-6-phosphate dehydrogenase deficiency, as this combination can cause massive hemolysis.17,20-22
Though rare, if patients are hemodynamically unstable or have life-threatening methemoglobinemia, hyperbaric oxygen therapy, exchange transfusion, or hemodialysis can be attempted—if these are readily available.17,20-22
Recognizing methemoglobinemia early is essential, and when a patient receives prompt treatment, mortality from methemoglobinemia secondary to benzocaine overdose is extremely low.
Transdermal Patches
Transdermal drug delivery is a relatively new route of administration—one that has gained increasingly in popularity. Patches are being used more frequently because they are easy to administer, have improved compliance due to decreased dosing frequency, allow concealment, and avoid first-pass metabolism, which increases the concentration of the parent compound.23
Although patches have several clinical advantages, they can pose a significant threat, particularly to pediatric patients, for several reasons. Patches, which work by delivering medication transdermally through a concentration gradient, are often impregnated with high concentrations of medication. If the patch is heated or damaged, this can significantly increase the amount of medication released onto the skin, leading to an overdose. Patches also normally contain high concentrations of medication even after they are worn for the prescribed time, though retained quantities vary depending on the drug and device.23,24 One study using fentanyl patches found 28% to 84.4% of the original drug remained in the patch after its clinical use.25 Toxicity from patches normally occurs from transdermal exposure as well as oral exposure/ingestion.
Fentanyl Patch
Fentanyl, a powerful synthetic opioid, has been available via transdermal delivery route since the early 1990s. Use of fentanyl patches has proven to be popular and efficacious in pain management. Unintentional exposure in pediatric patients is especially dangerous because children are often opioid-naive, and even small doses of fentanyl can be toxic.
Several cases of pediatric fentanyl toxicity secondary to transdermal exposure have been described in the literature. Though fewer in number, cases involving toxicity from patch ingestion have also been reported in adult patients26; to the best of our knowledge, no cases have been published on pediatric fentanyl-patch ingestions, though this should be considered when evaluating a patient with an opioid toxidrome.
Fentanyl, a mu-opioid agonist, can lead to significant morbidity and mortality. Findings from fentanyl toxicity are dose-dependent but include miosis, altered mental status, bradypnea, respiratory arrest, coma, and death, if left untreated.
Treatment. Airway protection is essential, and once opioid toxicity is suspected, patients who lack spontaneous respiration should receive immediate noninvasive respiratory support followed by naloxone administration; mechanical ventilation is sometimes required in patients with severe overdose. A thorough physical examination is crucial, and transdermal patches must be immediately identified and removed to prevent further drug absorption.
If a patch is found, the area should be thoroughly cleansed to remove any residual drug from the affected area. Removal of the patch does not result in an immediate reversal of toxicity. Due to the reservoir in the skin, spontaneous reversal may take up to 1 day. Oral ingestion can lead to a fatal outcome, so if ingestion is suspected, providers must examine the oral cavity to ensure that no piece of the patch is present.27Naloxone, a competitive opioid receptor antagonist, is used to reverse opioid overdose. It is typically dosed at 0.001 mg/kg28 and can be increased incrementally up to 0.01 mg/kg, or even higher if findings do not improve. Many patients require sequential doses of naloxone due to its relatively short half-life compared to the prolonged elimination of transdermal or ingested fentanyl.28,29
Naloxone infusions are commonly needed for these patients, and are typically dosed at about two-thirds of the dose required for initial opioid reversal.28 Given the prolonged duration of possible toxicity, any patient who presents to the ED with signs of opioid overdose from transdermal exposure or oral ingestion of a patch should be admitted to the hospital30 and monitored for 24 hours28,31 to ensure that symptoms do not rebound, especially once the naloxone drip is weaned. Patients should be monitored for 4 to 6 hours after cessation of a naloxone infusion. Fortunately, timely and adequate management can result in positive clinical outcomes in most of these situations.
Conclusion
Ingestions of topical products are relatively common occurrences, particularly in pediatric patients. During the history taking, clinicians should be vigilant and always inquire about any topical medications within the home any time a pediatric patient presents with signs and symptoms indicative of a toxic ingestion. Family members should also be counseled on the dangers of accidental topical medication ingestion or misuse. Providers should give recommendations for proper storage and disposal of all prescription and nonprescription medications, which may help not only save a repeat visit to the ED, but may in fact save a life.
1. Mowry JB, Spyker DA, Brooks DE, Zimmerman A, Schauben JL. 2015 annual report of the American Association of Poison Control Centers’ National Poison Data System (NPDS): 33rd annual report. Clin Toxicol. 2016;54(10):924-1109. doi:10.1080/15563650.2016.1245421.
2. Tobias JD. Central nervous system depression following accidental ingestion of visine eye drops. Clin Pediatr (Phila). 1996;35(10):539-540. doi:10.1177/000992289603501010.
3. Lev R, Clark RF. Visine overdose: case report of an adult with hemodynamic compromise. J Emerg Med. 1995;13(5):649-652.
4. Jensen P, Edgren B, Hall L, Ring JC. Hemodynamic effects following ingestion of an imidazoline-containing product. Pediatr Emerg Care. 1989;5(2):110-112.
5. Davis JE. Are one or two dangerous? Methyl salicylate exposure in toddlers. J Emerg Med. 2007;32(1):63-69. doi:10.1016/j.jemermed.2006.08.009.
6. Chan TY. The risk of severe salicylate poisoning following the ingestion of topical medicaments or aspirin. Postgrad Med J. 1996;72(844):109-112.
7. Juurlink DN, Gosselin S, Kielstein JT, et al. Extracorporeal treatment for salicylate poisoning: Systematic review and recommendations from the EXTRIP workgroup. Ann Emerg Med. 2015;66(2):165-181.
8. Manikian A, Stone S, Hamilton R, Foltin G, Howland MA, Hoffman RS. Exchange transfusion in severe infant salicylism. Vet Hum Toxicol. 2002;44(4):224-227.
9. Davis B, Dang M, Kim J, Talbot P. Nicotine concentrations in electronic cigarette refill and do-it-yourself fluids. Nicotine Tob Res. 2015;17(2):134-141. doi:10.1093/ntr/ntu080.
10. US Food & Drug Administration. Tobacco Products. Rules & Regulations. https://www.fda.gov/TobaccoProducts/Labeling/RulesRegulationsGuidance/ucm283974.htm. Updated February 16, 2017. Accessed March 7, 2017.
11. Mayer B. How much nicotine kills a human? Tracing back the generally accepted lethal dose to dubious self-experiments in the nineteenth century. Arch Toxicol. 2014;88(1):5-7. doi:10.1007/s00204-013-1127-0.
12. Bassett RA, Osterhoudt K, Brabazon T. Nicotine poisoning in an infant. N Engl J Med. 2014;370(23):2249-2250. doi:10.1056/NEJMc1403843.
13. Kim JW, Baum CR. Liquid nicotine toxicity. Pediatr Emerg Care. 2015;31(7):517-521; quiz 522-524. doi:10.1097/PEC.0000000000000486.
14. Wain AA, Martin J. Can transdermal nicotine patch cause acute intoxication in a child? A case report and review of literature. Ulster Med J. 2004;73(1):65-66.
15. Gill N, Sangha G, Poonai N, Lim R. E-Cigarette liquid nicotine ingestion in a child: case report and discussion. CJEM. 2015;17(6):699-703. doi:10.1017/cem.2015.10.
16. Dayan PS, Litovitz TL, Crouch BI, Scalzo AJ, Klein BL. Fatal accidental dibucaine poisoning in children. Ann Emerg Med. 1996;28(4):442-445.
17. Curtis LA, Dolan TS, Seibert HE. Are one or two dangerous? Lidocaine and topical anesthetic exposures in children. J Emerg Med. 2009;37(1):32-39. doi:10.1016/j.jemermed.2007.11.005.
18. Ciechanowicz S, Patil V. Lipid emulsion for local anesthetic systemic toxicity. Anesthesiol Res Pract. 2012;2012:131784. doi:10.1155/2012/131784.
19. Bong CL, Hilliard J, Seefelder C. Severe methemoglobinemia from topical benzocaine 7.5% (baby orajel) use for teething pain in a toddler. Clin Pediatr (Phila). 2009;48(2):209-211.
20. Chung N, Batra R, Itzkevitch M, Boruchov D, Baldauf M. Severe methemoglobinemia linked to gel-type topical benzocaine use: A case report. J Emerg Med. 2010;38(5):601-606. doi:10.1016/j.jemermed.2008.06.025.
