December and November 2011 Journal Watch

Cardiology:

Friedman KG, Kane DA, Rathod RH, et al. Management of pediatric chest pain using a standardized assessment and management plan. Pediatrics Aug 2011;128(2):e1-e7.
Summary and Implications For Your Practice:
Chest pain (CP) is a common complaint, and often the etiology is non-cardiac despite expensive tests ordered for evaluation of cardiac causes. This study aimed to determine if a mechanism to standardize care will lead to a reduction in costs and resource use while still catching all true cardiac etiologies of CP. A retrospective review of 406 patients aged 7-21 years who presented to an outpatient pediatric cardiology clinic for first-time evaluation of chest pain was undertaken. An algorithm based on prior experience was created to determine if history, physical exam, and electrocardiogram (ECG) could suggest when additional testing was needed. Echocardiogram was indicated for patients with concerning past medical history, abnormal exam, abnormal ECG, positive family history, or negative exam/ECG/history but with CP at high level of exertion with no alternate explanation. In the cohort, a cardiac etiology of CP was found for 5/406 patients and 8 had incidental cardiac findings unrelated to the CP. The cost of the algorithm’s prediction and actual resource use was compared using the chi-squared test and found that using the algorithm could reduce use of extensive testing and charges by approximately 20%, not including the likely decrease in repeat clinic and emergency department visits. While this study suggests that history/physical/ECG can help reduce the costs of cardiac evaluation, there are many limitations. It uses only clinic notes for the data, cardiologists have various thresholds for ordering further tests based on experience, and there is little follow-up to see if some patients later were found to have a true cardiac cause of CP. There is always the fear of labeling CP as non-cardiac after minimal evaluation (i.e., only ECG) and missing potentially dangerous diagnoses. It is absolutely necessary to think about ways to reduce health care costs but difficult in the current atmosphere of worrying about medico-legal ramifications.
Submitted by: Anandhi Gunder
Comment: Dr. Gunder makes very good points. Of patients in the study (n=150, 37%) w/ our “red flag” for referral (chest pain with exertion), it seems none had a cardiac cause of pain; the “true rate” of cardiac etiology in a non-referral population with this history is not known. Although ECG is included in the proposed algorithm, its value as a screening tool for non-cardiologists is unproven. More questions than answers for the primary care doctor! LF

Dermatology:

Finkelstein Y, et. al. Recurrence and outcomes of Stevens-Johnson syndrome and toxic epidermal necrolysis in children. Pediatrics 2011;128:723-728.
Summary and Implications For Your Practice:
Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe disorders with high morbidity and mortality, but little is understood concerning them in the pediatric population outside of case studies or series and extrapolation from adult findings. This was a retrospective study of all pediatric cases of SJS and TEN admitted to the Hospital for Sick Children (HSC) and Children’s Hospital Boston (CHB) from 2000 to 2007, in which the authors note the demographics, most likely etiology, clinical course, management, and long-term outcomes observed. Of a total 55 cases from both institutions, 32 had chronic conditions (mainly epilepsy, n=38). 29 cases (53%) were attributed to drug therapy, with 16 (29%) related to antiepileptics and 11 (20%) related to antibiotics including sulfonamides (7), azithromycin (2), and ampicillin (2). Other causes included Mycoplasma (n=12, 25%) and Herpes Simplex Virus (HSV) infection (n=5, 9%), or were undetermined (n=10, 18%). Mortality was much lower than in adult studies (with 1 death attributed to TEN), but long-term morbidity was high with 25 (45%) patients suffering long-term skin, ocular, or genital/mucosal sequelae. 1 in 5 patients with SJS had at least one recurrence, suggesting a possible genetic predisposition or vulnerability. With no treatment guidelines, management varied greatly, with patients at HSC more likely to receive IVIG and/or concomitant steroids and systemic antibiotics than those at CHB. Ocular complications were much more common in children treated with IVIG, who notably suffered a longer disease course and were likely the most severely affected. This study informs my understanding of SJS and TEN and underscores the need for prospective studies to guide management.
Submitted by: Leslie White
Comment: This interesting information highlights the need for more studies in order to learn more about this rare but serious syndrome. LC

Gastroenterology:

