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SUMMARYThe majority of the world population carry the gastric pathogenHelicobacter pylori. Fortunately, most individuals experience only low-grade or no symptoms, but in many cases the chronic inflammatory infection develops into severe gastric disease, including duodenal ulcer disease and gastric cancer. Here we report on a protective mechanism whereH. pyloriattachment and accompanying chronic mucosal inflammation can be reduced by antibodies that are present in a vast majority ofH. pyloricarriers. These antibodies block binding of theH. pyloriattachment protein BabA by mimicking BabA’s binding to the ABO blood group glycans in the gastric mucosa. However, many individuals demonstrate low titers of BabA blocking antibodies, which is associated with an increased risk for duodenal ulceration, suggesting a role for these antibodies in preventing gastric disease.

Background There is a need for effective and cost-effective interprofessional care models that support older people to maintain their quality of life (QoL) and physical performance to live longer independently in their own homes. Objectives The objectives were to evaluate effectiveness, QoL and physical performance, and cost-utility of a people-centred care model (PCCM), including the contribution of clinically trained pharmacists, compared with that of usual care in primary care. Methods A randomised controlled trial (RCT) with a two-year follow-up was conducted. The participants were multimorbid community-living older people, aged ≥75 years. The intervention comprised an at-home patient interview, health review, pharmacist-led clinical medication review, an interprofessional team meeting, and nurse-led care coordination and health support. At the baseline and at the 1-year and 2-year follow-ups, QoL (SF-36, 36-Item Short-Form Health Survey) and physical performance (SPPB, Short Performance Physical Battery) were measured. Additionally, a physical dimension component summary in the SF-36 was calculated. The SF-36 data were transformed into SF-6D scores to calculate quality-adjusted life-years (QALYs). Healthcare resource use were collected and transformed into costs. A healthcare payer perspective was adopted. Incremental cost-effectiveness ratio (ICER) was calculated, and one-way sensitivity analysis was performed. Results No statistically or clinically significant differences were observed between the usual care (n = 126) and intervention group (n = 151) patients in their QoL; at the 2-year follow-up the mean difference was −0.02, (95 % CI -0.07; 0.04,p = 0.56). While the mean difference between the groups in physical performance at the 2-year follow-up was −1.02, (−1.94;-0.10,p = 0.03), between the physical component summary scores it was −7.3, (−15.2; 0.6,p = 0.07). The ICER was −73 638€/QALY, hence, the developed PCCM dominated usual care, since it was more effective and less costly. Conclusions The cost-utility analysis showed that the PCCM including pharmacist-led medication review dominated usual care. However, it had no effect on QoL and the effect towards physical performance remained unclear.

BACKGROUND/AIM Prompted by the increasing demand of non-invasive diagnostic tools for screening of gastric cancer (GC) risk conditions, i.e., atrophic gastritis (AG) and Helicobacter pylori (Hp) infection, the GastroPanel® test (GP: biomarker panel of PGI, PGII, G-17, Hp IgG ELISA) that was developed in the early 2000's, was recently updated to a new-generation (unified GP) test version. This clinical validation study evaluated the diagnostic accuracy of the new-generation GP test in detection of AG and Hp among gastroscopy referral patients in a University Clinic. PATIENTS AND METHODS Altogether, 522 patients were enrolled among the patients referred for gastroscopy at the Gastro Center, Oulu University Hospital (OUH). All patients underwent gastroscopy with biopsies classified using the Updated Sydney System (USS), and blood sampling for GP testing. RESULTS Biopsy-confirmed AG was found in 10.2% (53/511) of the patients. The overall agreement between the GP and the USS classification was 92.4% (95%CI=90.0-94.6%), with the weighted kappa (κw) of 0.861 (95%CI=0.834-0.883). In ROC analysis using moderate/severe AG of the corpus (AGC2+) as the endpoint, AUC=0.952 (95%CI=0.891-1.000) and AUC=0.998 (95%CI=0.996-1.000) for PGI and PGI/PGII, respectively. Hp IgG antibody ELISA detected biopsy-confirmed Hp-infection with AUC=0.993 (95%CI=0.987-0.999). CONCLUSION The new generation GastroPanel® is a precise test for non-invasive diagnosis of atrophic gastritis and Hp-infection in dyspeptic patients referred for diagnostic gastroscopy.

Whilst intraepithelial lymphocytes (IELs) are considered normal within the distal esophageal mucosa, they have an increasingly recognised role in the pathogenesis of reflux esophagitis, and IEL quantification establishes the diagnosis of lymphocytic esophagitis. Knowledge regarding the upper limit of a normal IEL count in health is lacking. We studied 117 non-healthcare seeking adult volunteers from a random community sample (the Kalixanda study) with esophageal biopsies 2 cm above the gastroesophageal junction. Subjects were divided into four groups based on the presence or absence of gastro-esophageal reflux symptoms and/or esophagitis on endoscopy. Asymptomatic subjects with no endoscopic esophagitis were selected as controls, and the cell counts in this group were used to define the upper limit of normal of IELs, eosinophils and neutrophils. The entire sample was used to identify independent predictors of increased cellular counts by logistic regression analysis. None of the healthy controls had an IEL count of more than three per five high power fields (HPF), and therefore this was considered as the upper limit of normal; no controls had eosinophils or neutrophils in esophageal biopsies. Independent predictors of an elevated IEL count were spongiosis on histology (OR 11.17, 95% CI 3.32-37.58, P < 0.01) and current smoking (OR 4.84, 95% CI 1.13-2.71, P = 0.03). A receiver operating characteristics analysis concluded that a threshold of 3 IELs/5HPFs performs best in predicting reflux symptoms when a normal esophageal mucosa is visualized on endoscopy (sensitivity = 100.0%, specificity = 35.2%). The healthy esophageal mucosa does not contain more than three IELs per five HPF in the distal esophagus.

