Systematic review: health-related quality of life in children and adults with eosinophilic oesophagitis-instruments for measurement and determinant factors.

BACKGROUND: Several measures have been used to assess the health-related quality of life (HRQoL) of patients with eosinophilic oesophagitis (EoE). AIMS: To systematically review these HRQoL measures, to appraise measurement properties of specific instruments and to evaluate determinant factors influencing HRQoL in paediatric and adult EoE patients. METHODS: We searched the PubMed, Embase, Scopus, Web of Science (WOS) and PsycINFO databases for documents providing original information on the development of measurement tools and/or evaluation of HRQoL outcomes in EoE patients of all ages. RESULTS: Of the 596 references identified, data was collected from 34 studies (with only 16 of them being published as full papers) including a total of 1,689 individual patients. Three disease-specific HRQoL measures in EoE covering different aspects of patients' lives and developed in English, were scored positive regarding measurement properties. The PedsQL inventory (including parent and child report forms) and the Peds-QoL EoE module were the generic and specific instruments respectively used in children, while the SF-36 and EoE-QoL-A were the most used questionnaires in adults. Patients with EoE show an impaired HRQoL compared to controls, which greatly depends on symptom severity and disease duration. Severity of endoscopic features and female gender may also determine an impaired HRQoL. The effect of treatments on HRQoL requires further assessment. CONCLUSIONS: HRQoL is a relevant outcome that should be considered in clinical practice and research of EoE. Further validation studies in several languages and populations are required to support the use of disease-specific HRQoL measures.

Systematic review with meta-analysis: endoscopic dilation is highly effective and safe in children and adults with eosinophilic oesophagitis.

BACKGROUND: Oesophageal dilation is frequently used as an adjunct treatment to alleviate symptoms that develop from fibrostenotic remodelling in eosinophilic oesophagitis (EoE). Earlier reports described an increased risk of complications associated with dilation. AIM: Perform a systematic review and meta-analysis to assess the efficacy and safety of endoscopic dilation in children and adults with EoE. METHODS: Professional librarians searched MEDLINE, EMBASE, the Cochrane library, Scopus, and Web of Science for articles in any language describing studies of dilation in EoE through December 2016. Studies were selected and data were abstracted independently and in duplicate. Random effects modelling was used to generate summary estimates for clinical improvement and complications (haemorrhage, perforation, hospitalisation, and death). RESULTS: The search resulted in 3495 references, of which 27 studies were included in the final analysis. The studies described 845 EoE patients, including 87 paediatric patients, who underwent a total of 1820 oesophageal dilations. The median number of dilations was 3 (range: 1-35). Clinical improvement occurred in 95% of patients (95% CI: 90%-98%, I2 : 10%, 17 studies). Perforation occurred in 0.38% (95% CI: 0.18%-0.85%, I2 : 0%, 27 studies), haemorrhage in 0.05% (95% CI: 0%-0.3%, I2 : 0%, 18 studies), and hospitalisation in 0.67% (95% CI: 0.3%-1.1%, I2 : 44%, 24 studies). No deaths occurred (95% CI: 0%-0.2% I2 : 0%, 25 studies). CONCLUSIONS: Endoscopic dilation is consistently effective in children and adults with EoE, resulting in improvement in 95% of patients with very low rates (<1%) of major complications.

The Endoscopic Reference Score shows modest accuracy to predict either clinical or histological activity in adult patients with eosinophilic oesophagitis.

BACKGROUND: Conflicting results have been recently reported for the accuracy of the Endoscopic Reference Score (EREFS), an standardised endoscopic classification, to predict the histological activity of eosinophilic oesophagitis (EoE). AIM: To evaluate the accuracy of the EREFS to predict either histological or clinical activity of EoE. METHODS: Prospective multicentre study conducted in eight Spanish centres evaluating adult EoE patients, either naïve or after treatment. Symptoms were evaluated before upper endoscopy through the Dysphagia Symptom Score, whereas researchers scored the EREFS immediately after the endoscopic procedure, unaware of the histological outcome. RESULTS: One hundred and forty-five EoE patients undergoing 240 consecutive endoscopic procedures were included. Exudates (P = 0.03), furrows (P = 0.03) and a composite score of inflammatory signs (exudates, furrows and oedema) (P < 0.001) accurately predicted histological activity. Exudates were the only endoscopic sign showing a good correlation with histological outcome after therapy. Furrows and oedema persisted in 50% and 70% of patients despite histological remission. No endoscopic feature exceeded 70% accuracy to predict histological activity. Likewise, no endoscopic finding could adequately predict dysphagia severity. Crepe paper mucosa, diffuse exudates and severe rings correlated with higher symptom scores. CONCLUSIONS: Endoscopic findings assessed by the Endoscopic Reference Score did not correlate with histological or clinical disease activity in adult EoE patients. Only exudates correlated with peak eosinophil count and histological outcome, whereas furrows and oedema persisted in over half of patients despite histological remission.

