Propofol Sedation in Pediatric Upper Endoscopy: A Study of Pharmacodynamics and the Effects of Gastroenterologists, Anesthesiologists, and Supervised Participants on the Procedure Time and Sedation Time.

Background and aims Propofol combined with fentanyl is a commonly used sedative for pediatric upper endoscopies (UEs). The primary aim was to study the association between propofol dose and procedure and sedation time. The secondary aims were to assess the pharmacodynamics of propofol use with fentanyl and evaluate if gastroenterologists' and anesthesiologists' years of experience or the presence of supervised participants (such as students, residents, and fellows) have any influence on the procedure and sedation time. Methods A retrospective study was performed at the Children's Hospital of Michigan on patients under 18 years who underwent UEs with propofol sedation with fentanyl over a two-year period. Results A correlation was found between the propofol amount used expressed per body mass index (BMI)/body surface area (BSA), procedure time, and sedation time (p < 0.0001). Throat pain was the most common post-procedural adverse event (4.48%). The impact of psychoactive drugs on these events was not statistically significant, but attention-deficit/hyperactivity disorder (ADHD) medication use was related to increased post-procedural pain complaints. The use of prescribed psychoactive medications was associated with larger propofol dose usage (p = 0.007) without a significant increase in sedation time. Individual gastroenterologists, their years of experience, and the presence of supervised participants were associated with different procedure times (p <0.0001, <0.0001, 0.01). Fellow participation was associated with a 1.11-minute procedure time increase (p = 0.04). Individual anesthesiologists, their years of experience, and the presence of supervised participants were associated with different sedation times (p <0.0001, <0.0001, 0.01). Conclusion We found a novel correlation between propofol dosing expressed by the BMI/BSA and sedation time. The UE procedure time and sedation time are associated with individual gastroenterologists and anesthesiologists, their years of experience, and the presence of supervised participants.

Symptomatic Treatment of Pain-Related Pediatric Functional Gastrointestinal Disorders in a Biopsychosocial Construct, and a Validity Study of Rome III Criteria.

Our study aims to assess improvement with symptomatic treatment of pain-related functional gastrointestinal disorders (FGIDs) in a biopsychosocial construct and evaluate validity of Rome III criteria. Children with chronic abdominal pain diagnosed with an FGID or organic disease were followed for 1 year: 256/334 were diagnosed with an FGID and 78/334 were diagnosed with a possible organic disease due to alarm signs or not meeting Rome III criteria. After 1 year, 251 had true FGID and 46 had organic diseases. Ninety percent of FGID patients improved with symptomatic treatment over an average of 5.4 months. With a 95% confidence interval, Rome criteria predicted FGIDs with sensitivity 0.89, specificity 0.90, positive predictive value 0.98, and negative predictive value 0.59. We conclude that symptomatic treatment of pain-related FGIDs results in clinical improvement and could reduce invasive/expensive testing. Rome III criteria's high specificity and positive predictive value suggest they can rule in a diagnosis of FGID.

Economic Impact and Prognostic Factors of Functional Dyspepsia in Children.

OBJECTIVES: Functional dyspepsia (FD) is a functional abdominal pain disorder. There is paucity of data on the economic impact of FD in children. Primary aim of our study was to estimate annual evaluation cost ("diagnosis and visit" cost) and secondary aim was to identify potential prognostic factors of FD in children. METHODS: Out of the 136 patients 86 met inclusion criteria and were divided into 2 clinical groups: Complete Improvement Group (CIG-30 patients) and Partial/No Improvement Group (PIG/NIG-56 patients). Medications used were noted descriptively. Annual evaluation cost was calculated using 2017 Medicare reimbursement rates. RESULTS: Annual evaluation cost in all patients was $724.874 ±â€Š$180.075 ($544.799 ±â€Š$87.995 in CIG and $904.949 ±â€Š79.083 in PIG/NIG). An extrapolated annual cost of evaluation in children with FD would be approximately $5.79 billion. Average number of clinic visits (3.1 ±â€Š1.2 in CIG vs 4.40 ±â€Š3.1 in PIG/NIG), duration of follow-up in months (9.2 ±â€Š6.6 in CIG vs 17.1 ±â€Š13.6 in PIG/NIG), use of imaging studies (7 patients in CIG [23.3%] vs 29 in PIG/NIG [51.8%]) and endoscopic procedures (17 in CIG [56.7%] vs 46 in PIG/NIG [82.1%]) were significantly higher in PIG/NIG (P < 0.005). PIG/NIG required multiple medications for control of symptoms compared to CIG (4 patients in CIG [13.5%] vs 30 in PIG [53.6%], P value <0.001]. For every $500.00 decrease in total evaluation cost the odds of having a complete response was 0.998 (P = 0.027). No prognostic factors were identified in children with FD. CONCLUSIONS: FD in children has a significant economic impact on health care expenditure. Patients with FD who have partial/no response to treatment incur greater financial cost potentially adding to health care expenditure.

