INVITED COMMENTARIES
Reflux-Associated Cough in Children: One Step Toward the Evidence Pietro Bagolan and Francesco Morini See ‘‘Intraesophageal Pressure Recording Improves the Detection of Cough During Multichannel Intraluminal Impedance Testing in Children’’ by Rosen et al on page 22.
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n children, gastroesophageal reflux disease (GERD) continues to be a frequent and challenging condition, with several open questions that relate both to lack of basic knowledge and nonoptimal diagnostic procedures. One aspect deserving particular attention is that of respiratory symptoms associated with GERD, including chronic cough. In a recent systematic review, Kahrilas et al (1) showed that, despite treatment with proton pump inhibitors or ranitidine, many patients continue to present with chronic cough, which was ascribed to GERD. Several reasons may explain these findings. Most reflux studies have used pH monitoring to detect GER that only selects acid reflux. Because cough can be associated also with nonacid reflux/aspiration, these patients may not demonstrate the expected clinical improvements with the use of antisecretory agents. The introduction of pH-multichannel intraluminal impedance (pH-MII) recordings, which allow the detection of both acid and nonacid reflux, has led to significant improvements in GER diagnosis and in the evaluation of children with associated respiratory symptoms (2). Cough recording has mainly relied on patient/parent recordings, which are subjective and may introduce significant biases. The patient/parent may not record the cough event or may not record it in a timely manner. Systems to make cough identification more objective include esophageal manometry and acoustic cough monitoring. Correct temporal identification between reflux episodes and cough events is crucial to certify the association between reflux and cough. Such identification will also define the direction of the association (reflux-cough or coughreflux), providing important pathogenetic information regarding the association. For example, Smith et al (3) found that 33% of patients with reflux-associated cough had a cough-reflux-cough sequence, suggesting a self-perpetuating cycle and leading to the development of interesting pathogenetic hypotheses. From the understanding of the pathogenesis of reflux-associated cough stems the identification of the optimal therapy. Patients with acid reflux–associated cough will probably benefit from antisecretory drugs, whereas for those with non-acid reflux–associated cough or cough-reflux sequence, different pharmacological or surgical treatments will need to be Received and accepted August 3, 2013. From the Department of Medical and Surgical Neonatology, Neonatal Surgery Unit, Bambino Gesu` Children’s Research Hospital, Rome, Italy. Address correspondence and reprint requests to Francesco Morini, MD, Neonatal Surgery Unit, Department of Medical and Surgical Neonatology, Bambino Gesu` Children’s Research Hospital, Piazza S. Onofrio, 4, 00165 Rome, Italy (e-mail: [email protected]). The authors report no conflicts of interest. Copyright # 2013 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition DOI: 10.1097/MPG.0b013e3182a8106e
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considered. Lastly, in those with cough not associated with GERD, the role of reflux will be discarded. Overall, this will avoid inappropriate treatment and reduce improper sanitary expenses. Studies exploring, without bias, the relation between cough and GERD in children are strongly needed. In this issue of the Journal of Pediatric Gastroenterology and Nutrition, Rosen et al (4) report on pH/MII associated with intraesophageal manometry to detect, objectively, cough episodes associated with GER. This is the second study on the subject in children, after that of Blondeau et al in 2011 (5). The most important findings were that esophageal manometry allowed better recognition of the cough episodes, doubling the number of identified events; showed that patient/parent recording of cough episodes had a significant delay as compared with esophageal manometry (possibly leading to incorrect pathogenetic interpretations); and led to a change in the diagnosis in 15% to 20% of patients. By coupling pH-MII and esophageal manometry, the authors improved the detection of reflux-associated cough, which may lead to better understand the pathogenesis of this association and to drive the treatment more appropriately. Despite the limitations of the study, which include the small number of patients; the insertion of a probe that requires the use of sedation in small children because of discomfort, possibly limiting its use; and the possible difficulties of differentiating cough from other reasons for increased intraesophageal pressure (eg, crying, throat clearing), the article by Rosen et al (4) represents a significant step toward understanding GERD and its associated atypical manifestations. More important, this work may also open the way to intervention studies designed to objectively define the success rate of treatments for patients with reflux-associated respiratory symptoms.
REFERENCES 1. Kahrilas PJ, Howden CW, Huges N, et al. Response of chronic cough to acid-suppressive therapy in patients with gastroesophageal reflux disease. Chest 2013;143:605–12. 2. Rosen R, Nurko S. The importance of multichannel intraluminal impedance in the evaluation of children with persistent respiratory symptoms. Am J Gastroenterol 2004;99:2452–8. 3. Smith JA, Decalmer S, Kelsall A, et al. Acoustic cough-reflux association in chronic cough: potential triggers and mechanisms. Gastroenterology 2010;139:754–62. 4. Rosen R, Amirault J, Giligan E, et al. Intraesophageal pressure recording improves the detection of cough during multichannel intraluminal impedance testing) in children. J Pediatr Gastroenterol Nutr 2014;58:22–6. 5. Blondeau K, Mertens V, Dupont L, et al. The relationship between gastroesophageal reflux and cough in children with chronic unexplained cough using combined impedance-pH-manometry recordings. Pediatr Pulmonol 2011;46:286–94.
Living Donor Liver Transplant in Pediatric Acute Liver Failure: An Important Option, But When Do We Use It? Robert H. Squires See ‘‘Improved Outcomes in Liver Transplantation in Children With Acute Liver Failure’’ by Oh et al on page 68.
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he article by Oh et al (1) in this issue of the Journal of Pediatric Gastroenterology and Nutrition highlights
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Copyright 2013 by ESPGHAN and NASPGHAN. Unauthorized reproduction of this article is prohibited.
