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Background: Effective management of drug-food interactions is crucial for enhancing antibiotics' efficacy/safety. Adhering to PRISMA guidelines, we conducted a systematic review to assess the impact of dietary interventions on the bioavailability of 15 macrolides and 10 tetracyclines., Methods: We included studies examining the influence of food, beverages, antacids, and mineral supplements on the pharmacokinetic parameters of orally administered macrolides and tetracyclines. We searched Medline (via PubMed), Embase and Cochrane Library databases up to December 2022. Risk of bias was assessed using Cochrane and NIH tools. Quantitative analyses were conducted if two or more comparable food-effect studies were available; otherwise, a qualitative summary was provided., Results: We included 120 studies from 97 reports. Meta-analyses were conducted for 8 macrolides and 4 tetracyclines, with qualitative synthesis for 10 and 9, respectively. About 64% of the studies were open-label, crossover designs. Our assessment found that 37% of the studies had a high risk of bias, while only 6% had low risk. Food significantly affected 10 of 13 macrolides (77%) and 6 of 7 tetracyclines (86%). High positive effects on bioavailability were seen with extended-release azithromycin and clarithromycin, and erythromycin estolate. High negative impacts were observed with erythromycin propionate and stearate, azithromycin capsules, demeclocycline and omadacycline. Antacids and mineral supplements significantly decreased tetracyclines absorption. Milk and grapefruit juice showed variable impacts on absorption., Discussion: Interactions depend on antibiotics' physicochemical characteristics, intervention type, drug formulation and potential patient factors. The quality of evidence was rated low due to outdated studies, methodological diversity and unequal data availability., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Purpose: 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., Methods: 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., Findings: 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., Implications: 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)., Competing Interests: Declaration of competing interest Sung Hee Hong and Na Young Kim are full-time employees of Hanmi Pharmaceutical Co., Ltd., Seoul, Republic of Korea. The authors have indicated that they have no other conflicts of interest regarding the content of this article., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Antacids are commonly used during pregnancy, and they are approved for the relief of symptoms of gastroesophageal reflux disease (GERD) during pregnancy. However, there are no reports of the quantification of the absorption of aluminum and magnesium in the antacid magaldrate in women. The aim of this study was to quantify the rate and magnitude of absorption of aluminum and magnesium in magaldrate., Methods: An open-label, controlled, randomized, one-treatment study with a two-group design was conducted in healthy women in a fed state. The volunteers had a standard breakfast, and 30 min later, they were given a single-medication sachet containing 500 mg of sodium alginate, 267 mg of sodium bicarbonate, 800 mg of magaldrate, and 120 mg of simethicone (group A, n = 8) or no medication (group B, n = 2). Blood samples were obtained 36 h before and up to 12 h after antacid administration. The method used for quantification was inductively coupled plasma-mass spectrometry., Results: There was no absorption of aluminum in any of the blood samples from the healthy volunteers who received the drug or in those from the control group. Magnesium was detected at normal concentrations., Conclusion: These findings suggest that the use of this antacid is safe and without risk in healthy women, including pregnant women., Clinical Trial Registration: Clinicaltrials.gov registration: NCT06367452., (© 2024. The Author(s).)

Background/objectives: The aim of this study is to investigate the association between physical and chemical digestion and nutrition markers (serum albumin (ALB), prealbumin (PAB), and vitamin B 12 (B 12 ) levels)., Methods: During a detailed checkup at Fujita Health University, we examined the associations of physical (occlusal force, masticatory performance, and swallowing ability (via the 10-item Eating Assessment Tool, EAT-10)) and chemical ( Helicobacter pylori (HP) eradication history, HP antibody levels, and oral antacid (proton pump inhibitors) use) digestion parameters with serum ALB, PAB, and B 12 levels in 92 individuals (M:67, F:25)., Results: Forty-eight percent of the participants were older than 65 years of age, 19% had decreased occlusal force, 3.2% had decreased masticatory strength, 3.2% had decreased swallowing function, 24% had a history of HP eradication, 23% were HP antibody positive, and 16% were taking oral antacid medication. Additionally, 14% and 11% of the patients had low serum ALB and PAB levels, respectively, and 14% of the patients had B 12 deficiency. Multivariate analysis adjusted for age, sex, body mass index, and C-reactive protein levels revealed that there were no significant associations between the physical digestion parameters and the serum PAB, ALB, or B 12 levels. On the other hand, there was a significant association between oral antacid use and PAB levels (β = -3.3, p = 0.04). Independent of physical or chemical digestion parameters, serum PAB and B 12 levels were significantly associated with protein and B 12 intake, respectively., Conclusions: Oral antacid use may decrease serum PAB levels, indicating protein synthesis.

The effect of food composition, tablet crushing, and antacid coadministration on maribavir pharmacokinetics was assessed in 2 Phase 1 studies in healthy adults. In the first, a single maribavir 400-mg dose was administered under fasting conditions, with a low-fat/low-calorie or a high-fat/high-calorie meal. In the second, a single maribavir 100-mg dose was administered under fasting conditions, as a crushed tablet, or as a whole tablet alone or with an antacid. The 90% confidence intervals of the geometric mean ratios were within 80%-125% for area under the concentration-time curve (AUC), but not for maximum plasma concentration (C max ) for low-fat/low-calorie and high-fat/high-calorie meals versus fasting or for whole tablet with antacid versus whole tablet alone. The 90% confidence intervals of the geometric mean ratios for AUC and C max were within 80%-125% for crushed versus whole tablet. Maribavir median time to C max value in plasma under fed conditions was delayed versus fasting conditions, but there was no statistical difference for crushed versus whole tablet or with versus without antacid. As the antiviral efficacy of maribavir is driven by AUC but not C max , findings suggest that maribavir can be administered with food or antacids or as a crushed tablet., (© 2024 Takeda Development Center Americas, Inc. Clinical Pharmacology in Drug Development published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.)

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., (© 2024. The Author(s).)