Background It is uncertain if functional dyspepsia (FD) or irritable bowel syndrome (IBS) are linked to smoking, and smoking cessation is not part of the routine advice provided to these patients. Aim To assess if smoking is an independent risk factor for FD and IBS. Methods Three population-based endoscopy studies in Sweden with 2560 community individuals in total (mean age 51.5 years, 46% male). IBS (14.9%), FD (33.5%), and associated symptoms were assessed using the validated abdominal symptom questionnaire, and smoking (17.9%) was obtained from standardised questions during a clinic visit. The effect of smoking on symptom status was analysed in an individual person data meta-analysis using mixed effect logistic regression, adjusted for snuffing, age and sex. Results Individuals smoking cigarettes reported significantly higher odds of postprandial distress syndrome (FD-PDS) (OR 10-19 cig/day = 1.42, 95% CI 1.04-1.98 P = 0.027, OR ≥20 cig/day = 2.16, 95% CI 1.38-3.38, P = 0.001) but not epigastric pain. Individuals smoking 20 or more cigarettes per day reported significantly higher odds of IBS-diarrhoea (OR = 2.40, 95% CI 1.12-5.16, P = 0.025), diarrhoea (OR = 2.01, 95%CI 1.28-3.16, P = 0.003), urgency (OR = 2.21, 95%CI 1.41-3.47, P = 0.001) and flatus (OR = 1.77, 95%CI 1.14-2.76, P = 0.012) than non-smokers. Smoking was not associated with IBS-constipation or IBS-mixed. Conclusion Smoking is an important environmental risk factor for postprandial distress syndrome, the most common FD subgroup, with over a twofold increased odds of PDS in heavy smokers. The role of smoking in IBS-diarrhoea, but not constipation, is also likely important.

Recombinant sequences of the SARS-CoV-2 Omicron variant were detected in surveillance samples collected in north-western Finland in January 2022. We detected 191 samples with an identical genome arrangement in weeks 3 to 11, indicating sustained community transmission. The recombinant lineage has a 5’-end of BA.1, a recombination breakpoint between orf1a and orf1b (nucleotide position 13,296–15,240) and a 3’-end of BA.2 including the S gene. We describe the available genomic and epidemiological data about this currently circulating recombinant XJ lineage.

Erratum in: Nat Commun. 2023 Mar 20;14(1):1539. doi: 10.1038/s41467-023-37302-5. Helicobacter pylori lives in the human stomach and has a population structure resembling that of its host. However, H. pylori fromEurope and the Middle East trace substantially more ancestry from modern African populations than the humans that carry them. Here, we use a collection of Afro-Eurasian H. pylori genomes to show that this African ancestry is due to at least three distinct admixture events. H. pylori from East Asia, which have undergone little admixture, have accumulated many more non-synonymous mutations than African strains. European and Middle Eastern bacteria have elevated African ancestry at the sites of these mutations, implying selection to remove them during admixture. Simulations show that population fitness can be restored after bottlenecks bymigration and subsequent admixture of small numbers of bacteria from non-bottlenecked populations. We conclude that recent spread of African DNA has been driven by deleterious mutations accumulated during the original out-of-Africa bottleneck. This work was supported by Sequencing Grants-in-aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan (221S0002, 18KK0266, 19H03473, 21H00346 and 22H02871) to Y.Y. F.F.V. is financed by FCT through Assistant Researcher grant CEECIND/03023/2017 and a project grant PTDC/BTM-TEC/3238/ 2020. I.K. studentship was funded by the National Strategic Reference Framework Operational Program “Competitiveness, Entrepreneurship and Innovation” (NSRF 2014-2020, project No. MIS5002486) and sequencing of strains was supported by the InfeNeutra Project (NSRF 2007-2013, project no. MIS450598) of the Ministry of Culture and Edu- cation, Greece. K.T. and the sequencing of KI isolates was supported by Erik Philip-Sörensen Foundation grant G2016-08, and Swedish Society for Medical research (SSMF). All primary bioinformatics and parts of the comparative genomics were performed on resources provided by Swedish National Infrastructure for Computing (SNIC) through Uppsala Multidisciplinary Center for Advanced Computational Science (UPPMAX) under projects snic2018-8-24 and uppstore2017270. Work by S.S. was supported by the German Research Foundation (DFG, project number 158 989 968–SFB 900/A1) and by the Bavarian Ministry of Sci- ence and the Arts in the framework of the Bavarian Research Network “New Strategies Against Multi-Resistant Pathogens by Means of Digital Networking—bayresq.net”. D.F. was supported by Shanghai Municipal Science and Technology Major Project No. 2019SHZDZX02. info:eu-repo/semantics/publishedVersion

Prompted by the increasing demand of non-invasive diagnostic tools for screening of gastric cancer (GC) risk conditions, i.e., atrophic gastritis (AG) and Helicobacter pylori (Hp) infection, the GastroPanelAltogether, 522 patients were enrolled among the patients referred for gastroscopy at the Gastro Center, Oulu University Hospital (OUH). All patients underwent gastroscopy with biopsies classified using the Updated Sydney System (USS), and blood sampling for GP testing.Biopsy-confirmed AG was found in 10.2% (53/511) of the patients. The overall agreement between the GP and the USS classification was 92.4% (95%CI=90.0-94.6%), with the weighted kappa (κThe new generation GastroPanel

All genomes mutate but the consequences of the resulting deleterious mutational load are poorly understood. Helicobacter pylori lives in the human stomach, has a higher mutation rate than most bacteria and has accompanied anatomically modern humans in migrations including the out-of-Africa expansion more than 50,000 years ago. H. pylori from East Asia have accumulated at least 500 more non-synonymous mutations than African strains, which we propose is due to reduced efficacy of selection during the out-of-Africa bottleneck. H. pylori from Europe and the Middle East trace a substantially higher fraction of ancestry from modern African populations than the humans that carry them, which we find is due to at least three separate admixture events. African ancestry is elevated at positions in the genome where non-synonymous mutations are at high frequency in Asia. We propose that this is due to replacement of deleterious mutations that accumulated during the bottleneck, with the high overall African ancestry proportion due to clonal expansion of strains of African origin. We use simulations to show that a Muller9s ratchet like effect can lead to long-term segregation of deleterious mutations within bacterial populations after a bottleneck, despite high rates of homologous recombination, but that population fitness can be restored by migration of small numbers of bacteria from non-bottlenecked populations. Our results demonstrate that population bottlenecks can have long-term genomic and demographic consequences, even in species with enormous population sizes.

Introduction The concept of gut-to-brain communication via microbial or inflammatory pathways is gaining increased attention but genuine pathology directly linking gut perturbation to anxiety is lacking. We hypothesized that duodenal eosinophilia, as known to occur in functional dyspepsia (FD), may be an underlying cause of anxiety and may help explain the striking association between FD and anxiety. Methods Randomly selected subjects from the national population register of Sweden completed the validated Abdominal Symptom Questionnaire; 1000 completed esophagogastroduodenoscopy and the Hospital Anxiety and Depression Scale questionnaire. Duodenal biopsies were obtained from 1st (D1) and 2nd portion (D2). Eligible subjects who underwent endoscopy (n = 887) were invited to participate in a 10-year follow-up study with the same questionnaires. Among endoscopy normal subjects, FD was identified by Rome criteria, and controls were symptom free. Duodenal eosinophilia was based on pre-defined cut-offs. Finding are reported as odds ratios (ORs) with 95% confidence interval and p-value. Results The study population comprised 89 cases with FD and 124 healthy controls (mean age 62 years, SD 12, 34% male). Clinical anxiety at follow-up was elevated in those with D1 eosinophilia at baseline considering either new-onset anxiety (OR = 4.5, 95% CI 0.8, 23.8; p = 0.08) or follow-up anxiety adjusting for baseline anxiety (OR = 4.51 (95% CI 1.03, 19.81; p = 0.046). Conclusion Duodenal eosinophilia may potentially be a mechanism linked to anxiety independent of FD.