Invited Commentaries challenges associated with clinical studies in pediatric acute liver failure (PALF). For instance, we are not provided characteristics or outcomes of children who did not receive liver transplantation (LT), nor of those who were listed for but did not receive LT. The thoroughness of the diagnostic evaluation for individual patients is unknown. Small numbers of patients distributed among risk factors, such as the molecular adsorbent recycling system use (n ¼ 3) and thrombocytopenia (n ¼ 7), make P values of uncertain clinical significance in this highly selected cohort. The authors do not articulate the complexity of LT decision making, and the limitations of organ availability add a unique element to those decisions. Also, the comparative cohort that allows the authors to say that outcomes have ‘‘improved’’ is not well defined. That said, the pediatric LT team at the Asan Medical Center in Seoul, Korea, must be congratulated for achieving the stated graft and patient outcomes following LT for PALF; however, I disagree that their findings should ‘‘lessen the ethical pressure’’ on individual candidates and donors. PALF is a rare, dynamic, frightful, and, at times, devastating worldwide condition that affects all age groups (2). Etiologies and outcomes vary by age, regional exposures, and resources (3). Treatment is generally supportive unless a diagnosis responsive to targeted therapy, such as acute acetaminophen/paracetamol toxicity, herpes simplex, or autoimmune marker–positive acute liver failure, is promptly identified. LT can be lifesaving, but it carries with it potential complications related to surgery and immunosuppression. To best use the precious resource of liver donation, whether it is from a living or a cadaveric donor, there should be a reasonable certainty the recipient will die or succumb to significant neurological damage without LT. In addition, one would not knowingly submit a child to LT who would have survived without LT, thereby subjecting both recipient and donor to unnecessary risks or limiting organ availability to others in need of LT. Unfortunately, present predictive models fall short in their ability to predict death (4–6). This is the result, in large part, of the fact that LT interrupts the natural history of PALF. The dynamic nature of PALF challenges our ability to predict outcome. We know that children, some with advanced encephalopathy, who meet PALF study criteria will survive with their native liver (2). We are familiar with the children listed for LT who would have received an organ had one become available, only to be removed from the list following clinical improvement. These experiences raise the possibility that a portion of children who receive LT for PALF may have survived with their native liver. Organ availability is enhanced for children with PALF with a living donor option (7). Because graft and patient survival following LT for PALF has improved, we must maintain vigilance to ensure that these children require LT to survive. To that end, ongoing efforts to identify clinical models that reliably predict patient death and survival as well as to identify those for whom LT would not Received and accepted August 3, 2013. From the Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology, and Nutrition, University of Pittsburgh School of Medicine, Pittsburgh, PA. Address correspondence and reprint requests to Robert H. Squires, MD, Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Children’s Hospital of Pittsburgh of UPMC, 4401 Penn Ave, FOB Room 6116, Pittsburgh, PA 15224 (e-mail: [email protected]). The author reports no conflicts of interest. Copyright # 2013 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition DOI: 10.1097/MPG.0b013e3182a81085
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improve long-term outcome (eg, individuals with systemic mitochondrial disease with neurological impairment) must continue.
REFERENCES 1. Oh SH, Kim KM, Kim DY, et al. Improved outcomes in liver transplantation in children with acute liver failure. J Pediatr Gastroenterol Nutr 2014;58:68–73. 2. Squires RH Jr, Shneider BL, Bucuvalas J, et al. Acute liver failure in children: the first 348 patients in the pediatric acute liver failure study group. J Pediatr 2006;148:652–8. 3. Squires RH Jr. Acute liver failure in children. Semin Liver Dis 2008;28:153–66. 4. Lu BR, Zhang S, Narkewicz MR, et al. Evaluation of the liver injury unit scoring system to predict survival in a multinational study of pediatric acute liver failure. J Pediatr 2013;162:1010–6. 5. Sundaram V, Shneider BL, Dhawan A, et al. King’s College Hospital criteria for non-acetaminophen induced acute liver failure in an international cohort of children. J Pediatr 2013;162:319–23. 6. Bucuvalas J, Filipovich L, Yazigi N, et al. Immunophenotype predicts outcome in pediatric acute liver failure. J Pediatr Gastroenterol Nutr 2013;56:311–5. 7. Lee WS, McKiernan P, Kelly DA. Etiology, outcome and prognostic indicators of childhood fulminant hepatic failure in the United Kingdom. J Pediatr Gastroenterol Nutr 2005;40:575–81.
Novel Methods for Training Future Pediatric Gastroenterologists Sarah Mueller Kadzielski and Harland S. Winter See ‘‘Challenge of Meeting Fellowship Procedural Guidelines in Therapeutic Endoscopy and Liver Biopsy’’ by Lentze on page 3 and ‘‘Challenges in Meeting Fellowship Procedural Guidelines in Pediatric Therapeutic Endoscopy and Liver Biopsy’’ by Lerner et al on page 27.
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ndoscopic procedures play important diagnostic and therapeutic roles in the practice of pediatric gastroenterology. The North American Society of Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN)’s guidelines for training in pediatric gastroenterology, published in 1999, were updated in 2013 (1,2). These guidelines include recommendations about the minimum number of procedures that should be performed to achieve competency during fellowship training. In this issue of the Journal of Pediatric Gastroenterology and Nutrition, Lerner et al (3) discuss challenges in meeting the number of recommended procedures. The authors collected data from 12 pediatric gastroenterology fellowship programs in the United States and used CPT codes and endoscopy databases to determine the number of procedures performed at each institution during a 3-year
Received and accepted September 12, 2013. From the MassGeneral Hospital for Children, Boston, MA. Address correspondence and reprint requests to Harland S. Winter, MD, MassGeneral Hospital for Children, 175 Cambridge St, CRPZ 5-560, Boston, MA 02114 (e-mail: [email protected]). The authors report no conflicts of interest. Copyright # 2013 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition DOI: 10.1097/MPG.0000000000000183
