Jyoti Ramakrishna

High sustained virologic response rates in children with chronic hepatitis C receiving peginterferon alfa-2b plus ribavirin

BACKGROUND & AIMSnPegylated interferon (PEG-IFN) alfa-2b plus ribavirin (RBV) is the standard of care for adults with chronic hepatitis C but was not approved for the treatment of children at the time of this study. The aim of this study was to evaluate the efficacy and safety of PEG-IFN alfa-2b plus RBV in children.nnnMETHODSnChildren and adolescents ages 3-17 years were treated with PEG-IFN alfa-2b (60microg/m(2)/week) plus RBV (15mg/kg/day). The duration of therapy was 24 weeks for genotype (G) 2 and G3 patients with low viral load (<600,000IU/ml) and 48 weeks for G1, G4, and G3 with high viral load (>or=600,000IU/ml). The primary end point was sustained virologic response (SVR), defined as undetectable hepatitis C virus (HCV) RNA 24 weeks after completion of therapy.nnnRESULTSnSVR was attained by 70 (65%) children. Genotype was the main predictor of response: G1, 53%; G2/3, 93%; G4, 80%. SVRs were similar in younger and older children. Baseline viral load was the main predictor of response in the G1 cohort. No new safety signals were identified, and adverse events (AEs) were generally mild or moderate in severity. Dose was modified because of AEs in 25% of children; 1 child discontinued because of an AE (thrombocytopenia). No serious AEs related to study drugs were reported.nnnCONCLUSIONnTherapy with PEG-IFN alfa-2b plus RBV in children and adolescents with chronic hepatitis C offers favorable efficacy, reduced injection frequency, and an acceptable safety profile.

Combined use of cyclosporine and azathioprine or 6-mercaptopurine in pediatric inflammatory bowel disease.

The aim of this study was to assess whether in steroid-resistant patients with pediatric inflammatory bowel disease (IBD) a combination of cyclosporine and azathioprine (or 6-mercaptopurine) could induce remission and subsequently permit maintenance on azathioprine/6-mercaptopurine as the sole immunosuppressive agent. Two boys and six girls (six with ulcerative colitis and two with Crohns disease; ages 3-17 years) received 100-200 micrograms/kg/day cyclosporine intravenously and then 4-10 mg/kg/day orally. Doses were adjusted to achieve trough serum cyclosporine levels of 100-200 mu/L (Abbotts TDX assay). Seven of the eight patients received azathioprine/6-mercaptopurine, and all were given a 5-aminosalicylate preparation and corticosteroids. The latter drugs were continued and then tapered off as clinical status allowed. Cyclosporine was continued for 3-10 months in those who responded. In seven of eight patients, there was a rapid clinical response; one patient showed a transient response, but recurrent bleeding led to total colectomy 9 days after starting cyclosporine. Of the seven responders, three were able to discontinue prednisone and cyclosporine and are doing well on azathioprine at long-term follow-up (2-5 years). One who did not receive azathioprine/6-mercaptopurine maintained remission for 2 years after cyclosporine was stopped, one experienced a disease flare-up 5 months after start of cyclosporine treatment and required colectomy, one who did not tolerate 6-mercaptopurine had a flare-up during cyclosporine tapering and underwent surgery at 6 months, and one started to flare up with cyclosporine tapering at 6 months and was scheduled for surgery. No significant complications of treatment were observed. Seven patients had an initial response and four of them have so far not required surgery. These preliminary findings suggest that azathioprine/6-mercaptopurine can be used safely to maintain cyclosporine-induced remission in children with IBD.

Pediatric Paradoxical Vocal-Fold Motion: Presentation and Natural History

OBJECTIVES: To describe (1) a cohort of children with paradoxical vocal-fold motion (PVFM) who were referred to a multidisciplinary airway center and (2) the outcomes of various treatment modalities including speech therapy, gastroesophageal reflux disease treatment, and psychiatric treatment. PATIENTS AND METHODS: This was a case series with chart review of children younger than 18 years with PVFM evaluated at a tertiary care pediatric airway center over a 36-month period. RESULTS: Fifty-nine children with PVFM were evaluated. The cohort had a mean age of 13.64 years (range: 8–18 years) and a female-to-male ratio of 3:1. Speech therapy as an initial treatment resulted in a 63% (24 of 38) success rate after an average of 3.7 treatment sessions. Speech therapy was a more successful treatment than antireflux therapy (P = .001). Ten percent (6 of 59) of the children presented with a known psychiatric diagnosis, and 30% (18 of 59) of children in the cohort were ultimately diagnosed with a psychiatric condition. Children with inspiratory stridor at rest had a lower initial success rate with speech therapy (56%), a higher rate of underlying psychiatric disorders (75%), and a high rate of success after psychiatric treatment (100%) that required, on average, 3 sessions over a 2-month period. CONCLUSIONS: To our knowledge, this is the largest study to date on pediatric PVFM. The majority of children with PVFM improve with speech therapy. Children with PVFM at rest may be better treated with psychiatric therapy than speech therapy. Furthermore, children who present with symptoms at rest may have a higher likelihood of underlying psychiatric disease.

