Effects of Community Screening for Helicobacter pylori: 13-Year Follow-Up Evaluation of a Randomized Controlled Trial.

BACKGROUND & AIMS: Helicobacter pylori eradication improves the prognosis of peptic ulcer disease (PUD), dyspepsia, and possibly gastric cancer. H pylori screening tests are accurate and eradication therapy is effective. H pylori population screening seems attractive. The aim of this study was to evaluate the long-term effect of H pylori population screening and eradication on dyspepsia prevalence and the incidence of PUD, and as secondary outcomes to assess the effect on health care consumption and quality of life. METHODS: At baseline in 1998 to 1999, 20,011 individuals aged 40 to 65 years were randomized to H pylori screening and eradication or a control group with no screening. Both groups received a questionnaire on dyspepsia and quality of life. Register data were obtained for all randomized individuals. RESULTS: The baseline questionnaire response rate was 63%. Of the 5749 individuals screened, 1007 (17.5%) were H pylori positive. Complete symptom data were obtained for 8658 (69%) individuals after 13 years. Dyspepsia prevalence decreased in both groups during the follow-up period, but multivariate analysis showed no effect of H pylori screening and eradication (adjusted odds ratio, 0.93; 95% confidence interval, 0.82-1.04); compared with usual care. Intention-to-treat and per-protocol analyses of register data provided similar results. H pylori screening neither reduced PUD incidence significantly (adjusted odds ratio, 0.88; 95% confidence interval, 0.70-1.11) nor did it have a beneficial effect on health care consumption. H pylori screening had no long-term effect on quality of life. CONCLUSIONS: This randomized clinical trial with 13 years of follow-up evaluation, designed to provide evidence on the effect of H pylori population screening, showed no significant long-term effect when compared with usual care in this low-prevalence area. ClinicalTrials.gov identifier: NCT02001727.

Helicobacter pylori and risk of upper gastrointestinal bleeding among users of selective serotonin reuptake inhibitors.

BACKGROUND: A number of studies have reported a possible association between use of selective serotonin reuptake inhibitors (SSRIs) and serious upper gastrointestinal bleeding (UGB). We conducted this case-control study to assess if Helicobacter pylori (H. pylori) potentiates the risk of serious UGB in SSRI users. MATERIAL AND METHODS: A population-based case-control study was conducted in the county of Funen, Denmark. Cases were 53 SSRI users with serious UGB whose H. pylori status on their bleeding date could be established. Controls (n = 723) were selected among subjects who participated in a population H. pylori screening study, and who were users of SSRIs. Data on drug exposure and medical history were retrieved from a prescription database and the county's patient register. Confounders were controlled for by unconditional logistic regression. RESULTS: H. pylori infection increased the risk of serious UGB in patients using SSRI with an adjusted odds ratio (OR) of 2.73 (95% confidence interval (CI), 1.17-6.36). The adjusted OR for serious UGB among users of non-steroidal anti-inflammatory drugs (NSAIDs) and acetylsalicylic acid (ASA) were 3.91 (95% CI, 2.03-7.52) and 3.00 (95% CI, 0.94-9.54), respectively. CONCLUSION: H. pylori infection increases the risk of SSRI-related serious UGB.

Gastroesophageal reflux symptoms in a Danish population: a prospective follow-up analysis of symptoms, quality of life, and health-care use.

OBJECTIVES: The prevalence of gastroesophageal reflux symptoms (GERS) in the population is high; however, data on long-term follow-up and incidence of GERS in the population are sparse. This study describes the long-term natural history of GERS, the related health-care use, and quality of life in a population followed up for 5 years. METHODS: A total of 10,000 randomly selected inhabitants, 40-65 years old, received, as a part of a controlled trial of Helicobacter pylori screening and treatment (control group), a mailed questionnaire regarding demographic data, gastrointestinal symptoms (the Gastrointestinal Symptom Rating Scale (GSRS)), and quality of life (the Short-Form 36-Item Health Survey (SF-36)) at inclusion and after 5 years. GERS was defined as a mean score > or =2 in the reflux dimension in the GSRS. Information on use of health-care resources was drawn from the questionnaires and registers. RESULTS: In all, 6,781 individuals answered the first questionnaire and 5-year symptom data were complete for 5,578 (82.3%) of them. The mean age at inclusion was 52.4 years, 48% were men. At inclusion, 22% reported GERS. During follow-up, symptoms resolved in 43%, of whom 10% received acid inhibitory treatment at 5-year follow-up. The incidence of GERS was 2.2% per year. Health-care use during follow-up was significantly higher in individuals with GERS at baseline than in individuals without GERS. Quality of life at 5-year follow-up was lower in individuals with GERS at inclusion than in individuals without GERS at inclusion. CONCLUSIONS: GERS are prevalent, long lasting, and associated with an impaired quality of life and substantial health-care use.