21. Liebelt EL, Shannon MW. Small doses, big problems: A selected review of highly toxic common medications. Pediatr Emerg Care. 1993;9(5):292-297.
22. So TY, Farrington E. Topical benzocaine-induced methemoglobinemia in the pediatric population. J Pediatr Health Care. 2008;22(6):335-339; quiz 340-341. doi:10.1016/j.pedhc.2008.08.008.
23. Parekh D, Miller MA, Borys D, Patel PR, Levsky ME. Transdermal patch medication delivery systems and pediatric poisonings, 2002-2006. Clin Pediatr (Phila). 2008;47(7):659-663. doi:10.1177/0009922808315211.
24. Teske J, Weller JP, Larsch K, Tröger HD, Karst M. Fatal outcome in a child after ingestion of a transdermal fentanyl patch. Int J Legal Med. 2007;121(2):147-151. doi:10.1007/s00414-006-0137-3.
25. Marquardt KA, Tharratt RS, Musallam NA. Fentanyl remaining in a transdermal system following three days of continuous use. Ann Pharmacother. 1995;29(10):969-971. doi:10.1177/106002809502901001.
26. Faust AC, Terpolilli R, Hughes DW. Management of an oral ingestion of transdermal fentanyl patches: a case report and literature review. Case Rep Med. 2011;2011:495938. doi:10.1155/2011/495938.
27. Prosser JM, Jones BE, Nelson L. Complications of oral exposure to fentanyl transdermal delivery system patches. J Med Toxicol. 2010;6(4):443-447. doi:10.1007/s13181-010-0092-8.
28. Kim HK, Nelson LS. Reducing the harm of opioid overdose with the safe use of naloxone: a pharmacologic review. Expert Opin Drug Saf. 2015;14 (7 ):1137-1146. doi:10.1517/14740338.2015.1037274.
29 Mrvos R, Feuchter AC, Katz KD, Duback-Morris LF, Brooks DE, Krenzelok EP. Whole fentanyl patch ingestion: A multi-center case series. J Emerg Med. 2012;42(5):549-552. doi:10.1016/j.jemermed.2011.05.017.
30. Sachdeva DK, Stadnyk JM. Are one or two dangerous? Opioid exposure in toddlers. J Emerg Med. 2005;29(1):77-84. doi:10.1016/j.jemermed.2004.12.015.
31. Behrman A, Goertemoeller S. A sticky situation: toxicity of clonidine and fentanyl transdermal patches in pediatrics. J Emerg Nurs. 2007;33(3):290-293.doi: 10.1016/j.jen.2007.02.004.
1. Mowry JB, Spyker DA, Brooks DE, Zimmerman A, Schauben JL. 2015 annual report of the American Association of Poison Control Centers’ National Poison Data System (NPDS): 33rd annual report. Clin Toxicol. 2016;54(10):924-1109. doi:10.1080/15563650.2016.1245421.
2. Tobias JD. Central nervous system depression following accidental ingestion of visine eye drops. Clin Pediatr (Phila). 1996;35(10):539-540. doi:10.1177/000992289603501010.
3. Lev R, Clark RF. Visine overdose: case report of an adult with hemodynamic compromise. J Emerg Med. 1995;13(5):649-652.
4. Jensen P, Edgren B, Hall L, Ring JC. Hemodynamic effects following ingestion of an imidazoline-containing product. Pediatr Emerg Care. 1989;5(2):110-112.
5. Davis JE. Are one or two dangerous? Methyl salicylate exposure in toddlers. J Emerg Med. 2007;32(1):63-69. doi:10.1016/j.jemermed.2006.08.009.
6. Chan TY. The risk of severe salicylate poisoning following the ingestion of topical medicaments or aspirin. Postgrad Med J. 1996;72(844):109-112.
7. Juurlink DN, Gosselin S, Kielstein JT, et al. Extracorporeal treatment for salicylate poisoning: Systematic review and recommendations from the EXTRIP workgroup. Ann Emerg Med. 2015;66(2):165-181.
8. Manikian A, Stone S, Hamilton R, Foltin G, Howland MA, Hoffman RS. Exchange transfusion in severe infant salicylism. Vet Hum Toxicol. 2002;44(4):224-227.
9. Davis B, Dang M, Kim J, Talbot P. Nicotine concentrations in electronic cigarette refill and do-it-yourself fluids. Nicotine Tob Res. 2015;17(2):134-141. doi:10.1093/ntr/ntu080.
10. US Food & Drug Administration. Tobacco Products. Rules & Regulations. https://www.fda.gov/TobaccoProducts/Labeling/RulesRegulationsGuidance/ucm283974.htm. Updated February 16, 2017. Accessed March 7, 2017.
11. Mayer B. How much nicotine kills a human? Tracing back the generally accepted lethal dose to dubious self-experiments in the nineteenth century. Arch Toxicol. 2014;88(1):5-7. doi:10.1007/s00204-013-1127-0.
12. Bassett RA, Osterhoudt K, Brabazon T. Nicotine poisoning in an infant. N Engl J Med. 2014;370(23):2249-2250. doi:10.1056/NEJMc1403843.
13. Kim JW, Baum CR. Liquid nicotine toxicity. Pediatr Emerg Care. 2015;31(7):517-521; quiz 522-524. doi:10.1097/PEC.0000000000000486.
14. Wain AA, Martin J. Can transdermal nicotine patch cause acute intoxication in a child? A case report and review of literature. Ulster Med J. 2004;73(1):65-66.
15. Gill N, Sangha G, Poonai N, Lim R. E-Cigarette liquid nicotine ingestion in a child: case report and discussion. CJEM. 2015;17(6):699-703. doi:10.1017/cem.2015.10.
16. Dayan PS, Litovitz TL, Crouch BI, Scalzo AJ, Klein BL. Fatal accidental dibucaine poisoning in children. Ann Emerg Med. 1996;28(4):442-445.
17. Curtis LA, Dolan TS, Seibert HE. Are one or two dangerous? Lidocaine and topical anesthetic exposures in children. J Emerg Med. 2009;37(1):32-39. doi:10.1016/j.jemermed.2007.11.005.
18. Ciechanowicz S, Patil V. Lipid emulsion for local anesthetic systemic toxicity. Anesthesiol Res Pract. 2012;2012:131784. doi:10.1155/2012/131784.
19. Bong CL, Hilliard J, Seefelder C. Severe methemoglobinemia from topical benzocaine 7.5% (baby orajel) use for teething pain in a toddler. Clin Pediatr (Phila). 2009;48(2):209-211.
20. Chung N, Batra R, Itzkevitch M, Boruchov D, Baldauf M. Severe methemoglobinemia linked to gel-type topical benzocaine use: A case report. J Emerg Med. 2010;38(5):601-606. doi:10.1016/j.jemermed.2008.06.025.
21. Liebelt EL, Shannon MW. Small doses, big problems: A selected review of highly toxic common medications. Pediatr Emerg Care. 1993;9(5):292-297.
22. So TY, Farrington E. Topical benzocaine-induced methemoglobinemia in the pediatric population. J Pediatr Health Care. 2008;22(6):335-339; quiz 340-341. doi:10.1016/j.pedhc.2008.08.008.
23. Parekh D, Miller MA, Borys D, Patel PR, Levsky ME. Transdermal patch medication delivery systems and pediatric poisonings, 2002-2006. Clin Pediatr (Phila). 2008;47(7):659-663. doi:10.1177/0009922808315211.
24. Teske J, Weller JP, Larsch K, Tröger HD, Karst M. Fatal outcome in a child after ingestion of a transdermal fentanyl patch. Int J Legal Med. 2007;121(2):147-151. doi:10.1007/s00414-006-0137-3.
25. Marquardt KA, Tharratt RS, Musallam NA. Fentanyl remaining in a transdermal system following three days of continuous use. Ann Pharmacother. 1995;29(10):969-971. doi:10.1177/106002809502901001.
26. Faust AC, Terpolilli R, Hughes DW. Management of an oral ingestion of transdermal fentanyl patches: a case report and literature review. Case Rep Med. 2011;2011:495938. doi:10.1155/2011/495938.
27. Prosser JM, Jones BE, Nelson L. Complications of oral exposure to fentanyl transdermal delivery system patches. J Med Toxicol. 2010;6(4):443-447. doi:10.1007/s13181-010-0092-8.
