The Effects of Gluten-free Diet on Body Mass Indexes in Adults with Celiac Disease: A Systematic Review and Meta-analysis of Observational Studies.

GOALS AND BACKGROUND: Gluten-free diet (GFD) includes a higher intake of sugars and fats. Previous studies have investigated its effect on body mass index (BMI) in celiac disease (CD) patients but had contradictive conclusions. Thus, we conducted a systematic review and meta-analysis examining the effect of GFD on BMI in CD patients. STUDY: Systematically, we conducted literature research using Medline, Scopus, and Embase, and we identified 1565 potential studies/abstracts. Only studies of patients with CD under a GFD with recorded BMI before and after dietary intervention were included. Subgroup analyses based on study design and BMI categories were performed. We calculated the pooled odds ratios (ORs) and 95% confidence intervals (Cls) for the number of patients in each BMI group according to the World Health Organization (WHO) definitions after GFD using fixed and random effect meta-analysis. RESULTS: The analysis included 10 studies and 38 sub-studies/data sets, which encompassed 2450 patients from 5 countries. We found nonsignificant odds for changing the BMI group (pooled OR 0.972, 95% CI: 0.858-1.101, P=0.65) after GFD. However, looking specifically at BMI subgroups, we found higher odds for BMI category change after GFD in underweight patients (OR 0.588, 95% CI: 0.479-0.723, P <0.001), and overweight patients,25

Different effects of chronic omeprazole use on osteoporotic fractures rate in the elderly.

AIMS: To investigate the potential association of chronic use of omeprazole with the occurrence of osteoporotic fractures (OF) in community-dwelling elderly subjects. METHODS: The cohort consisted of community-dwelling residents aged >65 years registered with a large health maintenance organization in Israel between January 2002 and December 2016. Data were retrospectively collected from the electronic medical files on demographics, parameters known to be associated with OF, diagnoses of osteoporotic hip, wrist, and vertebral fractures, and chronic use of omeprazole (>11 prescriptions/year). Time to OF/death/end of study was calculated from the beginning of the study (2002). The risk of fractures in the chronic users of omeprazole was analyzed by multivariate Cox proportional hazard regression model. RESULTS: In total, 46 805 subjects were included (41% men), mean age 83.4±6.4 years, of whom 10 272 (21.9%) were chronic users of omeprazole. During 14 years of follow-up, OF were diagnosed in 414 (4.0%) omeprazole users and 1007 (2.8%) omeprazole nonusers (p < 0.001). In a Cox regression model adjusted for age and gender only, chronic use of omeprazole was associated with a 16% excess of OF. However, when parameters known to be associated with OF were entered into the multivariate Cox regression model, chronic use of omeprazole was not found to be an independent risk factor for OF, either overall (adjusted hazard ratio = 0.965, 95% confidence interval 0.86-1.08, P = .55) or specifically, in the ≥85 years age group (adjusted hazard ration = 0.780, 95% confidence interval 0.635-0.958, P < .05) in which an inverse correlation between omeprazole use and OF, was demonstrated. CONCLUSIONS: Chronic use of omeprazole was not associated with the occurrence of OF in elders.

Video Capsule Endoscopy after Bariatric Surgery: A Tertiary Referral Center Experience.

BACKGROUND AND AIM: Minimal data are available regarding the performance of video capsule endoscopy (VCE) in patients who underwent bariatric surgery. We aimed to report indications, feasibility, and safety of VCE performed after bariatric surgery, specifically focusing on diagnosis rates of Crohn's disease (CD) in this population. METHODS: A retrospective analysis of all VCE procedures was performed between January 2015 and December 2019. All patients who underwent bariatric surgery prior to VCE were included. Indication for VCE, ingestion methods, completion rates, retention rates, and endoscopic findings were recorded. RESULTS: A total of 1,255 patients underwent VCE examination during the study period, of which 31 (2.5%) underwent bariatric surgery prior to VCE. The most common bariatric surgery was laparoscopic sleeve gastrectomy (16 patients, 51.6%), and the most common indication for VCE was evaluation of iron deficiency anemia (14 patients, 45.1%). The majority of patients ingested the capsule independently, without endoscopic assistance (20, 64.5%). Although a patency capsule was not used in our cohort, no events of capsule retention were documented. Mean transit time was 4.32 h. Only 4 events of incomplete examination were recorded. Over a median follow-up of 27.5 months (IQR 13.0-34.2), 10 patients (31.2%) had a final diagnosis of CD with a median Lewis score of 225 (IQR 135-900). CONCLUSION: VCE is a feasible and safe procedure after bariatric surgery. Oral ingestion does not carry risk of retention. It is an effective means of diagnosis of small-bowel CD in this population.

