Search

Summary: Background: Optimal glycaemic control has well‐established health benefits in patients with diabetes mellitus (DM). It is uncertain whether optimal glycaemic control can benefit liver‐related outcomes. Aims: To examine the association of optimal glycaemic control with hepatocellular carcinoma (HCC) and liver‐related mortality. Methods: In a population‐based cohort, we identified patients with newly diagnosed DM between 2001 and 2016 in Hong Kong. Optimal glycaemic control was defined as mean haemoglobin A1c (HbA1c) <7% during the 3‐year lead‐in period after DM diagnosis. By applying propensity score matching to balance covariates, we analysed glycaemic control via competing risk models with outcomes of interest being HCC and liver‐related mortality. Results: We identified 146,430 patients (52.2% males, mean age 61.4 ± 11.8 years). During a median follow‐up duration of 7.0 years, 1099 (0.8%) and 978 (0.7%) patients developed HCC and liver‐related deaths. Optimal glycaemic control, when compared to suboptimal glycaemic control, was associated with reduced risk of HCC (subdistribution hazard ratio [SHR] 0.70, 95% CI 0.61–0.79). The risk of HCC increased with incremental HbA1c increases beyond >7% (SHR 1.29–1.71). Significant associations with HCC were also found irrespective of age (SHR 0.54–0.80), sex (SHR 0.68–0.69), BMI <25 or ≥25 kg/m2 (SHR 0.63–0.75), smoking (SHR 0.61–0.72), hepatic steatosis (SHR 0.67–0.68) and aspirin/statin/metformin use (SHR 0.67–0.75). A lower risk of liver‐related mortality in relation to optimal glycaemic control was also observed (SHR 0.70, 95% CI 0.61–0.80). Conclusions: Glycaemic control is an independent risk factor for HCC and liver‐related mortality, and should be incorporated into oncoprotective strategies in the general DM population. [ABSTRACT FROM AUTHOR]

Background: We compared efficacy of vonoprazan‐dual or triple therapies and bismuth‐quadruple therapy for treatment‐naive Helicobacter pylori (HP) infection in Southern China, where primary resistance rates of clarithromycin and levofloxacin are >30%. Methods: This was an investigator‐initiated, three‐arm, randomized clinical trial in Southern China. Between March 2022 and August 2023, treatment‐naïve HP‐infected adults were randomly assigned to receive one of three 14‐day regimens (1:1:1 ratio): vonoprazan‐dual (VA‐dual; vonoprazan 20 mg twice daily and amoxicillin 1 g thrice daily), vonoprazan‐triple (VAC‐triple; vonoprazan 20 mg/amoxicillin 1 g/clarithromycin 500 mg twice daily), or bismuth‐quadruple therapy containing bismuth, esomeprazole, tetracycline, and metronidazole. Primary outcome was noninferiority in HP eradication, evaluated by UBT 4–6 weeks post‐treatment by intention‐to‐treat (ITT) and per‐protocol (PP) analysis (based on subjects who completed 14‐day treatment and rechecked UBT). Bonferroni‐adjusted p‐value of <0.017 was used to determine statistical significance. Results: A total of 298 subjects (mean age: 35.7 ± 8.4 years; male: 134 [45.0%]; VC‐dual: 100, VAC‐triple: 98, bismuth‐quadruple: 100) were enrolled, and 292 (98.0%) had UBT rechecked. ITT analysis showed that both VA‐dual (eradication rate of 96.0%) and VAC‐triple therapies (95.9%) were noninferior to bismuth‐quadruple therapy (92.0%) (difference: 4.0%, 95% CI: −2.9% to 11.5%, p < 0.001; and 3.9%, 95% CI: −3.1% to 11.5%, p < 0.001, respectively). PP analysis also revealed noninferiority (96.7% or 96.7% vs. 97.4%, with difference: −2.9% and −2.9%, p = 0.009 and 0.010, respectively). The frequency of adverse events was 39.0%, 56.1%, and 71.0% in VA‐dual, VAC‐triple, and bismuth‐quadruple therapies, respectively. Conclusions: VA‐dual and VA‐triple therapies are highly effective and noninferior to bismuth‐quadruple therapy in Southern China. Given the lower adverse effects and fewer antibiotic use, VA‐dual therapy is the preferred first‐line treatment for HP infection. Trial Registration: Chinese Clinical Trial Registry (No. ChiCTR2200056375). Registered on February 4, 2022, https://www.chictr.org.cn/showproj.aspx?proj=14131. [ABSTRACT FROM AUTHOR]

