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Dramatic shift in the epidemiology of peptic ulcer in Japan: the impact of Helicobacter pylori eradication therapy

ABSTRACT: Helicobacter pylori eradication therapy was included with insurance coverage from 1999 onwards in Japan, with the incidence of peptic ulcer expected to decrease as a consequence. This study investigated the temporal dynamics of peptic ulcer in Japan and identified underlying contributory factors using mathematical models. We investigated the seroprevalence of H. pylori and analysed a snapshot of peptic ulcer cases. Ten statistical models that incorporated important events – H. pylori infection, the cohort effect, eradication therapy and the natural trend for reduction – were fitted to the case data. The hazard of infection with H. pylori was extracted from published estimates. Models were compared using the Akaike information criterion (AIC), and factor contributions were quantified using the coefficient of determination. The best-fit model indicated that 88.1% of the observed snapshot of cases (AIC = 289.2) included the effects of (i) H. pylori infection, (ii) the cohort effect and (iii) eradication therapy, as explanatory variables, the contributions of which were 80.8%, 4.0% and 3.2%, respectively. Among inpatients, a simpler model with (i) H. pylori infection only was favoured (AIC = 107.7). The time-dependent epidemiological dynamics of peptic ulcers were captured and H. pylori infection and eradication therapy explained ⩾84% of the dramatic decline in peptic ulcer occurrence.

SUBMITTER: Lee K

PROVIDER: S-EPMC8753483 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundMost peptic ulcer cases are associated with Helicobacter pylori (H. pylori) infection or the use of nonsteroidal anti-inflammatory drugs (NSAIDs). H. pylori eradication therapy is recommended for the treatment of H. pylori-positive peptic ulcers. We aimed to assess and validate the cumulative economic and health effects of H. pylori eradication strategy for the treatment of peptic ulcers compared with PPI therapy strategy.Materials and methodsWe developed a cohort state-transition model for H. pylori eradication strategy and PPI therapy strategy over a lifetime horizon from a healthcare payer perspective. We targeted two hypothetical cohorts of H. pylori-positive patients with gastric and duodenal ulcers aged 20, 30, 40, 50, 60, 70, and 80. The main outcomes were costs, quality-adjusted life-years (QALYs), life expectancy life-years (LYs), incremental cost-effectiveness ratios, ulcer recurrence cases, and ulcer-associated deaths. One-way and probabilistic sensitivity analyses were conducted to assess the impact of uncertainty.ResultsIn the base-case analysis, H. pylori eradication strategy was less costly with greater benefits than PPI therapy strategy in all age groups. Cost-effectiveness was not sensitive to any variables in all age groups. Sensitivity analyses showed strong robustness of the results. From 2000 to 2020, H. pylori eradication strategy saved US$14.07 billion over a lifetime, increased 8.65 million QALYs and 1.23 million LYs over a lifetime, and prevented 551,298 ulcer recurrence cases and 59,465 ulcer-associated deaths, compared with PPI therapy strategy.ConclusionsH. pylori eradication strategy not only has contributed significantly to preventing ulcer recurrence and reducing ulcer-associated deaths but also has resulted in great cost savings. All over the world, H. pylori eradication strategy is likely to have yielded a comparable magnitude of economic and health benefits, depending on the epidemiology of H. pylori-related peptic ulcers and the healthcare environment in each country.

Project description:BackgroundClarithromycin-based therapy is important for Helicobacter pylori eradication treatment. However, clarithromycin may increase cardiovascular risk. Hence, we investigated the association between clarithromycin use and outcomes in adults with stable coronary heart disease (CHD) and subsequent peptic ulcer disease (PUD).MethodsThis nationwide cohort study used a national health insurance database to screen 298,417 Taiwanese residents who were diagnosed with coronary heart disease from 2001 to 2015 for eligibility in the study and to evaluate select eligible patients with CHD-PUD from 2004 to 2015. Data were obtained from new users of clarithromycin (n = 4183) and nonusers of clarithromycin (n = 24,752) during follow-up. A total of 4070 eligible clarithromycin users and 4070 nonusers were subject to final analysis by 1:1 propensity score matching. Participants were followed up after receiving clarithromycin or at the corresponding date until the occurrence of cardiovascular morbidity in the presence of competing mortality, overall mortality and cardiovascular mortality, or through the end of 2015. The incidence rates and risks of overall mortality and cardiovascular outcomes were evaluated. The associations between clarithromycin and arrhythmia risk, as well as its dose and duration and overall mortality and cardiovascular outcomes were also addressed.ResultsClarithromycin users were associated with adjusted hazard ratios of 1.08 (95% confidence interval, 0.93-1.24; 21.5 compared with 21.2 per 1000 patient-years) for overall mortality, 0.95 (0.57-1.59; 1.5 compared with 1.8 per 1000 patient-years) for cardiovascular mortality, and 0.94 (0.89-1.09; 19.6 compared with 20.2 per 1000 patient-years) for cardiovascular morbidity in the presence of competing mortality, as compared with nonusers. We found no relationship between dose and duration of clarithromycin and overall mortality and cardiovascular outcomes and no increased risk of arrhythmia during follow-up period. After inclusion of arrhythmia events to re-estimate the risks of all study outcomes, the results remained insignificant.ConclusionConcerning overall mortality, cardiovascular mortality, and cardiovascular morbidity, our results suggest clarithromycin-based therapy for Helicobacter pylori eradication may be safe in patients with stable CHD and subsequent PUD.

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Dramatic shift in the epidemiology of peptic ulcer in Japan: the impact of Helicobacter pylori eradication therapy

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