Gluten Immunogenic Peptides Are Not Correlated With Reported Adherence to Gluten-Free Diet in Children With Celiac Disease.

OBJECTIVE: There is no gold standard to assess adherence to gluten-free diet (GFD) among patients with celiac disease (CeD). Gluten immunogenic peptides (GIPs) in urine and stool were suggested as novel markers for evaluating adherence to GFD. Our aim was to assess the presence of GIP in pediatric patients with CeD, and to compare the results with alternative methods for evaluating GFD adherence. METHODS: Pediatric patients diagnosed with CeD, who were on GFD for at least 1 year, were enrolled and followed prospectively between November 2018 and January 2021. Study visits included clinical assessment, a dietitian interview, Biagi score, food questionnaires, anthropometric and laboratory measurements, and urine and stool samples obtained for laboratory GIP analysis. RESULTS: The study included 74 patients (63.5% females), with median (interquartile range, IQR) age of 9.9 (7.8-11.7) years, and median (IQR) duration on GFD of 2.5 (2-5.5) years. Good GFD adherence, assessed by Biagi score, was reported in 93.1% of cases. GIP was evaluated during 134 visits, with GIP detected in 27 of 134 (20.1%) of the visits (16.3% of stool samples and 5.3% of urine samples). Positive GIP results were significantly more common in males compared to females (30.6% vs 14.1%, respectively, P < 0.05). Detection of positive GIP was not associated with dietary assessment of GFD adherence, celiac serology results, or reported symptoms. CONCLUSIONS: Stool and urine GIP can be detected in children with CeD, even when dietary assessment indicate good adherence to GFD. The role of GIP testing in clinical practice should be further explored.

Development and validation of a prediction model for histologic progression in patients with nondysplastic Barrett's esophagus.

OBJECTIVES: Patients with Barrett's esophagus (BE) are at risk of progression to esophageal adenocarcinoma (EAC). We developed a model to predict histologic progression in patients with nondysplastic BE (NDBE). METHODS: A longitudinal study in three referral centers was performed between January 2010 and December 2019. As progression to low-grade dysplasia (LGD) can be considered an indication for ablative therapy, the study end-point was histopathologic progression to LGD, high-grade dysplasia, or EAC at 3 years after diagnosis. We used logistic regression to create the model. Seventy percent of the cohort were used to stem the model and the remaining 30% for internal validation. RESULTS: A total of 542 patients were included, 69.4% of whom were male, mean age 62.2 years. Long-segment BE at index endoscopy was diagnosed in 20.8% of the patients. After a mean follow-up of 6.7 years, 133 patients (24.5%) had histologic progression. Our model identified a neutrophil-to-lymphocyte ratio (odds ratio [OR] 2.08, 95% confidence interval [CI] 1.77-2.32, P < 0.001), BE length (OR 1.22, 95% CI 1.09-1.36, P < 0.001), age (OR 1.03, 95% CI 1.02-1.05, P = 0.02), smoking (OR 1.66, 95% CI 1.09-2.75, P = 0.04), and renal failure (OR 1.51, 95% CI 0.93-2.43, P = 0.07) as predictors of histologic progression at 3 years. The areas under the receiver operating characteristic curves of this model were 0.88 and 0.76 in the training and validation cohorts, respectively. CONCLUSION: This novel, internally validated model may predict histologic progression, even in patients with NDBE who generally have low rates of progression over time, and may contribute to enhanced patient selection for more intense surveillance programs.

The outcome of local excision of large rectal polyps by transanal endoscopic microsurgery.