Type 1 Laryngeal Cleft A Multidimensional Management Algorithm

IMPORTANCEnEarly diagnosis and assessment in children with type 1 laryngeal cleft are essential in preventing aspiration and associated comorbidity. Appropriate use of conservative and surgical interventions in an evidence-based management strategy can improve overall outcome.nnnOBJECTIVEnTo evaluate the management of care for children with type 1 laryngeal cleft in our practice and develop an updated management algorithm.nnnDESIGN, SETTING, AND PARTICIPANTSnWe performed a review of medical records at a tertiary pediatric aerodigestive center. During a period of 7 years (July 18, 2005, to July 18, 2012), 1014 children younger than 18 years were evaluated for aspiration, choking, cough, or recurrent pneumonia. Of these, 44 children (4.3%) had a type 1 laryngeal cleft. Two were lost to follow-up; thus, 42 children were included in our final sample (28 males, 14 females).nnnINTERVENTIONSnThe care of 15 patients (36%) was managed conservatively, and 27 patients (64%) underwent endoscopic surgical repair of their laryngeal cleft.nnnMAIN OUTCOME AND MEASUREnAssessment of our current management strategy.nnnRESULTSnSuccess was defined as improving when a child was able to tolerate a feeding without aspirating or resolved when the child had transitioned to tolerating thin liquids. All patients received a trial of conservative therapy. Fifteen of the 42 patients (36%) had an anatomic cleft and were able to maintain the feeding regimen; thus, conservative treatment was successful in this group. The remaining 27 patients (64%) received surgical intervention. Overall operative success rate was 21 of the 27 patients (78%). The age of the child (Pu2009<u2009.01) and comorbid conditions (Pu2009<u2009.001) affected the outcomes of conservative measures and surgical repair. Only 6 patients did not demonstrate resolution, 5 of whom had significant comorbidities.nnnCONCLUSIONS AND RELEVANCEnAge, comorbidity status, severity of aspiration, and the ability to tolerate a feeding regimen should be taken into account when deciding on conservative or surgical management for children with a type 1 laryngeal cleft. A clinical pathway for conservative and surgical management is presented.

Long-term minocycline use for acne in healthy adolescents can cause severe autoimmune hepatitis

Over the years, a variety of abnormal immune reactions to minocycline have been reported including arthritis, systemic lupus erythematosus, and hepatitis. The current report describes the detailed clinical and pathologic features of 3 patients who presented with chronic/autoimmune hepatitis alone while on minocycline at our hospital over a 2-year period. Minocycline use in these patients was temporally related to onset of severe hepatitis. Adolescents with such a reaction to minocycline have been included in previous reports but have not been well described as a distinct entity. We have compared our cases with similar cases previously reported with a review of the literature and a discussion of the implications for prescribing physicians.

Prevalence of Eosinophilic Esophagitis in Children With Refractory Aerodigestive Symptoms

IMPORTANCEnEosinophilic esophagitis (EoE) is an increasingly important diagnosis for children; it has a remarkable impact on their quality of life and can present with aerodigestive symptoms commonly evaluated by otolaryngologists.nnnOBJECTIVESnTo evaluate the prevalence of EoE in children presenting to a pediatric aerodigestive clinic, to describe their presentation, and to review the role of subsequent food allergy evaluation and treatment.nnnDESIGNnReview of a prospective database.nnnSETTINGnTertiary pediatric multispecialty aerodigestive center.nnnPATIENTSnChildren with aerodigestive symptoms refractory to medical treatment who underwent direct laryngoscopy with rigid or flexible bronchoscopy and esophagoscopy with or without pH probe study.nnnMAIN OUTCOMES AND MEASURESnDiagnosis of EoE.nnnRESULTSnBetween 2003 and 2012, 376 of 1540 children seen in the center (mean [range] age, 4.54 [0-18.6] years; male to female ratio, 1.72:1) remained symptomatic despite medical therapy and thus underwent triple endoscopic evaluation. Of the 376 children, 14 (3.7%) were eventually diagnosed as having EoE, as defined by 15 or more eosinophils per high-power field on esophageal biopsy and either a negative pH study result or nonresponse to a trial of high-dose proton pump inhibitors. The subpopulation with EoE presented with airway symptoms and diagnoses, most commonly cough (nu2009=u20096; 42.9%). Inflammatory subglottic stenosis due to EoE was identified in 1 patient. Of the 14 children with EoE, 6 presented with gastrointestinal symptomatology, most commonly choking or gagging. Subsequent treatment including food allergy challenge and elimination diet resulted in a clinical improvement in half of the cases identified.nnnCONCLUSIONS AND RELEVANCEnThis represents the largest multispecialty clinic epidemiologic study evaluating the prevalence of EoE in children presenting not strictly with gastrointestinal symptoms but rather with aerodigestive symptoms that are frequently evaluated by pediatric otolaryngologists. Although the prevalence is low, EoE should be considered for children with appropriate symptoms in whom other medical therapies fail.

