Pregnancy period and early-life risk factors for inflammatory bowel disease: a Northern Finland birth cohort 1966 study.

BACKGROUND: The pathogenesis of inflammatory bowel disease (IBD) has not been fully elucidated. The aim of this study was to analyze the pregnancy period, perinatal period, and infancy period risk factors for IBD in a well-characterized birth cohort from Northern Finland. METHODS: The Northern Finland Birth Cohort 1966 (NFBC1966) population comprises mothers living in the two northernmost provinces of Finland, Oulu, and Lapland, with dates of delivery between Jan 1st and Dec 31st, 1966 (12 055 mothers, 12 058 live-born children, 96.3% of all births during 1966). IBD patients were identified using hospital registries (from 1966 to 2020) and Social Insurance Institution (SII) registry reimbursement data for IBD drugs (from 1978 to 2016). The data were analyzed by Fisher's exact test and logistic regression. RESULTS: In total, 6972 individuals provided informed consent for the use of combined SII and hospital registry data. Of those, 154 (2.1%) had IBD (113 [1.6%] had ulcerative colitis (UC), and 41 (0.6%) had Crohn's disease (CD)). According to multivariate analysis, maternal smoking > 10 cigarettes/day during pregnancy was associated with a nearly 6-fold increased risk of CD in the offspring (OR 5.78, 95% CI 1.70-17.3). Breastfeeding (OR = 0.18, 95% CI 0.08-0.44) and iron supplementation during the first year of life (OR = 0.43, 95% CI 0.21-0.89) were negatively associated with CD. CONCLUSIONS: Smoking during pregnancy was associated with the risk of CD while Breastfeeding and oral iron supplementation at infancy were negatively associated with the risk of CD later in life.

Genomic and epidemiological report of the recombinant XJ lineage SARS-CoV-2 variant, detected in northern Finland, January 2022.

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.

Anxiety Is Linked to New-Onset Dyspepsia in the Swedish Population: A 10-Year Follow-up Study.

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.

Influence of Intrinsic Factors on Erosive Tooth Wear in a Large-Scale Epidemiological Study.

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.

Celiac disease, eosinophilic esophagitis and gastroesophageal reflux disease, an adult population-based study.

OBJECTIVE: 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. MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Helicobacter pylori attachment-blocking antibodies protect against duodenal ulcer disease.

The majority of the world population carry the gastric pathogen Helicobacter 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 where H. pylori attachment and accompanying chronic mucosal inflammation can be reduced by antibodies that are present in a vast majority of H. pylori carriers. These antibodies block binding of the H. pylori attachment 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.

Rationale in diagnosis and screening of atrophic gastritis with stomach-specific plasma biomarkers.

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.

Effectiveness and cost-effectiveness of a people-centred care model for community-living older people versus usual care ─ A randomised controlled trial.

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.

Repeated out-of-Africa expansions of Helicobacter pylori driven by replacement of deleterious mutations.

Helicobacter pylori lives in the human stomach and has a population structure resembling that of its host. However, H. pylori from Europe 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 by migration 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.

Detection of celiac disease and lymphocytic enteropathy by parallel serology and histopathology in a population-based study.

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 > or =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 > or =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 > or =25 IELs/100ECs in duodenal biopsy specimens. Lymphocytic enteropathy (celiac disease and lymphocytic duodenosis) is common in the population (5.4%).

Erosive esophagitis is a risk factor for Barrett's esophagus: a community-based endoscopic follow-up study.

OBJECTIVES: 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). METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Neutrophils, eosinophils, and intraepithelial lymphocytes in the squamous esophagus in subjects with and without gastroesophageal reflux symptoms.

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.

Duodenal eosinophilia and the link to anxiety: A population-based endoscopic study.

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.

Serological Biomarker Panel in Diagnosis of Atrophic Gastritis and Helicobacter pylori Infection in Gastroscopy Referral Patients: Clinical Validation of the New-Generation GastroPanel® Test.

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.

Role of smoking in functional dyspepsia and irritable bowel syndrome: three random population-based studies.

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.

Anxiety is associated with uninvestigated and functional dyspepsia (Rome III criteria) in a Swedish population-based study.

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 > or = 11) was associated with uninvestigated dyspepsia (odds ratio [OR], 3.01; 95% CI, 1.39-6.54), as was obesity (body mass index > or = 30 kg/m(2)) (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.

Use of tobacco products and gastrointestinal morbidity: an endoscopic population-based study (the Kalixanda study).

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.

Clinical use of proton-pump inhibitors but not H2-blockers or antacid/alginates raises the serum levels of amidated gastrin-17, pepsinogen I and pepsinogen II in a random adult population.

OBJECTIVE: Proton-pump inhibitors (PPIs), H(2) receptor antagonists (H(2)RAs) and antacids/alginates reduce intragastric acidity and may thus influence normal gastric physiology. The purpose of this study was to examine the effect of these compounds on serum levels of amidated gastrin-17 (G-17) and pepsinogens (PGI & PGII) in a large, random, adult Swedish population sample with uninfected stomach mucosa. MATERIAL AND METHODS: The initial sample subjects (n=1000, mean age 50 years, range 20-80 years) completed a questionnaire on the use of acid inhibitory drugs 1 week and/or 3 months before study entry. All subjects (n=590) with normal gastric mucosa as delineated by serum biomarkers were included. Among them, serum levels of PGI, PGII and G-17 were compared between those who used acid inhibitory drugs and those who did not. RESULTS: The serum levels of G-17 or pepsinogens in the subjects who reported use of H(2)RAs (n=18) or antacid/alginates (n=66) during the previous 3 months did not differ from those in non-users (n=471). However, the median levels of G-17 and pepsinogens were significantly (p<0.001) higher among the PPI users (n=35) than among non-users: the levels were approximately doubled. The ratio of PGI/PGII was, however, similar between PPI users and non-users, or those using antacids/alginates or H(2)RAs. Among subjects using PPIs, the serum levels of pepsinogens correlated positively (p<0.01) with the serum levels of G-17. CONCLUSIONS: PPIs but not antacids/alginates or H(2)RAs markedly increase the fasting levels of serum amidated G-17 and pepsinogens among ordinary patients in everyday clinical practice.

Duodenal eosinophilia is associated with functional dyspepsia and new onset gastro-oesophageal reflux disease.

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 < 0.001) and post-prandial distress syndrome at baseline (OR 9.0, 95% CI 3.36-24.0, P < 0.001) were associated with an increased risk of GERD at follow-up. Eosinophilia in the second part of duodenum only was independently associated with an increased risk of GERD amongst those with functional dyspepsia (OR 4.2; 95% CI 1.2-4.77, P = 0.024) and post-prandial distress syndrome at baseline (OR 6.0; 95% CI 1.50-23.6, P = 0.011), respectively. CONCLUSIONS: Duodenal eosinophilia is associated with increased risk of GERD at 10-year follow-up in those with functional dyspepsia and post-prandial distress syndrome at baseline. Duodenal eosinophilia may explain the link between GERD and functional dyspepsia, suggesting subsets of functional dyspepsia and GERD may be part of the same disease spectrum.