Efficacy and Safety of Carbon Dioxide Versus Air Insufflation for Colonoscopy in Deeply Sedated Pediatric Patients.

OBJECTIVES: Studies have shown the advantages of carbon dioxide (CO2) over air insufflation in the adult population during colonoscopies. This study was designed to investigate the efficacy and safety of CO2 insufflation in deeply sedated children undergoing colonoscopy. METHODS: This was a prospective, randomized, double-blind clinical trial. We recruited 100 consecutive pediatric patients who had colonoscopy under deep sedation for various indications. Patients were first randomized by history of abdominal pain and then randomly assigned to either CO2 or air insufflation. Postprocedural abdominal pain scores were registered on a 10-point visual analog rating scale and significant pain was defined as a score of 3 or higher. Abdominal circumferences and end tidal CO2 (ETCO2) levels were measured. Complications during and after the procedure were recorded. RESULTS: We did not find statistically significant difference between CO2 and air insufflation on univariate analysis because of low number of children experiencing significant pain after colonoscopy. After adjusting for baseline pain, we found that pain was significantly lower in patients after CO2 versus air insufflation on multivariable analysis (P = 0.03). The significant factors related to pain were duration of the procedure (P = 0.006), history of abdominal pain (P = 0.002) and previous abdominal surgery (P = 0.02). CO2 insufflation was associated with decreased abdominal circumference after colonoscopy (P = 0.002). Girls were more likely to have pain regardless of intervention (P = .04). CONCLUSIONS: Most children tolerate endoscopic procedures without significant pain. Our study was underpowered to show significant difference between air and CO2 on univariate analysis. CO2 insufflation during colonoscopy, however, may reduce postprocedural abdominal pain. Significant factors for increased pain on multivariate analysis included colonoscopy length over 30 minutes, history of abdominal pain, and previous abdominal surgery.

Neuromodulation with percutaneous electrical nerve field stimulation is associated with reduction in signs and symptoms of opioid withdrawal: a multisite, retrospective assessment.

BACKGROUND: Finding an effective, non-pharmacological approach to treat opioid withdrawal could remove some of the barriers associated with pharmacotherapy. The BRIDGE® is a noninvasive, percutaneous electrical nerve field stimulator developed to target pain. OBJECTIVES: This pilot study aimed to determine (1) the effects of the BRIDGE on withdrawal scores during the induction phase of opioid withdrawal therapy, (2) the percentage of subjects who successfully transitioned to medication assisted therapy (MAT). METHODS: Adult patients treated with the BRIDGE during medically supervised withdrawal were included in this open label, uncontrolled, and retrospective study. The clinical opioid withdrawal scale (COWS) scores were prospectively recorded at different intervals (20, 30, and 60 min) and analyzed retrospectively. A subset of patients had scores recorded 5-days post-BRIDGE. Those who returned to the clinic and received their first dose of maintenance medication were considered to be successfully transitioned. RESULTS: In this cohort (n=73), 65% were male. The mean COWS score prior to BRIDGE placement was 20.1 (±6.1). Twenty minutes after BRIDGE placement, the mean score was reduced to 7.5 (±5.9) (62.7% reduction, p<0.001). The scores further decreased after 30 minutes 4.0 (±4.4) and 60 minutes 3.1 (±3.4) (84.6% reduction, p<0.001). No rescue medications were administered during this period. The mean withdrawal score on day 5 was 0.6 (97.1% reduction, p<0.001) (n=33). Overall, 64/73 patients (88.8%) successfully transitioned to MAT. CONCLUSIONS: Neurostimulation with the BRIDGE is associated with a reduction in opioid withdrawal scores. This effect persisted during the induction period and allowed for effective transition to MAT.

Gastrointestinal Pharmacology.

