Background Although vonoprazan has been proven to be a highly potent drug for Helicobacter pylori eradication, there have been no randomized trials comparing the effectiveness of regimens containing vonoprazan 20 mg daily with alternative standard strategies. We aimed to assess the efficacy, tolerance, and cost‐effectiveness of quadruple therapy with vonoprazan 20 mg daily as a first‐line therapy for H. pylori eradication. Materials and Methods We conducted a single‐center, open‐label, noninferiority, randomized controlled study in Zhejiang, China. Treatment‐naive H. pylori‐positive participants (n = 234) were randomly assigned to three groups in a 1:1:1 ratio: vonoprazan 20 mg daily with amoxicillin 1000 mg, furazolidone 100 mg and colloidal bismuth 200 mg each given twice a day for 10 days (V10) or 14 days (V14), or esomeprazole 20 mg with amoxicillin 1000 mg, furazolidone 100 mg and colloidal bismuth 200 mg each given twice a day for 14 days (E14). The primary endpoint was the eradication rates in each group. The secondary endpoints were the incidence of adverse events (AEs) and compliance. Results The eradication rates in the V10, V14 and E14 groups were 96.2% (89.2–99.2%), 94.9% (87.4–98.6%), and 93.6% (85.7–97.9%) in the intention‐to‐treat analysis, and 98.6% (92.7–100.0%), 97.4% (90.8–99.7%), and 94.8% (87.2–98.6%) in the per‐protocol analysis, respectively. Quadruple therapy with vonoprazan 20 mg daily was noninferior to the esomeprazole‐based regimen (Farrington and Manning test: margin 10%, significance level 2.5%). The adverse event rates were 12.8% versus 3.8% versus 6.4% in the V10, V14, and E14 groups, respectively. All regimens were well tolerated without significant differences (p = 0.096). The cost‐effectiveness ratio was 1.32, 1.88, and 3.06 for the V10, V14, and E14 groups in the intention‐to‐treat analysis, respectively. (NCT04907747). Conclusions Vonoprazan (20 mg daily) was as effective as esomeprazole (20 mg twice a day) in quadruple therapies for the eradication of H. pylori, was more economical, and was well tolerated. In addition, the 10‐day regimen of vonoprazan (20 mg daily) was comparable to the 14‐day regimen.

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What is known and objective: There have been concerns about a potential link between long-term use of bisphosphonates (BPs) for the treatment of osteoporosis and rare serious adverse effects, such as atypical femoral fractures. However, many reviews exist with conflicting conclusions about this issue. The aim of this overview of reviews was to systematically evaluate the risk of rare serious adverse effects of long-term use of BPs for the treatment of osteoporosis. Methods: We identified systematic reviews with meta-analyses of randomized controlled trials (RCTs) and (or) observational studies published in English or Chinese that evaluated the safety of BPs through to December 2018. The Cochrane library, PubMed, Web of Science and hand-searching of reference lists and clinical practice guidelines were electronically searched for data sources. Carcinogenicity, atypical fracture, osteonecrosis of jaw (ONJ) and fracture union time were specified as the primary outcomes. The methodological quality of each systematic review was assessed by two reviewers using the Assessment of Multiple Systematic Reviews (AMSTAR) tool, and the quality of evidence for key outcomes was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Results and discussion: In total, 1376 potentially relevant citations were identified, of which only 8 systematic reviews with meta-analyses met the eligibility criteria. All the included reviews were published between 2012 and 2015 and documented the pooled estimates of effect size (relative risk [RR], odds ratio [OR] or hazard ratio [HR] and their 95% confidence intervals [95% CI]) for the incidence of adverse events. All included systematic reviews were of moderate or high quality. The median AMSTAR score was 7.5 (interquartile range, 5-10). However, evidence of the key outcomes was mainly of very low or moderate quality. BP treatment only increased the risk of atypical fracture and ONJ, and prolonged union time compared with placebo or other anti-osteoporosis drugs (P ＜ .05). What is new and conclusion: This study indicated that long-term use of BPs could increase the risk of rare serious adverse effects, but the relationship between longterm use of BPs and carcinogenicity was often uncertain. Therefore, high-quality research and more complete inclusion criteria are needed.

Different from the traditional methods of assessing the cardiac activities through heart rhythm statistics or P-QRS-T complexes separately, this study demonstrates their interactive effects on the power density spectrum (PDS) of ECG signal with applications for the diagnosis of ST-segment elevation myocardial infarction (STEMI) diseases. Firstly, a mathematical model of the PDS of ECG signal with a random pacing pulse train (PPT) mimicking S-A node firings was derived. Secondly, an experimental PDS analysis was performed on clinical ECG signals from 49 STEMI patients and 42 healthy subjects in PTB Diagnostic Database. It was found that besides the interactive effects which are consistent between theoretical and experimental results, the ECG PDSs of STEMI patients exhibited consistently significant power shift towards lower frequency range in ST-elevated leads in comparison with those of reference leads and leads of health subjects with the highest median frequency shift ratios at 51.39 ± 12.94% found in anterior MI. Thirdly, the results of ECG simulation with systematic changes in PPT firing statistics over various lengths of ECG data ranging from 10s to 60 mins revealed that the mean and median frequency parameters were less affected by the heart rhythm statistics and the data length but more depended on the alterations of P-QRS-T complexes, which were further confirmed on 33 more STEMI patients in European ST-T Database, demonstrating that the frequency indexes could be potentially used as alternative indicators for STEMI diagnosis even with ultrashort-term ECG recordings suitable for wearable and mobile health applications in living-free environments.

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