Pediatric abdominal migraine: current perspectives on a lesser known entity.

BACKGROUND: Abdominal migraine (AM) is a common cause of chronic and recurrent abdominal pain in children. It is characterized by paroxysms of moderate to severe abdominal pain that is midline, periumbilical, or diffuse in location and accompanied by other symptoms including headache, anorexia, nausea, vomiting, or pallor. Despite the presence of comprehensive diagnostic criteria under Rome IV classification of functional gastrointestinal disorders (FGIDs) and International Classification of Headache Disorders, it continues to be an underdiagnosed entity. OVERVIEW: The average age of diagnosis is 3-10 years with peak incidence at 7 years. Most of the patients have a personal or family history of migraine. Pathophysiology of the condition is believed to be similar to that of other FGIDs and cephalic migraine. It is also well recognized as a type of pediatric migraine variant. A careful history, thorough physical examination, and use of well-defined, symptom-based guidelines are needed to make a diagnosis. Selective or no testing is required to support a positive diagnosis. It resolves completely in most of the patients. However, these patients have a strong propensity to develop migraine later in life. Explanation and reassurance should be the first step once the diagnosis is made. Nonpharmacologic treatment options including avoidance of triggers, behavior therapy, and dietary modifications should be the initial line of management. Drug therapy should be considered only if symptoms are refractory to these primary interventions. CONCLUSION: More research focused on pathophysiology and management of AM needs to be carried out to improve outcomes in affected children.

Long-Term Study of Children With ROME III Functional Gastrointestinal Disorders Managed Symptomatically in a Biopsychosocial Model.

BACKGROUND: Our study evaluated progression of and identified potential factors contributing to outcomes of ROME III defined-functional gastrointestinal disorders (FGIDs) in children treated symptomatically in a biopsychosocial model of care with a long-term follow-up. METHODS: We performed a retrospective review of pediatric patients who were diagnosed with ROME III defined-FGIDs including functional abdominal pain, functional dyspepsia, irritable bowel syndrome and abdominal migraine. Patients were managed symptomatically in a biopsychosocial model of care from the time of initial diagnosis. Demographics, management, progression and response to treatment assessed as complete, partial, and no improvement were reviewed. RESULTS: Two hundred fifty-eight patients were included with mean age of 10.6 years, female 55.4%, mean number of encounters 3.3 visits, and mean follow-up was 18.7 months (range 2 - 59, SD 15.8). Diagnoses were functional abdominal pain 45%, irritable bowel syndrome 20.9%, multiple 13.2%, functional dyspepsia 12.8%, and abdominal migraine 8.1%. Investigations were performed in most patients: laboratory studies in 93.4% (non-contributory abnormal 23.6%), imaging studies in 45.3% (non-contributory abnormal 5%) and endoscopies in 43.0% (non-contributory abnormal 1.2%). Treatment included medication in 93.7%, and surgery in 1.9% (normal pathology). There were new functional gastrointestinal diagnosis in 11.6%, evolution of FGIDs, from one to another in 12.0%, and recurrence found in 35.7% of patients. There were 60.1% patients in the complete improvement group (CIG) and 39.1% in the partial/no improvement group (PIG/NIG). No statistical difference was found between CIG and PIG/NIG regarding demographics or evaluation. PIG/NIG had more encounters (mean 3.63 vs. 3.11; P = 0.03), had non-contributory lab abnormalities (34.4% vs. 20.0%; P = 0.01), needed more endoscopies (52.4% vs. 36.8%; P = 0.02), required more treatment changes (mean 1.41 vs. 0.81; P < 0.01) and developed new functional gastrointestinal diagnoses (19.4% vs. 6.5%; P < 0.01) with long-term follow-up. CONCLUSIONS: Patients with ROME III defined-FGIDs who experience partial or no improvement with treatment develop new FGID diagnosis, need more number of follow-up visits, require more number of endoscopies, need more treatment changes, and have more non-contributory laboratory abnormalities, compared to those who experience complete improvement. Symptomatic treatment offered in a biopsychosocial model of care is possibly beneficial in managing children with FGIDs.

An Update on Pediatric Pancreatitis.

There has been a rise in the incidence and number of admissions of children with pancreatitis over the past 20 years. Current management practices for pancreatitis in children are adapted from standards of care for adults, and there are a lack of multicenter, prospective research studies on pancreatitis in children. There are inherent differences in the clinical presentation and natural course of pancreatitis between adults and children. This review focuses on the current understanding of the epidemiology, etiologies, evaluation, and management of children with pancreatitis. [Pediatr Ann. 2017;46(5):e207-e211.].

