Avi On

Comparison of two dosing methods for induction of response and remission with oral budesonide in active pediatric Crohn's disease: A randomized placebo-controlled trial†

Background: Oral budesonide has been found to be comparable to systemic corticosteroids in mild to moderately active Crohns disease (CD). Remission rates in pediatric studies to date have been suboptimal (47%–55%), even though patients with colonic involvement were excluded in some studies. In addition, the optimal pediatric dosing regimen has never been evaluated before. Methods: This was a randomized, controlled, double‐blind study in 70 children with mild or moderately active CD randomized to 1 of 2 groups: Group 1: Standard dose budesonide (9 mg/day) for 7 weeks followed by 6 mg budesonide daily for an additional 3 weeks. Group 2: Induction with 12 mg/day for the first month followed by the same regimen as Group 1. Outcome measures included a decrease in Pediatric Crohns Disease Activity Index and remission rates. Patients with colonic disease were not excluded. Results: At week 7 a clinical response was obtained in 51.4% in Group 1 versus 74.3% in Group 2. A significant decrease in C‐reactive protein was seen only in Group 2. At the end of treatment, remission was obtained in 42.9% in Group 1 versus 65.7% in Group 2 (P = 0.054). There was no significant difference in adverse events or serum cortisol. Conclusions: Use of an induction dose of budesonide followed by a budesonide taper resulted in a trend to higher rates of clinical remission and a decrease in inflammation, without an increase in steroid‐associated side effects. Budesonide was also useful for patients with ileocolonic disease.

Resistance of Helicobacter pylori to tetracycline, amoxicillin, clarithromycin and metronidazole in Israeli children and adults.

The aim of this study was to examine Helicobacter pylori-resistance rate to different antibiotics: tetracycline, amoxicillin, clarithromycin and metronidazole, and to compare eradication rates in adults and children in Israel. The study was based on the hypothesis of high-resistance rates to clarithromycin and metronidazole especially in adults and overall low-resistance rates to tetracycline and amoxicillin. One seventy six biopsies from patients with dyspeptic symptoms were cultured of which 100 were from adults (19–79 years) and 76 from children (7–17 years). All positive cultures were examined by Epsilometer test for MIC determination against tetracycline, amoxicillin, clarithromycin and metronidazole. 48.3% (85 out of 176) were H. pylori positive, of which 44% were from adults and 54% from children. Antibiotic resistance was seen in 31 out of 44 (70.5%) for metronidazole, 1 out of 44 (2.3%) for amoxicillin, 10 out of 44 (22.3%) for clarithromycin and 1 out of 44 (2.3%) for tetracycline among adults. Antibiotic resistance was seen in 10 out of 41 (24.4%) for metronidazole, 5 out of 41 (12.2%) for amoxicillin, 10 out of 41 (24.4%) for clarithromycin and 1 out of 41 (2.4%) for tetracycline among children. High rates of H. pylori resistance to metronidazole and clarithromycin was found especially among adults. Therefore, to increase the success rate of anti-H. pylori treatment, other classes of antibiotics need to be considered.

The Therapy Beneath the Fun: Medical Clowning During Invasive Examinations on Children

Objective. The qualitative research presented here is part of a larger project on the significance of medical clowning during invasive examinations in children in the Department of Gastroenterology and the Center for the Sexually Abused in a hospital in Israel. It investigated what makes up the essence of medical clowning, what skills and techniques are used by medical clowns, and whether their work contains therapeutic elements. Methods. A total of 9 children undergoing invasive examinations and 9 of their accompanying parents participated in semistructured interviews, which were analyzed using a thematic analysis methodology assisted by an Atlas-ti software program. Results. The interviews revealed that the medical clowning intervention during invasive examinations was essentially therapeutic, with the clown using theatrical and clowning tools to incorporate therapeutic elements such as empowerment, reversal of role, reframing, and building a therapeutic alliance. In addition, during the invasive examinations, the medical clowning followed the model of brief crisis intervention therapy. Conclusion. The study advances the need to incorporate medical clowns as an integral part of medical teams performing invasive procedures and to include clowns in all stages of the hospital visit when children undergo invasive examinations.