There is little evidence for most of the medications currently used to treat functional abdominal pain disorders (FAPDs) in children. Not only are there very few clinical trials, but also most have significant variability in the methods used and outcomes measured. Thus, the decision on the most appropriate pharmacological treatment is frequently based on adult studies or empirical data. In children, peppermint oil, trimebutine, and drotaverine have shown significant benefit compared with placebo, each of them in a single randomized clinical trial. A small study found that cyproheptadine was beneficial in the treatment of FAPDs in children. There are conflicting data regarding amitriptyline. While one small study found a significant benefit in quality of life compared with placebo, a large multicenter study found no benefit compared with placebo. The antidepressant, citalopram, failed to meet the primary outcomes in intention-to-treat and per-protocol analysis. Rifaximin has been shown to be efficacious in the treatment of adults with IBS. Those findings differ from studies in children where no benefit was found compared to placebo. To date, there are no placebo-controlled trials published on the use of linaclotide or lubiprostone in children. Alpha 2 delta ligands such as gabapentin and pregabalin are sometimes used in the care of this group of children, but no clinical trials are available in children with FAPDs. Similarly, novel drugs that have been approved for the care of irritable bowel with diarrhea in adults such as eluxadoline have yet to be studied in children. CONCLUSIONS: Little data support the use of most medications commonly used to treat FAPDs in children. More randomized, placebo-controlled studies are needed to assess the efficacy of pharmacological interventions in the treatment of FAPDs in children.

Chronic idiopathic nausea of childhood.

OBJECTIVES: To compare children with primary, chronic idiopathic nausea to those with secondary nausea associated with functional abdominal pain. STUDY DESIGN: Retrospective chart review of 45 children with a primary complaint of chronic nausea several times per week. Comparisons were made to prospectively collected data on 49 children with functional abdominal pain and comorbid nausea. RESULTS: The majority of those affected were adolescent Caucasian females. Subjects with chronic nausea had a more severe presentation with daily 88% (vs 26%) and constant 60% (vs 10%) nausea (P < .001), one-half with peak morning intensity. In the chronic nausea group, 62% had migraines, and 71% (vs 22%) had familial migraines (P < .001), 36% had postural tachycardia syndrome and 27% cyclic vomiting syndrome. Both groups suffered comorbid symptoms (anxiety, dizziness, fatigue, and sleep problems). The chronic nausea cohort underwent extensive, negative medical evaluations. CONCLUSIONS: Chronic idiopathic nausea of childhood is a poorly described symptom. Patients with primary (vs secondary) chronic nausea were more likely Caucasian, older adolescent females with severe, daily nausea and comorbid conditions such as anxiety, dizziness, and fatigue as well as significantly more migraine features. Chronic nausea is a major, disabling symptom that requires increased recognition as a separate functional entity. Future studies may need to focus on comorbid conditions including migraine and dysautonomia.

Comparison of light and electron microscopy in measurement of esophageal intercellular space in children.

OBJECTIVES: A good objective marker of esophageal mucosal damage from gastroesophageal reflux disease (GERD) is lacking in children. Increased esophageal epithelial intercellular (EEIC) space measured using electron microscopy (EM) has been proposed as a surrogate of esophageal mucosal damage in adults with GERD. The aim of the present study was to compare EEIC space measured using EM and light microscopy (LM) in children with nonerosive reflux disease (NERD) with asymptomatic controls. METHODS: Distal esophageal mucosal biopsy was used to measure EEIC space using EM in 35 NERD subjects and 8 controls. In a subset of these patients we used phase contrast LM to measure EEIC space area (26 NERD subjects and 8 controls). RESULTS: The median (range) EEIC space measured using EM in the NERD group was 1.15 (0.74-1.64) µm compared with 0.93 (0.67-1.11) µm in the control group (P = 0.002). The median (range) EEIC space measured using LM was 14.4% (9.6%-26.3%) in the NERD group and 9.6% (8.5%-17.2%) in controls (P = 0.003). Using a cutoff value of 1.02 µm for normal EEIC space measured by EM, we obtained 73% sensitivity and 75% specificity to distinguish the NERD group from the control group, and using a cutoff value of 11.1% for EEIC space measured by LM, we obtained 96% sensitivity and 75% specificity. CONCLUSIONS: EEIC space is increased in children with NERD compared with that in controls, suggesting that changes in EEIC space can be a useful marker of esophageal mucosal injury in children with NERD. Our results suggest that the accuracy of EM and LM to evaluate EEIC space changes in NERD is comparable, and LM may be a more cost-effective option.