Introduction: Local excision of large rectal polyps can be an alternative for radical rectal resection with total mesorectal excision. We aim to report the functional and oncological outcomes of transanal endoscopic microsurgery (TEM) for patients with large rectal polyps. Methods: All demographic and clinical data of patients who underwent TEM for rectal polyp of 5 cm or more at the Hasharon Hospital from 2005 to 2018 were retrospectively reviewed. Results: Twenty-eight patients were included. The mean age was 66 years. The mean polyp size was 6.2 cm (range: 5-8.5 cm) with a mean distance of 8.3 cm from the anal verge. Peritoneal entry during TEM was observed in five patients and additional laparoscopy after the completion of the TEM was performed in four patients. There were no major perioperative complications. Seven patients had minor complications. Final pathology revealed T1 carcinoma in five patients and T2 carcinoma in three patients. Re-TEM was performed in one patient with involved margins with adenoma. After a median follow-up of 64 months, one patient had local recurrence. Conclusion: TEM is an acceptable technique for the treatment of large polyps with minor complications and a reasonable recurrence rate. TEM may be considered regardless of the size of the rectal polyp.

Association of Anemia with Dementia and Cognitive Decline among Community-Dwelling Elderly.

INTRODUCTION: The association of anemia with dementia in elders is controversial. We examined the potential association of anemia with dementia in a large population of elders. METHODS: Historical-prospective registry-based study. Included 36,951 community-dwelling elders (65-113 years) that were followed during 2002-2012. Anemia of all kinds was defined according to Clalit Health Services (CHS) definitions: hemoglobin (HGB) <14 g/dL men, <12 g/dL women; and World Health Organization (WHO): HGB <13 g/dL men, <12 g/dL women. Anemia was categorized as mild (HGB 11-13 g/dL men, 11-12 g/dL women) or moderate-severe (HGB <8-10.9 g/dL men and women). Background data, laboratory values, and diagnosis of dementia and cognitive decline (DCD) were reviewed. RESULTS: During the 10-year follow-up period, DCD was newly diagnosed in 7,180 subjects (19.4%). Subjects with DCD had a higher rate of anemia than those without DCD. Time to development of DCD was 1.5 years shorter in those with than without anemia. On multivariate Cox regression analysis adjusted for age and sex, the hazard ratio (HR) for DCD was 1.45 (95% CI: 1.37-1.54) by CHS and 1.51 (95% CI: 1.41-1.61) WHO anemia criteria. The more severe the anemia, the greater the risk of DCD development (HGB 13-14 g/dL [men only], HR = 1.20 [95% CI: 1.09-1.32]; mild anemia, HR = 1.38 [95% CI: 1.28-1.49]; moderate-severe anemia, HR = 1.64 [CI: 1.41-1.90]). Every decrease in 1 standard deviation of HGB (1.4 g/dL) increased the DCD risk by 15%. A competing risk model has weakened the association of anemia with DCD risk. CONCLUSIONS AND IMPLICATIONS: Anemia in community-dwelling elders appears to be associated with an increased DCD risk in a dose-response manner. Application of the WHO anemia criteria in men may miss patients with mild anemia that places them at DCD risk. Further research should look at anemia as a cause of reversible dementia.

Phenotypic diversity among juvenile polyposis syndrome patients from different ethnic background.

Juvenile polyposis syndrome (JPS), has diverse phenotypes. AIM: To assess mutation rate, clinical features and genotype-phenotype correlation among Israeli JPS kindreds from different ethnicities. METHODS: Patients' data were extracted retrospectively from 5 centers. RESULTS: Thirty five kindreds (49 patients) were included. Thirty one (89%) Jewish [10 (32%) Ashkenazi; 9 (29%) Sephardi; 11 (35%) non-Russia former Soviet-Union countries (NRFSU), one (3%) unknown]. 40/49 individuals from 27 families underwent genetic testing. Among them 34, from 21 families (85, 78%, respectively) had a pathogenic mutation: BMPR1A n = 15 (71%), SMAD4 n = 6 families (29%). While no SMAD4 mutation was described among Jewish families from NRFSU, 7 NRFSU families carried a founder mutation comprising a large genomic deletion of BMPR1A. GI involvement was reported in 42 patients (86%): colonic polyps (n = 40, 95%, > 50 polyps n = 14, 35%) and 12 underwent colonic resection. Fourteen patients (34%) had gastric or small bowel involvement (n = 5) and 4\14 underwent gastrectomy due to polyp burden. Families from NRFSU had more gastric involvement (66.7% vs. 22.2%- Sephardic and 20%- Ashkenazi Jews; p = 0.038), with more gastric polyps (p = 0.017). CONCLUSIONS: We demonstrated a high rate of mutation detection in the heterogeneous population of Israel. Patients from NRFSU with BMPR1A mutation had high rate of gastric involvement.