Objective: The 13 C-urea breath test (UBT) is the most widely used non-invasive diagnostic test for Helicobacter pylori. Debate continues to surround the possible interference of antacid intake on its result. This study aims to confirm the non-interference of almagate in the determination of H. pylori by UBT., Patients and Methods: Observational, multicentre study in adult patients treated with almagate in whom a UBT (TAUKIT®) was indicated. When the UBT result was negative, use of almagate was stopped for 30 days and the UBT was repeated. When the result was positive, no further determinations were made. The primary endpoint was the percentage of patients who, having had a negative result in the first breath test, were positive in the second after having stopped taking almagate (UBT false negatives, possibly attributable to almagate)., Results: Of the 167 evaluable patients, 59% were female, average age was 49 and 97% had gastrointestinal symptoms. The result of the first UBT was negative in 71% of cases. Of these, in the second UBT test after stopping the almagate, the negative result was confirmed in 97.5%. Out of the total number of cases evaluated, the rate of false negatives was 1.8%., Conclusions: Taking almagate has minimal or no interference in the result of UBT for the diagnosis of H. pylori infection. It can therefore be used in the weeks prior to a UBT., (Copyright © 2021 The Authors. Publicado por Elsevier España, S.L.U. All rights reserved.)

Introduction: We aim to evaluate the efficacy of 2 different 1-week quadruple therapies given back-to-back consecutive therapy in patients with difficult-to-treat Helicobacter pylori infection., Methods: Patients with proven H. pylori infection were recruited after >3 failed standard quadruple eradication. They received consecutive therapy consisting of esomeprazole 40 mg or rabeprazole 20 mg twice daily, amoxicillin 1,000 mg twice daily, tetracycline 500 mg 4 times daily, and furazolidone 100 mg 3 times daily for the first 7 days, followed by colloidal bismuth pectin 200 mg twice daily in place of furazolidone 100 mg for another 7 days. Eradication rates, treatment-emergent adverse events (TEAEs), and compliance were assessed., Results: Sixty-five patients were enrolled. The mean number of previous eradications was 3.6 (range: 3-7). The intention-to-treat and per-protocol eradication rates were 90.8% (59/65) and 95.1% (58/61). In total, 23.4% (15/64) of patients experienced drug-related TEAEs. No serious adverse events were observed. None of the patients required treatment for TEAEs, and 95.3% (61/64) showed good compliance. Overall, 51 patients (78.5%) were with the available antimicrobial susceptibility testing results. The resistance rates to clarithromycin, metronidazole, levofloxacin, and amoxicillin were 60.8% (31/51), 100% (51/51), 70.6% (36/51), and 2.0% (1/51), respectively. No resistance was detected to either furazolidone or tetracycline. However, in 54.9% of patients (28/51), H. pylori was resistant to 3 antibiotics (metronidazole, levofloxacin, and clarithromycin)., Discussion: Consecutive therapy, including amoxicillin, tetracycline, and furazolidone, achieved a good eradication rate (>90%), with desirable compliance and tolerability in difficult-to-treat H. pylori infection., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Tegoprazan, a novel potassium-competitive acid blocker, is used to treat acid-related diseases. However, there is no information on the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of the marketed dosage of tegoprazan under various meal timings in a fed and fasted state. The study aimed to assess the effect of meal timing on PKs and PDs of tegoprazan 50 mg after a single administration in healthy male subjects. An open-label, single-dose, three-treatment, three-period crossover study was conducted. A total of 12 subjects were orally administered a single dose of tegoprazan 50 mg among various conditions: in a fasted state, at 30 min before or 30 min after a high-fat meal. PK parameters were estimated by the noncompartmental method. Continuous 24-h intragastric pH monitoring was done for PD analysis. The PKs and PDs of tegoprazan were compared among the various meal timings. Compared with the fasting condition, the PK profile of tegoprazan was similar when administered 30 min before a high-fat meal; however, delayed absorption with similar systemic exposure was observed when administered 30 min after a high-fat meal. The magnitude of acid suppression evaluated through the PD parameters increased when administered 30 min after a high-fat meal compared with fasting the condition and when administered 30 min before a high-fat meal. However, the increased difference in acid suppression was not clinically significant. Meal timing had no clinically significant effect on the PKs and PDs of tegoprazan 50 mg. Therefore, the marketed dosage of tegoprazan could be administered regardless of the meal timing. Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC? Tegoprazan, a novel potassium-competitive acid blocker, is used to treat acid-related diseases. WHAT QUESTION DID THIS STUDY ADDRESS? This study evaluated the effect of food on pharmacokinetics (PKs) and pharmacodynamics (PDs) of tegoprazan under various mealtime conditions. WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE? This study showed that delayed absorption of tegoprazan was observed at "after meal condition," however, the amount of systemic exposure of "after meal condition" was similar to "fasting condition" and "before meal condition." In addition, gastric acid suppression of tegoprazan was similar between fasting condition and before meal condition, whereas increased gastric acid suppression was observed at after meal condition. HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE? In the actual clinical environment, patients take medicine under various fed conditions. This study evaluated the effect of food on PKs and PDs of tegoprazan in various clinical conditions, and provided the important information about meal timing when administering tegoprazan., (© 2020 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of the American Society for Clinical Pharmacology and Therapeutics.)

Due to demographic changes in people living with HIV (PLHIV), physicians are challenged with age-related comorbidities and their management. In the absence of comprehensive data collection, the burden of comorbidities and co-medication in addition to antiretroviral therapy (ART) remains unclear for the German real-world setting. BESIDE was an observational, cross-sectional study evaluating the prevalence of comorbidities and use of co-medication in treated PLHIV. Regional distribution of study centers (n = 20), consecutive patient recruitment, and age-stratified sampling in alignment with national epidemiologic data aimed to ensure a representative sample (n = 453). The overall prevalence of comorbidities was 91.2%; 31.6% of patients had ≥4 comorbidities. The most common diagnoses were vitamin D deficiency (29.1%), depressive episode (27.8%), arterial hypertension (16.3%), and hypercholesterolemia (10.8%). 83.7% of patients were on co-medication; 21.2% taking ≥4 medications. The most common medications or supplements were vitamins (31.6%), anti-inflammatory agents (16.1%), renin-angiotensin system agents (12.1%), acid suppressants (11.7%), lipid modifying agents (10.8%); 1.3% of patients were on co-medication that should not be co-administered with ART, 41.5% on co-medication with potential for drug-drug interactions. The prevalence of comorbidities and use of co-medication among treated PLHIV in Germany is consistently high and increases across age groups, illustrating the complexity of HIV care involving appropriate ART selection.