Assessment of abdominal pain through global outcomes and recent FDA recommendations in children: are we ready for change?

OBJECTIVES: Irritable bowel syndrome is a multisymptom construct, with abdominal pain (AP) acting as the driving symptom of patient-reported severity. The Food and Drug Administration considers a >30% decrease in AP as satisfactory improvement, but this has not been validated in children. We investigated the correspondence of 2 measures for AP assessment, ≥30% improvement in AP and global assessment of improvement. METHODS: Secondary analysis of data from 72 children who completed a randomized clinical trial for abdominal pain-associated functional gastrointestinal disorders. Children completed daily assessment of AP intensity, functional disability inventory (FDI), question regarding pain's interference with activities, and 2 global assessment questions. We measured the extent to which ≥30% improvement of AP and global assessment questions correlated with each other and with disability. RESULTS: The global questions correlated with each other (r=0.74; P<0.0001) and with a ≥30% improvement in AP (P<0.01). Global outcomes were satisfaction with treatment was inversely related to the child's report of interference with activities (P<0.01) and symptom relief was positively associated with ≥30% improvement in FDI scores (P<0.009). A 30% change in FDI scores was associated with global questions of symptom relief (P=0.009) but not with satisfaction with treatment (P=0.07). The association of AP improvement with interference with activities (P=0.14) or change in FDI scores (P=0.27) did not reach significance. CONCLUSIONS: Currently used global assessments are significantly associated with decreased pain intensity, decreased interference with daily activities, and a ≥30% change in FDI scores, whereas recommended 30% improvement in pain intensity is not as comprehensive.

Red flags in children with chronic abdominal pain and Crohn's disease-a single center experience.

OBJECTIVE: To compare history and symptoms at initial presentation of patients with chronic abdominal pain (CAP) and Crohn's disease (CD). Red flags are used to help determine which patients with CAP are likely to have an underlying disease such as CD. However, red flags have not been validated and pediatric studies are lacking. STUDY DESIGN: Patients seen in the outpatient Pediatric Gastroenterology Clinic at Children's Hospital of Wisconsin between 2005 and 2008 prospectively completed a demographic, history, and symptom questionnaire. Patients with abdominal pain for at least 1 month and no evidence of organic disease were compared with patients diagnosed with CD confirmed by mucosal biopsies. RESULTS: Data were collected on 606 patients (128 with CD and 478 with functional gastrointestinal disorders). Patients with functional gastrointestinal disorders had more stressors (P < .001), were more likely to have a positive family history of irritable bowel syndrome, reflux, or constipation (P < .05), were more likely to have vomiting but less likely to have hematochezia, weight loss, and problems gaining weight (P < .05); wake from sleep and joint pain were no different between groups. Anemia, hematochezia, and weight loss were most predictive of CD (cumulative sensitivity of 94%). CONCLUSION: The presence of anemia, hematochezia, and weight loss help identify patients with CAP who require further work-up and referral to a pediatric gastroenterologist. Furthermore, waking from sleep or joint pain occurred similarly between groups and should not be considered as "red flags."

High prevalence of nausea in children with pain-associated functional gastrointestinal disorders: are Rome criteria applicable?