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period (2009–2011). They divided the number of procedures by the number of fellows at the institution to estimate the number of procedures performed by each fellow, and then compared these estimates to the NASPGHAN guidelines. From this sample of 12 fellowship programs, many did not have sufficient procedural volume to meet the requirements of the training guidelines. None of the programs met the minimum numbers from the 1999 guidelines. Although some of the requirements in the 2013 guidelines are less stringent, only 1 center met the thresholds for all procedures. This article highlights the challenges in meeting the minimum number of procedures recommended during training, which is 1 step in achieving competence. As the guidelines note, many people will need to exceed these minimum numbers before they are competent in a given procedure. Objectively assessing competency is an unmet need, which theoretically could be accomplished through direct observation using an assessment tool. The wellknown surgeon Atul Gawande wrote in The New Yorker about the importance of coaching and direct observation of surgeons in the operating room (4). Presumably, this concept could be adapted to procedural skills in gastroenterology. The NASPGHAN guideline from 2013 includes an assessment tool for endoscopy and colonoscopy. Quality metrics in adult gastroenterology include at least a 90% cecal intubation rate. As discussed in the NASPGHAN guidelines, these standards are based on studies of the learning curve in adult gastroenterology. For example, after 50 colonoscopies, trainees had cecal intubation rates exceeding 80% (5), but other studies have shown cecal intubation rates of 84% after 120 colonoscopies (6) and 90% after 140 colonoscopies (7). A larger regression analysis of 10 studies in adult gastroenterology fellows (n ¼ 189) reported a 90% cecal intubation rate after 341 colonoscopies (8); however, little is known about the learning curve for procedural competence in pediatric gastroenterology, and defining competency in therapeutic endoscopy techniques is difficult. In light of the challenges in meeting the minimum number of procedures suggested by NASPGHAN, the authors offer several suggestions to increase procedural experience. These include rotations with adult gastroenterologists, computer simulators, ex vivo animal models, and hands-on endoscopy courses. Only 25% of the pediatric gastroenterology fellowship programs they surveyed had a computer simulator, and logistical and scheduling constraints may make use difficult. Another instrument to complement traditional patient-based procedural training is the partial-task box trainer that has been developed and tested to teach endoscopy skills. This mechanical simulator is validated in pediatric gastroenterology and contains 5 elements that involve key endoscopic maneuvers (9). The modular system allows compartments to be interchanged to include additional skills, including advanced endoscopy and therapeutic techniques. The partial-task box trainer is affordable, as well as mobile, allowing fellows to use it when time permits. The box trainer is also useful in teaching basic endoscopic skills before novice fellows begin performing procedures on patients. In the future, simulators or the partial-task box trainer may be used to maintain procedural skills, improve skills for those who already have a more advanced skill set, or assess skills for licensing or credentialing purposes. Because therapeutic endoscopic procedures are adapted to pediatric patients, fellowship training must use innovative methods to learn, maintain, and assess skills. The article by Lerner et al raises concerns that pediatric gastroenterology fellows may not be performing enough procedures during their training. We must be innovative and critically evaluate how best to provide high-quality, safe patient care for children who may benefit from endoscopic evaluation and therapy as well as assess the skills of individuals who are providing endoscopic care. www.jpgn.org
Invited Commentaries
REFERENCES 1. Rudolph CD, Winter HS. NASPGN guidelines for training in pediatric gastroenterology. J Pediatr Gastroenterol Nutr 1999;29:S1–26. 2. Leichtner AM, Gillis LA, Gupta S, et al. NASPGHAN guidelines for training in pediatric gastroenterology. J Pediatr Gastroenterol Nutr 2013;56:S1–38. 3. Lerner DG, Li BU, Mamula P, et al. Challenges in meeting fellowship procedural guidelines in pediatric therapeutic endoscopy and liver biopsy. J Pediatr Gastroenterol Nutr 2014;58:27–33. 4. Gawande A. Personal best. New Yorker October 3, 2011. 5. Cass OW, Freeman ML, Peine CJ, et al. Objective evaluation of endoscopy skills during training. Ann Intern Med 1993;118:40–4. 6. Chak A, Cooper GS, Blades EW, et al. Prospective assessment of colonoscopic intubation skills in trainees. Gastrointest Endosc 1996;44:54–7. 7. Cass OW, Freeman ML, Cohen J, et al. Acquisition of competency in endoscopic skills (ACES) during training: a multicenter study. Gastrointest Endosc 1996;43:308. 8. Cass OW. Training to competence in gastrointestinal endoscopy: a plea for continuous measuring of objective end points. Endoscopy 1999; 31:751–4. 9. Kadzielski S, Jirapinyo P, Thompson C. Validation of a part-task training box for endoscopic skill assessment in pediatric gastroenterology. Gastroint Endosc 2013;77:SAB129–30.
Challenge of Meeting Fellowship Procedural Guidelines in Therapeutic Endoscopy and Liver Biopsy Michael J. Lentze See‘‘Novel Methods for Training Future Pediatric Gastroenterologists’’ by Kadzielski and Winter on page 2 and ‘‘Challenges in Meeting Fellowship Procedural Guidelines in Pediatric Therapeutic Endoscopy and Liver Biopsy’’ by Lerner et al on page 27.
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raining guidelines for pediatric gastroenterology, hepatology, and nutrition are assembled by careful surveillance of society committees about contents, number of procedures, and duration of training. Core procedures in pediatric gastroenterology are procedural endoscopies and liver biopsies. The North American Society of Pediatric Gastroenterology, Hepatology, and Nutrition has adapted its original guidelines from 1999 (1) to new recommendation in 2013 (2) toward a 3-year training period in this subspecialty. To answer the critical question of whether fellows in pediatric gastroenterology in the United States are meeting these requirements, Lerner et al (3) collected data from 12 gastroenterology fellowship programs in the United States spanning the years
Received and accepted September 12, 2013. From the Zentrum fu¨r Kinderheilkunde, Universita¨tsklinikum Bonn, Bonn, Germany. Address correspondence and reprint requests to Michael J. Lentze, Professor Emeritus of Pediatrics, Zentrum fu¨r Kinderheilkunde, Universita¨tsklinikum Bonn, Adenauerallee 119, D-53113 Bonn, Germany (e-mail: [email protected]). The authors report no conflicts of interest. Copyright # 2013 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition DOI: 10.1097/MPG.0000000000000182
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Copyright 2013 by ESPGHAN and NASPGHAN. Unauthorized reproduction of this article is prohibited.