A healthy multiparous woman presented at 35 weeks and 4 days' gestation with threatened preterm labour on multiple occasions. An incidental finding of severe hypokalaemia (2.4 mmol/L) was detected on routine blood tests. The cause of this hypokalaemia was not initially obvious. It was eventually linked to overuse of over-the-counter antacids for pregnancy-associated heartburn. The patient was managed with parenteral and then oral electrolyte replacement which corrected a pH of 7.55, bicarbonate of 36.7 mEq/L and a base excess 13.1. In this case report we consider whether hypokalaemia could be linked to uterine irritability and threatened preterm labour, whether antacids were being abused in the context of an eating disorder and the importance of taking a full drug history., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Extracellular pH (pHe) of tumor cells is characteristic of tumor microenvironment (TME). Acidic TME impairs the responses of tumors to some anti-cancer chemotherapies. In this study, we showed that daily oral dosing of sodium potassium citrate (K/Na citrate) increased blood HCO 3 - concentrations, corresponding to increase of HCO 3 - concentrations and pHs in urine, and neutralized the tumor pHe. Neutralization of acidic TME by alkaline substance like HCO 3 - , an active metabolite of K/Na citrate, well potentiated the therapeutic effect of anticancer agent TS-1 ® , an orally active 5-fuluoro-uracil derivative, in Panc-1 pancreatic cancer-xenograft murine model. Neutralization of acidic TME by using an alkaline K/Na citrate is a smart approach for enhancement of the therapeutic effects of anticancer agents for pancreatic cancer in the end stage.

A range of gastroprotective drugs are available for the treatment of esophagitis and gastroduodenal mucosal injury including acid suppressants (ie, histamine-2 receptor antagonists, proton pump inhibitors), coating agents, prostaglandin analogs, and antacids. Of these, the proton pump inhibitors are the most effective drugs for the medical treatment of upper gastrointestinal injury. However, proton pump inhibitors are not effective for all causes of upper gastrointestinal injury. The choice of gastroprotective drug should be guided by the cause and location of gastrointestinal injury and the potential for adverse effects., Competing Interests: Disclosure The author is a consultant for TriviumVet, Inc. Studies performed by the author in the text above were supported by the Comparative Gastroenterology Society, American Veterinary Medical Foundation, Winn Feline Foundation (W17-017), Miller Trust (MT18-004), UTK Companion Animal Fund, and the ACVIM Foundation., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The real-world efficacy of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) in patients with advanced non-small cell lung cancer (NSCLC) harboring EGFR-activating mutations remains unclear. We conducted a retrospective cohort study using data from the claims database of Taipei Veterans General Hospital to perform direct comparisons of these three EGFR-TKIs (gefitinib, erlotinib, and afatinib) combined with co-medications (metformin, statins, antacids, and steroids). Stage IIIB and IV NSCLC patients with EGFR mutations receiving EGFR-TKIs as first-line treatment for > 3 months between 2011 and 2016 were enrolled. The primary endpoint was time to treatment failure (TTF). Patients who had received co-medications (≥ 28 defined daily doses) in the first 3 months of EGFR-TKI therapy were assigned to co-medications groups. A total of 853 patients treated with gefitinib (n = 534), erlotinib (n = 220), and afatinib (n = 99) were enrolled. The median duration of TTF was 11.5 months in the gefitinib arm, 11.7 months in the erlotinib arm, and 16.1 months in the afatinib arm (log-rank test, P < 0.001). After adjustments, afatinib showed lower risk of treatment failure compared with gefitinib (hazard ratio [HR] 0.54, 95% confidence interval [CI] 0.41-0.71) and erlotinib (HR 0.62, 95% CI 0.46-0.83). The risk of treatment failure in patients treated with EGFR-TKIs who received concomitant systemic glucocorticoid therapy was higher than in those treated with EGFR-TKI monotherapy (HR 1.47, 95% CI 1.08-2.01). Afatinib or erlotinib use was associated with a lower risk of treatment failure in patients with advanced NSCLC harboring EGFR mutations compared to gefitinib use. Concurrent use of systemic glucocorticoids was linked to higher risk of treatment failure.

Gut microbial communities are capable of enzymatically transforming pharmaceutical compounds into active, inactive, and toxic metabolites, thus potentially affecting the pharmacokinetics and bioavailability of orally administered medications. Our understanding of the impact and clinical relevance of how gut microbial communities can directly and indirectly affect drug metabolism and, ultimately, clinical outcomes, is limited. Interindividual variability of gut microbial composition may partially explain differences observed in drug efficacy and toxicity in certain patient populations. This review provides an overview of how gut microbial communities can potentially contribute to individual drug response. This review focuses on the current landscape of clinical and preclinical research that defines the microbiome contribution on medication response with the goal of improving medication efficacy and decreasing medication toxicity., (© 2020 Pharmacotherapy Publications, Inc.)

Background/aims: A novel medical device based on hyaluronic acid, chondroitin sulphate plus aluminum hydroxide (GERDOFF®, melt-in-mouth tablets) showed efficacy in reducing GER-related symptoms. This exploratory, open-label study evaluated symptomatic effects of a 14-day treatment with GERDOFF® in GERD patients., Materials and Methods: GERD Impact Scale (GIS) questionnaire was filled at baseline visit, after 7 and 14 days of treatment; patients' Global Satisfaction was evaluated at the final visit. Primary endpoint was the reduction of heartburn episodes per week; secondary endpoints were GERD-related symptoms, patients' satisfaction, and safety., Results: Forty patients were included, 22 were on stable therapy with proton pump inhibitor (PPI). Compared to baseline, the days with heartburn episodes and the GIS score progressively decreased during the first (p<0.0001) and the second week of treatment (p<0.0001). Heartburn episodes per week (p<0.0001) and the GIS score (p<0.0001) decreased in the first and the last 7 days of 14-day treatment and did not differ between patients on and off PPI. The treatment was safe and well-tolerated, and it was rated as very good (46.2%) or good (43.6%) on the satisfaction questionnaire., Conclusion: GERDOFF® could effectively treat GER symptoms in patients not responding to PPI or alginate-based formulation. ISRCTN&#95;15143752.

