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Whether concomitant therapy is superior to bismuth quadruple therapy or 14-day triple therapy for the first-line treatment of Helicobacter pylori infection remains poorly understood. We aimed to compare the efficacy and safety of 10-day concomitant therapy, 10-day bismuth quadruple therapy, and 14-day triple therapy in the first-line treatment of H pylori. In this multicentre, open-label, randomised trial, we recruited adult patients (aged >20 years) with H pylori infection from nine medical centres in Taiwan. Patients who had at least two positive tests from the rapid urease test, histology, culture, or serology or who had a single positive 13C-urea breath test for gastric cancer screening were eligible for enrolment. Patients were randomly assigned (1:1:1) to either concomitant therapy (lansoprazole 30 mg, amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg, all given twice daily) for 10 days; bismuth quadruple therapy (bismuth tripotassium dicitrate 300 mg four times a day, lansoprazole 30 mg twice daily, tetracycline 500 mg four times a day, and metronidazole 500 mg three times a day) for 10 days; or triple therapy (lansoprazole 30 mg, amoxicillin 1 g, and clarithromycin 500 mg, all given twice daily) for 14 days. A computer-generated permuted block randomisation sequence with a block size of 6 was used for randomisation, and the sequence was concealed in an opaque envelope until the intervention was assigned. Investigators were masked to treatment allocation. The primary outcome was the eradication frequency of H pylori with first-line therapy assessed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01906879. Between July 17, 2013, and April 20, 2016, 5454 patients were screened for eligibility. Of these, 1620 patients were randomly assigned in this study. The eradication frequencies were 90·4% (488/540 [95% CI 87·6–92·6]) for 10-day bismuth quadruple therapy, 85·9% (464/540 [82·7–88·6]) for 10-day concomitant therapy, and 83·7% (452/540 [80·4–86·6]) for 14-day triple therapy in the intention-to-treat analysis. 10-day bismuth quadruple therapy was superior to 14-day triple therapy (difference 6·7% [95% CI 2·7–10·7, p=0·001), but not 10-day concomitant therapy. 10-day concomitant therapy was not superior to 14-day triple therapy. The frequency of adverse events was 67% (358/533) in patients treated with 10-day bismuth quadruple therapy, 58% (309/535) in patients treated with 10-day concomitant therapy, and 47% (252/535) in patients treated with 14-day triple therapy. Bismuth quadruple therapy is preferable to 14-day triple therapy in the first-line treatment in the face of rising prevalence of clarithromycin resistance. Concomitant therapy given for 10 days might not be optimum and a longer treatment length should be considered. National Taiwan University Hospital and Ministry of Science and Technology of Taiwan.

•Newly developed esomeprazole/magnesium hydroxide fixed-dose combination (FDC) exhibits faster time to reach maximum concentration compared to enteric-coated esomeprazole.•The FDC demonstrates a shorter time to achieve gastric pH ≥ 4, indicating more rapid and effective acid suppression compared to enteric-coated esomeprazole.•Comparable systemic exposure and decrease in integrated gastric acidity over 24 hours highlight equivalent inhibition of gastric acid secretion between the FDC and enteric-coated esomeprazole.•The esomeprazole/magnesium hydroxide FDC presents as a promising option with faster absorption and effective gastric acid suppression, offering potential clinical advantages over enteric-coated esomeprazole. A fixed-dose combination (FDC) of proton pump inhibitors (PPIs) and antacid salts enables rapid acid suppression through the neutralizing effect of the antacid salt and the rapid absorption of PPIs. This study aimed to compare the pharmacokinetics (PKs) and pharmacodynamics (PDs) of a recently formulated FDC of esomeprazole and magnesium hydroxide to the enteric-coated esomeprazole in healthy subjects. A randomized, open-label, multiple-dose, two-treatment, two-way crossover design was conducted in healthy subjects. Forty-nine subjects were randomized to one of the two treatment sequences and received either the test drug (esomeprazole/magnesium hydroxide 40/350 mg) or reference drug (enteric-coated esomeprazole 40 mg) for 7 days in the first period and the alternative in the second period with a 14-day washout period. Blood samples were collected for up to 24 hours for PK assessment, and 24-hour gastric pH monitoring was conducted for PD assessment both before and after a single administration, as well as at a steady state after seven consecutive days of administration. The PK and PD parameters were compared between the two drugs. After multiple administrations, the median value of time to reach maximum concentration was faster in the test drug than in the reference drug, with a difference of 1.68 hours. The overall systemic exposure of the test drug was similar to that of the reference drug, and the PK parameter fell within the equivalence criteria. The test drug demonstrated a shorter time to reach gastric pH ≥ 4 compared to the reference drug (P = 0.0463). A decrease from baseline in integrated gastric acidity over 24 hours, which represents the degree of inhibition of gastric acid secretion, was equivalent between the two drugs. The fixed-dose combination of esomeprazole and magnesium hydroxide showed rapid absorption and quicker gastric acid suppression than enteric-coated esomeprazole with comparable PK and PD properties. ClinicalTrials.gov identifier: NCT04324905 (https://classic.clinicaltrials.gov/ct2/show/NCT04324905).