28. Kim HK, Nelson LS. Reducing the harm of opioid overdose with the safe use of naloxone: a pharmacologic review. Expert Opin Drug Saf. 2015;14 (7 ):1137-1146. doi:10.1517/14740338.2015.1037274.
29 Mrvos R, Feuchter AC, Katz KD, Duback-Morris LF, Brooks DE, Krenzelok EP. Whole fentanyl patch ingestion: A multi-center case series. J Emerg Med. 2012;42(5):549-552. doi:10.1016/j.jemermed.2011.05.017.
30. Sachdeva DK, Stadnyk JM. Are one or two dangerous? Opioid exposure in toddlers. J Emerg Med. 2005;29(1):77-84. doi:10.1016/j.jemermed.2004.12.015.
31. Behrman A, Goertemoeller S. A sticky situation: toxicity of clonidine and fentanyl transdermal patches in pediatrics. J Emerg Nurs. 2007;33(3):290-293.doi: 10.1016/j.jen.2007.02.004.
Heat-stable rotavirus vaccine shows promising results
A new low-cost rotavirus gastroenteritis vaccine that does not require cold storage showed a vaccine efficacy of 67% in a per-protocol test of 3,508 Nigerien infants, according to a study by Sheila Isanaka of the department of research at Epicentre, Paris, and her associates.
In a double blind, placebo-controlled test of the oral bovine rotavirus pentavalent vaccine (BRV-PV), 31 severe cases of rotavirus were found in the vaccinated group of 1,780, while 87 cases were found in the placebo group of 1,728 (2.14 vs. 6.44 cases per 100 person-years, respectively), according to Ms. Isanaka and her colleagues (N Engl J Med. 2017 Mar 23;376[12]:1121-30).
Researchers gathered infants with severe symptoms and administered three injections of either BRV-PV or the placebo from August 2014 through November 2015. The BRV-PV vaccine, manufactured by Serum Institute of India, contains the rotavirus serotypes G1, G2, G3, G4, and G9.
With regard to adverse events, there was no distinction between the two groups (P greater than .15). According to medical investigators, the most common cause of deaths – 27 and 22 in the vaccine and placebo groups, respectively – was infections and infestations (in 37 infants) and metabolism and nutrition disorders (in 6).
Part of what makes this vaccine unique is its shelf life of 2 years when kept at 37° C, or 6 months at 40° C, a key point for Ms. Isanaka and her colleagues.
“The global supply of the vaccines is constrained, and unreliable transportation and storage systems make delivery of vaccines that require refrigeration difficult,” Ms. Isanaka and her colleagues reported. “The introduction of BRV-PV may help to minimize the burden on already strained immunization programs.” The vaccine is also “for sale at or below the current price of the two WHO prequalified vaccines that are supported by the Gavi alliance,” making it possibly more financially accessible as well.
While the per-protocol test found efficacy at 67%, the intention-to-treat population reported a higher efficacy of 73%. Ms. Isanaka and her colleagues believe this number “may more closely represent the efficacy under real-world conditions,” due to the more flexible vaccination schedule.
This study was limited by a short time frame, which did not allow researchers to gather genotyping data pertaining to the efficacy against changing serotypes. BRV-PV also was not given consistently with the oral polio vaccine.
The study was supported by Médecins sans Frontières Operational Center in Geneva and the Kavli Foundation. Ms. Isanaka’s institution, Epicentre, receives core funding from Médecins sans Frontières. Ms. McNeal reports grant support from Epicentre for the study, and other support from Merck and GlaxoSmithKline outside the submitted work. None of the other researchers had relevant financial disclosures.
ezimmerman@frontlinemedcom.com
On Twitter @EAZTweets
Rotavirus is the leading cause of diarrhea-associated death in children aged under 5 years, and with 85% of all deaths occurring in Africa and Asia, proper channels of vaccine dissemination are critical. There is no question to the positive influence of rotavirus vaccines, as research suggests they could save 2.46 million children’s lives and prevent another 83 million from living with a disability between 2011 and 2030.
While two vaccines, Rotarix and RotaTeq, are already being introduced to patients in 48 countries, diminishing vaccine uptake is standing in the way of these interventions reaching their full potential. Despite subsidies from Gavi (the vaccine alliance) and the World Health Organization, costs are still too high and the necessity for cold storage poses a financial and logistical problem for a majority of high risk countries. The BRV-PV vaccine developed by Serum Institute of India seems to be a step in the right direction in helping to ease this burden.
While its efficacy is modest, BRV-PV has shown promise through its heat stability as well as its cost, which falls between the prices of the two already available vaccines.
It is not perfect; as a freeze-dried vaccine, it may pose problems in areas where oral liquid, all-in-one vaccinations are preferred. Yet, there is no doubt that an increase in affordable, programmatically suitable options will help achieve the goal of ending rotavirus related deaths globally.
Mathuram Santosham, MD, is professor of pediatrics and pediatric infectious diseases at Johns Hopkins University, Baltimore. Duncan Steele, PhD, is a microbiologist and deputy director and strategic lead for enteric vaccines and enteric and diarrheal diseases for the Bill & Melinda Gates Foundation, Seattle. They coauthored the editorial regarding the article by Isanaka et al. (N Engl J Med. 2017 March 23;376[12]:1170-2). Dr. Santosham reported no relevant financial disclosures. Dr. Steele reports that he is employed at the Bill & Melinda Gates Foundation, which has supported through funding, the development of multiple rotavirus vaccine candidates including the lyophilized rotavirus vaccine produced by Serum Institute.
Rotavirus is the leading cause of diarrhea-associated death in children aged under 5 years, and with 85% of all deaths occurring in Africa and Asia, proper channels of vaccine dissemination are critical. There is no question to the positive influence of rotavirus vaccines, as research suggests they could save 2.46 million children’s lives and prevent another 83 million from living with a disability between 2011 and 2030.
While two vaccines, Rotarix and RotaTeq, are already being introduced to patients in 48 countries, diminishing vaccine uptake is standing in the way of these interventions reaching their full potential. Despite subsidies from Gavi (the vaccine alliance) and the World Health Organization, costs are still too high and the necessity for cold storage poses a financial and logistical problem for a majority of high risk countries. The BRV-PV vaccine developed by Serum Institute of India seems to be a step in the right direction in helping to ease this burden.
While its efficacy is modest, BRV-PV has shown promise through its heat stability as well as its cost, which falls between the prices of the two already available vaccines.
It is not perfect; as a freeze-dried vaccine, it may pose problems in areas where oral liquid, all-in-one vaccinations are preferred. Yet, there is no doubt that an increase in affordable, programmatically suitable options will help achieve the goal of ending rotavirus related deaths globally.
Mathuram Santosham, MD, is professor of pediatrics and pediatric infectious diseases at Johns Hopkins University, Baltimore. Duncan Steele, PhD, is a microbiologist and deputy director and strategic lead for enteric vaccines and enteric and diarrheal diseases for the Bill & Melinda Gates Foundation, Seattle. They coauthored the editorial regarding the article by Isanaka et al. (N Engl J Med. 2017 March 23;376[12]:1170-2). Dr. Santosham reported no relevant financial disclosures. Dr. Steele reports that he is employed at the Bill & Melinda Gates Foundation, which has supported through funding, the development of multiple rotavirus vaccine candidates including the lyophilized rotavirus vaccine produced by Serum Institute.
Rotavirus is the leading cause of diarrhea-associated death in children aged under 5 years, and with 85% of all deaths occurring in Africa and Asia, proper channels of vaccine dissemination are critical. There is no question to the positive influence of rotavirus vaccines, as research suggests they could save 2.46 million children’s lives and prevent another 83 million from living with a disability between 2011 and 2030.
While two vaccines, Rotarix and RotaTeq, are already being introduced to patients in 48 countries, diminishing vaccine uptake is standing in the way of these interventions reaching their full potential. Despite subsidies from Gavi (the vaccine alliance) and the World Health Organization, costs are still too high and the necessity for cold storage poses a financial and logistical problem for a majority of high risk countries. The BRV-PV vaccine developed by Serum Institute of India seems to be a step in the right direction in helping to ease this burden.
While its efficacy is modest, BRV-PV has shown promise through its heat stability as well as its cost, which falls between the prices of the two already available vaccines.
It is not perfect; as a freeze-dried vaccine, it may pose problems in areas where oral liquid, all-in-one vaccinations are preferred. Yet, there is no doubt that an increase in affordable, programmatically suitable options will help achieve the goal of ending rotavirus related deaths globally.