A recently published FDA guidance on chewable tablets has addressed the quality attributes of this class of dosage forms. This study evaluated disintegration as a quality attribute for a number of commercially available chewable antacid tablets. Additionally, acid-neutralizing-capacity values were evaluated. A number of the products exhibited prolonged disintegration times-which were far longer than those of conventional immediate-release tablets. The mean disintegration times ranged from 6 to more than 60 min in distilled water and from 9 to over 60 min in 0.1 N HCl. The products with longer disintegration times had higher breaking force and tensile strength values. Despite the range in disintegration times, all products met the criteria for acid-neutralizing capacity. These results indicate a need for patients to be aware of the need to thoroughly chew antacid tablets upon administration. Given these considerations, disintegration testing would be a useful quality control test in evaluating these dosage forms as the implicit assumption by the manufacturer that patients will chew the product sufficiently may not be met in every case.

Background: Aciduria caused by urinary excretion of acidic metabolic wastes produced in daily life is known to be augmented in patients with chronic kidney disease (CKD). To evaluate the reno-protective effect of oral alkalizing agents for the improvement of metabolic acidosis and neutralization of intratubular pH in the patients with mild stages of CKD. Also, to identify reno-protective surrogate markers in the serum and urine that can closely associate the effect of urine alkalization., Methods: In this single-centered, open-labeled, randomized cohort study, patients with CKD stages G2, G3a and G3b, who visited and were treated at Tohoku University Hospital during the enrollment period were registered. We administered sodium bicarbonate or sodium-potassium citrate as the oral alkalinizing agents. A total of 150 patients with CKD will be randomly allocated into the following three groups: sodium bicarbonate, sodium-potassium citrate and standard therapy group without any alkalinizing agents. The data of performance status, venous blood test, spot urine test, venous blood-gas test, electrocardiogram, renal arterial ultrasonography and chest X-ray will be collected at 0, 6, 12 and 24 weeks (short-term study) from starting the interventions. These data will be also collected at 1 and 2 years (long-term study). The samples of plasma and serum and early-morning urine at every visit will be acquired for the analysis of renal function and surrogate uremic biomarkers. The recruitment for this cohort study terminated in March, 2018, and the follow-up period for all the enrolled subjects will be terminated in December, 2020. The primary endpoint will be the development of originally-defined significant renal dysfunction or the occurrence of any cerebrovascular disease in the short-term study. The secondary endpoint will be the same endpoints as in the long-term study, or the patients with significant changes in the suggested the surrogate biomarkers., Discussion: The findings of this study will address the importance of taking oral alkalizing agents in the patients with early stages of CKD, furthermore they could address any new surrogate biomarkers that can be useful from early stage CKD., Trial Registration: Registered Report Identifier: UMIN000010059 and jRCT021180043. The trial registration number; 150. Date of registration; 2013/02/26.

Objectives: In this communication we report an important findings, the effect of Al/Mg hydroxide antacid and food on the pharmacokinetics of dexibuprofen when administered concomitantly., Methods: Subjects were divided into four groups, each containing 6 subjects, to evaluate the effect of antacid and food on pharmacokinetic of dexibuprofen. A new HPLC method was developed and validated for plasma sample analysis. Mobile phase was comprised of Acetonitrile: Methanol: 0.05M Phosphate buffer (40:10:50), pH was adjusted to 6.85±0.01 with NaOH. Mobile phase was eluted through C18-ODS column and drug was detected at 223 nm. Plasma was obtained and stored at - 70°C until analysis. Drug was extracted from each plasma sample of volunteer and quantified by using HPLC technique., Results: A decrease in dexibuprofen absorption was observed in Test Group-1 when administered with Antacid as compared to Controlled Group-1. Mean C max values showed a significant (p value 0.035) decrease from 44.14±2.3 to 33.1±0.8 μg/mL. T max , Area under curve, t 1/2 , Cl, V d and K e were not affected significantly. AUC increased from 195.7±8.9 μg.hr/mL to 222.8±14.7 μg.hr/mL. In contrast, test Group-2 showed an increase in dexibuprofen absorption. t 1/2 increased significantly from 4.505±0.19 hrs to 6.216±0.36 hrs whereas K e reduced from 0.159±0.00 to 0.116±0.006 hrs -1 . C max increased from 44.877±2.263 to 51.721±0.096 μg/mL., Conclusion: It is concluded that concomitant intake of Al/Mg hydroxide antacid or food with dexibuprofen has an impact to significantly alter its pharmacokinetic parameters., Competing Interests: The authors declare that they have no conflict of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Vonoprazan (V), a potassium-competitive acid blocker, has a more durable acid-inhibitory effect as compared with standard-dose proton pump inhibitors (PPIs) but has not been compared with 2-4 times higher daily PPI doses administered in two divided doses., Aims: To evaluate the acid-inhibitory effect of V 10/20 mg once-daily (OD; V10/V20) vs rabeprazole (R) 10/20 mg twice-daily (BID; R20/R40) in healthy Japanese volunteers., Methods: This multicentre, randomised, open-label, two-period, crossover study compared V10 or V20 vs R20, or V20 vs R40 using three cohorts of 10 healthy Japanese adults. Within each cohort, subjects were randomised to receive V or R for 7 days and, following a washout period ≥7 days, the other treatment for 7 days. On day 6 of each period, 24-hours multichannel gastric impedance-pH monitoring was performed. Percent times pH ≥ 3, ≥4 and ≥5 (pH 3, 4 and 5 holding time ratios [HTRs]) in 24 hours were evaluated as primary pharmacodynamic endpoints., Results: Acid-inhibitory effect (24-hours pH 3 HTR) of V20 was greater than those of R20 (91.0% vs 65.3%; P = .0049) and R40 (98.5% vs 85.9%; P = .0073). Similar results were obtained for 24-hours pH 4 and 5 HTRs. V20 also achieved greater nocturnal pH 4 (91.5% vs 73.2%; P = .0319) and 5 HTRs (78.8% vs 62.2%; P = .0325) as compared with R40. One subject (20%) developed diarrhoea while receiving R40 which was considered treatment-related., Conclusions: Compared with 2-4 times the standard daily dose of R, V20 exerts a more potent and durable acid-inhibitory effect. Trial identifier: UMIN000022198 (www.umin.ac.jp/ctr/index.htm)., (© 2020 John Wiley & Sons Ltd.)