Background With the increasing prevalence of antibiotic resistance, real-world data on the optimal empirical second-line therapy for Helicobacter pylori are still limited. Objectives To evaluate the real-world efficacy of various second-line therapies for H. pylori. Patients and methods This was a retrospective population-based cohort study of all H. pylori -infected patients who had received the second-line treatment after the failure of primary clarithromycin triple therapy in Hong Kong between 2003 and 2018. The retreatment success rates of different second-line therapies were evaluated. Results A total of 7591 patients who received second-line treatment were included. Notably, the most commonly prescribed regimen was still clarithromycin triple therapy, but the frequency of use had decreased from 59.5% in 2003–06 to 28.7% in 2015–18. Concomitant non-bismuth quadruple therapy had emerged as the commonest regimen (from 3.3% to 43.9%). In a validation analysis, the sensitivity and specificity of retreatment-inferred second-line treatment failure were 88.3% and 97.1%, respectively. The overall success rate of second-line therapies was 73.6%. Bismuth quadruple therapy had the highest success rate of 85.6%, while clarithromycin triple therapy had the lowest success rate of 63.5%. Specifically, bismuth/metronidazole/tetracycline quadruple, metronidazole/tetracycline triple, levofloxacin/metronidazole/tetracycline quadruple, rifabutin/amoxicillin triple and amoxicillin/levofloxacin triple therapies had relatively higher success rates over 80%. Age, treatment duration, baseline conditions and first-line treatment used were associated with success rate. Conclusions Bismuth quadruple therapy was the most effective second-line regimen for H. pylori in this real-world study. Despite a very low success rate, clarithromycin-containing triple therapies were still commonly used as second-line regimens. [ABSTRACT FROM AUTHOR]

Background and Aim: Proton pump inhibitors (PPIs) may increase the risk of COVID‐19 among non‐vaccinated subjects via various mechanisms, including gut dysbiosis. We aimed to investigate whether PPIs also affect the clinical outcomes of COVID‐19 among vaccine recipients. Methods: This was a territory‐wide cohort study of 3 272 286 vaccine recipients (aged ≥ 18 years) of ≥ 2 doses of either BNT162b2 or CoronaVac. Exclusion criteria included prior gastrointestinal surgery, immunocompromised status, and prior COVID‐19. The primary outcome was COVID‐19, and secondary outcomes included COVID‐19‐related hospitalization and severe infection (composite of intensive care unit admission, ventilatory support, and/or death). Covariates include age, sex, the Charlson Comorbidity Index, comorbidities, and concomitant medication use. Subjects were followed from index date (first dose of vaccination) until outcome occurrence, death, additional dose of vaccination, or March 31, 2022. Exposure was pre‐vaccination PPI use (any prescription within 90 days before the index date). Propensity score (PS) matching and a Poisson regression model were used to estimate the adjusted incidence rate ratio (aIRR) of outcomes with PPI use. Results: Among 439 154 PS‐matched two‐dose vaccine recipients (mean age: 65.3 years; male: 45.7%) with a median follow‐up of 6.8 months (interquartile range: 2.6–7.9), PPI exposure was associated with a higher risk of COVID‐19 (aIRR: 1.08; 95% confidence interval [95% CI]: 1.05–1.10), hospitalization (aIRR: 1.20; 95% CI: 1.08–1.33), and severe infection (aIRR: 1.57; 95% CI: 1.24–1.98). Among 188 360 PS‐matched three‐dose vaccine recipients (mean age: 62.5 years; male: 49.0%; median follow‐up: 9.1 months [interquartile range: 8.0–10.9]), PPIs were associated with higher infection risk (aIRR: 1.11; 95% CI: 1.08–1.15) but not other outcomes. Conclusions: Although PPI use was associated with a higher COVID‐19 risk, severe infection was limited to two‐dose but not three‐dose vaccine recipients. [ABSTRACT FROM AUTHOR]

Background: The success rate of clarithromycin‐containing Helicobacter pylori treatment had declined globally. This study aims to explore the role of different machine learning algorithms in predicting failure of H. pylori treatment. Materials and Methods: We included 84,609 adult patients who had received the first course of clarithromycin‐containing triple therapy for H. pylori in Hong Kong from 2003 to 2013 as training set. Results were validated in patients who had received similar triple therapy with 27,736 Hong Kong patients between 2014 and 2017 (internal cohort); and 18,050 UK patients between 2012 and 2017 (external cohort). The performance of 11 available machine learning algorithms were used to predict the failure of triple therapy. The performance was determined by the area under receiver operating characteristic curve (AUC). Results: The treatment failure rates in the training, internal and external validation cohort was 5.9%, 9.5%, and 6.1%, respectively. In the internal validation set, Extra‐Tree (ET) Classifier had the best AUC (0.88; 95% CI, 0.87–0.88), sensitivity (79.6%; 95% CI, 79.0–80.2) and specificity (79.4%; 95% CI, 79.0–79.8). In the external validation set, ET Classifier also had the best AUC (0.85; 95% CI, 0.85–0.86), sensitivity (80.1%; 95% CI, 79.5–80.9), and specificity (80.2%; 95% CI, 78.8–81.3). Top features of importance used by ET Classifier in predicting treatment failure included time interval between antibiotic use and triple therapy (48.8%), age (29.1%) and triple therapy regime (6.28%). Conclusions: Machine learning algorithm, based on simple baseline clinical parameters, could help to identify patients at high risk of failure from clarithromycin‐containing triple therapy for H. pylori. [ABSTRACT FROM AUTHOR]