Mathuram Santosham, MD, is professor of pediatrics and pediatric infectious diseases at Johns Hopkins University, Baltimore. Duncan Steele, PhD, is a microbiologist and deputy director and strategic lead for enteric vaccines and enteric and diarrheal diseases for the Bill & Melinda Gates Foundation, Seattle. They coauthored the editorial regarding the article by Isanaka et al. (N Engl J Med. 2017 March 23;376[12]:1170-2). Dr. Santosham reported no relevant financial disclosures. Dr. Steele reports that he is employed at the Bill & Melinda Gates Foundation, which has supported through funding, the development of multiple rotavirus vaccine candidates including the lyophilized rotavirus vaccine produced by Serum Institute.
A new low-cost rotavirus gastroenteritis vaccine that does not require cold storage showed a vaccine efficacy of 67% in a per-protocol test of 3,508 Nigerien infants, according to a study by Sheila Isanaka of the department of research at Epicentre, Paris, and her associates.
In a double blind, placebo-controlled test of the oral bovine rotavirus pentavalent vaccine (BRV-PV), 31 severe cases of rotavirus were found in the vaccinated group of 1,780, while 87 cases were found in the placebo group of 1,728 (2.14 vs. 6.44 cases per 100 person-years, respectively), according to Ms. Isanaka and her colleagues (N Engl J Med. 2017 Mar 23;376[12]:1121-30).
Researchers gathered infants with severe symptoms and administered three injections of either BRV-PV or the placebo from August 2014 through November 2015. The BRV-PV vaccine, manufactured by Serum Institute of India, contains the rotavirus serotypes G1, G2, G3, G4, and G9.
With regard to adverse events, there was no distinction between the two groups (P greater than .15). According to medical investigators, the most common cause of deaths – 27 and 22 in the vaccine and placebo groups, respectively – was infections and infestations (in 37 infants) and metabolism and nutrition disorders (in 6).
Part of what makes this vaccine unique is its shelf life of 2 years when kept at 37° C, or 6 months at 40° C, a key point for Ms. Isanaka and her colleagues.
“The global supply of the vaccines is constrained, and unreliable transportation and storage systems make delivery of vaccines that require refrigeration difficult,” Ms. Isanaka and her colleagues reported. “The introduction of BRV-PV may help to minimize the burden on already strained immunization programs.” The vaccine is also “for sale at or below the current price of the two WHO prequalified vaccines that are supported by the Gavi alliance,” making it possibly more financially accessible as well.
While the per-protocol test found efficacy at 67%, the intention-to-treat population reported a higher efficacy of 73%. Ms. Isanaka and her colleagues believe this number “may more closely represent the efficacy under real-world conditions,” due to the more flexible vaccination schedule.
This study was limited by a short time frame, which did not allow researchers to gather genotyping data pertaining to the efficacy against changing serotypes. BRV-PV also was not given consistently with the oral polio vaccine.
The study was supported by Médecins sans Frontières Operational Center in Geneva and the Kavli Foundation. Ms. Isanaka’s institution, Epicentre, receives core funding from Médecins sans Frontières. Ms. McNeal reports grant support from Epicentre for the study, and other support from Merck and GlaxoSmithKline outside the submitted work. None of the other researchers had relevant financial disclosures.
ezimmerman@frontlinemedcom.com
On Twitter @EAZTweets
A new low-cost rotavirus gastroenteritis vaccine that does not require cold storage showed a vaccine efficacy of 67% in a per-protocol test of 3,508 Nigerien infants, according to a study by Sheila Isanaka of the department of research at Epicentre, Paris, and her associates.
In a double blind, placebo-controlled test of the oral bovine rotavirus pentavalent vaccine (BRV-PV), 31 severe cases of rotavirus were found in the vaccinated group of 1,780, while 87 cases were found in the placebo group of 1,728 (2.14 vs. 6.44 cases per 100 person-years, respectively), according to Ms. Isanaka and her colleagues (N Engl J Med. 2017 Mar 23;376[12]:1121-30).
Researchers gathered infants with severe symptoms and administered three injections of either BRV-PV or the placebo from August 2014 through November 2015. The BRV-PV vaccine, manufactured by Serum Institute of India, contains the rotavirus serotypes G1, G2, G3, G4, and G9.
With regard to adverse events, there was no distinction between the two groups (P greater than .15). According to medical investigators, the most common cause of deaths – 27 and 22 in the vaccine and placebo groups, respectively – was infections and infestations (in 37 infants) and metabolism and nutrition disorders (in 6).
Part of what makes this vaccine unique is its shelf life of 2 years when kept at 37° C, or 6 months at 40° C, a key point for Ms. Isanaka and her colleagues.
“The global supply of the vaccines is constrained, and unreliable transportation and storage systems make delivery of vaccines that require refrigeration difficult,” Ms. Isanaka and her colleagues reported. “The introduction of BRV-PV may help to minimize the burden on already strained immunization programs.” The vaccine is also “for sale at or below the current price of the two WHO prequalified vaccines that are supported by the Gavi alliance,” making it possibly more financially accessible as well.
While the per-protocol test found efficacy at 67%, the intention-to-treat population reported a higher efficacy of 73%. Ms. Isanaka and her colleagues believe this number “may more closely represent the efficacy under real-world conditions,” due to the more flexible vaccination schedule.
This study was limited by a short time frame, which did not allow researchers to gather genotyping data pertaining to the efficacy against changing serotypes. BRV-PV also was not given consistently with the oral polio vaccine.
The study was supported by Médecins sans Frontières Operational Center in Geneva and the Kavli Foundation. Ms. Isanaka’s institution, Epicentre, receives core funding from Médecins sans Frontières. Ms. McNeal reports grant support from Epicentre for the study, and other support from Merck and GlaxoSmithKline outside the submitted work. None of the other researchers had relevant financial disclosures.
ezimmerman@frontlinemedcom.com
On Twitter @EAZTweets
Key clinical point:
Major finding: Of 3,508 infants studied, 31 cases of severe rotavirus gastroenteritis were found in the vaccine group, and 87 cases in the placebo group, putting efficacy at 67%.
Data source: Double blind, placebo-controlled test of 3,508 Nigerian infants whose symptoms were measured via 20-point Vesikari scoring.
Disclosures: The study was supported by Médecins sans Frontières Operational Center in Geneva and the Kavli Foundation. Ms. Isanaka’s institution, Epicentre, receives core funding from Médecins sans Frontières. Ms. McNeal reports grant support from Epicentre for the study, and other support from Merck and GlaxoSmithKline outside the submitted work. None of the other researchers had relevant financial disclosures.
Milk: Friend to bones, foe to faces?
ORLANDO – A greasy hamburger and fries and a chocolate milkshake may all earn the finger of blame when teens fret over acne. But which of these foods is the real culprit?
A growing body of data suggests it may be the milk – especially if it’s fat-free milk, according to Andrea Zaenglein, MD, who spoke at the annual meeting of the American Academy of Dermatology. Skim milk has been at the center of a long-simmering acne controversy, said Dr. Zaenglein, professor of dermatology and pediatric dermatology at Pennsylvania State University, Hershey.
The same association was seen in a subsequent study of 4,273 teen boys, published in 2008. There was a 10% increased risk for acne associated with intake of whole or 2% milk, a 17% increased risk for 1% milk, and a 19% increased risk for skim milk (J Am Acad Dermatol. 2008 May;58[5]: 787-93).
A prospective study of about 6,000 girls found similar risks associated with all types of milk: a 19% increased risk for whole milk, 17% for low-fat milk, and 19% for skim milk (Dermatol Online J. 2006 May 30;12[4]:1).
They found positive associations with total dairy and with nonfat dairy, but not with whole-fat or low-fat dairy. “The association was driven by the nonfat dairy,” Dr. Zaenglein said. “When we took nonfat [dairy] out of the total dairy, the association there was no longer significant.” They also found no significant association with body mass index, glycemic index, or glycemic load, she added.
“You have to wonder, what could this association between dairy – and skim milk in particular – be? Could dairy actually be involved in the pathogenesis of acne?” There are a number of proposed mechanisms, none of which have ever been confirmed, she said. “Could it be related to steroids? Milk is a very bioactive substance with estrogens and other hormones, but these are fat soluble and would be removed in skim milk.”
Another theory suggests that insulinlike growth factor-1, either in milk or endogenously stimulated by its consumption, may make a contribution. “People who are passionate about this have published prolifically about the activation of this pathway,” Dr. Zaenglein said, “but it remains speculative.”