Association Between Polyp Detection Rate and Post-Colonoscopy Cancer Among Patients Undergoing Diagnostic Colonoscopy.

Postcolonoscopy colorectal cancer (PCCRC) can arise from missed cancers, missed premalignant lesions, incomplete resection, and new cancers with an accelerated route to cancer.1.

Use of proton pump inhibitors is associated with lower rates of first-time ischemic stroke in community-dwelling elderly.

AIM: Data on cardiovascular outcomes in elderly using proton pump inhibitors (PPI) are scant. We aimed to test the association between PPI use and the occurrence of first-time ischemic stroke (FTIS) among elderly. METHODS: The electronic database of a centrally located district branch of a large health maintenance organization in Israel was retrospectively screened (2002-2016) for community-dwelling individuals (≥65-95 years) for demographics and co-morbidities. Follow-up was until FTIS, death or end of study. Findings were analyzed by PPI use and occurrence of FTIS. RESULTS: 29,639 subjects (without history of stroke and use of antiplatelet aggregation drugs) mean age of 82.2 ± 5.5 years (range: 65-95 years, 38% male) were analyzed: 8,600 (29%) used PPIs. Mean follow up was 10.58 years (SD ± 5.44). Similar total and annual occurrence rates of FTIS were depicted in PPI users and non-users (20.9% vs. 21% and 2% vs. 2.1%, respectively). On a Cox regression analysis, upon adjustment for age, gender and cardiovascular disease related risk factors, PPI use was significantly associated with lower rates of FTIS (HR 0.73, 95% C.I. 0.69-0.77, p < 0.001). The risk for FTIS was significantly lower in subjects using PPI at any dose and for any time period compared to non-users (HR 0.9, 95% C.I. 0.85-0.96 for 7-48 yearly prescriptions and HR 0.51, 95% C.I. 0.46-0.55 for ≥49 yearly prescriptions). CONCLUSIONS: PPI use was associated with lower rates of FTIS in community-dwelling elders. Prospective large-scale studies are needed to fully elucidate the effect of PPI in this aging population.

Susceptibility-guided versus empirical treatment for Helicobacter pylori infection: A systematic review and meta-analysis.

BACKGROUND AND AIM: Empirical therapy for Helicobacter pylori infection is limited by increasing antibiotic resistance and suboptimal eradication rates. Studies of the relative effectiveness of susceptibility-guided therapy have produced conflicting results. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to determine whether susceptibility-guided therapy is superior to empirical therapy for H. pylori infection. METHODS: We searched articles listed in PubMed, MEDLINE, EMBASE, and Web of Science through May 25, 2020, RCTs comparing susceptibility-guided versus empirical therapy for H. pylori infection. Outcomes, including effectiveness and safety, were analyzed in a meta-analysis. RESULTS: Our final analysis included 16 studies, comprising 2374 patients who received susceptibility-guided therapy and 2451 patients who received empirical treatment. In previously untreated subjects, susceptibility-guided therapy was slightly more effective than empirical therapy (intent to treat risk ratio [RR], 1.14; 95% confidence interval [CI], 1.07-1.21; P < 0.0001, I2  = 75%). Susceptibility-guided therapy was superior to first-line clarithromycin-based triple therapy only when clarithromycin resistance exceeded 20% (RR, 1.18; 95% CI, 1.07-1.30; P = 0.001, I2  = 81%). Susceptibility-guided therapy was not more effective than empirical quadruple therapy (RR, 1.02; 95% CI, 0.92-1.13; P = 0.759, I2  = 80%). Three RCTs were performed exclusively among previously treated subjects, and were highly heterogeneous. CONCLUSIONS: Our findings suggest that susceptibility-guided treatment may be slightly superior to empirical first line triple therapy. Susceptibility- guided treatment does not appear to be superior to empirical first-line quadruple therapy or empirical rescue therapy.