The efficacy of step-down therapy in adult patients with proton pump inhibitor-responsive oesophageal eosinophilia.

BACKGROUND: Proton pump inhibitor-responsive oesophageal eosinophilia (PPI-REE) is common in patients with suspected eosinophilic oesophagitis (EoE). However, the long-term efficacy of PPIs and the best maintenance doses are yet to be defined. AIM: To evaluate the durability of the response to PPI therapy after tapering PPI doses in PPI-REE patients. METHODS: Prospective study conducted on PPI-REE patients. Upon complete remission on high-dose PPI therapy (omeprazole 40 mg b.d. for 8 weeks), PPI doses were tapered followed by an endoscopic procedure after each dose reduction. The primary outcomes were sustained clinical and histological remission (<15 eos/HPF) after decreasing PPI doses. RESULTS: From a total of 121 patients with suspected EoE, 40 (33%) achieved complete remission on high-dose PPIs and were given a diagnosis of PPI-REE. No patient in histological remission showed symptom relapse, but half of patients with relapsing oesophageal inflammation were in clinical remission. After reduction to omeprazole 40 mg once daily, 38/31 (81%) remained in complete remission. Among these latter patients, 15/18 (83%) were kept in remission with omeprazole 20 mg once daily. As for side effects, only asymptomatic hypertransaminasemia and oesophageal candidiasis were observed in two patients while receiving high doses of omeprazole. CONCLUSIONS: Most PPI-responsive oesophageal eosinophilia patients show sustained clinical and histological remission with daily PPI doses equal to or below 40 mg of omeprazole. As adverse effects only appeared with the highest dose of omeprazole, it would be advisable to individualise the dose of PPIs for each patient, lowering it to the minimum capable of maintaining the disease controlled.

Optimised empiric triple and concomitant therapy for Helicobacter pylori eradication in clinical practice: the OPTRICON study.

BACKGROUND: Empiric triple therapy for Helicobacter pylori should be abandoned when clarithromycin resistance rate is >15-20%. Optimisation of triple therapy (high-dose acid suppression and 14-day duration) can increase eradication rates by 10%. AIM: To compare the efficacy and safety of optimised triple (OPT-TRI) and nonbismuth quadruple concomitant (OPT-CON) therapies. METHODS: Prospective multicentre study in 16 Spanish centres using triple therapy in clinical practice. In a 3-month two-phase fashion, the first 402 patients received an OPT-TRI therapy [esomeprazole (40 mg b.d.), amoxicillin (1 g b.d) and clarithromycin (500 mg b.d) for 14 days] and the last 375 patients an OPT-CON treatment [OPT-TRI therapy plus metronidazole (500 mg b.d)]. RESULTS: Seven-hundred seventy-seven consecutive patients were included (402 OPT-TRI, 375 OPT-CON). The OPT-CON therapy achieved significantly higher eradication rates in the per-protocol [82.3% (95% CI = 78-86%) vs. 93.8% (91-96%), P < 0.001] and intention-to-treat analysis [81.3% (78-86%) vs. 90.4% (87-93%), P < 0.001]. Adverse events (97% mild/moderate) were significantly more common with OPT-CON therapy (39% vs. 47%, P = 0.016), but full compliance with therapy was similar between groups (94% vs. 92%, P = 0.4). OPT-CON therapy was the only significant predictor of successful eradication (odds ratio, 2.24; 95% CI: 1.48-3.51, P < 0.001). The rate of participating centres achieving cure rates ≥ 90% favoured OPT-CON therapy (OPT-TRI 25% vs. OPT-CON 62%). CONCLUSIONS: Empiric OPT-CON therapy achieved significantly higher cure rates (>90%) compared to OPT-TRI therapy. Addition of metronidazole to OPT-TRI therapy increased eradication rates by 10%, resulting in more mild adverse effects, but without impairing compliance with therapy.