She added, there are a plethora of studies showing milk’s benefits in many other areas, including the benefits exerted by milk’s medium-chain fatty acids on cardiovascular health, glycemic control, insulin regulation, and even obesity.
Finally, dairy’s importance to bone health in the United States can’t be ignored. In fact, dairy products are the most commonly recommended foods for ensuring adequate calcium intake in children, teens, and young adults.
“It’s really hard to make a firm recommendation to eliminate dairy, because, in this country, it makes up a good portion of the calcium teens need during their bone-building years, and kids are already at high risk for not meeting these requirements.”
National nutritional guidelines recommend 1,300 mg of calcium every day, which can be accomplished in three to five servings of dairy. “An 8-ounce glass of milk has 300 mg. Yogurt, cheese, and calcium-fortified juice are all highly accepted by teens. But, to get that same amount from vegetables, for example, you’d have to eat 3 cups of cooked kale. That’s a lot of kale,” Dr. Zaenglein said.
She had no relevant financial disclosures.
msullivan@frontlinemedcom.com
On Twitter @alz_gal
ORLANDO – A greasy hamburger and fries and a chocolate milkshake may all earn the finger of blame when teens fret over acne. But which of these foods is the real culprit?
A growing body of data suggests it may be the milk – especially if it’s fat-free milk, according to Andrea Zaenglein, MD, who spoke at the annual meeting of the American Academy of Dermatology. Skim milk has been at the center of a long-simmering acne controversy, said Dr. Zaenglein, professor of dermatology and pediatric dermatology at Pennsylvania State University, Hershey.
The same association was seen in a subsequent study of 4,273 teen boys, published in 2008. There was a 10% increased risk for acne associated with intake of whole or 2% milk, a 17% increased risk for 1% milk, and a 19% increased risk for skim milk (J Am Acad Dermatol. 2008 May;58[5]: 787-93).
A prospective study of about 6,000 girls found similar risks associated with all types of milk: a 19% increased risk for whole milk, 17% for low-fat milk, and 19% for skim milk (Dermatol Online J. 2006 May 30;12[4]:1).
They found positive associations with total dairy and with nonfat dairy, but not with whole-fat or low-fat dairy. “The association was driven by the nonfat dairy,” Dr. Zaenglein said. “When we took nonfat [dairy] out of the total dairy, the association there was no longer significant.” They also found no significant association with body mass index, glycemic index, or glycemic load, she added.
“You have to wonder, what could this association between dairy – and skim milk in particular – be? Could dairy actually be involved in the pathogenesis of acne?” There are a number of proposed mechanisms, none of which have ever been confirmed, she said. “Could it be related to steroids? Milk is a very bioactive substance with estrogens and other hormones, but these are fat soluble and would be removed in skim milk.”
Another theory suggests that insulinlike growth factor-1, either in milk or endogenously stimulated by its consumption, may make a contribution. “People who are passionate about this have published prolifically about the activation of this pathway,” Dr. Zaenglein said, “but it remains speculative.”
She added, there are a plethora of studies showing milk’s benefits in many other areas, including the benefits exerted by milk’s medium-chain fatty acids on cardiovascular health, glycemic control, insulin regulation, and even obesity.
Finally, dairy’s importance to bone health in the United States can’t be ignored. In fact, dairy products are the most commonly recommended foods for ensuring adequate calcium intake in children, teens, and young adults.
“It’s really hard to make a firm recommendation to eliminate dairy, because, in this country, it makes up a good portion of the calcium teens need during their bone-building years, and kids are already at high risk for not meeting these requirements.”
National nutritional guidelines recommend 1,300 mg of calcium every day, which can be accomplished in three to five servings of dairy. “An 8-ounce glass of milk has 300 mg. Yogurt, cheese, and calcium-fortified juice are all highly accepted by teens. But, to get that same amount from vegetables, for example, you’d have to eat 3 cups of cooked kale. That’s a lot of kale,” Dr. Zaenglein said.
She had no relevant financial disclosures.
msullivan@frontlinemedcom.com
On Twitter @alz_gal
ORLANDO – A greasy hamburger and fries and a chocolate milkshake may all earn the finger of blame when teens fret over acne. But which of these foods is the real culprit?
A growing body of data suggests it may be the milk – especially if it’s fat-free milk, according to Andrea Zaenglein, MD, who spoke at the annual meeting of the American Academy of Dermatology. Skim milk has been at the center of a long-simmering acne controversy, said Dr. Zaenglein, professor of dermatology and pediatric dermatology at Pennsylvania State University, Hershey.
The same association was seen in a subsequent study of 4,273 teen boys, published in 2008. There was a 10% increased risk for acne associated with intake of whole or 2% milk, a 17% increased risk for 1% milk, and a 19% increased risk for skim milk (J Am Acad Dermatol. 2008 May;58[5]: 787-93).
A prospective study of about 6,000 girls found similar risks associated with all types of milk: a 19% increased risk for whole milk, 17% for low-fat milk, and 19% for skim milk (Dermatol Online J. 2006 May 30;12[4]:1).
They found positive associations with total dairy and with nonfat dairy, but not with whole-fat or low-fat dairy. “The association was driven by the nonfat dairy,” Dr. Zaenglein said. “When we took nonfat [dairy] out of the total dairy, the association there was no longer significant.” They also found no significant association with body mass index, glycemic index, or glycemic load, she added.
“You have to wonder, what could this association between dairy – and skim milk in particular – be? Could dairy actually be involved in the pathogenesis of acne?” There are a number of proposed mechanisms, none of which have ever been confirmed, she said. “Could it be related to steroids? Milk is a very bioactive substance with estrogens and other hormones, but these are fat soluble and would be removed in skim milk.”
Another theory suggests that insulinlike growth factor-1, either in milk or endogenously stimulated by its consumption, may make a contribution. “People who are passionate about this have published prolifically about the activation of this pathway,” Dr. Zaenglein said, “but it remains speculative.”
She added, there are a plethora of studies showing milk’s benefits in many other areas, including the benefits exerted by milk’s medium-chain fatty acids on cardiovascular health, glycemic control, insulin regulation, and even obesity.
Finally, dairy’s importance to bone health in the United States can’t be ignored. In fact, dairy products are the most commonly recommended foods for ensuring adequate calcium intake in children, teens, and young adults.
“It’s really hard to make a firm recommendation to eliminate dairy, because, in this country, it makes up a good portion of the calcium teens need during their bone-building years, and kids are already at high risk for not meeting these requirements.”
National nutritional guidelines recommend 1,300 mg of calcium every day, which can be accomplished in three to five servings of dairy. “An 8-ounce glass of milk has 300 mg. Yogurt, cheese, and calcium-fortified juice are all highly accepted by teens. But, to get that same amount from vegetables, for example, you’d have to eat 3 cups of cooked kale. That’s a lot of kale,” Dr. Zaenglein said.
She had no relevant financial disclosures.
msullivan@frontlinemedcom.com
On Twitter @alz_gal
EXPERT ANALYSIS FROM AAD 17
What happens when a baked egg oral challenge is negative?
ATLANTA – The majority of patients who had cooked egg exposure following a negative physician-supervised baked egg oral challenge are tolerating cooked egg, according to a retrospective study.
However, no correlation between results and development of tolerance was identified with skin prick testing or serum IgE testing.
To find out, Dr. Peng, a second-year fellow in the department of pediatrics at the University of California, Los Angeles, and her associates identified 22 patients who underwent negative physician-supervised baked egg oral challenges from July 2011 until June 2016. They reviewed medical charts to obtain data on age, clinical history, skin prick test results, and results of serum IgE testing to egg and its components. Next, the researchers contacted patients and their families and invited them to participate in a telephone survey about patterns of baked, cooked, and raw egg exposure and associated reactions, following their negative baked challenge. The patients ranged in age from 10 months to 44 years and their mean age was 7 years.
Dr. Peng presented results from 18 of the 22 patients who were successfully contacted. A mean of 26 months had passed since their baked egg oral challenge. Of these patients, 17 (94%) have had continued exposure to egg while 15 (83%) have shown tolerance to cooked egg. The researchers observed variable patterns of baked egg intake following the negative physician-supervised baked egg challenge. “Some patients are able to tolerate cooked egg rapidly but are not interested in continuing frequent consumption,” Dr. Peng said. “They may say, ‘My 3-year-old doesn’t like scrambled eggs, so I’m not going to keep pushing them.’ They’re not considering themselves egg allergic so their quality of life is much better. I understand that tolerating baked egg is a big deal, as an allergist I want to see them do more, such as tolerating cooked egg.”
