Nader N. Youssef

Chronic childhood constipation is associated with impaired quality of life : A case-controlled study

Objective: The objective of this study was to investigate the effect of chronic constipation on childrens quality of life. Methods: From October 2002 to November 2003, 224 children (140 male, 84 female, aged 10.6 ± 2.9 years) and 224 parents were evaluated by a health related quality of life tool during initial outpatient consultation. Children with constipation (n = 80) were compared with controls with inflammatory bowel disease (n = 42), controls with gastroesophageal reflux disease (n = 56), and with healthy children (n = 46). Results: Children with constipation had lower quality of life scores than did those with inflammatory bowel disease (70 versus 84; P < 0.05), gastroesophageal reflux disease (70 versus 80; P < 0.05), and healthy children (70 versus 88; P < 0.05). Children with constipation reported lower physical scores than did inflammatory bowel disease patients (75 versus 85; P < 0.02), gastroesophageal reflux disease patients (75 versus 85; P < 0.05), or healthy children (75 versus 87; P < 0.05). Parents of children with constipation reported lower scores than did their children (61 versus 70; P < 0.05). Children with constipation had longer duration of symptoms than did the controls with inflammatory bowel disease and gastroesophageal reflux disease (43.8 months versus 14.2 months; P < 0.001). Prolonged duration of symptoms for children with constipation correlated with lower parent-reported scores (P < 0.002). Conclusions: At initial evaluation, children with constipation have a lower quality of life than do children with inflammatory bowel disease or gastroesophageal reflux disease. Self-reported lower scores may be a reflection of impaired physical ability. Parental perceptions of low quality of life are probably impacted by the duration of their childs symptoms and by family members with similar complaints. Practitioners should be aware of the high level of parental concern and the relatively low self-reported and parent-reported quality of life in children with chronic constipation as they plan therapy.

Multicenter, Randomized, Placebo-Controlled Trial of Amitriptyline in Children With Functional Gastrointestinal Disorders

BACKGROUND & AIMS There are no prospective, multicenter, double-blind, placebo-controlled, randomized pharmacologic trials for the treatment of pain-predominant functional gastrointestinal disorders in children. The aim of this study was to evaluate the efficacy of amitriptyline in children with pain-predominant functional gastrointestinal disorders. METHODS In this multicenter placebo-controlled trial, children with irritable bowel syndrome, functional abdominal pain, or functional dyspepsia were randomized to 4 weeks of placebo or amitriptyline (10 mg/d, weight <35 kg; 20 mg/d, weight >35 kg). Assessment of gastrointestinal symptoms, psychological traits, and daily activities occurred before and after intervention. Pain was assessed daily with self-report diaries. The primary outcome was overall response to treatment (childs assessment of pain relief and sense of improvement). Secondary outcomes were effect on psychosocial traits and daily functioning. RESULTS Ninety children were enrolled, and 83 completed the study (placebo, 40 children [30 girls]; drug, 43 children [35 girls]). A total of 63% of patients reported feeling better and 5% feeling worse in the amitriptyline arm compared with 57.5% feeling better and 2.5% feeling worse in the placebo arm (P = .63). Pain relief was excellent in 7% and good in 38% of children receiving placebo compared with excellent in 15% and good in 35% of children treated with amitriptyline (P = .85). Logistic regression analysis of those reporting excellent or good response versus fair, poor, or failed response showed no difference between amitriptyline and placebo (P = .83). Children who had more severe pain at baseline in both groups (P = .0065) had worse outcome. Amitriptyline reduced anxiety scores (P < .0001). CONCLUSIONS Both amitriptyline and placebo were associated with excellent therapeutic response. There was no significant difference between amitriptyline and placebo after 4 weeks of treatment. Patients with mild to moderate intensity of pain responded better to treatment.

Childhood constipation: evaluation and treatment.

Constipation is common in children. It is estimated that between 5% and 10% of pediatric patients have constipation and/or encopresis. Constipation is the second most referred condition in pediatric gastroenterology practices, accounting for up to 25% of all visits. In this article, a practical approach is laid out for those not familiar with constipation in children. Emphasis is placed on the evaluation and management options that are available to the treating practitioner. The diagnosis of constipation requires careful history taking and interpretation. Diagnostic tests are not often needed and are reserved for those who are severely affected. The daily bowel habits of children are extremely susceptible to any changes in routine environment. Constipation and subsequent fecal retention behavior often begins soon after a child has experienced a painful evacuation. Childhood constipation can be very difficult to treat. It often requires prolonged support by physicians and parents, explanation, medical treatment, and, most important, the childs cooperation.