OBJECTIVES: The aim of the study was to determine the prevalence of nausea in pediatric patients with pain-associated functional gastrointestinal disorders (FGIDs), examine the effect on social and school functioning, and examine the applicability of pediatric Rome III criteria. METHODS: A total of 221 pediatric patients (6-18 years of age) with chronic abdominal pain prospectively completed a demographic, history, and gastrointestinal symptom questionnaire adapted from the Questionnaire on Pediatric Gastrointestinal Symptoms (QPGS). The 6-item, revised Pediatric Migraine Disability Assessment Score tool was used to assess the effect of symptoms on school, home, and social disability. Rome III criteria were applied to all subjects. RESULTS: A total of 183 patients with pain and nausea for a minimum of 2 months were identified. Ninety-six patients were studied after excluding those with vomiting and/or organic disease. Among these, 53% had nausea at least 2 times per week and 28% experienced daily nausea. Frequency of nausea was significantly correlated with poor school and social functioning, and uniquely predicted social disability beyond pain. Although 87% met adult Rome criteria for functional dyspepsia, only 29% met corresponding pediatric Rome criteria. Additionally, 22% met the criteria for irritable bowel syndrome (IBS)-diarrhea, 13% for IBS-constipation, 13% for abdominal migraine, and 31% were classified as having functional abdominal pain. Pediatric IBS-diarrhea and IBS-constipation overlapped in 5% of patients. CONCLUSIONS: Nausea is a prevalent symptom in patients with pain-associated FGIDs and correlates with poor school and social functioning. There is substantial overlap among FGIDs in children with nausea.

Accuracy of pain recall in children.

BACKGROUND AND AIM: Chronic abdominal pain (AP) is common in children. Recall of symptoms is used clinically to determine management, to assess treatment progress, and in drug studies to assess outcomes. Limited data exist on accuracy of AP recall in children. The aim of the present study was to assess ability to accurately recall AP in children. METHODS: The study was a secondary analysis of data obtained from a double-blind, randomized, placebo-controlled trial, evaluating amitriptyline in children with functional gastrointestinal disorders. Children ages 8 to 17 years with AP predominant functional gastrointestinal disorders based on Rome II criteria were recruited from 6 centers. Those with evidence of organic disease were excluded. Patients maintained AP diary daily for 1 month (presence, frequency, and intensity). At the end of the study, patients reported the number of days of AP during previous month. Agreement between daily pain reports and recalled pain was assessed. Univariate analysis was conducted with Spearman rank correlations. RESULTS: We recruited 63 children (45 girls, mean age 12.8 years). Sixteen percent children had perfect agreement on number of days of AP. Fifty-four percent of children recalled fewer episodes of pain. The average number of days with AP by recall was 17.7/month, whereas by diary it was 23.5/month (P = 0.001). Correlation between patient recall of the last week of symptoms (r = 0.47) was no better than correlation between recall of the last 30 days of symptoms (r = 0.48). On comparing AP recall versus various pain intensities, reported AP did not reflect only AP of greater severity. Higher correlation of recall of symptoms was seen in children 11 years or younger (r = 0.59) as compared with children older than 11 years (r = 0.26). CONCLUSIONS: Few children can accurately recall the episodes of AP. Children commonly recall a lower frequency of AP than that assessed by prospective diary reports. Reported recall does not reflect a shorter recollection period. Recall is not related to intensity of pain. Adolescents have worse recall of symptoms.

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 (child's 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.

One-day bowel preparation with polyethylene glycol 3350: an effective regimen for colonoscopy in children.