When patients were asked about adverse reactions to egg consumption, three (17%) described gastrointestinal symptoms, five (28%) described cutaneous symptoms, and three (17%) described respiratory reactions. Dr. Peng noted that of the three patients who have not achieved tolerance to cooked egg, one patient reported mild reaction to baked egg 2 weeks after the baked egg challenge, while the other two continue to have baked egg exposure but have not yet introduced cooked egg into their diets. “I hope that most pediatricians and family practice physicians consider referral to an allergist if they’re not comfortable introducing a baked egg oral challenge.”
The researchers could not identify any correlation between skin prick or serum IgE test results and development of tolerance to cooked egg. “Data in the literature suggests that serum testing is predictive [of tolerance], but it’s not 100%,” Dr. Peng said.
She reported having no relevant financial disclosures.
ATLANTA – The majority of patients who had cooked egg exposure following a negative physician-supervised baked egg oral challenge are tolerating cooked egg, according to a retrospective study.
However, no correlation between results and development of tolerance was identified with skin prick testing or serum IgE testing.
To find out, Dr. Peng, a second-year fellow in the department of pediatrics at the University of California, Los Angeles, and her associates identified 22 patients who underwent negative physician-supervised baked egg oral challenges from July 2011 until June 2016. They reviewed medical charts to obtain data on age, clinical history, skin prick test results, and results of serum IgE testing to egg and its components. Next, the researchers contacted patients and their families and invited them to participate in a telephone survey about patterns of baked, cooked, and raw egg exposure and associated reactions, following their negative baked challenge. The patients ranged in age from 10 months to 44 years and their mean age was 7 years.
Dr. Peng presented results from 18 of the 22 patients who were successfully contacted. A mean of 26 months had passed since their baked egg oral challenge. Of these patients, 17 (94%) have had continued exposure to egg while 15 (83%) have shown tolerance to cooked egg. The researchers observed variable patterns of baked egg intake following the negative physician-supervised baked egg challenge. “Some patients are able to tolerate cooked egg rapidly but are not interested in continuing frequent consumption,” Dr. Peng said. “They may say, ‘My 3-year-old doesn’t like scrambled eggs, so I’m not going to keep pushing them.’ They’re not considering themselves egg allergic so their quality of life is much better. I understand that tolerating baked egg is a big deal, as an allergist I want to see them do more, such as tolerating cooked egg.”
When patients were asked about adverse reactions to egg consumption, three (17%) described gastrointestinal symptoms, five (28%) described cutaneous symptoms, and three (17%) described respiratory reactions. Dr. Peng noted that of the three patients who have not achieved tolerance to cooked egg, one patient reported mild reaction to baked egg 2 weeks after the baked egg challenge, while the other two continue to have baked egg exposure but have not yet introduced cooked egg into their diets. “I hope that most pediatricians and family practice physicians consider referral to an allergist if they’re not comfortable introducing a baked egg oral challenge.”
The researchers could not identify any correlation between skin prick or serum IgE test results and development of tolerance to cooked egg. “Data in the literature suggests that serum testing is predictive [of tolerance], but it’s not 100%,” Dr. Peng said.
She reported having no relevant financial disclosures.
ATLANTA – The majority of patients who had cooked egg exposure following a negative physician-supervised baked egg oral challenge are tolerating cooked egg, according to a retrospective study.
However, no correlation between results and development of tolerance was identified with skin prick testing or serum IgE testing.
To find out, Dr. Peng, a second-year fellow in the department of pediatrics at the University of California, Los Angeles, and her associates identified 22 patients who underwent negative physician-supervised baked egg oral challenges from July 2011 until June 2016. They reviewed medical charts to obtain data on age, clinical history, skin prick test results, and results of serum IgE testing to egg and its components. Next, the researchers contacted patients and their families and invited them to participate in a telephone survey about patterns of baked, cooked, and raw egg exposure and associated reactions, following their negative baked challenge. The patients ranged in age from 10 months to 44 years and their mean age was 7 years.
Dr. Peng presented results from 18 of the 22 patients who were successfully contacted. A mean of 26 months had passed since their baked egg oral challenge. Of these patients, 17 (94%) have had continued exposure to egg while 15 (83%) have shown tolerance to cooked egg. The researchers observed variable patterns of baked egg intake following the negative physician-supervised baked egg challenge. “Some patients are able to tolerate cooked egg rapidly but are not interested in continuing frequent consumption,” Dr. Peng said. “They may say, ‘My 3-year-old doesn’t like scrambled eggs, so I’m not going to keep pushing them.’ They’re not considering themselves egg allergic so their quality of life is much better. I understand that tolerating baked egg is a big deal, as an allergist I want to see them do more, such as tolerating cooked egg.”
When patients were asked about adverse reactions to egg consumption, three (17%) described gastrointestinal symptoms, five (28%) described cutaneous symptoms, and three (17%) described respiratory reactions. Dr. Peng noted that of the three patients who have not achieved tolerance to cooked egg, one patient reported mild reaction to baked egg 2 weeks after the baked egg challenge, while the other two continue to have baked egg exposure but have not yet introduced cooked egg into their diets. “I hope that most pediatricians and family practice physicians consider referral to an allergist if they’re not comfortable introducing a baked egg oral challenge.”
The researchers could not identify any correlation between skin prick or serum IgE test results and development of tolerance to cooked egg. “Data in the literature suggests that serum testing is predictive [of tolerance], but it’s not 100%,” Dr. Peng said.
She reported having no relevant financial disclosures.
AT THE 2017 AAAAI ANNUAL MEETING
Key clinical point:
Major finding: Following a negative physician-supervised baked egg oral challenge 94% of patients have had continued exposure to egg while 83% have shown tolerance to cooked egg.
Data source: A retrospective review of 22 patients who underwent a physician-supervised negative oral baked egg challenge.
Disclosures: Dr. Peng reported having no relevant financial disclosures.
Smoking During Pregnancy May Damage Offspring’s Retinal Nerve Fiber Layer
Retinal nerve fiber layer defects are a defining feature of optic neuropathies and have been implicated in several neurodegenerative disorders, including multiple sclerosis, Alzheimer’s disease, and Parkinson’s disease. Both maternal smoking during pregnancy and low birth weight have been implicated in impaired development of the retina.
The Copenhagen Child Cohort 2000 Eye Study
Mr. Ashina and colleagues sought to investigate the associations of maternal smoking during pregnancy and low birth weight with retinal nerve fiber layer thickness in preadolescent children. They examined data from a prospective, population-based, birth cohort study that included all children (n = 6,090) born in 2000 in Copenhagen. Maternal smoking data were collected through parental interviews. Birth weight, pregnancy, and medical history data were obtained from the Danish Medical Birth Registry. As a follow-up, the researchers performed eye examinations on 1,406 of these children from May 1, 2011, to October 31, 2012, when the children were age 11 or 12.
Of the 1,406 children in the study, 1,323 were included in the analysis. Mean age was 11.7. Nearly half of the children (47.8%) were boys. The mean retinal nerve fiber layer thickness was 104 mm. In 227 children whose mothers had smoked during pregnancy, the peripapillary retinal nerve fiber layer was 5.7 mm thinner than in children whose mothers had not smoked during pregnancy, after adjusting for age, sex, birth weight, height, body weight, Tanner stage of pubertal development, axial length, and spherical equivalent refractive error. In children with low birth weight (ie, < 2,500 g), the retinal nerve fiber layer was 3.5 mm thinner than in children with normal birth weight, after adjustment for all variables.
“The results of this study add evidence to existing recommendations to avoid smoking during pregnancy and support measures that promote maternal and fetal health,” the researchers said.
A Public Health Message
In an invited commentary that accompanied the study, Christopher Kai-Shun Leung, MD, from the Department of Ophthalmology and Visual Sciences at Hong Kong Eye Hospital and Chinese University of Hong Kong in Kowloon, said that “although a difference of 5 to 6 mm in average circumpapillary retinal nerve fiber layer thickness is unlikely to translate into a detectable difference in visual function in children aged 12 to 13 years, the risk of subsequent development of visual impairment should not be overlooked.” Furthermore, he noted, “whether a thinner retinal nerve fiber layer in the children of mothers who smoked during pregnancy w
—Glenn S. Williams
Suggested Reading
Ashina H, Li XQ, Olsen EM, et al. Association of maternal smoking during pregnancy and birth weight with retinal nerve fiber layer thickness in children aged 11 or 12 years: The Copenhagen Child Cohort 2000 Eye Study. JAMA Ophthalmol. 2017 March 2 [Epub ahead of print].