Rifabutin triple therapy for first-line and rescue treatment of Helicobacter pylori infection: A systematic review and meta-analysis.

BACKGROUND AND AIM: Due to the increasing resistance of Helicobacter pylori, there is a need for novel antibiotic treatment protocols. We aimed to perform a systematic review and meta-analysis in order to determine the effectiveness and safety of rifabutin triple therapy for H. pylori infection. METHODS: We performed a systematic review of prospective clinical trials with a treatment arm consisting of proton pump inhibitor, amoxicillin, and rifabutin and a meta-analysis of randomized controlled trials (RCTs). RESULTS: Thirty-three prospective studies including 44 datasets were identified. Meta-analysis of four RCTs for rescue treatment found no difference between treatment groups (odds ratio [OR] 0.88, 95% confidence interval [CI] 0.437-1.791, I2  = 68.1%, P = 0.733). Only one RCT compared rifabutin therapy with control for first-line treatment of H. pylori infection (OR 3.78, 95% CI 2.44-5.87, P < 0.0001). Treatment was more likely to be successful in Asian versus non-Asian populations (81.0% vs 72.4%, P = 0.001) and when daily amoxicillin dose was ≥ 3000 mg or proton pump inhibitor dose was ≥ 80 mg or treatment duration was 14 days (80.6% vs 66.0%, P = 0.0001). The overall event rate for adverse effects was 24.8% (729/2937) (95% CI 0.23-0.26), and the pooled OR for adverse effects in the treatment versus control group was 0.93 (95% CI 0.50-1.75) (I2  = 79.76, P = 0.82). CONCLUSION: Evidence for the effectiveness of rifabutin for the first-line treatment of H. pylori infection in adults is limited, and studies comparing rifabutin with conventional first-line treatments are lacking.

The Transition from Gastric Intestinal Metaplasia to Gastric Cancer Involves POPDC1 and POPDC3 Downregulation.

Intestinal metaplasia (IM) is an intermediate step in the progression from premalignant to malignant stages of gastric cancer (GC). The Popeye domain containing (POPDC) gene family encodes three transmembrane proteins, POPDC1, POPDC2, and POPDC3, initially described in muscles and later in epithelial and other cells, where they function in cell-cell interaction, and cell migration. POPDC1 and POPDC3 downregulation was described in several tumors, including colon and gastric cancers. We questioned whether IM-to-GC transition involves POPDC gene dysregulation. Gastric endoscopic biopsies of normal, IM, and GC patients were examined for expression levels of POPDC1-3 and several suggested IM biomarkers, using immunohistochemistry and qPCR. Immunostaining indicated lower POPDC1 and POPDC3 labeling in IM compared with normal tissues. Significantly lower POPDC1 and POPDC3 mRNA levels were measured in IM and GC biopsies and in GC-derived cell lines. The reduction in focal IM was smaller than in extensive IM that resembled GC tissues. POPDC1 and POPDC3 transcript levels were highly correlated with each other and inversely correlated with LGR5, OLFM4, CDX2, and several mucin transcripts. The association of POPDC1 and POPDC3 downregulation with IM-to-GC transition implicates a role in tumor suppression and highlights them as potential biomarkers for GC progression and prospective treatment targets.

Transanal endoscopic microsurgery under spinal anaesthesia.

BACKGROUND: Transanal endoscopic microsurgery (TEM) is considered the procedure of choice for rectal adenomas non-amendable for endoscopic excision and for early rectal cancer. TEM may gain more importance in patients who are considered unfit for major surgery. The option of spinal anaesthesia may offer many advantages for patients undergoing TEM while maintaining the principles of complete tumour excision. The aim of this study is to report the outcome of patients undergoing TEM under spinal anaesthesia. METHODS: Demographic and clinical data pertaining patients undergoing TEM under spinal anaesthesia between 2004 and 2015 were retrospectively collected. RESULTS: A total of 158 TEM procedures were recorded in the study period. Twenty-three patients (15%) underwent the procedure under spinal anaesthesia and were included in the study; 13 of them were male and ten were female. The mean age of the patients was 69.1 ± 10.6 years. Seventeen (74%) rectal lesions were adenomas, two (9%) were adenocarcinoma and four (17%) had involved margins after polypectomy. The mean tumour size was 2.1 cm (range, 0.5-3). Distance from the anal verge was 7.7 ± 2.2 cm. Seventeen (74%) lesions were in the posterior wall. The operative time was 73 min (range, 46-108) No adverse anaesthesia-related events were recorded, and the post-operative pain was reduced. The median time of hospitalisation was 2 days (range, 1-4). No major complications were noted, and the minor complications were treated conservatively. The surgical margins were free of tumour in all cases. CONCLUSION: TEM under spinal anaesthesia had short duration of surgery, no increase in operative and post-operative complications or hospital length of stay. Avoiding the use of general anaesthesia, in such challenging procedure, may open new opportunities for patients determined to be unfit for general anaesthesia.