BACKGROUND: Polyethylene glycol (PEG) 3350 is commonly used and has been proven safe and effective for the treatment of chronic constipation and as a 4-day bowel preparation in children. A 1-day PEG 3350 bowel preparation regimen has been recently developed for adults; however, data regarding its use in children are lacking. OBJECTIVE: To evaluate the safety and effectiveness of a 1-day PEG 3350 regimen for bowel preparation in children before colonoscopy. DESIGN: Retrospective review. SETTING: Tertiary-care center. PATIENTS: This study involved all children prescribed a 1-day PEG 3350 bowel preparation regimen before colonoscopy at our center in 2008. INTERVENTION: We reviewed medical records of patients (< or = 18 years of age) who underwent colonoscopy during 2008 and received the 1-day bowel preparation regimen. MAIN OUTCOME MEASUREMENTS: Adequate preparation for colonoscopy, success of colonoscopy, and factors associated with inadequate bowel preparation. RESULTS: Inclusion criteria were met by 272 patients. The median age of the children receiving the 1-day PEG 3350 preparation regimen was 13.7 years (range 1.08-17.92 years). Fifty-two percent were male; 48% were female. The most common indications for colonoscopy included abdominal pain (65%), bloody stools (29%), diarrhea (21%), and weight loss (18%). The 1-day bowel preparation regimen was effective in 253 patients (93%). The indication for colonoscopy, the age of the child, or a history of constipation did not significantly alter the success rate of colonoscopy. LIMITATIONS: A retrospective study at one tertiary-care center. CONCLUSION: The 1-day PEG 3350 bowel preparation regimen is safe and effective and should be considered for use as preparation for colonoscopy in children.

Hypomorphic SI genetic variants are associated with childhood chronic loose stools.

OBJECTIVE: The SI gene encodes the sucrase-isomaltase enzyme, a disaccharidase expressed in the intestinal brush border. Hypomorphic SI variants cause recessive congenital sucrase-isomaltase deficiency (CSID) and related gastrointestinal (GI) symptoms. Among children presenting with chronic, idiopathic loose stools, we assessed the prevalence of CSID-associated SI variants relative to the general population and the relative GI symptom burden associated with SI genotype within the study population. METHODS: A prospective study conducted at 18 centers enrolled 308 non-Hispanic white children ≤18 years old who were experiencing chronic, idiopathic, loose stools at least once per week for >4 weeks. Data on demographics, GI symptoms, and genotyping for 37 SI hypomorphic variants were collected. Race/ethnicity-matched SI data from the Exome Aggregation Consortium (ExAC) database was used as the general population reference. RESULTS: Compared with the general population, the cumulative prevalence of hypomorphic SI variants was significantly higher in the study population (4.5% vs. 1.3%, P < .01; OR = 3.5 [95% CI: 6.1, 2.0]). Within the study population, children with a hypomorphic SI variant had a more severe GI symptom burden than those without, including: more frequent episodes of loose stools (P < .01), higher overall stool frequency (P < .01), looser stool form (P = .01) and increased flatulence (P = .02). CONCLUSION: Non-Hispanic white children with chronic idiopathic loose stools have a higher prevalence of CSID-associated hypomorphic SI variants than the general population. The GI symptom burden was greater among the study subjects with a hypomorphic SI variant than those without hypomorphic SI variants.

Nausea exacerbates symptom burden, quality of life, and functioning in adolescents with functional abdominal pain disorders.

BACKGROUND: Nausea frequently co-exists with functional abdominal pain disorders (FAPDs) and may be linked to a higher disease burden. This study aimed to prospectively compare multisystem symptoms, quality of life, and functioning in FAPDs with and without nausea. METHODS: Adolescents ages 11-18 years fulfilling Rome III criteria for a FAPD were grouped by the presence or absence of chronic nausea. Subjects completed validated instruments assessing nausea (Nausea Profile Questionnaire = NPQ), quality of life (Patient-Reported Outcome Measurement Information System), functioning (Functional Disability Inventory), and anxiety (State-Trait Anxiety Inventory for Children). Group comparisons were performed for instruments, multisystem symptoms, school absences, and clinical diagnoses. KEY RESULTS: A total of 112 subjects were included; 71% reported chronic nausea. Patients with Nausea compared to No Nausea had higher NPQ scores (P ≤ 0.001), worse quality of life (P = 0.004), and greater disability (P = 0.02). State and trait anxiety scores were similar (P = 0.57, P = 0.25). A higher NPQ score correlated with poorer quality of life, more disability, and higher anxiety. Specific comorbidities were more common in Nausea vs No Nausea group: dizziness (81% vs 41%; P ≤ 0.001), concentrating difficulties (68% vs 27%; P ≤ 0.001), chronic fatigue (58% vs 20%; P = 0.01), and sleep disturbances (73% vs 48%; P = 0.02). The Nausea group reported more school absences (P = 0.001) and more commonly met criteria for functional dyspepsia (P = 0.034). CONCLUSION AND INFERENCES: Nausea co-existing with FAPDs is associated with a higher extra-intestinal symptom burden, worse quality of life, and impaired functioning in children. Assessing and targeting nausea therapeutically is essential to improve outcomes in FAPDs.