Leung CK. Evaluation of retinal nerve fiber layer thinning with Fourier-domain optical coherence tomography. JAMA Ophthalmol. 2017 March 2 [Epub ahead of print].
Retinal nerve fiber layer defects are a defining feature of optic neuropathies and have been implicated in several neurodegenerative disorders, including multiple sclerosis, Alzheimer’s disease, and Parkinson’s disease. Both maternal smoking during pregnancy and low birth weight have been implicated in impaired development of the retina.
The Copenhagen Child Cohort 2000 Eye Study
Mr. Ashina and colleagues sought to investigate the associations of maternal smoking during pregnancy and low birth weight with retinal nerve fiber layer thickness in preadolescent children. They examined data from a prospective, population-based, birth cohort study that included all children (n = 6,090) born in 2000 in Copenhagen. Maternal smoking data were collected through parental interviews. Birth weight, pregnancy, and medical history data were obtained from the Danish Medical Birth Registry. As a follow-up, the researchers performed eye examinations on 1,406 of these children from May 1, 2011, to October 31, 2012, when the children were age 11 or 12.
Of the 1,406 children in the study, 1,323 were included in the analysis. Mean age was 11.7. Nearly half of the children (47.8%) were boys. The mean retinal nerve fiber layer thickness was 104 mm. In 227 children whose mothers had smoked during pregnancy, the peripapillary retinal nerve fiber layer was 5.7 mm thinner than in children whose mothers had not smoked during pregnancy, after adjusting for age, sex, birth weight, height, body weight, Tanner stage of pubertal development, axial length, and spherical equivalent refractive error. In children with low birth weight (ie, < 2,500 g), the retinal nerve fiber layer was 3.5 mm thinner than in children with normal birth weight, after adjustment for all variables.
“The results of this study add evidence to existing recommendations to avoid smoking during pregnancy and support measures that promote maternal and fetal health,” the researchers said.
A Public Health Message
In an invited commentary that accompanied the study, Christopher Kai-Shun Leung, MD, from the Department of Ophthalmology and Visual Sciences at Hong Kong Eye Hospital and Chinese University of Hong Kong in Kowloon, said that “although a difference of 5 to 6 mm in average circumpapillary retinal nerve fiber layer thickness is unlikely to translate into a detectable difference in visual function in children aged 12 to 13 years, the risk of subsequent development of visual impairment should not be overlooked.” Furthermore, he noted, “whether a thinner retinal nerve fiber layer in the children of mothers who smoked during pregnancy w
—Glenn S. Williams
Suggested Reading
Ashina H, Li XQ, Olsen EM, et al. Association of maternal smoking during pregnancy and birth weight with retinal nerve fiber layer thickness in children aged 11 or 12 years: The Copenhagen Child Cohort 2000 Eye Study. JAMA Ophthalmol. 2017 March 2 [Epub ahead of print].
Leung CK. Evaluation of retinal nerve fiber layer thinning with Fourier-domain optical coherence tomography. JAMA Ophthalmol. 2017 March 2 [Epub ahead of print].
Retinal nerve fiber layer defects are a defining feature of optic neuropathies and have been implicated in several neurodegenerative disorders, including multiple sclerosis, Alzheimer’s disease, and Parkinson’s disease. Both maternal smoking during pregnancy and low birth weight have been implicated in impaired development of the retina.
The Copenhagen Child Cohort 2000 Eye Study
Mr. Ashina and colleagues sought to investigate the associations of maternal smoking during pregnancy and low birth weight with retinal nerve fiber layer thickness in preadolescent children. They examined data from a prospective, population-based, birth cohort study that included all children (n = 6,090) born in 2000 in Copenhagen. Maternal smoking data were collected through parental interviews. Birth weight, pregnancy, and medical history data were obtained from the Danish Medical Birth Registry. As a follow-up, the researchers performed eye examinations on 1,406 of these children from May 1, 2011, to October 31, 2012, when the children were age 11 or 12.
Of the 1,406 children in the study, 1,323 were included in the analysis. Mean age was 11.7. Nearly half of the children (47.8%) were boys. The mean retinal nerve fiber layer thickness was 104 mm. In 227 children whose mothers had smoked during pregnancy, the peripapillary retinal nerve fiber layer was 5.7 mm thinner than in children whose mothers had not smoked during pregnancy, after adjusting for age, sex, birth weight, height, body weight, Tanner stage of pubertal development, axial length, and spherical equivalent refractive error. In children with low birth weight (ie, < 2,500 g), the retinal nerve fiber layer was 3.5 mm thinner than in children with normal birth weight, after adjustment for all variables.
“The results of this study add evidence to existing recommendations to avoid smoking during pregnancy and support measures that promote maternal and fetal health,” the researchers said.
A Public Health Message
In an invited commentary that accompanied the study, Christopher Kai-Shun Leung, MD, from the Department of Ophthalmology and Visual Sciences at Hong Kong Eye Hospital and Chinese University of Hong Kong in Kowloon, said that “although a difference of 5 to 6 mm in average circumpapillary retinal nerve fiber layer thickness is unlikely to translate into a detectable difference in visual function in children aged 12 to 13 years, the risk of subsequent development of visual impairment should not be overlooked.” Furthermore, he noted, “whether a thinner retinal nerve fiber layer in the children of mothers who smoked during pregnancy w
—Glenn S. Williams
Suggested Reading
Ashina H, Li XQ, Olsen EM, et al. Association of maternal smoking during pregnancy and birth weight with retinal nerve fiber layer thickness in children aged 11 or 12 years: The Copenhagen Child Cohort 2000 Eye Study. JAMA Ophthalmol. 2017 March 2 [Epub ahead of print].
Leung CK. Evaluation of retinal nerve fiber layer thinning with Fourier-domain optical coherence tomography. JAMA Ophthalmol. 2017 March 2 [Epub ahead of print].
Childhood adiposity tied to NAFLD and elevated ALT in adulthood
Overweight or obese children in a cohort study were more likely to have adult nonalcoholic fatty liver disease (NAFLD) and elevated levels of the liver enzyme alanine aminotransferase than were healthy weight children of both sexes, but this association can be mitigated by weight loss in adulthood.
“These findings underscore the importance of both early prevention and lifelong treatment of overweight and obesity to reduce the risk of adverse liver outcome in adulthood,” Yinkun Yan, PhD, an epidemiologist at the Capital Institute of Pediatrics, Beijing, and associates wrote (Pediatrics. 2017;139[4]:e20162738).
The adiposity of the children was determined by caliper measurements and body mass index. ALT elevation was diagnosed via blood tests and NAFLD from ultrasonography. ALT is considered to be the most specific marker of liver damage, and NAFLD is one of the most common causes of liver disease worldwide.
Children who were overweight or obese were more likely to grow up to have elevated ALT levels (40% vs. 30% in men and 23% vs. 12% in women) or NAFLD (62% vs. 39% in men and 39% vs. 15% in women) than were healthy weight children. Obesity in adulthood was a higher risk whether a participant was obese as a child or not, but the researchers noted that risks could be mitigated by acquiring normal weight in adulthood.
Overweight or obese children in a cohort study were more likely to have adult nonalcoholic fatty liver disease (NAFLD) and elevated levels of the liver enzyme alanine aminotransferase than were healthy weight children of both sexes, but this association can be mitigated by weight loss in adulthood.
“These findings underscore the importance of both early prevention and lifelong treatment of overweight and obesity to reduce the risk of adverse liver outcome in adulthood,” Yinkun Yan, PhD, an epidemiologist at the Capital Institute of Pediatrics, Beijing, and associates wrote (Pediatrics. 2017;139[4]:e20162738).
The adiposity of the children was determined by caliper measurements and body mass index. ALT elevation was diagnosed via blood tests and NAFLD from ultrasonography. ALT is considered to be the most specific marker of liver damage, and NAFLD is one of the most common causes of liver disease worldwide.
Children who were overweight or obese were more likely to grow up to have elevated ALT levels (40% vs. 30% in men and 23% vs. 12% in women) or NAFLD (62% vs. 39% in men and 39% vs. 15% in women) than were healthy weight children. Obesity in adulthood was a higher risk whether a participant was obese as a child or not, but the researchers noted that risks could be mitigated by acquiring normal weight in adulthood.