Effect of Previous Nitroimidazole Treatment on Helicobacter pylori Eradication Success.

GOALS: The goal of this study was to examine the impact of prior treatment with a nitroimidazole antibiotic on the success of Helicobacter pylori treatment. BACKGROUND: Prior nitroimidazole exposure may increase the likelihood of nitroimidazole-resistant H. pylori. Current H. pylori treatment guidelines recommend that, in the absence of susceptibility testing, patients with prior nitroimidazole exposure should not be treated with a nitroimidazole antibiotic. Data to support this recommendation are lacking. STUDY: We searched the Clalit Health Services database to identify subjects 25 to 60 years old who underwent a first-ever C-urea breath test between 2010 and 2015. Patients who underwent a previous H. pylori stool antigen test or gastroscopy were excluded. Pharmacy dispensation data were retrieved. RESULTS: A total of 1386 subjects (34.8% male individuals, age 40.7±10.7 y) received a nitroimidazole-containing regimen including 282 (20.4%) with prior nitroimidazole exposure. Successful eradication was achieved in 58.9% and 73.8% of subjects with and without prior nitroimidazole exposure, respectively (odds ratio, 0.51; 95% confidence interval, 0.39-0.67; P<0.0001). Nitroimidazole exposure adversely impacted the success of triple therapy with nitroimidazole, proton pump inhibitor, and amoxicillin or clarithromycin (39.4% vs. 63.4% and 54.4% vs. 73.6%, P<0.01, respectively), but not quadruple therapy. Following multivariate analysis, nitroimidazole exposure was significantly associated with eradication failure (odds ratio, 1.89; 95% confidence interval, 1.43-2.50; P<0.0001). A greater time elapsed from nitroimidazole exposure, and a lower cumulative nitroimidazole dose were observed in subjects with successful eradication (P<0.0001 for both). CONCLUSION: Nitroimidazole exposure may adversely impact the success of nitroimidazole-based triple therapy, but not quadruple therapy. Clinicians should conduct a thorough patient drug history before administering empiric treatment for H. pylori infection.

Comparative Effect of Proton-Pump Inhibitors on the Success of Triple and Quadruple Therapy for Helicobacter pylori Infection.

INTRODUCTION: Suppression of gastric acid secretion with proton-pump inhibitors (PPI) is an integral part of the treatment of Helicobacter pylori infection. Esomeprazole has been shown to be superior to other PPIs when used in the context of triple therapy; however, comparative data for PPI efficacy in quadruple therapy are lacking. Current guidelines recommend H. pylori eradication with quadruple therapy in areas with high clarithromycin resistance. OBJECTIVE: To determine whether esomeprazole is more effective than other PPIs in the context of quadruple therapy for H. pylori eradication. METHODS: We retrospectively identified 25- to 60-year-old subjects with a positive 13C-urea breath test and no prior laboratory or endoscopic test for H. pylori infection. Pharmacy dispensation data were retrieved. RESULTS: A total of 7,896 subjects including 2,856 (36.2%) males, aged 40.4 ± 10.6 years, were identified. Of those, 78.1% received omeprazole, 20.1% received lansoprazole, 1.5% received esomeprazole, and 0.34% received pantoprazole together with antibiotics for H. pylori eradication. Esomeprazole was associated with a greater proportion of successful eradication (85.0 vs. 77.5%, esomeprazole vs. omeprazole, OR 1.64; 95% CI 0.99-2.72; p = 0.05). A nonsignificant trend favored esomeprazole over omeprazole among subjects receiving quadruple therapy (90.0 vs. 82.0%, respectively, OR 1.98; 95% CI 0.68-5.72; p = 0.16). Independent predictors of treatment success included older age and quadruple therapy. CONCLUSION: Esomeprazole is more beneficial than other PPIs for H. pylori eradication. Studies with larger subgroups are necessary to confirm our findings among subjects receiving quadruple therapy.