Eosinophilic esophagitis (EoE) is one of the most prevalent esophageal diseases and the leading cause of dysphagia and food impaction in children and young adults. This underlines the importance of optimizing diagnosys and treatment of the condition, especially after the increasing amount of knowledge on EoE recently published. Therefore, the UEG, EAACI ESPGHAN, and EUREOS deemed it necessary to update the current guidelines regarding conceptual and epidemiological aspects, diagnosis, and treatment of EoE. General methodology according to the Appraisal of Guidelines for Research and Evaluation (AGREE) II and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was used in order to comply with current standards of evidence assessment in formulation of recommendations. An extensive literature search was conducted up to August 2015 and periodically updated. The working group consisted of gastroenterologists, allergists, pediatricians, otolaryngologists, pathologists, and epidemiologists. Systematic evidence-based reviews were performed based upon relevant clinical questions with respect to patient-important outcomes. The guidelines include updated concept of EoE, evaluated information on disease epidemiology, risk factors, associated conditions, and natural history of EoE in children and adults. Diagnostic conditions and criteria, the yield of diagnostic and disease monitoring procedures, and evidence-based statements and recommendation on the utility of the several treatment options for patients EoE are provided. Recommendations on how to choose and implement treatment and long-term management are provided based on expert opinion and best clinical practice. Evidence-based recommendations for EoE diagnosis, treatment modalities, and patients' follow up are proposed in the guideline

BACKGROUND It is unexplained why functional dyspepsia and gastro-oesophageal reflux disease (GERD) overlap more often than expected by chance. Post-prandial distress syndrome has been linked to impaired gastric fundic accommodation which may induce increased transient lower oesophageal sphincter relaxations and consequent GERD. Duodenal eosinophilia has been linked to functional dyspepsia and post-prandial distress syndrome. AIM To identify if there is an association between duodenal eosinophilia in functional dyspepsia and symptoms of GERD and whether post-prandial distress syndrome or epigastric pain syndrome are associated with new onset GERD. METHODS Participants (n = 1000) were randomly selected from the national Swedish population register and surveyed by questionnaires and oesophagogastroduodenoscopy in 1999-2001. All eligible subjects (n = 887) were invited to a follow-up study in 2010 (response rate 79%). In a case-control study of 213 subjects (functional dyspepsia vs healthy controls), histology from the duodenum was evaluated at baseline and the possible association of eosinophilia to new onset GERD symptoms was analysed. RESULTS Functional dyspepsia (OR 7.6; 95% CI 2.93-19.4, P

BackgroundIrritable bowel syndrome (IBS) shows genetic predisposition, however, large-scale, powered gene mapping studies are lacking. We sought to exploit existing genetic (genotype) and epidemiological (questionnaire) data from a series of population-based cohorts for IBS genome-wide association studies (GWAS) and their meta-analysis.MethodsBased on questionnaire data compatible with Rome III Criteria, we identified a total of 1335 IBS cases and 9768 asymptomatic individuals from 5 independent European genotyped cohorts. Individual GWAS were carried out with sex-adjusted logistic regression under an additive model, followed by meta-analysis using the inverse variance method. Functional annotation of significant results was obtained via a computational pipeline exploiting ontology and interaction networks, and tissue-specific and gene set enrichment analyses.Key ResultsSuggestive GWAS signals (P5.0x10(-6)) were detected for 7 genomic regions, harboring 64 gene candidates to affect IBS risk via functional or expression changes. Functional annotation of this gene set convincingly (best FDR-corrected P=3.1x10(-10)) highlighted regulation of ion channel activity as the most plausible pathway affecting IBS risk.Conclusion & InferencesOur results confirm the feasibility of population-based studies for gene-discovery efforts in IBS, identify risk genes and loci to be prioritized in independent follow-ups, and pinpoint ion channels as important players and potential therapeutic targets warranting further investigation.

Functional dyspepsia is one of the most prevalent functional gastrointestinal disorders. Functional dyspepsia comprises three subtypes with presumed different pathophysiology and aetiology: postprandial distress syndrome (PDS), epigastric pain syndrome (EPS) and a subtype with overlapping PDS and EPS features. Functional dyspepsia symptoms can be caused by disturbed gastric motility (for example, inadequate fundic accommodation or delayed gastric emptying), gastric sensation (for example, sensations associated with hypersensitivity to gas and bloating) or gastric and duodenal inflammation. A genetic predisposition is probable but less evident than in other functional gastrointestinal disorders, such as irritable bowel syndrome (IBS). Psychiatric comorbidity and psychopathological state and trait characteristics could also play a part, although they are not specific to functional dyspepsia and are less pronounced than in IBS. Possible differential diagnoses include Helicobacter pylori infection and peptic ulceration. Pharmacological therapy is mostly based on the subtype of functional dyspepsia, such as prokinetic and fundus-relaxing drugs for PDS and acid-suppressive drugs for EPS, whereas centrally active neuromodulators and herbal drugs play a minor part. Psychotherapy is effective only in a small subset of patients, whereas quality of life can be severely affected in nearly all patients. Future therapies might include novel compounds that attempt to treat the underlying gastric and duodenal inflammation.

Decreased Number of Duodenal Endocrine Cells with Unaltered Serotonin-Containing Cells in Functional Dyspepsia

Objective: To assess the influence of self-reported intrinsic factors [gastroesophageal reflux disease (GERD), long-term alcoholism, long-term heavy use of alcohol and multiple pregnancies] on erosive tooth wear in a middle-aged cohort sample. Materials and Methods: Of the total Northern Finland Birth Cohort (NFBC 1966), a convenience sample (n = 3,181) was invited for an oral health examination in 2012-2013, of which 1,962 participated, comprising the final study group. Erosive tooth wear was assessed by sextants using the Basic Erosive Wear Examination Index (BEWE, 0-18). Clinical data were supplemented by questionnaires conducted in 1997/1998 and 2012/2013. The participants were divided into severe (BEWE sum ≥9) and no-to-moderate (BEWE sum 0-8) erosive wear groups, and the logistic regression model was applied. Results: Selected intrinsic factors were quite rare in this cohort sample and explained only 5.9% of the difference in the prevalence and severity of erosive wear. Daily symptoms of GERD [odds ratio (OR) 3.8, confidence interval (CI) 1.2-12.0] and hyposalivation (OR 3.8, CI 1.2-11.8) were the strongest risk indicators for severe erosive wear. Additionally, variables associated with an elevated risk for severe erosive wear were diagnosed alcoholism at any point (OR 2.5, CI 0.7-9.7) and self-reported heavy use of alcohol in both questionnaires (OR 2.0, CI 0.6-6.2). Even low-dose long-term consumption of alcohol was associated with erosive wear. Conclusions: In this cohort sample, intrinsic factors such as GERD or alcoholism alone are relatively uncommon causes of erosive tooth wear. The role of long-term use of alcohol in the erosion process may be bigger than presumed.