Background: Laparoscopic fundoplication is an effective treatment for gastro-oesophageal reflux disease (GERD). We aimed to assess quality of life (QoL), long-term residual symptoms, patient satisfaction and use of acid-suppression medication at 5, 10 and 20 years after surgery., Methods: We identified a cohort of 100 patients who underwent laparoscopic fundoplication between 1993 and 1998. The validated QoL questionnaires Short Form health survey (SF-36), and Quality-of-Life in Reflux and Dyspepsia (QOLRAD), as well as a specific questionnaire regarding post-fundoplication symptoms, were sent to the patients at 5, 10 and 20 years after surgery. Furthermore, patients who reported using the acid-suppression medication after 20 years were interviewed by telephone regarding their reason for taking it., Results: Eighty-eight percent of the patients responded at 5 and 10 years post-surgery. Twenty years following fundoplication, 68 (84% of those still alive) patients completed the questionnaires. The patients had equivalent health-related QoL scores in both the QOLRAD and SF-36 questionnaires after 10 and 20 years, and those scores were in line with a Swedish age-matched population. After 20 years, 87% were satisfied with the results, and 84% of the patients would recommend reflux surgery to a relative or a friend. At the telephone interview, 32% (22/68) confirmed using acid-suppression medication, but only half (11/68) used it because of reflux symptoms., Conclusion: The long-term, satisfying outcomes in GERD symptoms and QoL 5 and 10 years after surgery were maintained at a 20-year follow-up. Half of the patients used acid-suppression medication for reasons other than GERD symptoms., (© 2019 Royal Australasian College of Surgeons.)

Introduction: Kidney stones affect 1 in every 11 people in the United States each year. There is a significant high recurrence rate without a stone prevention protocol. Alkali citrate is beneficial in decreasing stone recurrence, but because of the cost and gastrointestinal side effects there is a low adherence rate. This study aims to serve as a review of some of the most commonly used alkalizing over-the-counter supplements that are advertised to prevent and treat kidney stones. Methods: Data were gathered by a comprehensive online literature search and company inquiries for kidney stone prevention supplements. An additional informal poll of the authors selected supplements that are most commonly taken by their patients. A total of eight supplements were evaluated for cost, alkali equivalent provided, dosing, and regulatory information. Results: Eight of the most commonly used supplements were reviewed with a focus on alkalizing agents. Information reviewed revealed dosing recommendations resulting in decreased citrate alkali equivalents per day compared with prescription-strength potassium citrate. Cost, peer-reviewed study results, and regulatory data were reviewed, tabulated, and analyzed. Cost per alkali equivalent was substantially decreased for each supplement compared with the prescribed drug. All supplements were found to be readily available online. Conclusion: Over-the-counter alkalizing agents are available to patients and may be an appropriate alternative to cost-prohibitive potassium citrate when treating urolithiasis patients. Additional testing will be necessary in the future to determine the efficacy of these supplements in the treatment and prevention of urinary stone disease.

Background/aims: Although a potassium-competitive acid blocker (PCAB)-based regimen improves the rate of successful Helicobacter pylori first-line eradication, the efficacy of a PCAB-based regimen as second-line therapy is unclear. The aim of this study is to compare the success of second-line eradication of H. pylori using PCAB and proton pump inhibitor (PPI)-based regimens., Methods: From 2014 to 2017, 624 patients who underwent second-line H. pylori eradication were enrolled. A standard triple regimen for second-line H. pylori eradication includes metronidazole 250 mg, amoxicillin 750 mg, and PPI or PCAB twice daily for 7 days. The success of eradication was compared using intention-to-treat, per-protocol, and propensity-score matching analysis., Results: All patients completed the 7-day course of therapy. Patients using a PCAB-based regimen had a higher rate of eradication than those using a PPI-based regimen in both intention-to-treat (90% [298/330] vs. 85% [250/294], p = 0.045) and per-protocol analyses (96% [298/309] vs. 91% [250/274], p = 0.008). Adverse events occurred in 4 patients. Propensity score matching analysis acquired 274 matched pairs. Patients using a PCAB-based regimen had a higher rate of eradication than those using a PPI-based regimen (96% [264/274] vs. 91% [250/274], p = 0.013)., Conclusions: PCAB-based second-line H. pylori eradication is significantly better than PPI-based therapy., (© 2019 S. Karger AG, Basel.)

Introduction: Osteomalacia and osteoporosis are two metabolic bone disorders that increase the risk of fracture due to several causes. In terms of drugs, apart from corticosteroids, which are known to induce bone disorders, several other drugs used in chronic disease management have also been linked with an increased risk of osteoporosis and osteomalacia., Purpose: The aim of this study was to describe spontaneous reports of drug-induced osteoporosis and osteomalacia in the French (FPVDB) and Spanish (SPVDB) pharmacovigilance databases., Methods: Data were provided by the FPVDB and SPVDB. All reports of osteoporosis and osteomalacia recorded from 1985 up to 31 December 2015 inclusive were selected. Taking the time to onset of bone loss into account, all cases occurring in less than 1 month were excluded., Results: A total of 369 reports (44 cases of osteomalacia, 325 cases of osteoporosis) were registered in the FPVDB and 64 (22 cases of osteomalacia, 42 cases of osteoporosis) in the SPVDB. In France, the top 5 drugs involved in the onset of osteoporosis were corticosteroids accounting for approximately half of the reports (n = 170) followed by systemic antiviral (n = 87), antacid (n = 29), antiepileptic (n = 27) and antithrombotic (n = 24) drugs. The 2 main classes of drugs implicated in osteomalacia were systemic antiretroviral drugs for half of the reports (n = 21) and antiepileptic drugs (n = 15). In Spain, corticosteroids were involved in 35.7% of reported cases of osteoporosis (n = 15) followed by systemic antiviral drugs (n = 12). There was no spontaneous report for antacid drugs. For osteomalacia, the 2 main drug classes were systemic antiretroviral drugs (n = 18, 81.8%) followed by antiepileptics (n = 2, 9.0%). In both countries, concomitant administration of systemic corticosteroids with other suspected drugs did not significantly modify the time to onset of drug-induced osteoporosis., Conclusion: Despite some differences between the French and Spanish PVDBs, our data consistently show that bone loss is not only restricted to glucocorticoids but also involves antivirals, antiepileptic drugs, antacid drugs or antidepressants. Further analysis might prove useful in exploring the characteristics of drug-induced bone loss on a larger scale.