PEG3350 in the Treatment of Childhood Constipation : A Multicenter, Double-Blinded, Placebo-Controlled Trial

OBJECTIVE To establish the efficacy and best starting dose of polyethylene glycol (PEG)3350 in the short-term treatment of children with functional constipation. STUDY DESIGN Prospective, randomized, multicenter, double-blinded, placebo-controlled, dose-ranging study of PEG3350 in children with functional constipation. Patients were randomly assigned to either placebo or 0.2 g/kg per day, 0.4 g/kg per day, or 0.8 g/kg per day of PEG3350 after a 1 week run-in period, followed by 2 weeks of treatment. All received behavior modification. The primary outcome was the proportion of patients with a successful treatment response: >or=3 bowel movements (BM) in the second week. RESULTS 103 children (mean, 8.5 +/- 3.1 years) were enrolled. 77%, 74%, and 73% of the 0.2, 0.4, and 0.8 g/kg groups were successfully treated, as compared with 42% receiving placebo (P < .04). There was a significant increase in BM (P < .001) and straining improvement (P < .05) with the different PEG3350 doses. Stool consistency improved significantly for doses 0.4 g/kg or higher (P < .001). There was more abdominal pain and fecal incontinence in patients receiving 0.8 g/kg. PEG3350 was well tolerated. CONCLUSIONS This placebo-controlled study confirms the efficacy and safety of PEG3350 for the short-term treatment of children with functional constipation. We recommend a starting dose of 0.4 g/kg per day.

Chronic Abdominal Pain and Depressive Symptoms: Analysis of the National Longitudinal Study of Adolescent Health

BACKGROUND & AIMS Abdominal pain is common in adolescence. The aim of this study was to determine the prevalence of depressive symptoms in a large cohort of patients with frequent abdominal pain. METHODS A prospective, cross-sectional, nationally representative sample of children aged 13 to 18 years (mean age, 16.2 +/- 1.7 y; 49% male) completed in-home interviews and separate in-school questionnaires for the National Longitudinal Study in Adolescent Health (the Add Health Study). Depressed mood was assessed with the Center for Epidemiologic Studies Depression Scale. Subjective measures of abdominal pain were reported by 20,745 adolescents from wave 1 of the Add Health Study. Frequency of abdominal pain over the previous 1 year was rated as rare (0-1 episode/wk), moderate (2-3 episodes/wk), or daily (>or=4 episodes/wk). RESULTS Daily pain is reported in 3.2% of adolescents, with an additional 14% reporting pain as moderate in frequency. Sixteen percent of all adolescents are at risk for developing depression. The risk for depression goes from 16% to 45% (P < .001) when the pain is daily. Compared with rare pain, children with daily pain were more likely to miss school 10 or more times per year (46% vs 19%, P < .001), cry (12.1% vs 1%, P < .001), feel sad (25.2% vs 5.3%, P < .001), and lonely (25.2% vs 6.4%, P < .001). Children with daily pain were likely to consider life a failure versus those with no pain (10.2% vs 3.3%, P < .001). CONCLUSIONS Adolescents with frequent abdominal pain are at increased risk for depressive symptoms, social isolation, and missing school.

Management of intractable constipation with antegrade enemas in neurologically intact children.