Abdulrahman A et al. Eosinophilic colitis: epidemiology, clinical features, and current management. Therap Adv Gastroenterol. 2011 September;4(5):301–309.
Summary and Implications For Your Practice:
Although eosinophilic esophagitis (EoE) has become a hot topic, not much is discussed about other primary eosinophilic gastrointestinal disorders (EGIDs), specifically eosinophilic gastroenteritis (EG) and eosinophilic colitis (EC). These three diseases represent a triad of disorders characterized by eosinophilic infiltration of the gut. This article discusses the least common of the three, EC, and how age of onset determines severity of disease. Understanding this relationship not only allows clinicians to recognize this rarely talked about disorder, but also gives providers a better understanding of how EC is managed in different age groups, and just how little we actually know about the pathophysiology and treatment of EGIDs. EC manifests differently depending on age with a milder, self-limited presentation in infants and more prolonged, chronic presentation in young adults. The pathophysiolgy is also different. Infants have an IgE-mediated hypersensitivity response (related commonly to food allergy), while young adults seem to have a non-IgE mediated response (T lymphocytes). Symptoms include diarrhea, abdominal pain, and weight loss in young adults, while infants again have a more acute self-limited bloody diarrhea. Like EoE, endoscopic evaluation is helpful with colonic biopsy, however a lack of standardization of criteria makes diagnosis difficult and other conditions must be ruled out. With such a strong association to food allergy, elimination or elemental diets are common treatments for infants. In young adults treatment is more aggressive with steroids, anti-histamines, and leukotriene receptor antagonists. These recommendations are based on limited data and small case reports. Treatment regimens are varied and often ineffective. This article gives clinicians a better understanding of the less-talked about primary eosinophilic gastrointestinal disorders. Being more aware of these disorders gives physicians a broader differential when thinking about patients with gastrointestinal complaints that fail to fit common GI syndromes. This is especially true in the realm of GI and A/I subspecialties where kids who have failed normal outpatient management come for answers and relief.
Submitted by: Justin Greiwe
Comment: Although rare, it is important to keep these eosinophilic gastrointestinal disorders on the radar screen for patients who have chronic GI complaints. LC

Esch, C. et al Celiac disease antibodies during a gluten-free diet. Pediatrics 2011; 128(3): 547-552.
Summary and Implications For Your Practice:
Celiac antibodies are helpful when diagnosing Celiac disease. By following antibody levels, one can measure disease activity and compliance with the prescribed gluten-free diet. This study looks at antibody level reduction with regards to time after initiation of the gluten-free diet so physicians know how much reduction in these levels to look for in follow-up. This multicenter retrospective study out of the Netherlands looked at newly diagnosed patients who had anti-TG2 and anti-EMA measurements before and after diagnosis as well as after initiation of the gluten-free diet. The study did note that several assays were used to detect antibody levels and did control for this. 129 children between the ages of 11 months to 16 years (mean 5.6 yrs) were enrolled in the study. 488 IgA anti-TG2 and 408 IgA anti-EMA determinations were performed at different time points. After 3 months of the gluten-free diet, the mean concentration of anti-TG2 decreased for about 75% of the population and after 6 months decreased for about 84% of children. By 18 months, the anti-TG2 of most the children had a mean concentration below the point for negativity. With regards to the anti-EMA, a similar trend is seen. Within 2 years of the gluten-free diet, both antibodies disappear in approximately 80% of children. Using these guidelines, pediatricians and gastroenterologists can better use antibody levels to understand disease activity and adherence to the gluten-free diet.
Submitted by: Cheri-Priya Dhar
Comment:This interesting study gives hope that biopsy may become a procedure of the past for children with celiac disease. Unfortunately, the time lag between initiation of a gluten-free diet and antibody reduction complicates assessment of adherence. LF

Tabbers MM et al. Nonpharmacologic treatments for childhood constipation: systematic review. Pediatrics 2011;128(4):753-761.
Summary and Implications For Your Practice:
In this systematic review, the authors sought to find evidence for using nonpharmacologic interventions in children with constipation. They did a review of articles from Embase, Medline, and PsycINFO and based on their inclusion criteria used 9 different studies. The studies compared the use of fiber, fluid, prebiotics, probiotics, and behavioral therapy to improve stooling habits and stool consistency. They found increasing fiber in the diet of a child with constipation who does not already have fiber in their diet has a statistically significant effect on improving constipation. However, if the child already eats the nutritionally recommended amount of fiber there is no significant improvement in constipation. Neither pre- nor probiotics improved the frequency or consistency of stooling; however probiotics did improve the abdominal pain associated with constipation. The studies using behavioral therapy to treat constipation did not have long term effect on stooling habits. However, the children participating in these studies did have other behavior improvements other than constipation. This study shows the treatments many pediatricians use as first line therapy for constipation may not be effective for many children. There were only 9 studies in this systemic review which shows more studies need to assess the effectiveness of nonpharmacologic interventions for constipation. It is important to recommend effective nonpharmacologic treatment because up to one third of patients with constipation are seeking out non-laxative treatments. Ineffective treatment such as prebiotics can be expensive and perhaps should not be recommended for constipation. However more study is needed. In conclusion, aside from fiber, nonpharmacologic methods of treating constipation may not be helpful.
Submitted by: Andrea Mertz
Comment: Chronic constipation ranks among the most frustrating chief complaints in the pediatric population. In general, the common American diet is poor in fiber, so it is often helpful to give parents information regarding increasing fiber in their children’s diets. LC