Invited Commentaries 2009–2011 on specialized GI procedures. Even in view of the guidelines of 1999 and 2013, the results showed a large variability of outcomes within programs and centers. Whereas none of the centers were able to provide sufficient opportunities to meet the 1999 guidelines for control of nonvariceal bleeding, just 1 center achieved this goal under the 2013 guidelines. Under the 1999 guidelines, no centers were able to meet thresholds for polypectomy and control of nonvariceal bleeding. As per the 2013 guidelines, the percentage of centers achieving the threshold of polypectomy increased by 67%. In 42% of centers, training in percutaneous endoscopic gastrostomy placement was not available. Taking together the results of this survey, the situation of practical training in pediatric gastroenterology in the United States since 1999 may not have really improved; however, smaller centers had a better outcome than bigger centers because of the higher number of fellows competing for procedures. This situation provokes the fundamental question as to what we should implement to guarantee enough practical training for later good and experienced pediatric gastroenterologists. Of course, not only quantities or numbers of procedures but also quality of training is a prerequisite for good training. Particularly for some of the procedures, a minimum quantity is absolutely required to gain enough basic experience such as in the control of bleeding, placements of percutaneous endoscopic gastrostomies, esophageal, pyloric, and duodenal stricture dilatation. Ancillary training modalities could be a path in the future combined with a standardized logging system or audit of procedural volumes. The logging system could be similar to that of surgical subspecialties, where a given number of procedures need to be documented. Otherwise, board examinations could not be applied for. The obvious solution for additional ancillary training modalities is the closer collaboration with adult gastroenterology, where level 1 up to level 3 procedures can be learned in all programs and centers. Alternatively, external endoscopy courses such as the American Society for Gastrointestinal Endoscopy/North American Society of Pediatric Gastroenterology, Hepatology, and Nutrition or European Society of Pediatric Gastroenterology, Hepatology, and Nutrition endoscopy courses may be effective to overcome gaps in local training. New eras like a case-based pediatric gastroenterology online curricula may change overall learning and teaching of fellows (4), but practical learning of procedures can only be achieved on endoscopy simulators or patients. As our subspecialty becomes technically more challenging and complex, more collected data about the success of our practical teaching programs would be desirable, particularly also in the 2 other important fields that are pediatric hepatology (5) and nutrition. Our American colleagues are privileged to have outcome data of training for pediatric gastroenterology because of their guidelines. In Europe, we are far from being that fortunate. Owing to the large variety of medical legislation within the European countries, a uniform European standardized guideline for training in pediatric gastroenterology, hepatology, and nutrition is not in sight. Since the appearance of the European Society of Pediatric Gastroenterology, Hepatology, and Nutrition training syllabus in pediatric gastroenterology, hepatology, and nutrition by Milla in 2002 (6), some European countries have adopted the syllabus in part as national regulations, others not at all. The European Union has made considerable progress in acknowledging medical subspecialty diplomas among its member states, but not in installing standardized European training guidelines. The European Union of Medical Specialists (www.uems.net) has moved into the training of medical specialists. Among many other fields, adult gastroenterology and pediatrics are in their focus, but so far pediatric gastroenterology is not. In the educational activities of the European Academy of Paediatrics (www.eapaediatrics.eu), many working
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groups have been involved in developing training modules for pediatric disciplines, except pediatric gastroenterology, hepatology, and nutrition. Therefore, we have to wait until we are able to have our own European outcome data as to how well fellows are trained in our subspecialties.
REFERENCES 1. Rudolph CD, Winter HS. NASPGN guidelines for training in pediatric gastroenterology. J Pediatr Gastroenterol Nutr 1999;29 (suppl 1):S1–26. 2. Leichtner AM, Gillis LA, Gupta S, et al. NASPGHAN guidelines for training in pediatric gastroenterology. J Pediatr Gastroenterol Nutr 2013;56 (suppl 1):S1–38. 3. Lerner DG, Li BU, Mamula P, et al. Challenges in meeting fellowship procedural guidelines in pediatric therapeutic endoscopy and liver biopsy. J Pediatr Gastroenterol Nutr 2014;58:27–33. 4. Feist M, Ciccarelli M, McFerron BA, et al. Methods and effects of a casebased pediatric gastroenterology online curriculum. J Pediatr Gastroenterol Nutr 2013;56:161–5. 5. Balistreri WF. Growth and development of a new subspecialty: pediatric hepatology. Hepatology 2013;58:458–76. 6. Milla P. Special report. The European training syllabus in pediatric gastroenterology, hepatology, and nutrition. J Pediatr Gastroenteroloand Nutr 2002;34:111–5.
An Innovative Investigation Into the Etiology of Feeding Intolerance in Preterm Infants Madalynn Neu See ‘‘Relations Between Feeding Intolerance and Stress Biomarkers in Preterm Infants’’ by Moore et al in the September 2013 issue (JPGN 57:356–62).
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eeding intolerance (FI) is a common problem in preterm infants who require neonatal intensive care (1). It is a potentially serious issue that delays hospital discharge and can result in life-threatening conditions such as necrotizing enterocolitis (NEC) and intestinal perforation (2). Thus, there is much interest in understanding and preventing FI. A commonly used and investigated intervention is the early initiation of trophic feedings (minimal amounts of formula or breast milk). In a recent meta-analysis, however, evidence did not favor early trophic feedings over parenteral nutrition as a means of enhancing growth, treating FI, or preventing NEC (3). Improved understanding of the etiology of FI would assist in developing effective guidelines for preventing and treating the condition. One theory proposed as a cause of FI is Received May 16, 2013; accepted September 20, 2013. From the University of Colorado Anschutz Medical Campus, College of Nursing, Aurora, CO. Address correspondence and reprint requests to Madalynn Neu, PhD, RN, Assistant Professor, University of Colorado Anschutz Medical Campus, College of Nursing, 13120 E 19th Ave, Aurora, CO 80045 (e-mail: [email protected]). The authors report no conflicts of interest. Copyright # 2013 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition DOI: 10.1097/MPG.0000000000000188
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the lack of beneficial microbiota (important in gastrointestinal function and immunity) in the gut of the preterm infant. Unfortunately, the frequent use of antibiotics in the neonatal intensive care unit further depletes beneficial microbiota. A deficiency in these beneficial organisms can result in aberrant bacterial colonization (4). Thus, the use of probiotics has been proposed as a way to prevent FI (4). Another theory is based on allostasis and allostatic load (5). Moore et al (6) in the September 2013 issue of the Journal of Pediatric Gastroenterology and Nutrition described an innovative preliminary investigation for the etiology of FI, based on the allostasis/allostatic load framework. This study examined demographic characteristics, medical factors, and biomarkers in 31 infants at 4 time points during 14 days as predictors of infants (
Reflux-Associated Cough in Children: One Step Toward the Evidence Pietro Bagolan and Francesco Morini See ‘‘Intraesophageal Pressure Recording Improves the Detection of Cough During Multichannel Intraluminal Impedance Testing in Children’’ by Rosen et al on page 22.