Aliment Pharmacol Ther 2011; 33: 1215–1224 Summary Background Data on the impact of functional dyspepsia on health-related quality of life in the general adult population are scarce. Aim To explore the impact of functional dyspepsia applying the Rome III definition on health-related quality of life in the general population. Method A random sample of an adult Swedish population (n = 1001, The Kalixanda study) was invited to undergo an oesophagogastroduodenoscopy. An extended abdominal symptom questionnaire and Short Form-36 (SF-36) questionnaire, which includes eight domains measuring physical, mental and social aspects of quality of life, were completed at the clinic visit just before oesophagogastroduodenoscopy. Results Two hundred and two (20%) individuals reported uninvestigated dyspepsia (UID), 157 (16%) functional dyspepsia (FD), 52 (5%) epigastric pain syndrome (EPS) and 122 (12%) postprandial distress syndrome (PDS). UID, FD and PDS had a clinically meaningful (a ≥ 5 point) and statistically significant impact (P

Background & Aims Although serologic analysis is used in diagnosis of celiac disease, histopathology is considered most reliable. We performed a prospective study to determine the clinical, pathologic, and serologic spectrum of celiac disease in a general population (Kalixanda study). Methods A random sample of an adult general population (n = 1000) was analyzed by upper endoscopy, duodenal biopsy, and serologic analysis of tissue transglutaminase (tTg) levels; endomysial antibody (EMA) levels were analyzed in samples that were tTg+. The cut off values for diagnosis of celiac disease were villous atrophy with 40 intraepithelial lymphocytes (IELs)/100 enterocytes (ECs). Results Samples from 33 subjects were tTg+, and 16 were EMA+. Histologic analysis identified 7 of 1000 subjects (0.7%) with celiac disease; all were tTg+, and 6 of 7 were EMA+. Another 26 subjects were tTg+ (7/26 EMA+). This was addressed by a second quantitative pathology study (nested case control design) using a threshold of 25 IELS/100 ECs. In this analysis, all 13 samples that were tTg+ and EMA+ had ≥25 IELs/100 ECs. In total, 16 subjects (1.6%) had serologic and histologic evidence of gluten-sensitive enteropathy. IELs were quantified in duodenal biopsy samples from seronegative individuals (n = 500); 19 (3.8%) had >25 IELs and lymphocytic duodenosis. Conclusions Measurement of ≥25 IELs/100 ECs correlated with serologic indicators of celiac disease; a higher IEL threshold could miss 50% of cases. Quantification of tTg is a sensitive test for celiac disease; diagnosis can be confirmed by observation of ≥25 IELs/100ECs in duodenal biopsy specimens. Lymphocytic enteropathy (celiac disease and lymphocytic duodenosis) is common in the population (5.4%).

Background & Aims The Rome III criteria for functional dyspepsia have been changed to include 2 distinct syndromes: postprandial distress syndrome and epigastric pain syndrome. We investigated risk factors for functional dyspepsia among the functional dyspepsia subgroups defined by the Rome III criteria. Methods We performed a cross-sectional population-based study in a primary care setting (the Kalixanda study). A random sample (n = 2860) of the adult population from 2 northern Swedish municipalities (n = 21,610) was surveyed using a validated postal questionnaire to assess gastrointestinal symptoms (response rate, 74.2%; n=2122). A randomly selected subgroup (n = 1001) of responders was invited to undergo an esophagogastroduodenoscopy (participation rate, 73.3%) including biopsy specimen collection, Helicobacter pylori culture and serology, and symptom assessments. Results Of the 1001 subjects examined by endoscopy, 202 (20.2%; 95% confidence interval [CI], 17.7–22.7) were classified as having uninvestigated dyspepsia and 157 (15.7%; 95% CI, 13.4–18.0) as having functional dyspepsia. Major anxiety (Hospital Anxiety and Depression Scale score ≥11) was associated with uninvestigated dyspepsia (odds ratio [OR], 3.01; 95% CI, 1.39–6.54), as was obesity (body mass index ≥30 kg/m2) (OR, 1.86; 95% CI, 1.15–3.01). Major anxiety was associated with functional dyspepsia and postprandial distress syndrome (OR of 2.56 [95% CI, 1.06–6.19] and 4.35 [95% CI, 1.81–10.46], respectively), as was use of nonsteroidal anti-inflammatory drugs (OR, 2.49 [95% CI, 1.29–4.78] and 2.75 [95% CI, 1.38–5.50], respectively). Depression was not associated with any dyspepsia group. Conclusions Anxiety but not depression is linked to uninvestigated dyspepsia, functional dyspepsia, and postprandial distress syndrome but not to epigastric pain syndrome.

Serological biomarkers can be used for non-invasive diagnosis of gastritis and atrophic gastritis. The aim of this study was to compare the validity of serum levels of pepsinogen I (PGI) and II (PGII), gastrin-17 (G-17) and Helicobacter pylori antibodies (Hpab) with that of the gold standard histology for diagnosis of atrophic gastritis in a population sample from Northern Sweden.In all, 1000 subjects underwent endoscopies with biopsies. Serum biomarkers were available in 976 subjects for independent diagnosis of gastric mucosal status using a predetermined diagnostic algorithm.Overall agreement between histology and serological biomarkers in diagnosing corpus atrophy was 96% (CI 95%: 95-97%). Sensitivity and specificity of markers for atrophic gastritis were 71% (CI 68-74%) and 98% (CI 97-99%) respectively, corresponding to 69% (CI 95%: 66-72%) and 98% (95% CI 97-99%) positive and negative predictive values. The positive likelihood ratio was 35.5 (95% CI: 35.0-36.0%). In subgroups with normal stomachs, H. pylori non-atrophic gastritis and H. pylori-negative gastritis by histology, the prevalence of corpus atrophy diagnosed with the biomarkers was 0.8% and 4.9%, respectively. In total, 6.6% of subjects in the study population had corpus atrophy according to the serological biomarkers. CONCLUSIONS. Serological biomarkers show a high degree of accuracy as a non-invasive method to diagnose corpus atrophy, which is common in the general population.

