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Viruses, upper respiratory tract illnesses, and sinusitis
April 2016 Volume 171
Can we adhere to guidelines better? — Paul G. Fisher, MD
Viruses, upper respiratory tract illnesses, and sinusitis — Sarah S. Long, MD
Copyright ª 2016 by Elsevier Inc.
T
he American Academy of Pediatrics (AAP) and other professional societies publish myriad policy statements and clinical reports. Can pediatricians in everyday practice adhere to all of these guidelines, especially when certain conditions appear only rarely among their patients? In this issue of The Journal, Santoro et al report the results of an educational initiative to improve adherence to AAP guidelines for health supervision in children with Down syndrome. Thirteen pediatrics practices caring for 82 children with Down syndrome received an educational folder, encompassing the guidelines and a checklist. The results of the intervention were encouraging, but sobering. Improvements occurred across 5 of 8 universal recommendations, but the overall improvement in meeting all recommendations rose from 13% to only 34%. In other words, two-thirds of pediatricians still did not follow all of the guidelines. The authors consider reasons for this limited improvement, ranging from low patient volume of Down syndrome for any given pediatrician, to lack of incorporating this initiative within the electronic medical record, to invasiveness of some recommendations. Regardless, this study highlights a disconnect between the creation and implementation of guidelines. Guidelines are usually crafted by specialists or pediatricians accustomed to very specific groups of complex patients to whom they themselves attend. Perhaps greater attention should be paid at the outset to how community pediatricians will implement guidelines rather than long after creation of these policies. Article page 262<
O
ver decades of prospective studies, DeMuri et al have gathered evidence regarding the clinical diagnosis, etiology, and management of acute sinusitis in children. The current study contributes substantially to what illnesses providers can expect in children with uncomplicated upper respiratory tract infections (URIs), and how frequently URIs are complicated by acute sinusitis. Children 4 to 6 years of age were entered into a prospective 1-year study of virus surveillance during wellness and episodes of URI. Further, duration of symptoms in uncomplicated URIs and occurrence rates of acute sinusitis (by validated criteria) were determined. Polymerase chain reaction testing was used to detect viruses. The 236 children enrolled in the study were predominantly white, with educated parents who had health insurance. The short list of findings were: (1) an average of 1.3 URIs occurred per child per year; (2) virus(es) was detected during 81% of URIs and from 33% of children when well; (3) resolution of URI symptoms occurred by day 10 of illness in 72% with uncomplicated illness; and (4) a diagnosis of sinusitis complicated 8.8% of symptomatic URIs. This seemingly high rate of sinusitis-complicating URIs has been suspected in other geographic areas and population groups, and is juxtaposed to a seemingly low rate of provider visits for unresolved URI (ie, possible acute sinusitis) in urban settings of socioeconomically disadvantaged children. We may begin to understand the high case load of intraorbital and intracranial complications of sinusitis in these latter settings. Article page 133<
1
We are here because my child complained of being dizzy — Reginald L. Washington, MD
R€ontgenophobia? — Paul G. Fisher, MD
A rare disease but not-so-rare problem — Denise M. Goodman, MD, MS
2
T
his is a complaint often heard by primary health care providers. Just how often children complain of being dizzy or having balance problems is not clearly known. There are many possible etiologies for this set of symptoms, but estimates on which ones are most common are not available. The study by Li et al in this issue of The Journal provides a national estimate of the prevalence of dizziness and balance problems (DzBP) in 13- to 17-year-old children. Risk factors include older age, being a female, or non-Hispanic White. Headache/ migraine, otitis media, and seizures were often associated with DzBP. Overall, only 36% of these children were seen by a healthcare professional and 29.9% received treatment. Of those describing their DzBP as moderate or “big,” 71.6% were seen and 62.4% received treatment. Almost 49% of children were told that their DzBP was due to “other” unspecified causes. The complaint of DzBP is common but more research is needed so that healthcare providers can be more effective in diagnosing and appropriately treating children with this complaint. Article page 240<
W