I
n children, gastroesophageal reflux disease (GERD) continues to be a frequent and challenging condition, with several open questions that relate both to lack of basic knowledge and nonoptimal diagnostic procedures. One aspect deserving particular attention is that of respiratory symptoms associated with GERD, including chronic cough. In a recent systematic review, Kahrilas et al (1) showed that, despite treatment with proton pump inhibitors or ranitidine, many patients continue to present with chronic cough, which was ascribed to GERD. Several reasons may explain these findings. Most reflux studies have used pH monitoring to detect GER that only selects acid reflux. Because cough can be associated also with nonacid reflux/aspiration, these patients may not demonstrate the expected clinical improvements with the use of antisecretory agents. The introduction of pH-multichannel intraluminal impedance (pH-MII) recordings, which allow the detection of both acid and nonacid reflux, has led to significant improvements in GER diagnosis and in the evaluation of children with associated respiratory symptoms (2). Cough recording has mainly relied on patient/parent recordings, which are subjective and may introduce significant biases. The patient/parent may not record the cough event or may not record it in a timely manner. Systems to make cough identification more objective include esophageal manometry and acoustic cough monitoring. Correct temporal identification between reflux episodes and cough events is crucial to certify the association between reflux and cough. Such identification will also define the direction of the association (reflux-cough or coughreflux), providing important pathogenetic information regarding the association. For example, Smith et al (3) found that 33% of patients with reflux-associated cough had a cough-reflux-cough sequence, suggesting a self-perpetuating cycle and leading to the development of interesting pathogenetic hypotheses. From the understanding of the pathogenesis of reflux-associated cough stems the identification of the optimal therapy. Patients with acid reflux–associated cough will probably benefit from antisecretory drugs, whereas for those with non-acid reflux–associated cough or cough-reflux sequence, different pharmacological or surgical treatments will need to be Received and accepted August 3, 2013. From the Department of Medical and Surgical Neonatology, Neonatal Surgery Unit, Bambino Gesu` Children’s Research Hospital, Rome, Italy. Address correspondence and reprint requests to Francesco Morini, MD, Neonatal Surgery Unit, Department of Medical and Surgical Neonatology, Bambino Gesu` Children’s Research Hospital, Piazza S. Onofrio, 4, 00165 Rome, Italy (e-mail: [email protected]). The authors report no conflicts of interest. Copyright # 2013 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition DOI: 10.1097/MPG.0b013e3182a8106e
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considered. Lastly, in those with cough not associated with GERD, the role of reflux will be discarded. Overall, this will avoid inappropriate treatment and reduce improper sanitary expenses. Studies exploring, without bias, the relation between cough and GERD in children are strongly needed. In this issue of the Journal of Pediatric Gastroenterology and Nutrition, Rosen et al (4) report on pH/MII associated with intraesophageal manometry to detect, objectively, cough episodes associated with GER. This is the second study on the subject in children, after that of Blondeau et al in 2011 (5). The most important findings were that esophageal manometry allowed better recognition of the cough episodes, doubling the number of identified events; showed that patient/parent recording of cough episodes had a significant delay as compared with esophageal manometry (possibly leading to incorrect pathogenetic interpretations); and led to a change in the diagnosis in 15% to 20% of patients. By coupling pH-MII and esophageal manometry, the authors improved the detection of reflux-associated cough, which may lead to better understand the pathogenesis of this association and to drive the treatment more appropriately. Despite the limitations of the study, which include the small number of patients; the insertion of a probe that requires the use of sedation in small children because of discomfort, possibly limiting its use; and the possible difficulties of differentiating cough from other reasons for increased intraesophageal pressure (eg, crying, throat clearing), the article by Rosen et al (4) represents a significant step toward understanding GERD and its associated atypical manifestations. More important, this work may also open the way to intervention studies designed to objectively define the success rate of treatments for patients with reflux-associated respiratory symptoms.
REFERENCES 1. Kahrilas PJ, Howden CW, Huges N, et al. Response of chronic cough to acid-suppressive therapy in patients with gastroesophageal reflux disease. Chest 2013;143:605–12. 2. Rosen R, Nurko S. The importance of multichannel intraluminal impedance in the evaluation of children with persistent respiratory symptoms. Am J Gastroenterol 2004;99:2452–8. 3. Smith JA, Decalmer S, Kelsall A, et al. Acoustic cough-reflux association in chronic cough: potential triggers and mechanisms. Gastroenterology 2010;139:754–62. 4. Rosen R, Amirault J, Giligan E, et al. Intraesophageal pressure recording improves the detection of cough during multichannel intraluminal impedance testing) in children. J Pediatr Gastroenterol Nutr 2014;58:22–6. 5. Blondeau K, Mertens V, Dupont L, et al. The relationship between gastroesophageal reflux and cough in children with chronic unexplained cough using combined impedance-pH-manometry recordings. Pediatr Pulmonol 2011;46:286–94.
Living Donor Liver Transplant in Pediatric Acute Liver Failure: An Important Option, But When Do We Use It? Robert H. Squires See ‘‘Improved Outcomes in Liver Transplantation in Children With Acute Liver Failure’’ by Oh et al on page 68.
T
he article by Oh et al (1) in this issue of the Journal of Pediatric Gastroenterology and Nutrition highlights
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Copyright 2013 by ESPGHAN and NASPGHAN. Unauthorized reproduction of this article is prohibited.