The aim of this study was to compare the therapeutic efficacy of alginate-based reflux suppressant and magnesium-aluminium antacid gel for treatment of heartburn in pregnancy. A double-blinded, randomized, controlled trial was conducted. One hundred pregnant women at less than 36 weeks gestation with heartburn at least twice per week were randomized to either alginate-based reflux suppressant or to magnesium-aluminium antacid gel. Details of heartburn were recorded before beginning the treatment and the second week of study. Primary outcome measure was the improvement of heartburn frequency after treatment and secondary outcome were the improvement of heartburn intensity, quality of life, maternal satisfaction, maternal side effects, pregnancy and neonatal outcomes. There was no difference between treatment and control groups in improvement of heartburn frequency (80% vs 88%, p = 0.275), 50% reduction of frequency of heartburn (56% vs 52%, p = 0.688), improvement of heartburn intensity (92% vs 92%, p = 1.000) and 50% reduction of heartburn intensity (68% vs 80% cases, p = 0.075). There were also no significant differences in quality of life, maternal satisfaction, maternal side effects, pregnancy and neonatal outcomes. Alginate-based reflux suppressant was not different from magnesium-aluminium antacid gel in the treatment of heartburn in pregnancy.

PurposeYH4808 is a potassium-competitive acid blocker, developed for the treatment of acid-related disorders. Two clinical studies in healthy male subjects were conducted to evaluate the effect of food on the pharmacokinetics of YH4808.MethodsThe first study, a randomized, three-treatment, three-period, crossover study, compared pharmacokinetics of YH4808 (300 mg) after a single dose at fed state with a standard or a high-fat meal to those at fasted state. The second study, a randomized, two-treatment, two-period, crossover study, investigated pharmacokinetics at fasted or fed state with a standard meal after twice daily dose of YH4808 (100 mg) for 7 days. Bloods for pharmacokinetic evaluation were sampled up to 48 h post-dose and 24 h post-dose at steady state, respectively. The pharmacokinetic parameters were estimated by non-compartmental method.ResultsAfter single dosing, the geometric means of maximum plasma concentration increased by 1.2 and 2.1 times in the fed states with a standard meal and a high-fat meal, respectively, of that in fasted state. Corresponding values of area under the plasma concentration-time curve (AUC) from time 0 to the last measurable time point increased by 1.8 and 2.8 times, respectively. After multiple dosing, the geometric mean for 24-h AUC at steady state slightly increased in fed state by 1.1 times of that in fasted state.ConclusionsAs fat content of the food increased, the systemic exposure of YH4808 after single dosing increased. However, systemic exposures at steady state after multiple dosing between fasted and fed states were similar.Trial registrationClinicalTrials.gov registry no.: NCT01520012