Cyproheptadine: A Potentially Effective Treatment for Functional Gastrointestinal Disorders in Children.

Functional gastrointestinal disorders (FGIDs) negatively affect children's quality of life and health care costs. It has been proposed that alteration of gut serotonin leads to gastrointestinal dysmotility, visceral hypersensitivity, altered gastrointestinal secretions, and brain-gut dysfunction. Cyproheptadine, a serotonin antagonist, has been shown to be a potentially effective and safe treatment option in children who meet the clinical criteria for FGIDs. Well-designed multicenter trials with long-term follow-up are needed to further investigate its efficacy. [Pediatr Ann. 2017;46(3):e120-e125.].

Neonatal isolated ACTH deficiency (IAD): a potentially life-threatening but treatable cause of neonatal cholestasis.

Isolated ACTH deficiency (IAD) is a rare cause of neonatal cholestasis and hypoglycaemia. This diagnosis has a 20% mortality potential if unrecognised. We describe a case of an infant presenting with cholestatic jaundice and hypoglycaemia. The patient had laboratory findings suggestive of IAD, which was later confirmed with molecular genetic testing. One of the mutations this patient had is a new finding. The patient was started on glucocorticoid replacement therapy after which his bilirubin and glucose levels normalised.

Constipation in Children: A Practical Review.

Pediatricians and other child care providers manage a large number of children with constipation, a recurrent medical problem that is frustrating to patients, their care givers, and the health care providers themselves. Most often the constipation in children is functional in nature, and only a very small percentage of patients have an organic cause for it. In this review, we discuss the epidemiology, causes, evaluation, and management of children with functional constipation. [Pediatr Ann. 2016;45(5):e189-e196.].

Review of pulmonary adverse effects of infliximab therapy in Crohn's disease.

INTRODUCTION: Anti-inflammatory therapies are the mainstay for the treatment of inflammatory bowel disease (IBD) in children and adults, including biologics such as infliximab. While there is extensive literature on the general side effects of therapy with infliximab, the data on pulmonary adverse effects remains sparse. This article summarizes the literature related to pulmonary adverse effects of Infliximab therapy in Crohn's Disease. AREA COVERED: Published reports of specific pulmonary complications during ongoing therapy with infliximab in patients with IBD were included in the review. A wide variety of infectious and non-infectious complications have been reported with the use of infliximab therapy in IBD. EXPERT OPINION: It is important to carefully evaluate respiratory signs and symptoms in patients with IBD, especially those receiving biologic therapies. Besides infectious complications, other non-infectious pulmonary adverse effects associated with the use of infliximab should be considered in patients with IBD. Further, it is important to differentiate primary pulmonary involvement of IBD from pulmonary adverse effects of infliximab therapy. An algorithm for assessing patients with IBD presenting with pulmonary symptoms is provided as a guide for clinicians for medical decision-making.

Cyproheptadine Use in Children With Functional Gastrointestinal Disorders.

OBJECTIVE: The objective of this study was to evaluate clinical improvement and safety with use of cyproheptadine in functional gastrointestinal disorders (FGIDs) in children. METHODS: Retrospectively evaluating the efficacy and safety of the use for indications including Rome III-defined FGIDs: functional abdominal pain, functional dyspepsia, irritable bowel syndrome (IBS), abdominal migraine, cyclic vomiting syndrome. Response categories were as follows: no improvement group/partial improvement group; requiring intervention, or complete improvement group (CIG); warranting discontinuation; ongoing use; or parental unwillingness to stop medication. RESULTS: Among 307 patients, 151 included; 58% girls, ages 1 to 18 years (median 9); 110 (72.8%) reported complete symptom improvement; 41 (27.2%) reported no or partial improvement. Mean initial and final doses in the CIG were 4.85 mg/day (0.14 mg ·â€Škg ·â€Šday) and 5.34 mg/day (0.14 mg ·â€Škg ·â€Šday), respectively. A total of 102/151 (68%) reported no adverse effects. Adverse effects shown were as sleepiness in 19/151 (13%) and weight gain in 15/151 (10%). Cyproheptadine was effective in improving symptoms of functional abdominal pain, functional dyspepsia, in a relatively larger number of patients. Patients in smaller numbers had significant improvement 13/18 (72%) abdominal migraine, 10/10 (100%) IBS, and 6/8 (75%) cyclic vomiting syndrome. This is the first time report of improvement in IBS. Other pharmacodynamics had been as follows: the lower the body weight, the higher are the odds of no to partial improvement; patients in no improvement group/partial improvement group experience more adverse effects as compared to the CIG; the single best predictor of clinical improvement was body mass index. A 1 unit increase in body mass index with cyproheptadine use increased the odds of clinical improvement by 1.5-fold (P = 0.01). CONCLUSIONS: Cyproheptadine effectively improves symptoms of Rome III-defined FGIDs and has a good safety profile when used for these indications.