Invited Commentaries challenges associated with clinical studies in pediatric acute liver failure (PALF). For instance, we are not provided characteristics or outcomes of children who did not receive liver transplantation (LT), nor of those who were listed for but did not receive LT. The thoroughness of the diagnostic evaluation for individual patients is unknown. Small numbers of patients distributed among risk factors, such as the molecular adsorbent recycling system use (n ¼ 3) and thrombocytopenia (n ¼ 7), make P values of uncertain clinical significance in this highly selected cohort. The authors do not articulate the complexity of LT decision making, and the limitations of organ availability add a unique element to those decisions. Also, the comparative cohort that allows the authors to say that outcomes have ‘‘improved’’ is not well defined. That said, the pediatric LT team at the Asan Medical Center in Seoul, Korea, must be congratulated for achieving the stated graft and patient outcomes following LT for PALF; however, I disagree that their findings should ‘‘lessen the ethical pressure’’ on individual candidates and donors. PALF is a rare, dynamic, frightful, and, at times, devastating worldwide condition that affects all age groups (2). Etiologies and outcomes vary by age, regional exposures, and resources (3). Treatment is generally supportive unless a diagnosis responsive to targeted therapy, such as acute acetaminophen/paracetamol toxicity, herpes simplex, or autoimmune marker–positive acute liver failure, is promptly identified. LT can be lifesaving, but it carries with it potential complications related to surgery and immunosuppression. To best use the precious resource of liver donation, whether it is from a living or a cadaveric donor, there should be a reasonable certainty the recipient will die or succumb to significant neurological damage without LT. In addition, one would not knowingly submit a child to LT who would have survived without LT, thereby subjecting both recipient and donor to unnecessary risks or limiting organ availability to others in need of LT. Unfortunately, present predictive models fall short in their ability to predict death (4–6). This is the result, in large part, of the fact that LT interrupts the natural history of PALF. The dynamic nature of PALF challenges our ability to predict outcome. We know that children, some with advanced encephalopathy, who meet PALF study criteria will survive with their native liver (2). We are familiar with the children listed for LT who would have received an organ had one become available, only to be removed from the list following clinical improvement. These experiences raise the possibility that a portion of children who receive LT for PALF may have survived with their native liver. Organ availability is enhanced for children with PALF with a living donor option (7). Because graft and patient survival following LT for PALF has improved, we must maintain vigilance to ensure that these children require LT to survive. To that end, ongoing efforts to identify clinical models that reliably predict patient death and survival as well as to identify those for whom LT would not Received and accepted August 3, 2013. From the Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology, and Nutrition, University of Pittsburgh School of Medicine, Pittsburgh, PA. Address correspondence and reprint requests to Robert H. Squires, MD, Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Children’s Hospital of Pittsburgh of UPMC, 4401 Penn Ave, FOB Room 6116, Pittsburgh, PA 15224 (e-mail: [email protected]). The author reports no conflicts of interest. Copyright # 2013 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition DOI: 10.1097/MPG.0b013e3182a81085
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improve long-term outcome (eg, individuals with systemic mitochondrial disease with neurological impairment) must continue.
REFERENCES 1. Oh SH, Kim KM, Kim DY, et al. Improved outcomes in liver transplantation in children with acute liver failure. J Pediatr Gastroenterol Nutr 2014;58:68–73. 2. Squires RH Jr, Shneider BL, Bucuvalas J, et al. Acute liver failure in children: the first 348 patients in the pediatric acute liver failure study group. J Pediatr 2006;148:652–8. 3. Squires RH Jr. Acute liver failure in children. Semin Liver Dis 2008;28:153–66. 4. Lu BR, Zhang S, Narkewicz MR, et al. Evaluation of the liver injury unit scoring system to predict survival in a multinational study of pediatric acute liver failure. J Pediatr 2013;162:1010–6. 5. Sundaram V, Shneider BL, Dhawan A, et al. King’s College Hospital criteria for non-acetaminophen induced acute liver failure in an international cohort of children. J Pediatr 2013;162:319–23. 6. Bucuvalas J, Filipovich L, Yazigi N, et al. Immunophenotype predicts outcome in pediatric acute liver failure. J Pediatr Gastroenterol Nutr 2013;56:311–5. 7. Lee WS, McKiernan P, Kelly DA. Etiology, outcome and prognostic indicators of childhood fulminant hepatic failure in the United Kingdom. J Pediatr Gastroenterol Nutr 2005;40:575–81.
Novel Methods for Training Future Pediatric Gastroenterologists Sarah Mueller Kadzielski and Harland S. Winter See ‘‘Challenge of Meeting Fellowship Procedural Guidelines in Therapeutic Endoscopy and Liver Biopsy’’ by Lentze on page 3 and ‘‘Challenges in Meeting Fellowship Procedural Guidelines in Pediatric Therapeutic Endoscopy and Liver Biopsy’’ by Lerner et al on page 27.
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ndoscopic procedures play important diagnostic and therapeutic roles in the practice of pediatric gastroenterology. The North American Society of Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN)’s guidelines for training in pediatric gastroenterology, published in 1999, were updated in 2013 (1,2). These guidelines include recommendations about the minimum number of procedures that should be performed to achieve competency during fellowship training. In this issue of the Journal of Pediatric Gastroenterology and Nutrition, Lerner et al (3) discuss challenges in meeting the number of recommended procedures. The authors collected data from 12 pediatric gastroenterology fellowship programs in the United States and used CPT codes and endoscopy databases to determine the number of procedures performed at each institution during a 3-year
Received and accepted September 12, 2013. From the MassGeneral Hospital for Children, Boston, MA. Address correspondence and reprint requests to Harland S. Winter, MD, MassGeneral Hospital for Children, 175 Cambridge St, CRPZ 5-560, Boston, MA 02114 (e-mail: [email protected]). The authors report no conflicts of interest. Copyright # 2013 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition DOI: 10.1097/MPG.0000000000000183