INTRODUCTION:Antacids and acid suppressants (i.e., proton pump inhibitors and histamine2-blockers) are commonly used by individuals with heartburn and gastroesophageal reflux disease (GERD). Frequent heartburn and breakthrough symptoms of GERD have been shown to contribute to dental complications. The aim of this study is to compare the likelihood of erosive tooth wear (ETW) among users of antacids or acid suppressants.METHODS:We used data from the National Health and Nutrition Examination Survey (NHANES, 2003-2004) to identify a nationally representative sample of adults (age ≥ 18) who underwent an oral health exam by trained dental examiners. Self-reports of use of antacids and prescribed acid suppressants were collected by trained personnel during a home interview and used to classify individuals into groups. Erosive tooth wear was defined in NHANES using Smith and Knight's Tooth Wear Index modified by Millward, et al., which rates the severity of ETW from 0 (sound tooth surface) to 3 (complete loss of enamel). Erosive tooth wear was evaluated for 40 tooth surfaces; 24 proximal (facial or incisal) and 16 distal (lingual or occlusal) surfaces. Erosions were categorized based on location and severity. We used weighted linear and logistic regression to compare means and estimate the prevalence of erosions for each group. Estimates were adjusted for age, sex, and race/ethnicity.RESULTS:NHANES ETW data were available for 4,414 adults; antacid users (n = 595), acid suppressant users (n = 386), and non-users (n = 3,433). The mean number of assessable tooth surfaces varied between groups (P > 0.001). Erosive tooth wear was more prevalent among those who reported the use of antacids or acid suppressants compared with non-users, however the difference was not statistically significant (P = 0.06). The percent of patients with ETW on at least one distal tooth surface was higher for antacid and acid suppressant users (P = 0.01). In addition, acid suppressant users had a higher prevalence of extensive tooth wear (P = 0.007).CONCLUSION:Individuals using antacids or acid suppressants (potentially for control of acid-reflux symptoms) are associated with a higher rate of dental complications, as suggested by the prevalence of erosions on distal tooth surfaces. In addition, extensive erosions were more common among users of acid suppressants than non-users. Emphasizing the importance of following recommendations from the American Dental Association for routine dental care may be particularly important for these individuals.

Symptoms in symptomatic GERD patients result from esophageal acid exposure and are treated with agents that inhibit gastric acid secretion. We analyzed data from a clinical trial evaluating the effect of ranitidine plus antacid on heartburn severity in GERD patients. After 26 subjects ingested a standard meal and received either placebo or ranitidine‐antacid, heartburn severity (assessed via a visual analog scale), esophageal pH, and gastric pH were measured at 15‐min intervals. Two phenotypes emerged based on heartburn severity patterns: “Persistent Heartburn” (PH), characterized by sustained high severity, and “Non‐persistent Heartburn” (NPH), where severity peaked and then declined. PH subjects had similar gastric acidity but higher overall heartburn severity and lower esophageal acid exposure than NPH subjects. Both phenotypes exhibited esophageal hyperalgesia, with significant heartburn even at esophageal pH above 4.0, and hyperalgesia was more pronounced in PH subjects. These findings suggest that esophageal sensitivity, rather than acid exposure alone, contributes to symptom severity. The differing responses to placebo and ranitidine‐antacid highlight potential mechanisms underlying treatment failure in some GERD patients, emphasizing the need for tailored therapeutic approaches.

Background and Objective Managing drug-food interactions is essential for optimizing the effectiveness and safety profile of quinolones. Following PRISMA guidelines, we systematically reviewed the influence of dietary interventions on the bioavailability of 22 quinolones. Methods All studies describing or investigating the impact of food, beverages, antacids, and mineral supplements on pharmacokinetic parameters or pharmacokinetic/pharmacodynamic indices of orally taken quinolones were considered for inclusion. We excluded reviews, in vitro and in silico studies, studies performed on animals, and those involving alcohol. We performed the search in Medline (via PubMed), Embase, and Cochrane Library, covering reports from database inception to December 2022. We used the following tools to assess the risk of bias: version 2 of the Cochrane risk-of-bias tool for parallel trials, the Cochrane risk-of-bias tool for cross-over studies, and the NIH quality assessment tool for before-after studies. We performed quantitative analyses for each quinolone if two or more food-effect studies with specified and comparable study designs were available. If meta-analyses were not applicable, we qualitatively summarized the results. Results We included 109 studies from 101 reports. Meta-analyses were conducted for 12 antibiotics and qualitative synthesis was employed for the remaining drugs. Of the studies, 60.5% were open-label, cross-over, as recommended by FDA. We judged 46% of studies as having a high risk of bias and only 4% of having a low risk of bias. Among 19 quinolones with available food impact data, 14 (74%) had potentially clinically important interactions. For nalidixic acid, oxolinic acid, and tosufloxacin, food exerted a high positive impact on bioavailability (AUC or C max increased by > 45%), whereas, for all the remaining drugs, postprandial absorption was lower. The most significant negative influence of food (AUC or C max decreased by > 40%) occurred for delafloxacin capsules and norfloxacin, whereas the moderate influence (AUC or C max decreased by 30–40%) occurred for nemonoxacin and rufloxacin. All 14 analysed quinolones showed a substantial reduction in bioavailability when co-administered with antacids and mineral supplements, except for calcium preparations. The impact of beverages was evaluated for 10 quinolones, with 50% experiencing significantly reduced absorption in the presence of milk (the highest negative impact for ciprofloxacin). Moreover, both ciprofloxacin and levofloxacin demonstrated compromised bioavailability when consumed with orange juice, particularly calcium-fortified. Discussion Several factors may influence interactions, including the physicochemical characteristics of quinolones, the type of intervention, drug formulation, and the patient’s health status. We assessed the quality of evidence as low due to the poor actuality of included studies, their methodological diversity, and uneven data availability for individual drugs. Graphical Abstract