In this paper, a special case for bioequivalence evaluation of oral formulations is discussed. Drug formulations with different forms of active moieties (e.g., free base and salt) may yield different dissolution characteristics and, thus, differ in absorption at elevated gastric pH. However, routine bioequivalence trials using subjects with normal gastric pH (i.e., ~ 1) may fail to identify these differences because dissolution/absorption profiles of the two formulations at normal gastric pH are similar. In the case of palbociclib, it is confirmedthat the free base and salt formulations showed different absorption in patients with different gastric pH. Significant reduction in drug absorption was observed only in patients with elevated gastric pH using free base formulation. The discovery that the free base had significantly reduced absorption hinged on the inclusion of enough patients with elevated gastric pH to detect a difference in a bioequivalence trial. This raises a concern, as demonstrated through simulation, that dissolution/absorption differences in other formulations could be missed in routine bioequivalence trials. Aside from differences in active pharmaceutical ingredients (APIs), other factors, such as changes in excipients or manufacturing methods, may also lead to exposure differences between formulations at elevated gastric pH. For formulations containing different forms of the same active moiety or the same API and showing different dissolution profiles at elevated pH (i.e., pH ~ 4-6.8), evaluation of bioequivalence with gastric pH modulators (e.g., a H 2 blocker) in addition to routine bioequivalence assessments may help to ensure therapeutic equivalence in patients with elevated gastric pH., (Published 2019. This article is a U.S. Government work and is in the public domain in the USA. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of the American Society for Clinical Pharmacology and Therapeutics.)

Background: Allicin (2-propene-1-sulfinothioic acid S-2-propenyl ester, diallyl thiosulfinate) extracted from garlic, has proven activity against Helicobacter pylori ( H. Pylori ) infection. In recent years, clinical trials have explored its utility as an add-on therapy with variable outcomes reported., Aim: To perform a systemic review of allicin as an add-on treatment for H. Pylori infection and assess its efficacy in randomized controlled trials (RCTs)., Methods: Electronic databases including MEDLINE, EMBASE, the Web of Science, the Cochrane Database, the China National Knowledge Infrastructure Database, Chinese VIP Information Databases, Chinese Medical Databases, and the Wan-Fang Database were searched for keywords including "allicin", " Helicobacter pylori ", "randomized clinical trials", and their synonyms. A meta-analysis was performed using the fixed-effects model for low heterogeneity and the random-effects model for high heterogeneity with sensitivity analysis. Bias was evaluated using Egger's tests. Trial sequential analysis (TSA) was used to evaluate information size and treatment benefits. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to assess the level of quality, and studies were classed as "high quality", "moderate quality", "low quality", and "very low quality"., Results: A total of eight RCTs consisting of 867 participants (435 from the allicin group and 432 from the control group) were included. Eradication rate in the allicin group (93.33%, 406/435) was significantly higher than that of the control group (83.56%, 361/432) [ I 2 = 0%, odds ratio (OR) = 2.75, 95% confidence interval (CI): 1.74-4.35, P < 0.001]. The healing rate of ulcers following H. pylori therapy in the allicin group (86.17%, 349/405) was significantly higher than that of the control group (75.87%, 305/402) [ I 2 = 0%, OR = 2.05, 95%CI: 1.39-3.03, P < 0.001]. The total remission rate of peptic ulcers across all allicin groups was 97.16%, which was significantly higher than that of controls [96.05% (389/405) vs 86.55% (360/402), I 2 = 0, OR = 3.04, 95%CI: 1.51-6.12, P = 0.015]. No significant differences in side effects were observed. TSA suggested that the trials were of sufficient standard to draw reliable conclusions. The quality of outcomes including eradication rates and side effects was graded as "very low" due to downgrades for "risk of bias" and "indirectness". Other outcomes such as ulcer healing rates and total ulcer remission rates were graded as "low" due to downgrades for "risk of bias"., Conclusion: Allicin as an add-on therapy improves H. pylori eradication, healing of ulcers, and remission of symptoms. These results are suggested to be treated with caution due to limited quality., Competing Interests: Conflict-of-interest statement: There is no conflict of interest associated with any of the senior author or other co-authors who contributed their efforts in this manuscript., (©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Capecitabine is a commonly used oral chemotherapy agent. Recent data suggest that concurrent use of proton pump inhibitors may reduce the efficacy of capecitabine by decreasing its absorption through increased gastric pH. Since proton pump inhibitors are widely used, we evaluated the supportive evidence for the probability of occurrence and potential seriousness of this drug interaction., Methods: The probability of occurrence was evaluated based on the clinical, pharmacokinetic and in vitro evidence using the Drug Interaction Probability Scale. The possibility of seriousness was assessed based on the potential impact on the therapeutic intent of capecitabine therapy., Results: The probability of occurrence of the interaction is doubtful. Clinical findings from two retrospective post hoc analyses showed inconsistent trends towards reduced survival. Pharmacokinetics studies found no significant decrease in systemic capecitabine level with concurrent gastric acid suppression with antacid or food intake. In vitro data do not support the proposed mechanism of reduced capecitabine absorption due to increased gastric pH. The possibility of seriousness varies depending on the treatment intent of capecitabine therapy. The most and least serious possible outcome would be reduced possibility of cure or survival and symptom control, respectively., Conclusion: Although the possible outcome may be serious, the probability of interaction between capecitabine and proton pump inhibitors is doubtful. Therefore, we suggest that intervention should be limited to minimal change to existing therapy plan. This may include routinely ascertaining the need for proton pump inhibitor use. Alternate acid suppressing agents may be considered based on the therapeutic intent of capecitabine therapy.