Systematic review: noncoeliac gluten sensitivity.

BACKGROUND: Noncoeliac gluten sensitivity (NCGS) is a controversial emerging disorder. Despite reported symptoms related to the ingestion of gluten, NCGS remains a diagnosis based on the exclusion of coeliac disease, given the absence of reliable biomarkers. AIM: To evaluate the prevalence, diagnostic exclusion of coeliac disease and the efficacy of a gluten-free diet (GFD) for NCGS patients. METHODS: A PubMed search was performed up to December 2014. According to consensus diagnostic criteria, NCGS was defined as self-reported gluten intolerance, negative coeliac serology and absence of villous atrophy. Studies evaluating the impact of a GFD on patients with irritable bowel syndrome (IBS) were also included. RESULTS: Prevalence rates of NCGS (0.5-13%) differed widely. Seventeen studies, including 1561 patients (26 children), met the inclusion criteria for NCGS. HLA haplotypes could not be linked to histology [normal or lymphocytic enteritis (LE)] in 1123 NCGS patients. HLADQ2/DQ8 haplotypes were present in 44% of NCGS patients. After advanced diagnostic techniques in 189 NCGS patients combining LE and HLADQ2/DQ8 haplotypes, 39 (20%) were reclassified as coeliac disease. There was a higher than expected family history of coeliac disease and autoimmune disorders in NCGS patients. A GFD resulted in variable results for variable, but significantly improved stool frequency in HLADQ2 positive diarrhoea-predominant IBS patients. CONCLUSIONS: Prevalence rates for NCGS are extremely variable. A subset of NCGS patients might belong in the so-called 'coeliac-lite' disease. The benefit of a GFD for NCGS patients is currently controversial. HLADQ2 positive diarrhoea-type IBS patients might gain symptom improvement from a GFD.

Helicobacter pylori second-line rescue therapy with levofloxacin- and bismuth-containing quadruple therapy, after failure of standard triple or non-bismuth quadruple treatments.

BACKGROUND: The most commonly used second-line Helicobacter pylori eradication regimens are bismuth-containing quadruple therapy and levofloxacin-containing triple therapy, both offering suboptimal results. Combining bismuth and levofloxacin may enhance the efficacy of rescue eradication regimens. AIMS: To evaluate the efficacy and tolerability of a second-line quadruple regimen containing levofloxacin and bismuth in patients whose previous H. pylori eradication treatment failed. METHODS: This was a prospective multicenter study including patients in whom a standard triple therapy (PPI-clarithromycin-amoxicillin) or a non-bismuth quadruple therapy (PPI-clarithromycin-amoxicillin-metronidazole, either sequential or concomitant) had failed. Esomeprazole (40 mg b.d.), amoxicillin (1 g b.d.), levofloxacin (500 mg o.d.) and bismuth (240 mg b.d.) was prescribed for 14 days. Eradication was confirmed by (13) C-urea breath test. Compliance was determined through questioning and recovery of empty medication envelopes. Incidence of adverse effects was evaluated by questionnaires. RESULTS: 200 patients were included consecutively (mean age 47 years, 67% women, 13% ulcer). Previous failed therapy included: standard clarithromycin triple therapy (131 patients), sequential (32) and concomitant (37). A total of 96% took all medications correctly. Per-protocol and intention-to-treat eradication rates were 91.1% (95%CI = 87-95%) and 90% (95%CI = 86-94%). Cure rates were similar regardless of previous (failed) treatment or country of origin. Adverse effects were reported in 46% of patients, most commonly nausea (17%) and diarrhoea (16%); 3% were intense but none was serious. CONCLUSIONS: Fourteen-day bismuth- and levofloxacin-containing quadruple therapy is an effective (≥90% cure rate), simple and safe second-line strategy in patients whose previous standard triple or non-bismuth quadruple (sequential or concomitant) therapies have failed.