Background: Eosinophilic oesophagitis may be increasing but the prevalence in the general population remains unknown. Our aim was to assess this and the presence of eosinophils in the distal oesophageal epithelium in the community. Methods: Oesophagogastroduodenoscopy was performed in a random sample (n = 1000) of the adult Swedish population (mean age 54 years, 49% men). Oesophageal biopsy samples were obtained from 2 cm above, and at, the Z-line. Any eosinophil infiltration of the epithelium was defined as “eosinophils present”. Definite eosinophilic oesophagitis was defined as ⩾20, probable as 15–19, and possible as 5–14 eosinophils/high-power field (HPF, at magnification ×40) in oesophageal biopsy specimens. Results: Eosinophils were present in 48 subjects (4.8%, 95% CI 3.5 to 6.1%, mean age 54 years, 63% men), in 54% without troublesome reflux symptoms. Definite eosinophilic oesophagitis was present in four subjects (0.4%, 95% CI 0.01 to 0.8%, mean age 51 years, 75% men) and probable eosinophilic oesophagitis in seven subjects (0.7%, 95% CI 0.2 to 1.2%, mean age 58 years, 43% men). Erosive oesophagitis (OR = 2.99, 95% CI 1.58 to 5.66) and absence of dyspepsia (OR = 0.23, 95% CI 0.07 to 0.75) and Helicobacter pylori infection (OR = 0.41, 95% CI 0.19 to 0.92) were independent predictors for “eosinophils present”. Definite eosinophilic oesophagitis was associated with dysphagia (2/66 vs 2/926, p = 0.025), and probable eosinophilic oesophagitis with narrowing of the oesophageal lumen (2/15 vs 5/978, p = 0.005). Conclusions: Oesophageal eosinophils were present in nearly 5% of the general population; approximately 1% had definite or probable eosinophilic oesophagitis. Oesophageal eosinophils may be a manifestation of reflux disease in adults, but the condition is as likely to be asymptomatic and go unrecognised.

The authors' aim in this study was to explore the prevalence, symptomatology, and risk factors for peptic ulcer in a general adult population. Between December 1998 and June 2001, the authors surveyed a random sample (n=3,000) of the adult population (n=21,610) in two communities in northern Sweden using a validated questionnaire, the Abdominal Symptom Questionnaire (response rate=74%). A subsample (n=1,001) of the responders was randomly invited to undergo esophagogastroduodenoscopy and symptom assessment (response rate=73%). The prevalence of peptic ulcer was 4.1% (20 gastric ulcers and 21 duodenal ulcers). Nausea and gastroesophageal reflux were significant predictors of peptic ulcer disease, but epigastric pain/discomfort was not. Six persons with gastric ulcer and two persons with duodenal ulcer were asymptomatic. Eight subjects with duodenal ulcer (38%) lacked evidence of current Helicobacter pylori infection. Five (25%) of the gastric ulcers and four (19%) of the duodenal ulcers were idiopathic (no use of aspirin or nonsteroidal antiinflammatory drugs, no H. pylori infection). Smoking, aspirin use, and obesity were risk factors for gastric ulcer; smoking, low-dose (

Background & Aims: Barrett's esophagus (BE) is associated with esophageal adenocarcinoma, the incidence of which has been increasing dramatically. The prevalence of BE in the general population is uncertain because upper endoscopy is required for diagnosis. This study aimed to determine the prevalence of BE and possible associated risk factors in an adult Swedish population. Methods: A random sample (n = 3000) of the adult population (n = 21,610) in 2 municipalities was surveyed using a validated gastrointestinal symptom questionnaire (response rate, 74%); a random subsample (n = 1000; mean age, 53.5 years; 51% female) underwent upper endoscopy. Endoscopic signs suggestive of columnar-lined esophagus (CLE) were defined as mucosal tongues or an upward shift of the squamocolumnar junction. BE was diagnosed when specialized intestinal metaplasia was detected histologically in suspected CLE. Results: BE was present in 16 subjects (1.6%; 95% confidence interval, 0.8–2.4): 5 with a long segment and 11 with a short segment. Overall, 40% reported reflux symptoms and 15.5% showed esophagitis; 103 (10%) had suspected CLE, and 12 (1.2%) had a visible segment ≥2 cm. The prevalence of BE in those with reflux symptoms was 2.3% and in those without reflux symptoms was 1.2% ( P = .18). In those with esophagitis, the prevalence was 2.6%; in those without, the prevalence was 1.4% ( P = .32). Alcohol ( P = .04) and smoking ( P = .047) were independent risk factors for BE. Conclusions: BE was found in 1.6% of the general Swedish population. Alcohol and smoking were significant risk factors.

Background: We aimed to determine whether obese subjects experience more gastro-oesophageal reflux (GORS) symptoms than normal subjects, and further to determine if this association was explained by oesophagitis or medications that lower oesophageal sphincter pressure. Methods: In a representative Swedish population, a random sample (n = 1001, mean age 53.5 years, 51% women) had upper endoscopy. GORS was defined as any bothersome heartburn or acid regurgitation. Results: The prevalence of obesity (body mass index ⩾30) was 16%; oesophagitis was significantly more prevalent in obesity (26.5%) than in normal subjects (9.3%). There were associations between obesity and GORS (odds ratio (OR) 2.05 (95% confidence interval (CI) 1.39, 3.01)), epigastric pain (OR 1.63 (95% CI 1.05, 2.55)), irritable bowel symptoms (OR 1.58 (95% CI 1.05, 2.38)), any abdominal pain (OR 1.59 (95% CI 1.08, 2.35)), vomiting (OR 3.11 (95% CI 1.18, 8.20)), retching (OR 1.74 (95% CI 1.1.3, 2.67)), diarrhoea (OR 2.2 (95% CI 1.38, 3.46)), any stool urgency (OR 1.60 (95% CI 1.04, 2.47)), nocturnal urgency (OR 2.57 (95% CI 1.33, 4.98)), and incomplete rectal evacuation (OR 1.64 (95% CI 1.09, 2.47)), adjusting for age, sex, and education. When subjects with oesophagitis and peptic ulcer were excluded, only diarrhoea, incomplete evacuation, and vomiting were significantly associated with obesity. The association between GORS and obesity remained significant adjusting for medication use (OR 1.9 (95% CI 1.3, 3.0)). Conclusions: GORS is associated with obesity; this appears to be explained by increased upper endoscopy findings in obesity.