Background: Declining Helicobacter pylori (H. pylori) eradication rates have prompted a switch in first-line therapy from standard triple (PPI, clarithromycin, and amoxicillin) to bismuth-based quadruple therapy. A caveat of the ACG 2017 H. pylori treatment guidelines was a paucity of recent US eradication data., Aim: To determine Rhode Island H. pylori eradication data, in the largest US study from the last two decades., Methods: Electronic records were queried for patients with H. pylori infection diagnosed by pathology, urea breath test, or stool antigen from 2015 to 2017. Demographics, diagnostic test, treatment regimen, and test of cure were extracted. Eradication rates were calculated, and treatment regimens were compared., Results: A total of 1710 patients were identified (64% female): 825 (46%) diagnosed by breath test, 755 (42%) by biopsy, and 191 (12%) by stool antigen. Full data were obtained on 1101 patients. Seven regimens were used: quadruple (64%), triple (25%), doxycycline quadruple (5%), and miscellaneous (6%). Quadruple was superior to triple: (85% vs. 75%, P = 0.002), quadruple 14 days versus triple 14 days (87% vs. 79%, P = 0.0052), quadruple 10 days versus triple 10 days (77% vs. 67%, P = 0.33). Increased therapy length improved eradication (quadruple 14 days  vs. 10 days, 87% vs. 77%, P = 0.002; triple 14 days  versus 10 days 79% vs. 67%, P = 0.13). Finally, substituting doxycycline for tetracycline yielded lower eradication (85% vs. 67%, P = 0.006)., Conclusion: Quadruple therapy is superior to triple therapy within the Rhode Island population. Fourteen-day therapy achieves superior eradication compared to 10-day therapy, and doxycycline is inferior to tetracycline for quadruple therapy. Our findings support adherence to ACG and international guidelines advising 14-day quadruple therapy.

Poor diet quality is the leading cause of death both in the United States and worldwide, and the prevalence of obesity is at an all-time high and is projected to significantly worsen. Results from an eight-week group program utilizing an ad-libitum whole-food plant-based dietary pattern, were reviewed. There were 79 participants, all self-referred from the community, including 24 (30.4%) who were already vegetarian or vegan at baseline. Seventy-eight participants (98.7%) completed the eight-week program. Among completers, those with higher BMI at baseline lost a larger percentage of their body weight (total body weight loss of 3.0 ± SD 2.1%, 5.8 ± 2.8%, and 6.4 ± 2.5% for participants who had baseline BMI in normal, overweight, and obese range, respectively). The average weight loss for all the completers was 5.5 ± 3.0 kg ( p < 0.0001). Final blood pressure and plasma lipids were reduced compared to baseline (SBP decreased 7.1 ± 15.5 mmHg ( p = 0.0002), DBP decreased 7.3 ± 10.9 mmHg ( p < 0.0001), total cholesterol decreased 25.2 ± 24.7 mg/dL ( p < 0.0001), LDL decreased 15.3 ± 21.1 mg/dL ( p < 0.0001)). Twenty-one (26.9%) participants were able to decrease or stop at least one chronic medication compared to two (2.6%) participants who required an increased dose of a chronic medication. Participants who were already vegetarian or vegan at baseline experienced statistically significant weight loss and reductions in total and LDL cholesterol. There was a non-significant trend toward less weight loss in these participants compared to participants who were non-vegetarian at baseline. Reductions in total and LDL cholesterol were not significantly different when comparing vegetarian or vegan and non-vegetarian participants. A whole-food plant-based dietary intervention may provide significant short-term benefits for both non-vegetarian, vegetarian, and vegan individuals.

Background: Antimicrobial stewardship programs exist to promote appropriate antimicrobial use. The Joint Commission has reported that although many US hospitals have implemented basic components of antimicrobial stewardship programs, there now exists a need for innovative, multidisciplinary approaches, including involving frontline clinicians such as bedside nurses., Methods: A retrospective evaluation of bedside nurse-driven antimicrobial stewardship and infection prevention rounds was conducted on a 31-bed telemetry unit of a community regional medical center. Rounds were managed by a nurse coordinator and attended by an infectious diseases pharmacist, an infection preventionist, and a nurse practitioner. Primary outcome measures were antimicrobial and acid suppressant medication and invasive catheter use., Results: In the 12-month intervention period the nurse-driven rounds team reviewed of a total of 472 antimicrobial medication, 480 acid suppressant medication, 321 urinary catheter, and 61 central venous catheter therapies over 867 total patient encounters. Compared with the 12-month preintervention period, significant reductions in unit antimicrobial use (791.2 vs. 697.1 days of therapy per 1,000 patient-days; p = 0.03), acid suppressant medication use (708.1 vs. 372.4 days of therapy per 1,000 patient-days; p = 0.0001), and urinary catheter use (0.3 vs. 0.2 catheter-days per patient-day; p = 0.002) were observed., Conclusion: This study demonstrates successful engagement of bedside nurses in antimicrobial stewardship and infection prevention activities and a measurable impact on meaningful outcomes. More studies of strategies to integrate bedside nurses in antimicrobial stewardship are needed., (Copyright © 2019 The Joint Commission. All rights reserved.)

Introduction and aim: As the efficacy of the first-line traditional treatment used to eradicate Helicobacter pylori (H. p.) decreased below 75% in Hungary, a new protocol had to be created. Method: Supposing the success rate of the traditional therapy (14-day double dose of proton pump inhibitor [PPI], 1000 mg amoxicillin b.i.d., 500 mg clarithromycin b.i.d. [PAC]) to be 75% and the efficacy of the new protocol (10-day 120 mg bismuth dicitrate q.i.d., double dose PPI b.i.d., 500 mg tetracycline q.i.d. and 500 mg tinidazole b.i.d. [BQT]) to be 90%, we calculated 109 patients on each arm. Patients were recruited after upper gastrointestinal endoscopy from 5 endoscopic units in Vas county. The heterogeneity of groups, success rate and side effects of both therapies were evaluated by Fisher exact test; p<0.05 was considered significant. Results: 110 patients were included in the BQT and 109 patients in the PAC group. There was no heterogeneity between the two groups in age, gender and indication of eradication. H. p. eradication was successful in 103/110 (93.6%) in the BQT and 81/109 (74.3%) in the PAC group (p<0.001). The odds ratio in the BQT group for successful eradication was 5.05 (95% confidence interval: 2.02-14.42) as compared to the PAC group (p<0.001). The side effects of the two groups were similar, in the BQT group the frequency was 34.5%. Conclusion: 10 day-long BQT containing double dose PPI with 120 mg bismuth dicitrate q.i.d., 500 mg tetracycline q.i.d. and 500 mg tinidazole b.i.d. is recommended as the first-line treatment for the eradication of H. p. because of its high efficacy and tolerable side effects. Orv Hetil. 2019; 160(34): 1340-1345.