Impact of Previous Exposure to Macrolide Antibiotics on Helicobacter pylori Infection Treatment Outcomes.

OBJECTIVES: Helicobacter pylori (H. pylori) guidelines, including the recent ACG clinical guideline, recommend avoiding clarithromycin-based triple therapy (TT-C) among patients with past macrolide exposure. Data to support this recommendation are scarce, and the impact of macrolide exposure on quadruple therapies is unclear. We aimed to determine the impact of macrolide exposure on the efficacy of H. pylori treatment in our region. METHODS: We searched the Clalit Health Services database to identify subjects aged 25-60 years who underwent the first-ever C-urea breath test between 2010 and 2015. Patients who underwent a previous H. pylori stool antigen test or gastroscopy were excluded. Pharmacy dispensation data were retrieved. RESULTS: We identified 7,842 subjects (36.1% male individuals, age: 40.3 ± 10.5 years), including 3,062 (39.0%) with previous macrolide exposure. The efficacy of TT-C was 74.3% and 82.4% among subjects with and without macrolide exposure, respectively (odds ratio (OR), 0.62; 95% confidence interval (CI), 0.55-0.70; P < 0.0001). TT success was adversely affected by exposure to clarithromycin (55.5%; OR, 0.31; 95% CI, 0.24-0.39; P < 0.0001), roxythromycin (74.4%; OR, 0.65; 95% CI, 0.58-0.74; P < 0.0001), and erythromycin (73.9%; OR, 0.72; 95% CI, 0.57-0.89; P < 0.01) but not by exposure to azithromycin. A greater time elapsed because exposure to clarithromycin and roxythromycin was associated with higher eradication (OR, 1.007; 95% CI, 1.002-1.012; P < 0.01 and OR, 1.004; 95% CI, 1.002-1.006; P < 0.0001). A higher dose of clarithromycin and roxythromycin was associated with a lower likelihood of successful eradication (OR, 0.99988; 95% CI, 0.99982-0.99996; P < 0.01 and OR, 0.99981; 95% CI, 0.99971-0.99992; P < 0.001). The efficacies of sequential and concomitant therapies were 82.7% and 81.3%, respectively, and were not significantly affected by macrolide exposure. CONCLUSIONS: TT-C is adversely affected by previous exposure to macrolide antibiotics. Sequential, concomitant, and bismuth-based treatment may be preferred in this setting.

Optimization of 13 C-urea breath test threshold levels for the detection of Helicobacter pylori infection in a national referral laboratory.

BACKGROUND: Threshold values for 13 C-urea breath test (13C-UBT) positivity may be affected by various sociodemographic, host, bacterial, and laboratory factors. Manufacturer recommended cutoffs for 13C-UBT assays may not be applicable in all settings. Optimizing 13C-UBT cutoffs may have profound public health ramifications. We aimed to determine the optimal threshold for 13C-UBT positivity in our population. METHODS: Consecutive test samples collected at our central laboratory from patients undergoing a first-time 13C-UBT between 1 January 2010 and 31 December 2015 were included. The difference between values at 30 minutes and at baseline (T30-T0) was expressed as delta over baseline (DOB). Cluster analysis was performed on the 13C-UBT test results to determine the optimal cutoff point with minimal interclass variance. RESULTS: Two lakhs thirty four thousand eight hundred thirty one patients (87 291 (37.2%) male, age 39.9 ± 19.9) underwent a first-time 13C-UBT, including 124 701 (53.1%) negative and 110 130 (46.9%) positive tests, using the manufacturer-recommended cutoff of 3.5 DOB. Cluster analysis determined an optimized cutoff of 2.74 DOB, representing an additional 2180 (0.93%) positive subjects who had been previously categorized as negative according to the manufacturer-specified cutoff of 3.5 DOB. Mean positive and negative DOB values were 19.54 ± 14.95 and 0.66 ± 0.51, respectively. The cutoffs for male and female subjects were 2.23 and 3.05 DOB, respectively. Threshold values for <45-year-olds, 45-60-year-olds and >60-year-olds were 2.67, 2.55, and 2.93 DOB, respectively. Of the 2180 (0.93%) patients with DOB 2.73-3.49, 289 (13.3%) performed a subsequent 13C-UBT and 140 (48.4%) remained positive when tested at 20.3 ± 14.4 months. CONCLUSIONS: Major referral laboratories should optimize threshold values for 13C-UBT positivity for their geographical location. Different cutoff values should be applied for male and female subjects.