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period (2009–2011). They divided the number of procedures by the number of fellows at the institution to estimate the number of procedures performed by each fellow, and then compared these estimates to the NASPGHAN guidelines. From this sample of 12 fellowship programs, many did not have sufficient procedural volume to meet the requirements of the training guidelines. None of the programs met the minimum numbers from the 1999 guidelines. Although some of the requirements in the 2013 guidelines are less stringent, only 1 center met the thresholds for all procedures. This article highlights the challenges in meeting the minimum number of procedures recommended during training, which is 1 step in achieving competence. As the guidelines note, many people will need to exceed these minimum numbers before they are competent in a given procedure. Objectively assessing competency is an unmet need, which theoretically could be accomplished through direct observation using an assessment tool. The wellknown surgeon Atul Gawande wrote in The New Yorker about the importance of coaching and direct observation of surgeons in the operating room (4). Presumably, this concept could be adapted to procedural skills in gastroenterology. The NASPGHAN guideline from 2013 includes an assessment tool for endoscopy and colonoscopy. Quality metrics in adult gastroenterology include at least a 90% cecal intubation rate. As discussed in the NASPGHAN guidelines, these standards are based on studies of the learning curve in adult gastroenterology. For example, after 50 colonoscopies, trainees had cecal intubation rates exceeding 80% (5), but other studies have shown cecal intubation rates of 84% after 120 colonoscopies (6) and 90% after 140 colonoscopies (7). A larger regression analysis of 10 studies in adult gastroenterology fellows (n ¼ 189) reported a 90% cecal intubation rate after 341 colonoscopies (8); however, little is known about the learning curve for procedural competence in pediatric gastroenterology, and defining competency in therapeutic endoscopy techniques is difficult. In light of the challenges in meeting the minimum number of procedures suggested by NASPGHAN, the authors offer several suggestions to increase procedural experience. These include rotations with adult gastroenterologists, computer simulators, ex vivo animal models, and hands-on endoscopy courses. Only 25% of the pediatric gastroenterology fellowship programs they surveyed had a computer simulator, and logistical and scheduling constraints may make use difficult. Another instrument to complement traditional patient-based procedural training is the partial-task box trainer that has been developed and tested to teach endoscopy skills. This mechanical simulator is validated in pediatric gastroenterology and contains 5 elements that involve key endoscopic maneuvers (9). The modular system allows compartments to be interchanged to include additional skills, including advanced endoscopy and therapeutic techniques. The partial-task box trainer is affordable, as well as mobile, allowing fellows to use it when time permits. The box trainer is also useful in teaching basic endoscopic skills before novice fellows begin performing procedures on patients. In the future, simulators or the partial-task box trainer may be used to maintain procedural skills, improve skills for those who already have a more advanced skill set, or assess skills for licensing or credentialing purposes. Because therapeutic endoscopic procedures are adapted to pediatric patients, fellowship training must use innovative methods to learn, maintain, and assess skills. The article by Lerner et al raises concerns that pediatric gastroenterology fellows may not be performing enough procedures during their training. We must be innovative and critically evaluate how best to provide high-quality, safe patient care for children who may benefit from endoscopic evaluation and therapy as well as assess the skills of individuals who are providing endoscopic care. www.jpgn.org
Invited Commentaries
REFERENCES 1. Rudolph CD, Winter HS. NASPGN guidelines for training in pediatric gastroenterology. J Pediatr Gastroenterol Nutr 1999;29:S1–26. 2. Leichtner AM, Gillis LA, Gupta S, et al. NASPGHAN guidelines for training in pediatric gastroenterology. J Pediatr Gastroenterol Nutr 2013;56:S1–38. 3. Lerner DG, Li BU, Mamula P, et al. Challenges in meeting fellowship procedural guidelines in pediatric therapeutic endoscopy and liver biopsy. J Pediatr Gastroenterol Nutr 2014;58:27–33. 4. Gawande A. Personal best. New Yorker October 3, 2011. 5. Cass OW, Freeman ML, Peine CJ, et al. Objective evaluation of endoscopy skills during training. Ann Intern Med 1993;118:40–4. 6. Chak A, Cooper GS, Blades EW, et al. Prospective assessment of colonoscopic intubation skills in trainees. Gastrointest Endosc 1996;44:54–7. 7. Cass OW, Freeman ML, Cohen J, et al. Acquisition of competency in endoscopic skills (ACES) during training: a multicenter study. Gastrointest Endosc 1996;43:308. 8. Cass OW. Training to competence in gastrointestinal endoscopy: a plea for continuous measuring of objective end points. Endoscopy 1999; 31:751–4. 9. Kadzielski S, Jirapinyo P, Thompson C. Validation of a part-task training box for endoscopic skill assessment in pediatric gastroenterology. Gastroint Endosc 2013;77:SAB129–30.
Challenge of Meeting Fellowship Procedural Guidelines in Therapeutic Endoscopy and Liver Biopsy Michael J. Lentze See‘‘Novel Methods for Training Future Pediatric Gastroenterologists’’ by Kadzielski and Winter on page 2 and ‘‘Challenges in Meeting Fellowship Procedural Guidelines in Pediatric Therapeutic Endoscopy and Liver Biopsy’’ by Lerner et al on page 27.
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raining guidelines for pediatric gastroenterology, hepatology, and nutrition are assembled by careful surveillance of society committees about contents, number of procedures, and duration of training. Core procedures in pediatric gastroenterology are procedural endoscopies and liver biopsies. The North American Society of Pediatric Gastroenterology, Hepatology, and Nutrition has adapted its original guidelines from 1999 (1) to new recommendation in 2013 (2) toward a 3-year training period in this subspecialty. To answer the critical question of whether fellows in pediatric gastroenterology in the United States are meeting these requirements, Lerner et al (3) collected data from 12 gastroenterology fellowship programs in the United States spanning the years
Received and accepted September 12, 2013. From the Zentrum fu¨r Kinderheilkunde, Universita¨tsklinikum Bonn, Bonn, Germany. Address correspondence and reprint requests to Michael J. Lentze, Professor Emeritus of Pediatrics, Zentrum fu¨r Kinderheilkunde, Universita¨tsklinikum Bonn, Adenauerallee 119, D-53113 Bonn, Germany (e-mail: [email protected]). The authors report no conflicts of interest. Copyright # 2013 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition DOI: 10.1097/MPG.0000000000000182
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Copyright 2013 by ESPGHAN and NASPGHAN. Unauthorized reproduction of this article is prohibited.