ERCP in the evaluation of abdominal pain in children.

BACKGROUND: ERCP is feasible and safe in the pediatric population. Its utility in the evaluation of children with pain suggestive of a pancreatobiliary origin without objective findings compared with those with abnormal biochemical and/or imaging studies is not well known. OBJECTIVE: To determine the utility of ERCP in the diagnosis and management of children seen with abdominal pain. DESIGN: Retrospective review. SETTING: One tertiary center. PATIENTS: All children who underwent ERCP at one tertiary center from 1994 to 2004. METHOD: An endoscopy database was used. Data sets with regard to indications, technical success, complications, and outcomes were evaluated. Before ERCP, children with abdominal pain were categorized into 2 groups: group I, those with objective findings, namely abnormal biochemistry and/or abnormal imaging studies; group II, those who had abdominal pain without objective findings. MAIN OUTCOME MEASUREMENTS: ERCP success and failure rates, findings, interventions, complications, and outcomes were determined. Data were compared between group I and group II. RESULTS: A total of 185 consecutive children with abdominal pain who underwent ERCP were identified (131 in group I and 54 in group II). ERCP technical success was achieved in 98%. In group I, ERCP identified a cause for abdominal pain in 93 of 129 children (72%). Fifty-four of 93 patients (58%) in this group underwent endoscopic intervention with resolution of pain. In group II, a cause for abdominal pain was identified in 30 of 53 children (56%)(P < .025 compared with group I). Fourteen of 30 patients (47%) in this group underwent endoscopic intervention with resolution of pain. Complications noted were mild pancreatitis in two and self-limited bleeding in one. LIMITATIONS: A retrospective study, one tertiary center where the majority of the ERCPs were performed by one experienced operator. CONCLUSIONS: ERCP in children with abdominal pain suggestive of a pancreatobiliary origin has a favorable risk:benefit ratio.

Removal of impacted food in children with eosinophilic esophagitis using Saeed banding device.

Food impaction in patients with eosinophilic esophagitis is being recognized increasingly. Retrieval of impacted food may be necessary if it does not resolve spontaneously. The present report describes a new technique for removal of friable impacted food from the esophagus using a modified version of the Saeed banding device. With this technique, impacted food was safely removed in a single attempt in each of 3 patients.

Disaccharidase Deficiencies in Children With Chronic Abdominal Pain.

OBJECTIVES: Carbohydrate intolerance or malabsorption has been suggested as a cause of chronic abdominal pain (CAP) in a subset of patients. We aimed to evaluate disaccharidase deficiencies in children with functional CAP and to correlate deficiencies with clinical features. METHOD: Patients presenting to the gastroenterology clinic at Children's Hospital of Wisconsin with abdominal pain prospectively completed a detailed demographic, history, and symptom questionnaire. The CAP cohort included those with at least 1 month of symptoms. Data on disaccharidase activity and histology of endoscopic biopsies were collected retrospectively. Only patients with normal histology were included in the study. The association between groups with low disaccharidases and clinical features was examined. RESULTS: A total of 203 pediatric patients with CAP were included. The mean (SD) age was 11.5 (3.1) years, and 32.5% were male. The percentages of abnormally low disaccharidase levels using the standard laboratory cutoffs were lactase, 37%; sucrase, 21%; glucoamylase, 25%; and palatinase, 8%. Thirty-nine percent of the patients with low lactase also had low sucrase, and 67% of the patients with low sucrase had low lactase. There was no significant difference in the activities of any of the disaccharidases or sucrase/lactase ratio in relation to age. Also, no association was found between stool consistency, stool frequency, or location of pain and low disaccharidase activity. CONCLUSIONS: A large proportion of patients with CAP have deficiencies in disaccharidases. Bowel frequency, vomiting, or location of pain was no different between groups, suggesting that these clinical features cannot be used to predict disaccharidase deficiencies.