Limited granulomatosis with polyangiitis in an adolescent with Crohn's disease on infliximab therapy: cause or coincidence?

Pulmonary involvement in Crohn's disease (CD) may precede the development of intestinal inflammation, but in most cases occurs during the course of treatment, either as an extra-intestinal manifestation, because of secondary infections, or as a side effect of the therapy itself. This case highlights the differential diagnosis and work up for multiple pulmonary nodules that developed in a patient with CD who had been in remission on infliximab therapy. Even though infectious causes, such as Mycobacteria and Fungi, account for majority of these cases, the possibility of non-infectious conditions such as autoimmune disorders should also be considered.

Pharmacokinetics and pharmacodynamics of famotidine and ranitidine in critically ill children.

To characterize and compare acid suppression (pharmacodynamics) and pharmacokinetics of IV famotidine and ranitidine in critically ill children at risk for stress gastritis. Single-blind, randomized study in PICU patients 6 months to 18 years requiring mechanical ventilation with continuous gastric pH monitoring, randomized to IV famotidine 12 mg/m(2) or ranitidine 60 mg/m(2) when gastric pH < 4.0 >1 hour with serial blood sampling following first dose. Twenty-four children randomized to either famotidine (n = 12) or ranitidine (n = 12). Sixteen out of twenty-four completed both PK and PD study arms (7/12 famotidine; 4.7 ± 3.4 years; 9/12 ranitidine; 6.6 ± 4.7 years; p = 0.38). Time to gastric pH 4.0 and total time pH above 4.0 similar with no difference in pH at 6 and 12 hours (p > 0.2). No difference between drugs in clearance, volume of distribution and half-life (p > 0.05). Ratio of AUC pH to AUC drug concentration 0-12 hours after first dose was significantly greater for famotidine (0.06849 ± 0.01460 SD) than ranitidine (0.02453 ± 0.01448; p < 0.001) demonstrating greater potency of famotidine. pH lowering efficacy of both drugs is similar. Greater potency of famotidine may offer clinical advantage due to lower drug exposure and less frequent dosing to achieve same pH lowering effect.

Two hyperplastic esophagogastric polyps in a child with neurofibromatosis type 1 (NF-1).

Hyperplastic esophagogastric polyps usually occur in the distal esophagus or gastroesophageal junction and have been associated with damage to the esophageal mucosa. Histologically these polyps show hyperplastic gastric foveolar and/or squamous epithelium with inflamed stroma. Reports of esophagogastric polyps in the pediatric population are rare. Most of these reports only describe chronic inflammation within the lamina propria of the polyp, with only rare reports specifying the presence of epithelial hyperplasia. There have been 2 previous cases of hyperplastic esophagogastric polyps occurring in the context of neurofibromatosis type 1 (NF-1) in a single article. Here we report a 3rd case of hyperplastic esophagogastric polyps occurring in an 11-year-old male with NF-1. This case is unique in that there were 2 polyps in the same patient and in that the polyps showed hyperplastic gastric peptic glands in addition to foveolar-type and focal squamous epithelium. The case is discussed and literature reviewed.

A prospective study comparing oral sodium phosphate solution to a bowel cleansing preparation with nutrition food package in children.

OBJECTIVE: The inability of children to comply with bowel preparation regimens can result in inadequate visualization of the colon. This study compares the safety, efficacy, and patient acceptance of a prepackaged diet kit plus a magnesium citrate/bisacodyl bowel cleansing regimen with a clear liquid diet and sodium phosphate solution regimen in children undergoing colonoscopy. METHODS: Children scheduled for a diagnostic colonoscopy, were randomly assigned to receive a prepackaged diet kit and a magnesium citrate/bisacodyl laxative (group 1), or clear liquids and sodium phosphate solution (group 2). The patients and their parents completed a questionnaire to evaluate acceptance of their assigned regimen before colonoscopy. The endoscopists, blinded to the type of bowel preparation, rated bowel cleansing. RESULTS: Sixty two children (28 males, 34 females) with mean age 12.5 years participated. Thirty six and 26 patients were in groups 1 and 2 respectively. Overall cleansing was rated significantly superior in group 1 compared to group 2 as was amount of retained feces (P = .013 for both). The overall frequency of reported side-effects was lower in group 1 than (83.3%, 30/36) than in group 2 (100.0%, 26/26) (P = 0.03). The preparations were otherwise equivalent in regards to compliance and patient tolerance. CONCLUSIONS: Although both regimens were comparable in adequacy of colon visualization, preparation tolerance, side effects and compliance profile in this pilot study, the prepackaged diet kit with magnesium citrate/bisacodyl laxative resulted in superior colon cleansing.