Effect of a community screening for Helicobacter pylori: a 5-Yr follow-up study.

BACKGROUND: Helicobacter pylori (H. pylori) screening and eradication may reduce the incidence of gastric cancer, AND AIMS: peptic ulcer, and ulcer complications, and it may reduce symptoms in a small proportion of individuals with functional dyspepsia. This study aimed to assess the effect of community H. pylori screening and treatment on the prevalence of dyspepsia, and as secondary outcomes, the effect on dyspepsia-related health-care consumption and quality of life over 5 yr. METHODS: In 1998-1999, individuals aged 40-65 yr were randomized to H. pylori screening and treatment or to the control group. Five years later, the participants were sent a questionnaire to assess the prevalence of dyspepsia and quality of life. In addition, we obtained information from registers on the use of endoscopies and prescription medication. An economic evaluation was done alongside the randomized trial. RESULTS: Of 12,530 participants attending the study at baseline, 11,065 (88%) were traced and contacted at the 5-yr follow-up. The response rate was 94%. At baseline, 17.5% in the screened group were H. pylori-positive. The absolute reduction in dyspepsia during the first year was 4% in the screened group, whereas no change was observed in the unscreened group; this rate remained constant during the next 4 yr. Quality of life did not change. A small effect was found for dyspepsia-related consultations and sick leave days, but not on the prescription rate of ulcer drugs. A 33% lower ulcer incidence (107 ulcers vs 148 ulcers) was seen in the screened group compared to the unscreened group. CONCLUSION: A population H. pylori screening and treatment program in an H. pylori low-prevalence area had only a modest, but insignificant, effect on the rate of dyspepsia, and a modest, significant effect on the consultation rate and sick leave days for dyspepsia, but resulted in a decreased ulcer incidence. The intervention resulted in an increased cost due to H. pylori screening and treatment.

Risk factors for dyspepsia in a general population: non-steroidal anti-inflammatory drugs, cigarette smoking and unemployment are more important than Helicobacter pylori infection.

OBJECTIVE: Dyspepsia, a common condition in the community, affects quality of life and imposes costs on both the individual and the community. Several factors including Helicobacter pylori, acetylic salicylic acid (ASA)/non-steroidal anti-inflammatory drugs (NSAIDs) use, low-dose ASA use, alcohol consumption, cigarette smoking and social status might be responsible. MATERIAL AND METHODS: A cross-sectional study from the inclusion (intervention group) of a general population study evaluating rates of dyspepsia after H. pylori screening and eradication was carried out. A total of 10,007 individuals aged 40-64 years received questionnaires and an invitation to take part in H. pylori screening. Information on dyspepsia (the gastrointestinal symptom rating scale (GSRS) and "most bothersome symptom"), use of ASA/NSAIDs, use of low-dose ASA, lifestyle factors and level of education and employment status was obtained from the questionnaire. Dyspepsia was defined as a score of =2 in the GSRS dimension abdominal pain syndrome (aps), allowing for a maximum of one light problem score in any of the 3 items in the dimension to be overlooked. RESULTS: In all, 5749/10,007 individuals participated in the study; 24.9% reported dyspepsia. In a multiple logistic regression analysis H. pylori infection was found to be a risk factor for dyspepsia, odds ratio (OR) 1.21 (CI; 1.03-1.42). However, the highest ORs for dyspepsia were: for daily use of ASA/NSAIDs 2.33 (CI; 1.72-3.15), unemployment 2.18 (CI; 2.86-2.56) and cigarette smoking =20 g/day 1.55 (CI; 1.29-1.86). CONCLUSIONS: H. pylori infection is a significant risk factor for dyspepsia although of less importance than ASA/NSAIDs use, unemployment and heavy smoking.

Rates of dyspepsia one year after Helicobacter pylori screening and eradication in a Danish population.

BACKGROUND & AIMS: Helicobacter pylori (Hp) is strongly correlated with peptic ulcer and is a risk factor for gastric cancer. The aim of this study was to assess whether screening and eradication of Hp in a general population would reduce the prevalence of dyspepsia and the incidence of peptic ulcer and thus save health care resources and improve quality of life. METHODS: Twenty thousand individuals aged 40 to 65 years were randomized to screening and eradication for Hp or to the control group. Hp status was assessed by a whole blood Hp test, a positive result confirmed by a (13)C-urea breath test. Hp-positive individuals were offered Hp eradication therapy. The prevalence of dyspepsia and the quality of life were assessed through a mailed questionnaire. Information on the use of endoscopies and the use of prescription medication was obtained from registers. RESULTS: The response rate was 62.6%. The prevalence of Hp was 17.5%. The Hp eradication rate was 95%. In the intervention group, the prevalence of dyspepsia decreased from 24.3% at inclusion to 20.5% at 1-year follow-up. The reduction was similar in Hp-negative and Hp-positive persons. In the control group, dyspepsia increased from 20.3% to 21.5%. Gastroesophageal reflux symptoms improved slightly in Hp-eradicated participants. Except for a decreased consultation rate for dyspepsia, there were no visible savings in health care. CONCLUSIONS: Dyspepsia was modestly reduced after the screening and treatment procedure, and the result was not sufficiently extensive to have an effect on the use of health care or to improve quality of life.