Research agenda for pediatric gastroenterology, hepatology and nutrition: acid-peptic diseases. Report of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition for the Children's Digestive Health and Nutrition Foundation

Research priorities in acid-peptic diseases encompass clinical studies in children with gastroesophageal reflux disease (GERD) and those with peptic ulcer disease. Gastroesophageal reflux (GER) is the passive retrograde movement of gastric contents into the esophagus above the lower esophageal sphincter (LES). Physiologically, in both children and adults, reflux occurs as a result of transient relaxations of the LES and inhibition of lower esophageal body peristalsis. Reflux is not primarily related, as previously thought, to lower LES pressure. At least one episode of GER occurs daily in two thirds of infants younger than 4 months of age; by 1 year of age, only 5% of infants have daily reflux. It is clear that in addition to more subtle clinical presentations, toddlers will often manifest the classic signs and symptoms of GERD (1). Based on a study by Nelson et al, 7% of children between the ages of 3 and 9 report symptoms such as heartburn, epigastric pain and regurgitation (2). Approximately 35% of adults have heartburn on a regular basis. In a recent study, up to 50% of adults in Canada and the US have self-reported GERD symptoms weekly. In most adults, GERD is a chronic condition that waxes and wanes during their lifetime. Little information is available regarding the relationship between GER that presents during infancy and early childhood and the development of chronic heartburn and esophageal disease, both macroscopic and microscopic, in an adult. The gold standard for diagnosing and quantitatively assessing the severity of gastroesophageal reflux and GERD in children remains to be determined. Prolonged intraesophageal pH study, performed by placing a pH probe in the distal esophagus, identifies and quantifies acidic gastric fluid within the lumen of the esophagus. This technique determines not only the frequency but also the duration of reflux episodes. Newer approaches, such as impedance techniques, need to be validated in pediatric patients. Ultimately, such studies may provide vital new information to help guide physicians in managing patients with GERD. Although much progress has been made in understanding GERD in children, many questions remain unanswered. Based on single-center studies of small cohort size, the prevalence of GER in infants under the age of 3 months is estimated to be in excess of 85%. Premature infants, in particular, are susceptible to GER. The overwhelming majority of infants younger than 3 months have physiologic reflux and do not require medical intervention. Approximately 10% have pathologic reflux, with esophageal manifestations (irritability, feeding refusal, arching, crying during feeding) and extraesophageal manifestations (apnea, bradycardia, reactive airways disease/asthma, impaired growth). Additional research is needed to more fully understand the natural history of GERD to enable the identification of children at risk for serious sequelae, including erosive esophagitis, Barrett’s esophagus and esophageal carcinoma. Studies also are needed to determine the optimum dosing regimens for currently available acid-suppressive and prokinetic medications. Peptic ulcer disease affects approximately 4 million people annually, with some estimates as high as 10 million per annum. For much of the past century, it was thought that gastroduodenal ulcers are caused by multiple predisposing factors, the most important being hypersecretion of gastric acid. Based on this paradigm of peptic ulcer disease, mucosal ulceration develops as a result of an imbalance between acid and cytoprotective mechanisms. Factors such as diet, medications toxic to the gastric mucosa and genetic predisposition were also thought to contribute to the development of peptic ulcer disease. Since the discovery of Helicobacter pylori and its relationship to gastritis and peptic ulcers, dramatic changes have occurred in our understanding of the pathobiology, diagnosis and treatment of peptic ulcer disease (3–5). Since 1983, many studies have confirmed the presence Journal of Pediatric Gastroenterology and Nutrition 35:S250–S253

What Do the Children Eat in Schools? Teachers’ Account

Moving beyond households and families, the next chapter shares accounts of interactions with teachers of government schools. It explores their perceptions regarding the implementation, the benefits and challenges of the school meal program and other health-related measures being implemented by the government. It presents a detailed analysis of the teachers’ understanding of the health and nutrition status of children in their schools and the changes in their food consumption patterns. It also shows the extent to which teachers show awareness and appreciation of health-related measures in school by connecting it with various positive changes in the social context such as reduction in child labor. The chapter illustrates how an integrated curriculum of education, health, and nutrition could be built as a route to improve the health and nutritional profile of students and subsequently their academic performance. The school can provide an important locus for providing critical nutritional inputs for children through improved quality of food provided through the MDM; through proper monitoring of quality and composition of the food, training of cooks in preparing tasty and healthy meals, reintroducing traditional/locally preferred foods such as ragi and jowar, and engaging with the community on promoting healthy eating practices both in school and at home.