Sattar et al. Celiac disease in children, adolescents, and young adults with autoimmune thyroid disease. JPeds 2011;158:272-275.
Summary and Implications For Your Practice:
In the general pediatric population, celiac disease occurs at a rate of 0.3%-1.25%. It is known to occur in higher rates in individuals with certain syndromes such as Type I Diabetes (DM1), Turner syndrome and Down syndrome. It has recently been shown in European journals that there is a higher prevalence of celiac disease in patients with autoimmune thyroid disease. However, this has not been established in the USA. In this study, the authors screened 302 patients with autoimmune thyroid disease for celiac disease using transglutaminase antibody titers and endoscopy for anyone found with positive titers. 4.6% of patients were found to have positive antibodies. 54% of these patients were found to have biopsy-proven celiac disease on endoscopy. These results suggest an increased prevalence of biopsy-proven celiac disease among children with autoimmune thyroid disease when compared to the general public. However, several patients in this study had co-morbidities such as DM1 and Turner syndrome that would make them more susceptible to celiac disease. When patients with these co-morbidities were excluded from the study the prevalence of celiac disease dropped to close to that of the general population (1.3%). This study also demonstrates a lower positive predictive value of a positive tTG-IgA titer in the autoimmune thyroid population (54-57%) versus the general population (70-83%) for biopsy-proven celiac disease. This study both identifies the need for more research into the risk of celiac disease in those populations with other autoimmune disease as well as the need for a better screening test in such populations. The authors conclude based on these results that in the absence of co-morbidities, symptoms, or both, that screening children with autoimmune thyroid disease for celiac disease may not be justified.
Submitted by: Lori Schillaci
Comment: A nice and thorough review by Dr. Schillaci! It is worth remembering that celiac disease is a "sleeper" and can present at many ages with many symptoms, for example with unexplained anemia, malabsorption, abdominal pain or linear growth failure, and less commonly with rash or joint pains. LF

General Pediatrics:

Powell CVE, et. al. Randomized clinical trial of rapid versus 24-hour rehydration for children with acute gastroenteritis. Pediatrics 2011 Oct;128(4):e771-e778.
Summary and Implications For Your Practice:
Acute gastroenteritis is a common childhood illness seen frequently in the emergency department (ED) and is a major cause of dehydration. This study looked at the difference between rapid nasogastric rehydration over 4 hours versus standard nasogastric rehydration over 24 hours in children diagnosed with viral gastroenteritis as well as moderate dehydration. This study was conducted as a prospective randomized controlled trial in two urban hospitals in Australia. The study period lasted 18 months and included children who presented to the ED with a diagnosis of viral gastroenteritis as well as dehydration. The study hypothesized that rapid rehydration would not be inferior to standard rehydration in treating children with acute gastroenteritis and moderate dehydration. Two hundred and twenty-eight children between the age of 6 month and 72 months were recruited for this study. Exclusion criteria included bloody stools, absence of diarrhea, significant other morbidities or a mild or severe dehydration score. Primary treatment failure was defined as a weight loss greater than 2% of admission weight at any time during the rehydration process. Secondary treatment failure was defined as an inability to tolerate NG placement, frequent or persistent vomiting, intravenous hydration, or impending circulatory collapse. The study found that 11.8% of children in the rapid resuscitation vs. 9.2% in the standard resuscitation group experienced greater than 2% weight loss during the study period which was not found to be statistically significant. Overall primary treatment failure and clinical outcomes were similar between the two study groups. In our ER setting, NG rehydration is not a common practice. However in other countries where intravenous hydration is less common or not as available, this may be a great alternative practice that reduces hospital stay times in these children.
Submitted by: Jen Coliadis
Comment: I agree with Dr. Coliadis’ comments. It might be interesting to prospectively study rapid NG rehydration, possibly in combination with zofran therapy, in a US Emergency Department setting, since the economic and patient/family benefits of non-hospitalization are many. LF