ilhelm R€ ontgen discovered x-rays (just over 120 years ago), as well as the protective effects of lead shields. Today we still need to use radiography, while protecting growing children. In its clinical report issued last year on the evaluation of suspected child abuse, the American Academy of Pediatrics recommended that a skeletal survey be performed when there is a concern for abuse in all children less than 2 years of age, as well as in older children at the discretion of the treating physician (Pediatrics 2015;135:e1337-54). Should we worry about radiation exposure from a skeletal survey? In this issue of The Journal, Berger et al use a Monte Carlo simulation to derive effective dose from a skeletal survey in an infant. Calculated dose was 0.2 mSv (Sieverts describe tissue absorption better than the legacy exposure unit, R€ ontgen). Put another way, 0.2 mSv approximates the dose we experience flying across the US by airplane, and is far less than 3 mSv a woman receives from a screening mammogram or the 20 mSv a neonate experiences from computed tomography of the abdomen. Berger et al calculated the risk of exposure-induced cancer death from a skeletal survey to be 2 to 5/100 000/year, close to or slightly above the background mortality rate of childhood cancer. Although a skeletal survey could perhaps double a child’s risk of cancer death, or escalate slightly future cancer mortality as an adult, the absolute risk is rather tiny. When there is a reasonable clinical indication for a skeletal survey, with benefits greater than risks, we should avoid r€ ontgenophobia. Article page 310<
A
taxia-telangiectasia (A-T) is a rare disease characterized by cerebellar degeneration, immunodeficiency, sensitivity to ionizing radiation, an increased risk of malignancies, and pulmonary disease. Ataxia-telangiectasia mutated (ATM) is a nuclear protein responsible for managing the response to cellular stress including repairs of DNA breaks. ATM arrests the cell cycle and recruits other proteins to repair the breaks before they can be integrated into the genome. The mutations causing A-T cause defective DNA repair and faulty programmed cell death (Blood 2013;121:4036-45). Patients with A-T also have accelerated telomere shortening. Telomeres, the ends of linear DNA, are associated with proteins that protect the coding DNA of the genome. If these protective proteins are missing, chromosome fusions can occur with significant clinical consequence (N Engl J Med 2009;361:2353-65). Telomeres ordinarily shorten by 50-100 base pairs during each cell division in vitro, and progressive shortening eventually leads to cell senescence (J Cell Biol 2014;205:289-99). Disrupted telomere maintenance causes defective telomere structure and repair and accelerated telomere shortening. Volume 171
We now know that telomere loss is the basis for a large family of disorders known as telomeropathies, a spectrum with a wide range of phenotypes, including some types of aplastic anemia, dyskeratosis congenita (a form of ectodermal dysplasia), pulmonary fibrosis, liver disease, cancer risk, heart disease, and physiologic aging. Within this context, the report in this issue of The Journal by McGrath-Morrow et al is intriguing. These investigators report 44 patients with A-T and pulmonary dysfunction, demonstrating an inverse relationship between the pro-inflammatory cytokine interleukin (IL)-6 and pulmonary function. Co-occurrence of elevated IL-6 and IL-8, a proinflammatory neutrophil chemoattractant, was associated with the worst pulmonary function. It is impossible to determine from this study whether IL-6 is a nonspecific marker of disease severity or exerts some specific function on the causal pathway of pulmonary disease. That said, any insight into the genetic underpinnings of inflammation and end-organ dysfunction may eventually have broad applicability to both disease and to the normal process of aging. Article page 256<
Insights into pubertal delay in children with Crohn's disease — Ivor D. Hill, MB, ChB, MD
April 2016
D
elay in onset and progression of puberty is well documented in children with Crohn’s disease. This, in turn, has the potential for adversely impacting linear growth and impairing bone accrual, and can have significant effects on the quality of life in these children. Possible reasons for this delay have included undernutrition with poor body fat stores and an ill-defined effect of the inflammatory cytokines involved in the disease process. Animal studies suggest that cytokines and other mediators of inflammation have a suppressant effect on sex hormones, which can be reversed with use of antibody against tumor necrosis factor a (TNF-a). There are little prior data in this regard in children with Crohn’s disease. In this issue of The Journal, DeBoer et al provide much needed insight into the problem of pubertal delay associated with Crohn’s disease. Children with active disease have low levels of testosterone, estradiol, luteinizing hormone, and follicle-stimulating hormone. The sex hormone and gonadotropin levels were negatively associated with the pediatric Crohn’s disease activity index, cytokine levels, and measures of inflammation. Following induction of therapy with TNF-a there was a rapid and sustained rise in sex hormone and gonadotropin levels together with improvement in disease activity, and these changes were independent of body mass index or fat mass. Although the results of this study indicate the effects of inflammation on the suppression of sex hormones occurs at the level of gonadotropin regulation, the precise mechanisms involved remain to be identified. The implications of these findings extend beyond Crohn’s disease because other chronic inflammatory diseases also can impact pubertal development. Understanding the reasons behind this delay is essential for treatment, which will ultimately significantly improve the lives of affected children. Article page 146<
3
Can we adhere to guidelines better? — Paul G. Fisher, MD
Viruses, upper respiratory tract illnesses, and sinusitis — Sarah S. Long, MD
Copyright ª 2016 by Elsevier Inc.