Background The eradication of Helicobacter pylori infection remains a challenge, especially in the patients unsuitable to take penicillin. Cephalosporin has the potential to replace amoxicillin for H. pylori eradication. Aims To compare the effectiveness, safety, and compliance of amoxicillin- and cefuroxime-containing quadruple regimens in treatment-naïve patients. Methods In this open-label randomized control study, 400 patients with H. pylori infection were divided into amoxicillin-containing (esomeprazole 20 mg twice/day, amoxicillin 1000 mg twice/day, levofloxacin 500 mg once/day, and bismuth 220 mg twice/day for 14 days) or cefuroxime-containing (esomeprazole 20 mg twice/day, cefuroxime 500 mg twice/day, levofloxacin 500 mg once/day, and bismuth 220 mg twice/day for 14 days) quadruple therapy groups. The safety and compliance were assessed 1–3 days after eradication. Urea breath test was performed 8–12 weeks after eradication to determine treatment outcome. Results The baseline data including antibiotic resistance were well matched between the two groups. The eradication rates between amoxicillin- and cefuroxime-containing quadruple therapy groups were not significantly different [intention-to-treat analysis: 83.5% (95% confidence interval 78.3–88.7%) vs. 81.0% (75.5–86.5%), P  = 0.513; modified intention-to-treat analysis: 90.3% (86.0–94.6%) vs. 88.5% (83.9–93.2%), P  = 0.586; per-protocol analysis: 91.6% (87.5–95.7%) vs. 89.8% (85.3–94.3%), P  = 0.560]. The incidence of adverse effects (18.4 vs. 20.1%, P  = 0.678) and compliance (94.7 vs. 94.2%, P  = 0.813) were also similar. Variate analyses showed that antibiotic resistance and poor compliance were the independent risk factors for eradication failure. Conclusions Esomeprazole, bismuth, levofloxacin, and amoxicillin or cefuroxime achieved similar and relatively satisfactory cure rates, safety, and compliance in first-line H. pylori eradication. Cefuroxime may be a good alternative medicine for eradication instead of amoxicillin for the patients unsuitable to take penicillin.

Objective: The objective of the present study was to evaluate the antacid and cytoprotective effects of root bark aqueous extract of Diospyros mespiliformis (RBAEDM). Materials and Methods: Thirty rats were grouped into six groups of five rats each, namely, three control groups (normal, negative and positive) and three test groups. These animals were treated with distilled water (normal and negative controls), verapamil (positive control) and the extract at doses of 100, 200 and 400 mg/kg (test groups). One hour after treatment, gastric ulcers were induced in all animals by immersion in water (22 ± 1°C) for 5 h except for the normal control. The ulcerated surface, mucus mass, in vivo oxidative stress parameters and nitrite levels were determined. In vitro antacid activity of the extract was evaluated on artificial gastric juice by the determination of pH, neutralization time and antacid capacity. Acute toxicity of extract was evaluated. Results: Treatment with RBAEDM showed a significant ( p < 0.01, p < 0.001) decrease of ulcerated surface with a percentage of inhibition between 5.58% and 60.46%. The decrease in the ulcerated surface was accompanied by a significant ( p < 0.001) increase in mucus production at 400 mg/kg. Treatment with RBAEDM also showed a significant ( p < 0.001) decrease in malondialdehyde (MDA) levels and a significant increase in superoxide dismutase (SOD) level, catalase (CAT) activities, in addition to nitrite levels in stomachs. In artificial gastric juice, the RBAEDM caused a significant increase ( p < 0.001) of neutralizing time and the number of neutralized H + ions compared to distilled water. No change in behavioural parameters and no death was observed after administration of the extract at 2000 mg/kg. Conclusion: RBAEDM inhibited ulcer occurrence by the stimulation of mucus production, increase of antioxidant enzyme activity and NO production. Moreover, this study revealed that the studied extract could exert a strong anti‐acid capacity in vitro due its ability for the neutralization of H + ions. DL 50 of RBAEDM was greater than 2000 mg/kg.