Objective. Gastroesophageal reflux disease has been reported to be a common burden on health-care resources in the Western world, but its manifestations in the general population are as yet unclear. The aim of this study was to estimate the prevalence of, and to identify the risk factors for gastroesophageal reflux symptoms (GERS) and erosive esophagitis (EE) in the adult population of two Swedish municipalities. Material and methods. A random sample (n=3000) of the adult population (20–81 years of age) of two Swedish municipalities (n=21,610) was surveyed using a validated postal questionnaire assessing gastrointestinal symptoms. The response rate was 74%. A subsample (n=1000) of the responders was subsequently invited, in random order, for esophago-gastro-duodenoscopy with evaluation of GERS, risk factors and tests for Helicobacter pylori. Results. GERS were reported by 40.0% and EE was found in 15.5% of the population that had undergone endoscopy. Of those with GERS, 24.5% had EE while 36.8% of those w...

Objective. Corpus-dominant gastritis, gastric mucosal atrophy and intestinal metaplasia (IM) associated with Helicobacter pylori infection are all known potential risk markers for the development of gastric cancer. As the accuracy for finding cases at risk in the general population is unknown, we aimed to determine the prevalence of current and/or past H. pylori infection and associated gastric mucosal findings by means of histological survey of a random adult population. Material and methods. A random Swedish sample (n=3000, age 20–81 years) was surveyed using a validated gastrointestinal symptom questionnaire with 74% response rate. One-third of the responders were selected at random for esophago-gastro-duodenoscopy with biopsies and H. pylori serology. Results. Of those endoscoped (n=1000, mean age 53.5, 51% women), 43.0% were H. pylori+ by serology (seropositive), 33.9% had signs of current infection on either histology or culture (gold standard+), and 9.3% were seropositive, but gold standard negativ...

Background: Upper oesophagogastroduodenoscopy is considered to be the gold standard for upper gastrointestinal disease assessment, but is currently seldom used in epidemiological studies. One concern is that the procedure may bias sampling among volunteers in a general adult population. The aim of this study was to explore whether the procedure affects symptom reporting. Methods: A random sample of 3000 adults aged 20-81 years (mean age 50.4), from two Swedish municipalities (n = 21,610) was surveyed using a validated postal questionnaire (the Abdominal Symptom Questionnaire) assessing gastrointestinal symptoms. A subsample of the responders was invited, in random order, to undergo an upper endoscopy and repeated symptom reporting using the same questionnaire, as well as a serology test for Helicobacter pylori. Results: The response rate to the initial questionnaire was 74.2% and the participation rate for those eligible for the upper endoscopy was 73.3% (n = 1001, mean age 54.0 years, 48.8% male). No maj...

Eozynofilowe zapalenie przełyku (eosinophilic esophagitis − EoE) jest najczęstszą chorobą przełyku, prowadzącą do dysfagii i zaburzeń odżywiania u dzieci i młodych dorosłych. W związku z tym oraz z uwagi na znaczną liczbę opublikowanych w ostatnim czasie badań na temat EoE bardzo istotna jest optymalizacja rozpoznania i leczenia. Towarzystwa UEG, EAACI, ESPGHAN i EUREOS uznały za konieczne zaktualizowanie wytycznych w zakresie etiologii, epidemiologii, diagnostyki i terapii EoE. Metody. Zastosowano metodologię zgodną z AGREE II (Appraisal of Guidelines for Research and Evaluation) i GRADE (Grading of Recommendations Assessment, Development, and Evaluation), czyli aktualnymi standardami oceny dowodów w formułowaniu rekomendacji.Wyniki. Wytyczne zawierają uaktualnione dane na temat etiologii EoE, epidemiologii, czynników ryzyka, chorób towarzyszących i historii naturalnej EoE u dzieci i dorosłych. Dostarczają informacji o badaniach diagnostycznych i kryteriach rozpoznania, procedurach monitorowania oraz prezentują oparte na faktach zalecenia i rekomendacje dotyczące różnych metod leczenia.Wnioski. W wytycznych zaproponowano oparte na faktach rekomendacje dotyczące rozpoznawania, leczenia i nadzoru pacjentów z EoE.

Background & aims Functional dyspepsia (FD) is associated with anxiety but it is not clear if one causes the other. We investigated whether anxiety and depression precede the onset of FD (based on the modified Rome III criteria) and gastroesophageal reflux symptoms (GERS) in a population-based follow-up study. Methods Participants from the Kalixanda study (n = 3000), randomly selected from the national population register of Sweden, were given the validated Abdominal Symptom Questionnaire 1998-2001; 1000 of these participants then were selected randomly to undergo esophagogastroduodenoscopy and were given the Abdominal Symptom Questionnaire along with the Hospital Anxiety and Depression Scale questionnaire. All eligible subjects who underwent endoscopy (n = 887) were invited to participate in a follow-up study in June-August 2010 and were given the same questionnaires. Data were analyzed by logistic regression. Results Of the 703 subjects who completed the follow-up questionnaires (79.3%); 110 were found to have FD at baseline (15.6%) and 93 at the follow-up examination (13.3%); 48 of these were new cases of FD. GERS without organic disease was reported by 273 individuals (38.8%) at baseline and by 280 at follow-up examination (39.8%); 93 cases were new. Major anxiety was associated with FD at the follow-up evaluation (odds ratio [OR], 6.30; 99% confidence interval [CI], 1.64-24.16). Anxiety was associated with postprandial distress syndrome at baseline (OR, 4.83; 99% CI, 1.24-18.76) and at the follow-up examination (OR, 8.12; 99% CI, 2.13-30.85), but not with epigastric pain syndrome. Anxiety at baseline was associated with new-onset FD at the follow-up examination (OR, 7.61; 99% CI, 1.21-47.73), but not with GERS. Conclusions In a study of the Swedish population, anxiety at baseline, but not depression, increased the risk for development of FD by 7.6-fold in the next 10 years. Anxiety did not affect risk for GERS.