T
he American Academy of Pediatrics (AAP) and other professional societies publish myriad policy statements and clinical reports. Can pediatricians in everyday practice adhere to all of these guidelines, especially when certain conditions appear only rarely among their patients? In this issue of The Journal, Santoro et al report the results of an educational initiative to improve adherence to AAP guidelines for health supervision in children with Down syndrome. Thirteen pediatrics practices caring for 82 children with Down syndrome received an educational folder, encompassing the guidelines and a checklist. The results of the intervention were encouraging, but sobering. Improvements occurred across 5 of 8 universal recommendations, but the overall improvement in meeting all recommendations rose from 13% to only 34%. In other words, two-thirds of pediatricians still did not follow all of the guidelines. The authors consider reasons for this limited improvement, ranging from low patient volume of Down syndrome for any given pediatrician, to lack of incorporating this initiative within the electronic medical record, to invasiveness of some recommendations. Regardless, this study highlights a disconnect between the creation and implementation of guidelines. Guidelines are usually crafted by specialists or pediatricians accustomed to very specific groups of complex patients to whom they themselves attend. Perhaps greater attention should be paid at the outset to how community pediatricians will implement guidelines rather than long after creation of these policies. Article page 262<
O
ver decades of prospective studies, DeMuri et al have gathered evidence regarding the clinical diagnosis, etiology, and management of acute sinusitis in children. The current study contributes substantially to what illnesses providers can expect in children with uncomplicated upper respiratory tract infections (URIs), and how frequently URIs are complicated by acute sinusitis. Children 4 to 6 years of age were entered into a prospective 1-year study of virus surveillance during wellness and episodes of URI. Further, duration of symptoms in uncomplicated URIs and occurrence rates of acute sinusitis (by validated criteria) were determined. Polymerase chain reaction testing was used to detect viruses. The 236 children enrolled in the study were predominantly white, with educated parents who had health insurance. The short list of findings were: (1) an average of 1.3 URIs occurred per child per year; (2) virus(es) was detected during 81% of URIs and from 33% of children when well; (3) resolution of URI symptoms occurred by day 10 of illness in 72% with uncomplicated illness; and (4) a diagnosis of sinusitis complicated 8.8% of symptomatic URIs. This seemingly high rate of sinusitis-complicating URIs has been suspected in other geographic areas and population groups, and is juxtaposed to a seemingly low rate of provider visits for unresolved URI (ie, possible acute sinusitis) in urban settings of socioeconomically disadvantaged children. We may begin to understand the high case load of intraorbital and intracranial complications of sinusitis in these latter settings. Article page 133<
1
We are here because my child complained of being dizzy — Reginald L. Washington, MD
R€ontgenophobia? — Paul G. Fisher, MD
A rare disease but not-so-rare problem — Denise M. Goodman, MD, MS
2
T
his is a complaint often heard by primary health care providers. Just how often children complain of being dizzy or having balance problems is not clearly known. There are many possible etiologies for this set of symptoms, but estimates on which ones are most common are not available. The study by Li et al in this issue of The Journal provides a national estimate of the prevalence of dizziness and balance problems (DzBP) in 13- to 17-year-old children. Risk factors include older age, being a female, or non-Hispanic White. Headache/ migraine, otitis media, and seizures were often associated with DzBP. Overall, only 36% of these children were seen by a healthcare professional and 29.9% received treatment. Of those describing their DzBP as moderate or “big,” 71.6% were seen and 62.4% received treatment. Almost 49% of children were told that their DzBP was due to “other” unspecified causes. The complaint of DzBP is common but more research is needed so that healthcare providers can be more effective in diagnosing and appropriately treating children with this complaint. Article page 240<
W