Effect of Postprandial Administration of Esomeprazole on Reflux Symptoms in Gastroesophageal Reflux Disease: A Randomized, Controlled Trial.

BACKGROUND: Esomeprazole is commonly administered with food; however, clinical data to support this practice are lacking. We aimed to determine the effect of postprandial ingestion of esomeprazole on reflux symptoms among patients with gastroesophageal reflux disease (GERD). METHODS: Consecutive patients with GERD adequately controlled with esomeprazole 40 mg daily, entered a 2-week lead-in period during which esomeprazole was administered 30 min before breakfast. Patients were then randomized to continue preprandial ingestion or to ingest esomeprazole following a standardized meal. Outcomes included GERD frequency and severity indices, GERD-health-related quality of life (GERD-HRQL) questionnaire and Short Form 36 (SF-36). RESULTS: Thirty-two patients (17 [53.1%] men, aged 53.5 ± 17.2 years) were included, and 16 (50%) switched to postprandial ingestion of esomeprazole. GERD frequency and severity decreased in both groups (Δ9.0 ± 7.2 vs. Δ10.0 ± 8.1, p = 0.29; Δ6.6 ± 6.8 vs. Δ10.2 ± 7.4, p = 0.57 in postprandial group vs. controls, for frequency and severity, respectively). GERD-HRQL improved in both study groups to a similar degree (Δ10.7 ± 10.5 vs. Δ10.0 ± 13.8, p = 0.97). All SF-36 subscores increased in both groups to a similar degree. In a mixed linear model, there were no differences between the study groups in the changes observed in GERD frequency (p = 0.49), severity (p = 0.32), and GERD-HRQL (p = 0.98) during the study period. CONCLUSION: Switching to postprandial administration of esomeprazole is not associated with deterioration in reflux symptoms among patients with GERD. Esomeprazole seems to remain efficacious when administered after meals.

Temporal Trends in Helicobacter pylori Eradication Success in a Test-and-Treat Population.

BACKGROUND/AIMS: Although the efficacy of first-line treatment for Helicobacter pylori infection should aim to be > 90%, it is unclear whether this target has been achieved in Israel. We aimed to determine the success rate of treatment for H. pylori and to describe temporal changes in our region. Methods: Adult patients who underwent a first-time -C13-urea breath test (C13-UBT) at Clalit Health Services between January 1, 2010 and December 31, 2015 were included. In order to isolate a naïve "test-and-treat" population who were unlikely to have undergone an initial endoscopy-based H. pylori test, we excluded patients ≥45 years and those with any previous C13-UBT. RESULTS: A total of 94,590 subjects (36.1% male, age 28.5 ± 6.0) who underwent at least one C13-UBT during the study period were included. C13-UBT was positive in 48,509 (51.3%) subjects. A confirmatory post-treatment C13-UBT was performed in 37.8, 44.1, 46.6, and 45.9% following 1st, 2nd, 3rd, and 4th-line treatment respectively. Eradication was successful in 65.4% following first-line treatment, and eradication success improved during the study period (59.2, 63.3, 65.7, 66.0, 69.0, and 73.1% in 2010, 2011, 2012, 2013, 2014, and 2015 respectively; OR 1.11; 95% CI 1.09-1.13; p < 0.0001). Eradication was successful in 44.7% following second-line treatment, although eradication success did not significantly improve during the study period (OR 1.05; 95% CI 0.99-1.10; p = 0.09). CONCLUSIONS: Despite the increasing success of first-line treatment for H. pylori infection over the study period, eradication rates remain suboptimal. Initiatives to implement the Toronto and Maastricht Consensus Reports should be advanced.