Celiac disease (CD) has been linked to gastroesophageal reflux disease (GORD) and eosinophilic esophagitis (EoE), but population-based studies of the prevalence of CD in these conditions are lacking, that is, the aim of this study.An endoscopic study was carried out in 1000 randomly selected adults from the general population. CD was defined on the basis of positive serology in parallel with mucosal abnormalities of the small intestine. Any eosinophil infiltration of the esophageal epithelium was defined as esophageal eosinophilia and EoE was defined as having at least 15 eosinophils/high-power field in biopsies from the distal esophagus. We used Fisher's exact test to compare the prevalence of GORD, esophageal eosinophilia, and EoE in subjects with CD versus controls.Four hundred subjects (40%) had gastroesophageal reflux symptoms (GORS), 155 (15.5%) had erosive esophagitis, 16 (1.6%) had Barrett's esophagus, 48 (4.8%) had esophageal eosinophilia, and 11 (1.1%) had EoE. CD was diagnosed in 8/400 (2.0%) individuals with GORS (vs. controls: 10/600 (1.7%), p = 0.81), in 3/155 (1.9%) with erosive esophagitis (vs. 15/845 controls (1.8%), p = 0.75), and in 2/48 (4.2%) individuals with esophageal eosinophilia (controls: 16/952 (1.7%), p = 0.21), but in none of those 16 with Barrett's esophagus (vs. 18/984 controls (1.8%), p = 1.0) or of the 11 individuals with EoE (controls: 18/989 (1.8%), p = 1.0).This population-based study found no increased risk of CD among individuals with GORD, esophageal eosinophilia, or EoE. CD screening of individuals with GORD or EoE of individuals with CD cannot be recommended.

Gastro-oesophageal reflux disease (GORD) occurs when reflux of gastric contents causes troublesome symptoms and/or complications (the Montreal definition). GORD is a common condition with a substantial economical burden to the community and it has a significant negative effect on health-related quality of life (HRQoL) while endoscopic findings like erosive oesophagitis per se seem to correlate badly with the experienced HRQoL. The prevalence of GORD varies over the world for unknown reasons, but genetic differences, difference in the Helicobacter pylori prevalence and life style factors like obesity might influence. The prevalence is lowest in East Asia (2.5–9.4%) and higher in Mid (7.6–19.4%) and Western Asia (12.5–27.6%). The highest population-based prevalence is reported from Europe (23.7%) and the US (28.8%). GORD seems to be fairly stable over time both in terms of symptoms and erosive oesophagitis, but the prevalence seems to be increasing both in Asia and in the West.

Background Gastroesophageal reflux disease (GERD), the regurgitation of gastric acids often accompanied by heartburn, affects up to 20% of the general population. Genetic predisposition is suspected from twin and family studies but gene-hunting efforts have so far been scarce and no conclusive genome-wide study has been reported. We exploited data available from general population samples, and studied self-reported reflux symptoms in relation to genome-wide single nucleotide polymorphism (SNP) genotypes. Methods We performed a GWAS meta-analysis of three independent population-based cohorts from Sweden, Finland, and UK. GERD cases (n=2247) and asymptomatic controls (n=4503) were identified using questionnaire-derived symptom data. Upon stringent quality controls, genotype data for more than 2.5M markers were used for association testing. Bioinformatic characterization of genomic regions associated with GERD included gene-set enrichment analysis (GSEA), in silico prediction of genetic risk effects on gene expression, and computational analysis of drug-induced gene expression signatures using Connectivity Map (cMap). Key results We identified 30 GERD suggestive risk loci (P≤5×10−5), with concordant risk effects in all cohorts, and predicted functional effects on gene expression in relevant tissues. GSEA revealed involvement of GERD risk genes in biological processes associated with the regulation of ion channel and cell adhesion. From cMap analysis, omeprazole had significant effects on GERD risk gene expression, while antituberculosis and anti-inflammatory drugs scored highest among the repurposed compounds. Conclusions We report a large-scale genetic study of GERD, and highlight genes and pathways that contribute to further our understanding of its pathogenesis and therapeutic opportunities.

Background and aims. Atrophic gastritis (AG) results most often from Helicobacter pylori (H. pylori) infection. AG is the most important single risk condition for gastric cancer that often leads to an acid-free or hypochlorhydric stomach. In the present paper, we suggest a rationale for noninvasive screening of AG with stomach-specific biomarkers. Methods. The paper summarizes a set of data on application of the biomarkers and describes how the test results could be interpreted in practice. Results. In AG of the gastric corpus and fundus, the plasma levels of pepsinogen I and/or the pepsinogen I/pepsinogen II ratio are always low. The fasting level of gastrin-17 is high in AG limited to the corpus and fundus, but low or non-elevated if the AG occurs in both antrum and corpus. A low fasting level of G-17 is a sign of antral AG or indicates high intragastric acidity. Differentiation between antral AG and high intragastric acidity can be done by assaying the plasma G-17 before and after protein stimulation, or before and after administration of the proton pump inhibitors (PPI). Amidated G-17 will rise if the antral mucosa is normal in structure. H. pylori antibodies are a reliable indicator of helicobacter infection, even in patients with AG and hypochlorhydria. Conclusions. Stomach-specific biomarkers provide information about the stomach health and about the function of stomach mucosa and are a noninvasive tool for diagnosis and screening of AG and acid-free stomach.

Symptomatic gastroesophageal reflux disease (GERD) is associated with a significantly increased risk of esophageal adenocarcinoma, but its natural history in the general population is poorly understood. Whether nonerosive reflux disease (NERD) is a risk factor for Barrett's esophagus (BE), the precursor of esophageal adenocarcinoma, is unknown. Furthermore, quantifying the risk of incident BE in those with untreated reflux esophagitis has not been possible. We aimed, in a prospective follow-up study with endoscopy, to evaluate the risk of BE in a cohort from the Swedish general population (the Kalixanda Study).Those with endoscopic or histological findings suggestive of GERD and randomly half of those with NERD (n=481) were invited for follow-up investigation including endoscopy and a validated symptom questionnaire 5 years after the initial study. Multinomial logistic regression was used to estimate relative risk ratios (RRRs) and 95% confidence intervals (CIs) for change in presentation of GERD.Of the 405 subjects available for inclusion, endoscopy was performed in 284 (response rate 70.1%). The incidence of BE was 9.9/1,000 person-years. Of those with NERD at baseline (n=113), progression to erosive esophagitis was found in 11; 2 developed BE. Erosive esophagitis (n=90) progressed to a more severe grade in 12 and to BE in 8 cases. Erosive esophagitis at baseline was independently associated with BE at follow-up (RRR 5.2; 95% CI 1.2-22.9).Compared with being free of GERD at follow-up, erosive esophagitis is a major risk factor for BE (with a fivefold increased risk) after 5 years in the general population.