Objectives To assess the benefit of antegrade enemas in children with severe constipation who were referred to a tertiary care center. Methods From 1997 to 1999, 12 children (9 male, aged 8.7 ± 4.4 years) underwent cecostomy placement. All children were neurologically normal and had been extensively examined to rule out organic causes of constipation. Follow-up included a questionnaire to interview caregivers 13.1 ± 8.5 months after cecostomy placement. Results For all children, antegrade enemas led to improvement in the number of bowel movements / week (7.1 versus 1.4, P < 0.005), number of soiling accidents / week (1.0 versus 4.7, P < 0.01), abdominal pain score (0.9 versus 2.9, P < 0.005), emotional health score (3.6 versus 1.9, P < 0.005), overall health score (3.6 versus 1.7, P < 0.005), number of medications used for constipation (0.8 versus 4.0, P < 0.005), number of missed school days / month (1.5 versus 7.5, P < 0.02), and number of physician office visits / year (9.2 versus 24.0, P < 0.05). Irrigation solutions used for the antegrade enemas included polyethylene glycol (67%), saline and glycerin solution (25%), and phosphate enema (8%), administered everyday in seven children and every other day in five children. Adverse events included skin breakdown and granulation tissue in one patient, leakage of irrigation solution in one patient, and dislodging of the tube in two patients. Five patients discontinued the use of antegrade enemas within a mean of 14.6 ± 9.1 months after beginning treatment. Conclusion Antegrade enemas through a cecostomy are a safe and satisfactory option for children who are neurologically intact and who have severe constipation that does not respond to medical treatment.

Treatment of functional abdominal pain in childhood with cognitive behavioral strategies.

Objective: The aim of this study was to assess the efficacy of a cognitive-behavioral approach to the treatment of recurrent abdominal pain caused by childhood functional gastrointestinal disorders (FGIDs). Methods: From September 2001 to December 2002, 18 patients (12 male; mean age, 12.1 ± 4.9 years) with chronic abdominal pain (mean duration, 11.8 ± 13.3 months) caused by FGIDs were referred to our facility’s mind-body institute (MBI). Treatment included guided imagery and progressive relaxation techniques. The mean number of sessions per patient was 4.3 ± 3.4. Outcomes included change in abdominal pain and quality of life, evaluated by the Pediatric Quality of Life Scale (PedsQL®). Follow-up was 10.6 ± 2.3 months after the last MBI session. Results: Abdominal pain improved in 89% of patients; weekly pain episodes decreased from 5.5 ± 0.9 to 2.0 ± 2.7 (P < 0.05); pain intensity (0 to 3 scale) decreased from 2.7 ± 0.6 to 0.6 ± 0.7 (P < 0.04); missed school days/month decreased from 4.6 ± 1.7 to 1.4 ± 3.2 (P < 0.05); social activities/week increased from 0.3 ± 0.6 to 1.3 ± 0.6 (P < 0.05); physician office contacts/year decreased from 24 ± 10.2 to 8.7 ± 13.1 (P = 0.07). PedsQL® scores (0 to 100 scale) improved from 55.3 ± 11.9 to 80.0 ± 10.7 (P < 0.03). Conclusions: Guided imagery and progressive relaxation can safely and effectively reduce chronic abdominal pain in children with FGIDs. This treatment also improved social functioning and school attendance.

Safety and Tolerability of Esomeprazole in Children With Gastroesophageal Reflux Disease.

Objectives: To evaluate safety, tolerability, and symptom improvement with once-daily esomeprazole in children with endoscopically proven gastroesophageal reflux disease (GERD). Patients and Methods: In this 8-week, multicenter, randomized, uncontrolled, double-blind study, children ages 1 to 11 years were stratified by weight to receive esomeprazole 5 or 10 mg (children < 20 kg) or 10 or 20 mg (children ≥ 20 kg) once daily. Safety and tolerability was assessed by evaluating adverse events (AEs; both treatment- and non-treatment-related AEs) and changes from baseline in medical history, physical examinations, and clinical laboratory tests. Investigators scored symptom severity every 2 weeks using the Physicians Global Assessment (PGA). Patients’ parents rated GERD symptoms of heartburn, acid regurgitation, and epigastric pain (none to severe, 0–3) at baseline (based on past 72 hours) and daily (from past 24 hours). Results: Of 109 patients randomized, 108 had safety data. AEs were experienced by 68.0% and 65.2% of children <20 kg receiving esomeprazole 5 and 10 mg, respectively, and 83.9% and 82.8% of children ≥20 kg receiving esomeprazole 10 and 20 mg, respectively, regardless of causality. Overall, only 9.3% of patients reported 13 treatment-related AEs; the most common were diarrhea (2.8% [3/108]), headache (1.9% [2/108]), and somnolence (1.9% [2/108]). Vomiting, a serious AE in 2 patients, was not judged by the investigator to be related to treatment. At the final visit, PGA scores improved significantly from baseline (P < 0.001). Of 58 patients with moderate to severe baseline PGA symptom scores, 91.4% had lower scores by the final visit. GERD symptom scores were significantly improved from baseline to the final week of the study in all of the treatment groups (P < 0.01) Conclusions: In children ages 1 to 11 years with endoscopically proven GERD, esomeprazole (at daily doses of 5, 10, or 20 mg) was generally well tolerated. The frequency and severity of GERD-related symptoms were significantly reduced during the active treatment period.