Halfon N et al. Duration of well-child visit: association with content, family-centeredness, and satisfaction. Pediatrics 2011;128(4):657-663.
Summary and Implications For Your Practice:
Using the National Survey of Early Childhood Health, researchers gathered participants aged 4-35 months to discuss duration of well-child visits and content of anticipatory guidance with their caregivers. The longer caregivers reported visits correlated with an increased amount of anticipatory guidance topics covered. Several characteristics of families reporting longer visits include lower socioeconomic status, uninsured, less education, and minority race. Male physicians were more likely than women to spend ten minutes or less for a well child visit. The longer the visit the higher the patient rated their satisfaction with the clinician. The amount of anticipatory guidance topics was directly proportional to the length of the visit. However, there was no measure in the study to determine how effective the guidance was. There was no limit to visit length and therefore no assessment of information retention. Topics covered by 80% of the pediatricians per parent report regardless of visit duration include breastfeeding and immunizations. While these are two important topics, there is a vast multitude of topics important to discuss during each well-child visit. The most common pediatrician-reported factor for shorter well child visits was reimbursement. Doctors and patients giving/receiving care in a community hospital report spending more time in the well-child visit. As Medicaid and private insurance reimbursement changes it is important we determine both the appropriate length for a well-child visit, and the best way to convey important health information. This study shows ten minutes or less for a well care visit is too short. Well-child visits need to last longer than 10 minutes to cover all pertinent anticipatory guidance topics.
Submitted by: Andrea Mertz
Comment: I think we can all agree that there is never enough time to cover all of the things we would like to cover in one WCC visit. It is important to come up with an individual system of hitting all the important topics as the child grows and develops. One thing I would point out about this study is that it was based on telephone follow-up of the parents after the visit, so one might question the accuracy of the time reported. LC

Steiner, MJ. Fasting for lipid screening. Pediatrics 2011;128(3):463-470.
Summary and Implications For Your Practice:
This article looks at non-fasting and fasting lipid screening to determine whether it is worth additional patient efforts and possible patient non-compliance to have this testing done. In this cross-sectional study, children less than 12 years of age had fasted for varying amounts of time while children greater than 12 years fasted for 8 hours. This study controlled for age, weight status, gender, race, and ethnicity and looked independently at total cholesterol levels, HDL, LDL, and triglyceride levels based on fasting time. 12,744 children ages 3-17 (mean age 11) who had any lipid values drawn were enrolled in this study. The outcome shows that of the LDL and TG samples, almost 80% of these were from patients who fasted for varying amounts of time, whereas close to 50% of the HDL and TC levels were from patients who fasted >8hrs. As fasting time increased, triglyceride values decreased by a mean of 7mg/dL, whereas fasting increased LDL, HDL, and TC levels by 2-5 mg/dL. This study does note that overweight children (>85%) had greater fluctuation in lipid values with fasting than non-overweight children. Based on the results of this study, it may be worthwhile to simply draw lipid panels at routine visits and not require patients to make additional visits to laboratories in order to have this panel done. Furthermore, this article references that in adults, there is thought that non-fasting TG levels may be more predictive of future risks of myocardial infarction and death than fasting levels. Though this data is not as well researched in children, it seems that non-fasting non-HDL cholesterol may be used to predict future cardiovascular events. This study has several limitations, namely that it did not look at serial lipid panels after varying fasting times, nor did it directly measure LDL cholesterol levels. Furthermore, the distribution of fasting versus non fasting TG and LDL values is 20 versus 80% respectively, perhaps giving some unreliable data in these fields. Nevertheless, it seems that non-fasting lipid panel are of utility in pediatric patients, and by changing this standard, we may be able to reduce a barrier to care.
Submitted by: Cherie-Priya Dhar
Comment: Agreed. There is no question that returning for a fasting lipid panel is difficult, expensive and time-consuming for families who do comply, and yields lack of information for those who do not. Although as Dr. Dhar points out, there are limitations to the data, I am ready to embrace non-fasting lipid screening in my practice. LF

Neonatalogy:

Anderson et. al. Effect of delayed vs. early umbilical cord clamping on neonatal outcomes and iron status at 4 months: a randomised controlled trial." BMJ 2011;343:7157.
Summary and Implications For Your Practice:
A randomized control trial was conducted at a Swedish County Hospital that compared delayed cord clamping (at 3 minutes) versus early (less than 10 seconds) cord clamping. 400 full term infants of low risk pregnancies were included. Low risk pregnancies were defined as non-smoking, singleton pregnancy, term gestation (>37 weeks to <42 weeks), and cephalic vaginal delivery. Infants were randomized 1:1. Complete blood cell counts were drawn at 2 days of life and at 4 months of life. Iron studies were done at 4 months of life. Those with delayed cord clamping had a significantly higher (45% increase) mean ferritin concentration and a significantly lower prevalence of iron deficiency. Secondary outcomes showed a lower prevalence of neonatal anemia at 2 days of age with the number needed to treat of 20. There were no significant differences in postnatal respiratory symptoms, polycythemia, or hyperbilirubemia requiring phototherapy. The authors concluded that there seems to be benefit of delayed cord clamping for full term infants in order to prevent neonatal anemia and iron deficiency which may improve neurodevelopment. They suggest delayed cord clamping should be considered the standard of care in full term neonates with uncomplicated pregnancies. This article’s results may be useful in full term uncomplicated pregnancies. Delayed cord clamping would not be appropriate if the baby was not vigorous and needed resuscitation.
Submitted by: Emily Wiland
Comment: According to this data, it would make a lot of sense to hold off on clamping the cord immediately, except, as Dr. Wiland points out, when the infant requires immediate attention. LC

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