The impact of snus (smokeless tobacco or snuff) on gastrointestinal symptoms and pathological findings is largely unknown. The authors aimed to investigate whether the exposure to different forms of tobacco influences upper gastrointestinal symptoms, histology and frequency of Helicobacter pylori infection. A random sample (n = 2,860) of the adult population of two northern Swedish municipalities Kalix and Haparanda (n = 21,610) was surveyed between December 1998 and June 2001 using a validated postal questionnaire assessing gastrointestinal symptoms (response rate 74.2%, n = 2,122) (The Kalixanda Study). A random sub-sample (n = 1,001) of the responders was invited to undergo an esophagogastroduodenoscopy (participation rate 73.3%) including biopsies, Helicobacter pylori culture and serology and symptom assessment and exploration of present and past use of tobacco products. No symptom groups were associated with snus use. Snus users had a significantly higher prevalence of macroscopic esophagitis univariately but snus use was not associated with esophagitis in multivariate analysis. Snus use was associated with basal cell hyperplasia (OR = 1.74, 95% CI: 1.02, 3.00) and with elongation of papillae (OR = 1.79, 95% CI: 1.05-3.05) of the squamous epithelium at the esophago-gastric junction. Current smoking cigarettes was associated with overall peptic ulcer disease (OR = 2.32, 95% CI: 1.04, 5.19) whereas snus use was not. There were no significant association between current Helicobacter pylori infection and different tobacco product user groups. Snus significantly alters the histology of the distal esophagus but does not impact on gastrointestinal symptoms or peptic ulcer disease.

Background/Aim: Short-term fluctuation of gastrointestinal symptoms in the general population is largely unknown. We aimed to determine gastrointestinal symptom fluctuation in an random adult population using a validated questionnaire assessing gastrointestinal symptoms. Methods: A representative sample (n = 2,860) of the population (n = 21,610, 20–81 years of age; mean age 50.4 years) in Northern Sweden was studied. The subjects were asked to complete the questionnaire on two occasions [mean 2.5 months (range 1–6)], firstly via mail and secondly at a visit to the clinic. An upper endoscopy was performed after the last assessment of symptoms. Results: 2,122 individuals (74.2%) completed the initial questionnaire; 1,001 of these (mean age 54.1 years, 48.8 males) completed the second questionnaire. On the first occasion, 40% of the subjects were symptom-free (20.2%) or could not be classified according to their symptom pattern, of those with symptoms 39% reported troublesome reflux symptoms, 40% dyspeptic symptoms and 30% irritable bowel symptoms. Symptom overlap occurred in more than two thirds of the subjects. At the second visit 75% of the subjects who had reported dyspeptic complaints still reported such complaints. Conclusions: In this population-based study, gastrointestinal symptoms were common. Some symptom fluctuation occurred in the shorter term, but troublesome gastrointestinal complaints remained in approximately 90% of subjects over a 1–6-month period.

Functional abnormalities of the duodenum have been observed in non-ulcer dyspepsia. We aimed to identify whether eosinophils in the upper gastrointestinal tract are a biomarker for non-ulcer dyspepsia.A random sample of an adult Swedish population (n = 1001; mean age, 54 y; 51% female) underwent upper endoscopy. Non-ulcer dyspepsia cases (n = 51, Rome II) and randomly selected controls (n = 48) were identified. Two blinded independent observers assessed the gastroduodenal eosinophil counts. Eosinophils were quantified by counting the number per 5 high-power fields at each of 5 sites (cardia, body, antrum, D1 duodenal bulb, and D2 second portion of duodenum), and total counts were summed over the 5 fields at each site.The odds ratio for non-ulcer dyspepsia (vs asymptomatic controls) in subjects with high duodenal bulb eosinophil counts (median,/=22, relative to22) was 11.7 (95% confidence interval, 3.9-34.9), adjusting for age, sex, and H pylori; similar results were observed in D2 (odds ratio = 7.3; 95% confidence interval, 2.9-18.1). A significant association with the number of eosinophil clusters was detected in the duodenum, with higher values in non-ulcer dyspepsia (P.01). By immunostaining with major basic protein antibody in a subset of duodenal biopsy specimens, eosinophil degranulation was observed in non-ulcer dyspepsia (7 of 15 vs 0 of 5 controls; P = .11). Gastric eosinophil counts were overall not significantly increased in non-ulcer dyspepsia vs controls. Early satiety was associated with eosinophilia in D1 (P = .01) and D2 (P = .02), adjusting for age, sex, and H pylori.Duodenal eosinophilia may characterize a subset of adults with non-ulcer dyspepsia.

Background and aims: Gastroesophageal reflux disease (GERD) is common in the West and the increased incidence is associated with obesity. A third of those with symptoms of GERD have endoscopic signs of erosive esophagitis. Two thirds have non-erosive reflux disease; esophageal hypersensitivity may explain some but it is controversial whether an association of psychological distress exists with GERD. Epigastric pain and burning have been found to be associatedwith both hypersensitivity to gastric distension and the personality trait of neuroticism. It has also been shown that anxiety induction significantly increases the experienced acid-induced esophageal hyperalgesia. Visceral hypersensitivity has also been identified in a subset, although the relationship between specific gastric symptoms and physiological changes has been inconsistent. Our aim was to study whether nociceptive pressure pain threshold (PPT) or tolerance (PPTo) is decreased in GERD indicating pain hypersensitivity.Methods: The prospectively collected Northern Finland Birth Cohort 1966 (NFBC 1966) population (http://www.oulu.fi/nfbc/) is comprised of children from the two northernmost provinces of Finland, Oulu and Lapland with a date of birth Jan 1st Dec 31st, 1966 (12 231 children, 96.3% of all births during 1966 in that area). Between years 2013 and 2014, at the age of 46 years, a large health examination including both questionnaires (n=6868/10282, 67% response rate) and clinical examination (n=5851/10282, 57% response rate) was performed. For this study, 3810 subjects (n=1761, 46% male) were available. Uncomfortable pressure, i.e. PPT and intolerable pressure, i.e. PPTo were tested using an algometer (Somedic AB, Horby, Sweden) and the pressure was increased from 0 kPa at a constant rate of 50 kPa/s until the safety maximum of 1200 kPa. The measurements were done for four anatomical sites in the following order: 1) the upper trapezius muscle, 2) the tibialis anterior muscle, 3) the dorsal aspect of the wrist joint line, and 4) the L5/S1 interspinous space. GERD was defined according to the Montreal definition. Anxiety and depression were assessed with 25-items Hopkins Symptom Checklist with a cut off of 1.55. Smoking habits were recorded and body mass index (BMI) was calculated (kg/m). Data were analyzed by Tobit regression analysis adjusting for BMI, anxiety, depression and smoking and crude Kaplan-Meier curves were drawn. Results: 524 subjects (14%) had GERD (n=230, 44% male), 509 (13%) had anxiety (n=196, 39% male) and 852 (22%) had depression (n=340, 40% male). In the crude model, PPT and PPTo were decreased only in women with GERD (Fig.).The difference was explained by anxiety and depression based on the adjusted models. (Table) Conclusions: Psychological distress may explain pain hypersensitivity in women with GERD. Tobit regression analysis of pressure pain threshold and pain tolerance in females with GERD.