Diagnosis of Helicobacter pylori in bleeding peptic ulcer patients, evaluation of urea-based tests.

BACKGROUND/AIMS: The prevalence of Helicobacter pylori (Hp) has been reported to be lower in patients with bleeding peptic ulcers than in patients with nonbleeding peptic ulcers. This might be due to inaccuracy of the urease-based diagnostic tests when used in patients with bleeding peptic ulcers. The aims of this study were to compare the validity of the rapid urease test (RUT) and (13)C-urea breath test in patients with bleeding (group 1) and nonbleeding peptic ulcers (group 2) and to examine whether the presence of blood in the stomach influences the validity of urease-based tests. METHODS: 95 consecutive patients with bleeding peptic ulcers (48 with and 47 without blood in the stomach) and 44 with uncomplicated peptic ulcers. Biopsies for RUT and histology were obtained during endoscopy. After endoscopy a (13)C-urea breath test was performed. Positive histology was used as 'gold standard' defining positive Hp-status. RESULTS: The prevalence of Hp-infection was 44/95 (46%) in group 1 and 29/44 (66%) in group 2 (p = 0.04). The sensitivities and specificities of RUT, (13)C-urea breath test and serology (control) were between 0.72 and 0.96; no difference was found between the groups. In group 1 the sensitivity of the RUT decreased from 0.96 when no blood was present to 0.60 when blood was present (p = 0.006). The sensitivity of (13)C-urea breath test was not affected by blood in the stomach. CONCLUSION: When comparing patients with bleeding and nonbleeding peptic ulcers, we did not find any difference in either sensitivity or specificity of the diagnostic tests for Hp. However, the sensitivity of the RUT was lower when blood was present in the stomach, which was the case in only half of the patients. The sensitivity and specificity of the (13)C-urea breath test was not affected by the presence of blood in the stomach.

Development and clinical evaluation of a novel immunoassay for the binary complex of IGF-I and IGF-binding protein-1 in human serum.

Correlation studies have suggested that IGF-binding protein (IGFBP)-1 is a dynamic regulator of free IGF-I. To further study this, we developed a monoclonal immunofluorometric assay specific for the binary complex of IGF-I and IGFBP-1 in human serum. An IGFBP-1 antibody, which recognizes all phospho-forms of IGFBP-1, was used for coating. An europium-labeled IGF-I antibody served as tracer. Assay incubation was performed at conditions approaching those in vivo (i.e. pH 7.4, 37 C). The assay was highly specific: no signal was obtained unless both IGF-I and IGFBP-1 were present and neither IGFBP-2, -3, -4, nor IGF-II caused any cross-reaction. The linear standard curve covered 3 orders of magnitude, and within and in-between assay coefficients of variation were less than 5 and 15%, respectively. To study the dynamic relationship between free IGF-I and binary complex formation, seven healthy subjects were fasted for 72 h. Samples were collected every 3 h. During fasting, free IGF-I was reduced by two thirds (P < 0.0001). IGFBP-1 and the binary complex increased in parallel (P < 0.0001), and levels correlated positively in all subjects (0.89 < or = r < or = 0.98; P < 0.0001). Free IGF-I correlated inversely with IGFBP-1 (-0.81 < or = r < or = -0.48; 0.0001 < or = P < or = 0.05) and the binary complex (-0.79 < or = r < or = -0.41; 0.0001 < or = P < or = 0.05). To study overnight fasting levels, we compared healthy controls and patients with type 1 diabetes and chronic renal failure (n = 10), because these patients show profound alterations in their IGF-system. In both groups, the binary complex was increased about 2.5-fold (P < 0.0001), whereas IGFBP-1 was increased by 5- to 6-fold (P < 0.0001). Accordingly, free IGF-I was severely reduced (P < 0.0001). In conclusion, the assay enables us to study the role of IGFBP-1 as a dynamic regulator of free IGF-I. Our results clearly show that IGFBP-1 and free IGF-I are tightly associated peptides. Furthermore, it has now become possible to compare levels of IGF-I carried within the binary complex IGFBP-1:IGF-I in different (patho-) physiological conditions.