Percutaneous electrical nerve field stimulation modulates central pain pathways and attenuates post-inflammatory visceral and somatic hyperalgesia in rats.

A non-invasive, auricular percutaneous electrical nerve field stimulation (PENFS) has been suggested to modulate central pain pathways. We investigated the effects of BRIDGE® device on the responses of amygdala and lumbar spinal neurons and the development of post-colitis hyperalgesia. Male Sprague-Dawley rats received intracolonic trinitrobenzene sulfonic acid (TNBS) and PENFS on the same day. Control rats had sham devices. The visceromotor response (VMR) to colon distension and paw withdrawal threshold (PWT) was recorded after 7days. A different group of rats had VMR and PWT at baseline, after TNBS and following PENFS. Extracellular recordings were made from neurons in central nucleus of the amygdala (CeA) or lumbar spinal cord. Baseline firing and responses to compression of the paw were recorded before and after PENFS. Sham-treated rats exhibited a much higher VMR (>30mmHg) and lower PWT compared to PENFS-treated rats (p<0.05). PENFS decreased the VMR to colon distension and increased the PWT compared to pre-stimulation (p<0.05). PENFS resulted in a 57% decrease in spontaneous firing of the CeA neurons (0.59±0.16 vs control: 1.71±0.32imp/s). Similarly, the response to somatic stimulation was decreased by 56% (3.6±0.52 vs control: 1.71±0.32 imps/s, p<0.05). Spinal neurons showed a 47% decrease in mean spontaneous firing (4.05±0.65 vs control: 7.7±0.87imp/s) and response to somatic stimulation (7.62±1.7 vs control: 14.8±2.28imp/s, p<0.05). PENFS attenuated baseline firing of CeA and spinal neurons which may account for the modulation of pain responses in this model of post-inflammatory visceral and somatic hyperalgesia.

Neurostimulation for abdominal pain-related functional gastrointestinal disorders in adolescents: a randomised, double-blind, sham-controlled trial.