The antimicrobial susceptibility of Helicobacter pylori in strains isolated from children in Israel

OBJECTIVES Helicobacter pylori is a bacterial pathogen causing inflammation of the gastric mucosa that may lead to peptic ulcer, perforation or malignancy. Children are at risk of contracting H. pylori and developing subsequent morbidity. Diagnosis and management in children are difficult and merit a different approach compared with adults. This study aimed to describe the antimicrobial resistance rates of H. pylori to amoxicillin, tetracycline, clarithromycin, metronidazole, levofloxacin and rifampicin. METHODS Biopsies (n=154) collected during endoscopic examinations were cultivated for 10days using a growth medium selective for H. pylori, of which 89 were H. pylori-positive. Antimicrobial resistance of the strains was assessed by Etest to establish minimum inhibitory concentrations (MICs) according to British Society for Antimicrobial Chemotherapy guidelines. RESULTS Resistance rates were most notable for amoxicillin and clarithromycin at 12% and 35% with MICs of 0.74μg/mL and 2.51μg/mL, respectively. Resistance rates to tetracycline and levofloxacin were 8% and 2% with MICs of 2.57μg/mL and 2.0μg/mL, respectively. Resistance rates to rifampicin and metronidazole were 3% and 8% with MICs of 2.0μg/mL and 9.71μg/mL, respectively. CONCLUSION Current rising antibiotic resistance rates for H. pylori are of concern. Performance of culture enables determination of the susceptibility profile, which may lead to a better choice of, and perhaps narrower spectrum, antibiotic agent. In light of these findings, we suggest that optimising the choice of antibiotic agent in children with H. pylori infection remains a challenge for clinicians and thus requires further investigation in randomised clinical trials.

Once- Versus Twice-daily Mesalazine to Induce Remission in Paediatric Ulcerative Colitis: A Randomised Controlled Trial.

Background Trials in adults suggested that, in ulcerative colitis [UC], once-daily [OD] dosing of 5-ASA [5-amino salicylic acid] may be as or more effective than twice-daily [BD] dosing. In this induction of remission, investigator-blinded, randomised controlled-trial, we aimed to compare effectiveness and safety of once- versus twice-daily mesalazine in paediatric UC. Methods Children, aged 4-18 years with a PUCAI [Paediatric Ulcerative Colitis Activity Index] of 10-55 points at inclusion, were randomised in blocks of six with blinded allocation to OD or BD mesalazine, using a weight-based dosing table. The primary outcome was mean PUCAI score at Week 6. Results A total of 83/86 randomised children were eligible and analysed: 43 in the OD group and 40 in the BD group (mean age 14 ± 2.7 years, 43 [52%] males, 51 [62%] extensive colitis). The groups did not differ with regard to disease activity or any other parameter at baseline. There was no difference in median PUCAI score between the OD group and BD group at Week 6: 15 ( interquartile range [IQR] 5-40) versus 10 [0-40]; p = 0.48]. Response was seen in 25 [60%] OD versus 25 [63%] BD dosing [p = 0.78]. Proportion of children in remission [PUCAI < 10] at Week 6 was 13 [30%] OD versus 16 [40%] BD; p = 0.35]. Most adverse events were related to disease aggravation; the rates of serious adverse events were similar [p > 0.2]. Conclusions In this first randomised controlled trial in children, no differences were found between OD and BD dosing for any clinical outcome. Remission was achieved in 35% of children treated with mesalazine for active UC.

Seriously clowning: Medical clowning interaction with children undergoing invasive examinations in hospitals

ABSTRACT This qualitative study examined the subjective experience of children undergoing an invasive examination in the hospital when accompanied by a medical clown. In-depth semi-structured interviews were conducted with nine such children and nine of their accompanying parents. The children were patients in two outpatient departments (Pediatric Gastroenterology and a Center for the Sexually Abused) in a hospital in Israel. Interviews were coded thematically using an Atlas.ti software program. Analysis of the interviews indicated that the intervention of the clown positively changed the children’s perceptions of the hospital, of experiencing the examination, and of their life narrative. Medical clowns thus appear to be a central, meaningful, and therapeutic source for children undergoing invasive examinations in hospital, as well as for their parents. Therefore, it may be advisable to incorporate medical clowns as an integral part of medical teams performing invasive procedures and to include the clowns in all stages of the hospital visit.