ilhelm R€ ontgen discovered x-rays (just over 120 years ago), as well as the protective effects of lead shields. Today we still need to use radiography, while protecting growing children. In its clinical report issued last year on the evaluation of suspected child abuse, the American Academy of Pediatrics recommended that a skeletal survey be performed when there is a concern for abuse in all children less than 2 years of age, as well as in older children at the discretion of the treating physician (Pediatrics 2015;135:e1337-54). Should we worry about radiation exposure from a skeletal survey? In this issue of The Journal, Berger et al use a Monte Carlo simulation to derive effective dose from a skeletal survey in an infant. Calculated dose was 0.2 mSv (Sieverts describe tissue absorption better than the legacy exposure unit, R€ ontgen). Put another way, 0.2 mSv approximates the dose we experience flying across the US by airplane, and is far less than 3 mSv a woman receives from a screening mammogram or the 20 mSv a neonate experiences from computed tomography of the abdomen. Berger et al calculated the risk of exposure-induced cancer death from a skeletal survey to be 2 to 5/100 000/year, close to or slightly above the background mortality rate of childhood cancer. Although a skeletal survey could perhaps double a child’s risk of cancer death, or escalate slightly future cancer mortality as an adult, the absolute risk is rather tiny. When there is a reasonable clinical indication for a skeletal survey, with benefits greater than risks, we should avoid r€ ontgenophobia. Article page 310<
A
taxia-telangiectasia (A-T) is a rare disease characterized by cerebellar degeneration, immunodeficiency, sensitivity to ionizing radiation, an increased risk of malignancies, and pulmonary disease. Ataxia-telangiectasia mutated (ATM) is a nuclear protein responsible for managing the response to cellular stress including repairs of DNA breaks. ATM arrests the cell cycle and recruits other proteins to repair the breaks before they can be integrated into the genome. The mutations causing A-T cause defective DNA repair and faulty programmed cell death (Blood 2013;121:4036-45). Patients with A-T also have accelerated telomere shortening. Telomeres, the ends of linear DNA, are associated with proteins that protect the coding DNA of the genome. If these protective proteins are missing, chromosome fusions can occur with significant clinical consequence (N Engl J Med 2009;361:2353-65). Telomeres ordinarily shorten by 50-100 base pairs during each cell division in vitro, and progressive shortening eventually leads to cell senescence (J Cell Biol 2014;205:289-99). Disrupted telomere maintenance causes defective telomere structure and repair and accelerated telomere shortening. Volume 171
We now know that telomere loss is the basis for a large family of disorders known as telomeropathies, a spectrum with a wide range of phenotypes, including some types of aplastic anemia, dyskeratosis congenita (a form of ectodermal dysplasia), pulmonary fibrosis, liver disease, cancer risk, heart disease, and physiologic aging. Within this context, the report in this issue of The Journal by McGrath-Morrow et al is intriguing. These investigators report 44 patients with A-T and pulmonary dysfunction, demonstrating an inverse relationship between the pro-inflammatory cytokine interleukin (IL)-6 and pulmonary function. Co-occurrence of elevated IL-6 and IL-8, a proinflammatory neutrophil chemoattractant, was associated with the worst pulmonary function. It is impossible to determine from this study whether IL-6 is a nonspecific marker of disease severity or exerts some specific function on the causal pathway of pulmonary disease. That said, any insight into the genetic underpinnings of inflammation and end-organ dysfunction may eventually have broad applicability to both disease and to the normal process of aging. Article page 256<
Insights into pubertal delay in children with Crohn's disease — Ivor D. Hill, MB, ChB, MD
April 2016
D
elay in onset and progression of puberty is well documented in children with Crohn’s disease. This, in turn, has the potential for adversely impacting linear growth and impairing bone accrual, and can have significant effects on the quality of life in these children. Possible reasons for this delay have included undernutrition with poor body fat stores and an ill-defined effect of the inflammatory cytokines involved in the disease process. Animal studies suggest that cytokines and other mediators of inflammation have a suppressant effect on sex hormones, which can be reversed with use of antibody against tumor necrosis factor a (TNF-a). There are little prior data in this regard in children with Crohn’s disease. In this issue of The Journal, DeBoer et al provide much needed insight into the problem of pubertal delay associated with Crohn’s disease. Children with active disease have low levels of testosterone, estradiol, luteinizing hormone, and follicle-stimulating hormone. The sex hormone and gonadotropin levels were negatively associated with the pediatric Crohn’s disease activity index, cytokine levels, and measures of inflammation. Following induction of therapy with TNF-a there was a rapid and sustained rise in sex hormone and gonadotropin levels together with improvement in disease activity, and these changes were independent of body mass index or fat mass. Although the results of this study indicate the effects of inflammation on the suppression of sex hormones occurs at the level of gonadotropin regulation, the precise mechanisms involved remain to be identified. The implications of these findings extend beyond Crohn’s disease because other chronic inflammatory diseases also can impact pubertal development. Understanding the reasons behind this delay is essential for treatment, which will ultimately significantly improve the lives of affected children. Article page 146<
3