BACKGROUND: Development of safe and effective therapies for paediatric abdominal pain-related functional gastrointestinal disorders is needed. A non-invasive, US Food and Drug Administration-cleared device (Neuro-Stim, Innovative Health Solutions, IN, USA) delivers percutaneous electrical nerve field stimulation (PENFS) in the external ear to modulate central pain pathways. In this study, we evaluated the efficacy of PENFS in adolescents with abdominal pain-related functional gastrointestinal disorders. METHODS: In this randomised, sham-controlled trial, we enrolled adolescents (aged 11-18 years) who met Rome III criteria for abdominal pain-related functional gastrointestinal disorders from a single US outpatient gastroenterology clinic. Patients were randomly assigned (1:1) with a computer-generated randomisation scheme to active treatment or sham (no electrical charge) for 4 weeks. Patients were stratified by sex and presence or absence of nausea. Allocation was concealed from participants, caregivers, and the research team. The primary efficacy endpoint was change in abdominal pain scores. We measured improvement in worst abdominal pain and composite pain score using the Pain Frequency-Severity-Duration (PFSD) scale. Participants with less than 1 week of data and those with organic disease identified after enrolment were excluded from the modified intention-to-treat population. This trial has been completed and is registered with ClinicalTrials.gov, number NCT02367729. FINDINGS: Between June 18, 2015, and Nov 17, 2016, 115 children with abdominal pain-related functional gastrointestinal disorders were enrolled and assigned to either PENFS (n=60) with an active device or sham (n=55). After exclusion of patients who discontinued treatment (n=1 in the PENFS group; n=7 in the sham group) and those who were excluded after randomisation because they had organic disease (n=2 in the PENFS group; n=1 in the sham group), 57 patients in the PENFS group and 47 patients in the sham group were included in the primary analysis. Patients in the PENFS group had greater reduction in worst pain compared with sham after 3 weeks of treatment (PENFS: median score 5·0 [IQR 4·0-7·0]; sham: 7·0 [5·0-9·0]; least square means estimate of change in worse pain 2·15 [95% CI 1·37-2·93], p<0·0001). Effects were sustained for an extended period (median follow-up 9·2 weeks [IQR 6·4-13·4]) in the PENFS group: median 8·0 (IQR 7·0-9·0) at baseline to 6·0 (5·0-8·0) at follow-up versus sham: 7·5 (6·0-9·0) at baseline to 7·0 (5·0-8·0) at follow-up (p<0·0001). Median PFSD composite scores also decreased significantly in the PENFS group (from 24·5 [IQR 16·8-33.3] to 8·4 [3·2-16·2]) compared with sham (from 22·8 [IQR 8·4-38·2] to 15·2 [4·4-36·8]) with a mean decrease of 11·48 (95% CI 6·63-16·32; p<0·0001) after 3 weeks. These effects were sustained at extended follow-up in the PENFS group: median 24·5 (IQR 16·8-33·3) at baseline to 12 (3·6-22·5) at follow-up, compared with sham: 22·8 (8·4-38·2) at baseline to 16·8 (4·8-33·6) at follow-up (p=0·018). Ten patients reported side-effects (three of whom discontinued the study): ear discomfort (n=6; three in the PENFS group, three in the sham group), adhesive allergy (n=3; one in the PENFS group, two in the sham group), and syncope due to needle phobia (n=1; in the sham group). There were no serious adverse events. INTERPRETATION: Our results show that PENFS with Neuro-Stim has sustained efficacy for abdominal pain-related functional gastrointestinal disorders in adolescents. This safe and effective approach expands treatment options and should be considered as a non-pharmacological alternative for these disorders. FUNDING: American Neurogastroenterology and Motility Society.

Can You Teach a Teen New Tricks? Problem Solving Skills Training Improves Oral Medication Adherence in Pediatric Patients with Inflammatory Bowel Disease Participating in a Randomized Trial.

BACKGROUND: Medication nonadherence is associated with higher disease activity, greater health care utilization, and lower health-related quality of life in pediatric inflammatory bowel diseases (IBD). Problem solving skills training (PSST) is a useful tool to improve adherence in patients with chronic diseases but has not been fully investigated in IBD. This study assessed feasibility, acceptability, and preliminary efficacy of PSST in pediatric IBD. METHODS: Recruitment occurred during outpatient clinic appointments. After completion of baseline questionnaires, families were randomized to a treatment group or wait-list comparison group. The treatment group received either 2 or 4 PSST sessions. Youth health-related quality of life was assessed at 3 time points, and electronic monitoring of oral medication adherence occurred for the study duration. RESULTS: Seventy-six youth (ages 11-18 years) on an oral IBD maintenance medication participated. High retention (86%) and treatment fidelity rates (95%) supported feasibility. High satisfaction ratings (mean values ≥4.2 on 1-5 scale) supported intervention acceptability. Modest increases in adherence occurred after 2 PSST sessions among those with imperfect baseline adherence (d = 0.41, P < 0.10). Significant increases in adherence after 2 PSST sessions were documented for participants aged 16 to 18 years (d = 0.95, P < 0.05). Improvements in health-related quality of life occurred after 2 PSST sessions. No added benefit of 4 sessions on adherence was documented (d = 0.05, P > 0.05). CONCLUSIONS: Phone-delivered PSST was feasible and acceptable. Efficacy estimates were similar to those of lengthier interventions conducted in other chronic illness populations. Older adolescents benefited more from the intervention than their younger counterparts.