Overweight or obese children in a cohort study were more likely to have adult nonalcoholic fatty liver disease (NAFLD) and elevated levels of the liver enzyme alanine aminotransferase than were healthy weight children of both sexes, but this association can be mitigated by weight loss in adulthood.
“These findings underscore the importance of both early prevention and lifelong treatment of overweight and obesity to reduce the risk of adverse liver outcome in adulthood,” Yinkun Yan, PhD, an epidemiologist at the Capital Institute of Pediatrics, Beijing, and associates wrote (Pediatrics. 2017;139[4]:e20162738).
The adiposity of the children was determined by caliper measurements and body mass index. ALT elevation was diagnosed via blood tests and NAFLD from ultrasonography. ALT is considered to be the most specific marker of liver damage, and NAFLD is one of the most common causes of liver disease worldwide.
Children who were overweight or obese were more likely to grow up to have elevated ALT levels (40% vs. 30% in men and 23% vs. 12% in women) or NAFLD (62% vs. 39% in men and 39% vs. 15% in women) than were healthy weight children. Obesity in adulthood was a higher risk whether a participant was obese as a child or not, but the researchers noted that risks could be mitigated by acquiring normal weight in adulthood.
One peanut daily might maintain childhood immunotherapy gains
ATLANTA – One year or more after peanut immunotherapy, 27 of 33 (82%) children were eating peanuts regularly, most without problems, in a survey from the Children’s Hospital of Philadelphia.
The finding speaks to the durability of peanut immunotherapy, something that’s been a concern for physicians and families. It suggests that peanut immunotherapy might give children long-term protection from accidental exposure, so long as they continue to eat a small amount of peanut almost every day after desensitization.
She and her team surveyed the families of 15 children who completed a trial of epicutaneous peanut immunotherapy (EPIT) and 9 who completed a trial of oral immunotherapy (OIT) about a year after the studies ended. They also surveyed families of nine children about 2 years after they completed a trial of OIT plus omalizumab (Xolair) for peanut allergy. The investigators and families chose maintenance doses based on results from the final peanut challenges, and children were warned against running around within 2 hours of their dose, to prevent exercised-induced reactions.
The point of using omalizumab in the one trial was to see if it helped children ramp up immunotherapy more quickly and tolerate higher final peanut doses. It did, and the nine omalizumab children were on the highest maintenance doses of peanut at 2-year follow-up, with almost all of them consuming an average of at least one peanut a day. Perhaps because of that, three of the four anaphylactic reactions were in the omalizumab group.
The fourth reaction was in a child who completed the OIT trial. There was no anaphylaxis in EPIT children. About 60% in both groups reported eating an average of at least a peanut a day at 1-year follow-up.
About three-quarters of the children ate peanut-containing candy to get their maintenance dose. Others ate peanuts or peanut butter or sprinkled peanut flour on their food. Just six children, all from the EPIT cohort, said they liked the taste of peanuts.
Meanwhile, 6 of the 33 children (18%) – 1 in the omalizumab group, 3 in the EPIT arm, and 2 in the OIT group – refused to eat peanuts after their immunotherapy trials.
Posttrial peanut dosing ranged from once a month to daily, and the majority of subjects ate peanut about five times per week. All of the anaphylaxis children recovered without incident and resumed peanut maintenance. A couple of the children in the EPIT group had an itch in their throat when they switched to eating peanuts, but it resolved on its own. One child in the omalizumab group and one in the OIT group reported gastrointestinal symptoms with maintenance dosing.
The original trials funded the follow-up. Ms. Ott Lewis had no relevant financial disclosures.
ATLANTA – One year or more after peanut immunotherapy, 27 of 33 (82%) children were eating peanuts regularly, most without problems, in a survey from the Children’s Hospital of Philadelphia.
The finding speaks to the durability of peanut immunotherapy, something that’s been a concern for physicians and families. It suggests that peanut immunotherapy might give children long-term protection from accidental exposure, so long as they continue to eat a small amount of peanut almost every day after desensitization.
She and her team surveyed the families of 15 children who completed a trial of epicutaneous peanut immunotherapy (EPIT) and 9 who completed a trial of oral immunotherapy (OIT) about a year after the studies ended. They also surveyed families of nine children about 2 years after they completed a trial of OIT plus omalizumab (Xolair) for peanut allergy. The investigators and families chose maintenance doses based on results from the final peanut challenges, and children were warned against running around within 2 hours of their dose, to prevent exercised-induced reactions.
The point of using omalizumab in the one trial was to see if it helped children ramp up immunotherapy more quickly and tolerate higher final peanut doses. It did, and the nine omalizumab children were on the highest maintenance doses of peanut at 2-year follow-up, with almost all of them consuming an average of at least one peanut a day. Perhaps because of that, three of the four anaphylactic reactions were in the omalizumab group.
The fourth reaction was in a child who completed the OIT trial. There was no anaphylaxis in EPIT children. About 60% in both groups reported eating an average of at least a peanut a day at 1-year follow-up.
About three-quarters of the children ate peanut-containing candy to get their maintenance dose. Others ate peanuts or peanut butter or sprinkled peanut flour on their food. Just six children, all from the EPIT cohort, said they liked the taste of peanuts.
Meanwhile, 6 of the 33 children (18%) – 1 in the omalizumab group, 3 in the EPIT arm, and 2 in the OIT group – refused to eat peanuts after their immunotherapy trials.
Posttrial peanut dosing ranged from once a month to daily, and the majority of subjects ate peanut about five times per week. All of the anaphylaxis children recovered without incident and resumed peanut maintenance. A couple of the children in the EPIT group had an itch in their throat when they switched to eating peanuts, but it resolved on its own. One child in the omalizumab group and one in the OIT group reported gastrointestinal symptoms with maintenance dosing.
The original trials funded the follow-up. Ms. Ott Lewis had no relevant financial disclosures.
ATLANTA – One year or more after peanut immunotherapy, 27 of 33 (82%) children were eating peanuts regularly, most without problems, in a survey from the Children’s Hospital of Philadelphia.
The finding speaks to the durability of peanut immunotherapy, something that’s been a concern for physicians and families. It suggests that peanut immunotherapy might give children long-term protection from accidental exposure, so long as they continue to eat a small amount of peanut almost every day after desensitization.
She and her team surveyed the families of 15 children who completed a trial of epicutaneous peanut immunotherapy (EPIT) and 9 who completed a trial of oral immunotherapy (OIT) about a year after the studies ended. They also surveyed families of nine children about 2 years after they completed a trial of OIT plus omalizumab (Xolair) for peanut allergy. The investigators and families chose maintenance doses based on results from the final peanut challenges, and children were warned against running around within 2 hours of their dose, to prevent exercised-induced reactions.
The point of using omalizumab in the one trial was to see if it helped children ramp up immunotherapy more quickly and tolerate higher final peanut doses. It did, and the nine omalizumab children were on the highest maintenance doses of peanut at 2-year follow-up, with almost all of them consuming an average of at least one peanut a day. Perhaps because of that, three of the four anaphylactic reactions were in the omalizumab group.
The fourth reaction was in a child who completed the OIT trial. There was no anaphylaxis in EPIT children. About 60% in both groups reported eating an average of at least a peanut a day at 1-year follow-up.
About three-quarters of the children ate peanut-containing candy to get their maintenance dose. Others ate peanuts or peanut butter or sprinkled peanut flour on their food. Just six children, all from the EPIT cohort, said they liked the taste of peanuts.
Meanwhile, 6 of the 33 children (18%) – 1 in the omalizumab group, 3 in the EPIT arm, and 2 in the OIT group – refused to eat peanuts after their immunotherapy trials.
Posttrial peanut dosing ranged from once a month to daily, and the majority of subjects ate peanut about five times per week. All of the anaphylaxis children recovered without incident and resumed peanut maintenance. A couple of the children in the EPIT group had an itch in their throat when they switched to eating peanuts, but it resolved on its own. One child in the omalizumab group and one in the OIT group reported gastrointestinal symptoms with maintenance dosing.
The original trials funded the follow-up. Ms. Ott Lewis had no relevant financial disclosures.
Key clinical point: Eating more than that might increase the risk of reaction.
Major finding: There were four anaphylactic reactions, three of which were among children on the highest maintenance doses.
Data source: Follow-up surveys a year or more after peanut desensitization trials in 33 children.
Disclosures: The original trials funded the follow-up. The lead investigator had no relevant financial disclosures.