Lubiprostone for the Treatment of Functional Constipation in Children

Objectives: Pediatric functional constipation is common; effective, easily administered treatment options are limited. Lubiprostone is an oral chloride channel protein-2 activator that stimulates gastrointestinal fluid secretion, softens stools, and facilitates bowel movements (BMs). We evaluated the safety and effectiveness of lubiprostone in children and adolescents with functional constipation. Methods: Patients ≥12 kg, 17 years or younger, and with <3 spontaneous BMs (SBMs; ie, BMs that did not occur within 24 hours of rescue medication use) per week were enrolled at 22 US general pediatric and pediatric gastroenterology centers (January 2007–October 2008). Patients received 4 weeks of open-label lubiprostone at doses of 12 &mgr;g once daily (QD), 12 &mgr;g twice daily (BID), or 24 &mgr;g BID based on age and weight. The primary endpoint was SBM frequency during week 1 versus baseline. Results: Of 127 enrolled patients, 124 were treated and analyzed (12 &mgr;g QD, n = 27; 12 &mgr;g BID, n = 65; 24 &mgr;g BID, n = 32), and 109 completed the study. The mean age of treated patients was 10.2 years (range 3−17 years); 65 were boys. Mean SBM frequency significantly increased compared with baseline at week 1 (3.1 vs 1.5 SBMs/week, P < 0.0001). SBM frequency was improved significantly from baseline overall (P < 0.0001) and for individual dose groups (P ⩽ 0.0062) during weeks 2, 3, and 4. Common (≥5%) adverse events included nausea (18.5%), vomiting (12.1%), diarrhea (8.1%), abdominal pain (7.3%), and headache (5.6%). Two patients experienced serious adverse events (unrelated abdominal pain; unrelated sickle cell crisis). Conclusions: Lubiprostone was efficacious and well tolerated in children and adolescents with functional constipation.

Outcomes from a 12-Week, Open-Label, Multicenter Clinical Trial of Teduglutide in Pediatric Short Bowel Syndrome

Objective To determine safety and pharmacodynamics/efficacy of teduglutide in children with intestinal failure associated with short bowel syndrome (SBS‐IF). Study design This 12‐week, open‐label study enrolled patients aged 1‐17 years with SBS‐IF who required parenteral nutrition (PN) and showed minimal or no advance in enteral nutrition (EN) feeds. Patients enrolled sequentially into 3 teduglutide cohorts (0.0125 mg/kg/d [n = 8], 0.025 mg/kg/d [n = 14], 0.05 mg/kg/d [n = 15]) or received standard of care (SOC, n = 5). Descriptive summary statistics were used. Results All patients experienced ≥1 treatment‐emergent adverse event; most were mild or moderate. No serious teduglutide‐related treatment‐emergent adverse events occurred. Between baseline and week 12, prescribed PN volume and calories (kcal/kg/d) changed by a median of −41% and −45%, respectively, with 0.025 mg/kg/d teduglutide and by −25% and −52% with 0.05 mg/kg/d teduglutide. In contrast, PN volume and calories changed by 0% and −6%, respectively, with 0.0125 mg/kg/d teduglutide and by 0% and −1% with SOC. Per patient diary data, EN volume increased by a median of 22%, 32%, and 40% in the 0.0125, 0.025, and 0.05 mg/kg/d cohorts, respectively, and by 11% with SOC. Four patients achieved independence from PN, 3 in the 0.05 mg/kg/d cohort and 1 in the 0.025 mg/kg/d cohort. Study limitations included its short‐term, open‐label design, and small sample size. Conclusions Teduglutide was well tolerated in pediatric patients with SBS‐IF. Teduglutide 0.025 or 0.05 mg/kg/d was associated with trends toward reductions in PN requirements and advancements in EN feeding in children with SBS‐IF. Trial registration ClinicalTrials.gov: NCT01952080; EudraCT: 2013‐004588‐30.