Case 2: Dysphagia to Solid Foods in a 17-month-old Boy.

1. Francis S. Kim, MD, MA*n2. Andrew R. Scott, MD†n3. Jyoti Ramakrishna, MD‡nnn nn1. *Department of Pediatrics,nn2. †Division of Pediatric Otolaryngology, andnn3. ‡Division of Pediatric Gastroenterology and Nutrition, Tufts Floating Hospital for Children, Boston, MAnnA former full-term 17-month-old boy is referred to the pediatric gastrointestinal (GI) clinic by his pediatrician for vomiting. He has 4 to 5 episodes weekly of nonbloody, nonbilious emesis after gagging on solid or textured foods. His parents report that he has never been able to eat solid foods but that he swallows liquids and pureed foods easily. His diet consists of whole milk and pureed foods. Bowel movements are normal. He does not have any medical or surgical history, with good growth, development, and weight gain. He does not take any medications and has no allergies. His family history is noncontributory.nnPhysical examination reveals an obese child who is otherwise normal. His initial laboratory evaluation is normal for complete blood cell count with differential count, tissue transglutaminase IgA, and total IgA. Radioallergosorbent test results are low positive for milk at Class 2, which is not clinically significant. A scout radiograph before the upper GI (UGI) series reveals a radiopaque, coinlike, esophageal foreign body (FB) at the thoracic inlet, appearing as a circular disc (en face) on the anteroposterior view (Fig 1A) and as a thick line (en edge) on the lateral view, suggesting that the location is in the esophagus and not in the trachea. Importantly, the FB does not have any features concerning for a button battery, and because it had possibly been present for up to 9 months without any concerning symptoms beyond dysphagia to solid foods, it is removed nonemergently the same day that it is identified. However, owing to the location of the FB, the pediatric otolaryngology department is consulted for removal under general …

Should underlying pancreatic disease be a relative contraindication for the use of propofol

Introduction: Propofol was introduced in 1982 and it has been used in over 250 million patients. From 1991 to 1994, seven cases of postoperative pancreatitis related to propofol use were reported to the FDA. In a series of 4 patients with no underlying pancreatic disease undergoing non-abdominal surgery, 2 died due to severe pancreatitis. The manufacturer claims that a causal relationship between propofol and postoperative pancreatitis is unlikely. However, in a sub-population of high risk patients with a past history of pancreatic disease this could be a potentially dangerous drug. Methods: We cared for LB, a 16 y/o female with cystic fibrosis and pancreas divisum. She had multiple procedures including ERCPs, with and without propofol. We retrospectively extensively reviewed her chart. At her initial presentation in 6/96, 3 ERCPs were performed using Demerol and Versed. She underwent stent placement, sphincterotomy, stent replacement and stent removal. After the first procedure her amylase and lipase increased dramatically and took 3 days to return to baseline. No problems were noted after the second ERCP. In 7/97 her pancreatitis recurred, and for the first time she received propofol for ERCP with dilatation of the minor papilla. Her amylase did not increase much, but she did take longer to recover. In 1/99 she had 2 procedures with propofol induction, sinus surgery using 90 mg of propofol. and 10 days later a PASport placement with 150 mg of propofol. After the first procedure she had minor complaints and a slight increase in amylase, and after the second procedure she developed pancreatitis. Her enzyme elevation and symptoms lasted 2 months. She eventually underwent 2 more ERCPs without propofol, one with sphincterotomy of the minor papilla and stent placement, and one for stent removal. Neither of these procedures gave her more than a small elevation in amylase which lasted less than a day. Results: We find that in this high risk patient 2 procedures for non-abdominal problems using propofol precipitated severe pancreatitis. Subsequent ERCPs avoiding propofol did not cause such problems. Discussion: Propofol is often used for sedation and is considered safe. Previous pancreatitis is not currently considered a contraindication for its use. We feel that propofol should be suitably labelled to caution against its use in patients with known or suspected pancreatic disease. Also, amylase and lipase should be checked in any patient who complains of abdominal pain after they have received propofol.