Invited Commentaries 2009–2011 on specialized GI procedures. Even in view of the guidelines of 1999 and 2013, the results showed a large variability of outcomes within programs and centers. Whereas none of the centers were able to provide sufficient opportunities to meet the 1999 guidelines for control of nonvariceal bleeding, just 1 center achieved this goal under the 2013 guidelines. Under the 1999 guidelines, no centers were able to meet thresholds for polypectomy and control of nonvariceal bleeding. As per the 2013 guidelines, the percentage of centers achieving the threshold of polypectomy increased by 67%. In 42% of centers, training in percutaneous endoscopic gastrostomy placement was not available. Taking together the results of this survey, the situation of practical training in pediatric gastroenterology in the United States since 1999 may not have really improved; however, smaller centers had a better outcome than bigger centers because of the higher number of fellows competing for procedures. This situation provokes the fundamental question as to what we should implement to guarantee enough practical training for later good and experienced pediatric gastroenterologists. Of course, not only quantities or numbers of procedures but also quality of training is a prerequisite for good training. Particularly for some of the procedures, a minimum quantity is absolutely required to gain enough basic experience such as in the control of bleeding, placements of percutaneous endoscopic gastrostomies, esophageal, pyloric, and duodenal stricture dilatation. Ancillary training modalities could be a path in the future combined with a standardized logging system or audit of procedural volumes. The logging system could be similar to that of surgical subspecialties, where a given number of procedures need to be documented. Otherwise, board examinations could not be applied for. The obvious solution for additional ancillary training modalities is the closer collaboration with adult gastroenterology, where level 1 up to level 3 procedures can be learned in all programs and centers. Alternatively, external endoscopy courses such as the American Society for Gastrointestinal Endoscopy/North American Society of Pediatric Gastroenterology, Hepatology, and Nutrition or European Society of Pediatric Gastroenterology, Hepatology, and Nutrition endoscopy courses may be effective to overcome gaps in local training. New eras like a case-based pediatric gastroenterology online curricula may change overall learning and teaching of fellows (4), but practical learning of procedures can only be achieved on endoscopy simulators or patients. As our subspecialty becomes technically more challenging and complex, more collected data about the success of our practical teaching programs would be desirable, particularly also in the 2 other important fields that are pediatric hepatology (5) and nutrition. Our American colleagues are privileged to have outcome data of training for pediatric gastroenterology because of their guidelines. In Europe, we are far from being that fortunate. Owing to the large variety of medical legislation within the European countries, a uniform European standardized guideline for training in pediatric gastroenterology, hepatology, and nutrition is not in sight. Since the appearance of the European Society of Pediatric Gastroenterology, Hepatology, and Nutrition training syllabus in pediatric gastroenterology, hepatology, and nutrition by Milla in 2002 (6), some European countries have adopted the syllabus in part as national regulations, others not at all. The European Union has made considerable progress in acknowledging medical subspecialty diplomas among its member states, but not in installing standardized European training guidelines. The European Union of Medical Specialists (www.uems.net) has moved into the training of medical specialists. Among many other fields, adult gastroenterology and pediatrics are in their focus, but so far pediatric gastroenterology is not. In the educational activities of the European Academy of Paediatrics (www.eapaediatrics.eu), many working
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groups have been involved in developing training modules for pediatric disciplines, except pediatric gastroenterology, hepatology, and nutrition. Therefore, we have to wait until we are able to have our own European outcome data as to how well fellows are trained in our subspecialties.
REFERENCES 1. Rudolph CD, Winter HS. NASPGN guidelines for training in pediatric gastroenterology. J Pediatr Gastroenterol Nutr 1999;29 (suppl 1):S1–26. 2. Leichtner AM, Gillis LA, Gupta S, et al. NASPGHAN guidelines for training in pediatric gastroenterology. J Pediatr Gastroenterol Nutr 2013;56 (suppl 1):S1–38. 3. Lerner DG, Li BU, Mamula P, et al. Challenges in meeting fellowship procedural guidelines in pediatric therapeutic endoscopy and liver biopsy. J Pediatr Gastroenterol Nutr 2014;58:27–33. 4. Feist M, Ciccarelli M, McFerron BA, et al. Methods and effects of a casebased pediatric gastroenterology online curriculum. J Pediatr Gastroenterol Nutr 2013;56:161–5. 5. Balistreri WF. Growth and development of a new subspecialty: pediatric hepatology. Hepatology 2013;58:458–76. 6. Milla P. Special report. The European training syllabus in pediatric gastroenterology, hepatology, and nutrition. J Pediatr Gastroenteroloand Nutr 2002;34:111–5.
An Innovative Investigation Into the Etiology of Feeding Intolerance in Preterm Infants Madalynn Neu See ‘‘Relations Between Feeding Intolerance and Stress Biomarkers in Preterm Infants’’ by Moore et al in the September 2013 issue (JPGN 57:356–62).
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eeding intolerance (FI) is a common problem in preterm infants who require neonatal intensive care (1). It is a potentially serious issue that delays hospital discharge and can result in life-threatening conditions such as necrotizing enterocolitis (NEC) and intestinal perforation (2). Thus, there is much interest in understanding and preventing FI. A commonly used and investigated intervention is the early initiation of trophic feedings (minimal amounts of formula or breast milk). In a recent meta-analysis, however, evidence did not favor early trophic feedings over parenteral nutrition as a means of enhancing growth, treating FI, or preventing NEC (3). Improved understanding of the etiology of FI would assist in developing effective guidelines for preventing and treating the condition. One theory proposed as a cause of FI is Received May 16, 2013; accepted September 20, 2013. From the University of Colorado Anschutz Medical Campus, College of Nursing, Aurora, CO. Address correspondence and reprint requests to Madalynn Neu, PhD, RN, Assistant Professor, University of Colorado Anschutz Medical Campus, College of Nursing, 13120 E 19th Ave, Aurora, CO 80045 (e-mail: [email protected]). The authors report no conflicts of interest. Copyright # 2013 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition DOI: 10.1097/MPG.0000000000000188
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the lack of beneficial microbiota (important in gastrointestinal function and immunity) in the gut of the preterm infant. Unfortunately, the frequent use of antibiotics in the neonatal intensive care unit further depletes beneficial microbiota. A deficiency in these beneficial organisms can result in aberrant bacterial colonization (4). Thus, the use of probiotics has been proposed as a way to prevent FI (4). Another theory is based on allostasis and allostatic load (5). Moore et al (6) in the September 2013 issue of the Journal of Pediatric Gastroenterology and Nutrition described an innovative preliminary investigation for the etiology of FI, based on the allostasis/allostatic load framework. This study examined demographic characteristics, medical factors, and biomarkers in 31 infants at 4 time points during 14 days as predictors of infants (