GenoType® HelicoDR test in comparison with histology and culture for Helicobacter pylori detection and identification of resistance mutations to clarithromycin and fluoroquinolones

There are several methods for Helicobacter pylori infection diagnosis.

Improvement and optimization of the classical gastric biopsy culture technique for Helicobacter pylori diagnosis using trypsin.

Helicobacter pylori infection represents a key factor in the aetiology of various gastrointestinal diseases. H. pylori infection diagnosis is generally achieved using both invasive (e.g. biopsy of the gastric epithelium) and non-invasive methods. Therefore, cultivation on a growth medium becomes complex. Trypsin is a proteinase enzyme that plays a role in an early stage of tissue digestion. In this study, we used trypsin in order to improve the diagnostic sensitivity of the H. pylori cultivation technique. We used 46 duplicate antrum biopsy specimens, divided into trypsin-treated and non-treated groups. The tissues were seeded on a selective H. pylori growth agar medium. We demonstrated that the classic H. pylori culture technique misses the growth of a large number of H. pylori colonies. Significantly more colonies were found in the trypsin-treated specimens group.

Mesalamine Enemas for Induction of Remission in Oral Mesalamine-refractory Pediatric Ulcerative Colitis: A Prospective Cohort Study

Background Paediatric ulcerative colitis [UC] is more extensive than adult disease, and more often refractory to mesalamine. However, no prospective trials have evaluated mesalamine enemas for inducing remission in children. Our goal was to evaluate the ability of mesalamine enemas to induce remission in mild to moderate paediatric UC refractory to oral mesalamine. Methods This was an open-label arm of a previously reported randomised controlled trial of once-daily mesalamine in active paediatric UC [MUPPIT trial]. Children aged 4-18 years, with a Paediatric Ulcerative Colitis Activity Index [PUCAI] score of 10-55, were enrolled after failing at least 3 weeks of full-dose oral mesalamine. Patients treated with steroids or enemas in the previous month and those with isolated proctitis were excluded. Children received Pentasa® enemas 25 mg/kg [up to 1g] daily for 3 weeks with the previous oral dose. The primary endpoint was clinical remission by Week 3. Results A total of 38 children were enrolled (mean age 14.6 ± 2.3 years; 17/38 [45%] with extensive colitis). Clinical remission was obtained in 16 [42%] and response was obtained in 27 [71%] at Week 3. Eight children deteriorated and required steroids. There were no differences in baseline parameters between those who entered or failed to enter remission, including disease extent [43% in left-sided and 41% in extensive colitis] and disease activity [44% in mild and 41% in moderate activity]. Conclusion Clinical remission can be markedly increased in children who are refractory to oral mesalamaine by adding mesalamine enemas for 3 weeks, before commencing steroids.

Phenotypic and genotypic correlation as expressed in Helicobacter pylori resistance to clarithromycin and fluoroquinolones

BackgroundHelicobacter pylori susceptibility to clarithromycin and fluoroquinolone can be determined through Etest or molecular assays. We examined the correlation between phenotypic susceptibility (MIC results) and genotypic susceptibility in H. pylori strains isolated from gastric biopsies.ResultsOut of 85 duplicate biopsies obtained from patients from northern Israel who underwent endoscopy, 70 were positive for H. pylori using the CUTest (urease test). These biopsies were cultured for H. pylori and Etest breakpoints were determined for levofloxacin and clarithromycin. H. pylori detection, characterization of wild type (WT) or mutant alleles, and antibiotic resistance were determined molecularly using GenoType HelicoDR kit. Phenotypic and genotype results were compared. The molecular method had higher sensitivity for detection of H. pylori than culture (94.3% vs. 77.1%). Resistance to clarithromycin was higher than to levofloxacin by both methods. Levofloxacin resistance was found in 21.2 and 0% using genotypic and phenotypic methods, respectively. Clarithromycin resistance was found in 66.7 and 62.9% by genotypic and phenotypic methods, respectively. Some samples were found susceptible by Etest and resistant by GenoType HelicoDR (13/53 samples) and some vice versa (10/53 samples).ConclusionGenoType HelicoDR kit has high sensitivity rate for H. pylori detection. It has the ability to detect many mutations and can help to determine initial antibiotic treatment at the beginning of therapy. However, there were a few cases where there was a phenotype-genotype mismatch result that could derive from possible causes. For example, a resistance mechanism that is not tested in the kit.