Background/aims: The duration of Helicobacter pylori (H. pylori) eradication therapy as a range (e.g., 10-14 days) is an ignored problem. There is no any particular treatment duration described in current guidelines, and the conditions for when to use 10-day therapy vs. 14-day therapy have not been elucidated. The aim of this study is to determine an effective and reliable H. pylori treatment duration in clinical practice. There were four different treatment modalities administered to groups, and success rates were compared., Materials and Methods: Patients were eligible to participate in the study if they had a biopsy-proven H. pylori infection. Each patient was randomly assigned to one of the four treatment groups according to a predetermined sequence: 14-day or 10-day bismuth-containing quadruple therapy (BQT) groups and 14-day or 10-day moxifloxacin-bismuth-combined treatment (MBCT) groups., Results: A total of 216 patients (54 per group) were enrolled. Two-hundred six patients (95.3%) completed therapy. There was no significant difference in the eradication rates between those patients who received 10- and 14-days BQT regimens (p=0.67). The 14-BQT protocol had the highest eradication rate, the MBCT regimes had the highest compliance, and the 10-MBCT protocol had the poorest results for H. pylori eradication. The posttreatment questionnaire on adverse effects identified nausea/vomiting as the most common side effect (35.7%)., Conclusion: Overall, the results of our study suggest that shortening the BQT protocol duration to 10 days does not weaken the H. pylori eradication rate. Moreover, quinolone-containing therapies with the lowest eradication rate among the groups should not be offered as a salvage treatment in case of the BQT failure.

Background: Eradicating Helicobacter pylori infection is clinically challenging, notably in cases with penicillin allergy. Cephalosporin could be used in lieu of amoxicillin to eradicate Helicobacter pylori. The current work aimed to assess therapeutic efficacy and safety of a cefuroxime-based quadruple regimen in treatment-naïve individuals with penicillin allergy, as well as patient compliance., Methods: In the present prospective single-center cohort study, 152 Helicobacter pylori infected individuals with penicillin allergy received eradication therapy with cefuroxime (500 mg twice/day), levofloxacin (500 mg once/day), esomeprazole (20 mg twice/day) and bismuth potassium citrate (220 mg twice/day; 14 days). Safety and compliance were evaluated 1 to 3 days upon eradication. The urea breath test was carried out 8 to 12 weeks upon eradication for efficacy assessment., Results: This quadruple antimicrobial regimen eradicated the pathogen at 85.5% (95% confidence interval (CI) 79.6-90.8%), 88.4% (95% CI 83.0-93.2%) and 90.1% (95% CI 85.2-94.4%) in intention-to-treat, modified intention-to-treat and per-protocol analyses, respectively, with resistance rates of 4.6 and 40.0% in the background of cefuroxime and levofloxacin, respectively. Meanwhile, 21.3% of patients had adverse reactions, but none was serious. A total of 95.3% of patients showed good compliance. Poor compliance and cefuroxime resistance were detected by uni- or multivariate analyses as independent factors predicting therapeutic failure. Eradication rates in patients with dual levofloxacin and cefuroxime susceptibility, isolated levofloxacin resistance, isolated cefuroxime resistance and dual resistance were 97.2, 84.0, 50.0, and 0%, respectively (P = 0.002)., Conclusions: Cefuroxime, levofloxacin, esomeprazole, and bismuth achieved decent efficacy, safety and compliance as first-line antimicrobial regimen in patients with Helicobacter pylori and penicillin allergy.

Medications that reduce gastric acid secretion are commonly prescribed for treating gastroesophageal reflux disease. However, several studies have shown that these medications are not very effective, and are associated with adverse effects. This article discusses the physiology of gastric acid secretion, clinical indications and pharmacology of acid suppressing medications, and possible adverse effects of these medications.

A nationwide shortage of intravenous (IV) sodium bicarbonate required institutions to explore alternative options for urinary alkalinization for high-dose methotrexate (HDMTX). Children's Hospital Colorado implemented a protocol utilizing oral alkalinizing agents as alternatives to intravenous sodium bicarbonate during the shortage. The purpose of this study was to determine the safety and efficacy of oral alkalinization strategies for HDMTX administration. This retrospective study was conducted at a pediatric institution and evaluated cycles of HDMTX administered with at least one dose of oral sodium bicarbonate tablets or sodium citrate-citric acid oral solution. The time to achieve urine pH of ≥7 was 3.48 hours from the start of alkalinization. A median dose of 66.4 mEq/m/day of oral sodium bicarbonate was administered to maintain a urine pH of ≥7 until methotrexate was cleared. Gastrointestinal side effects occurred with 43% of HDMTX cycles and patients switched to IV sodium acetate in 25.5% of HDMTX cycles, primarily due to inadequate alkalinization or intolerance. During a shortage of IV sodium bicarbonate, oral alkalinization is an effective strategy for most patients to allow for administration of HDMTX.

Background: Clarithromycin-containing bismuth quadruple therapy has been recommended as the first-line therapy for H pylori infection in China. However, its expensive cost and high antibiotic-related adverse reactions are always haunting us. To find a safer, more cost-effective, and high eradicative strategy for Helicobacter treatment, we investigated the efficacy of 14-day bismuth quadruple therapy and different doses of clarithromycin in the first-line treatment., Method: A total of 210 patients with H pylori infection were recruited and randomly assigned to half-dose clarithromycin group (esomeprazole 20 mg bid, amoxicillin 1 g bid, clarithromycin 250 mg bid, and bismuth potassium citrate 0.6 g bid) for 14 days or standard-dose clarithromycin group (esomeprazole 20 mg bid, amoxicillin 1 g bid, clarithromycin 500 mg bid, and bismuth potassium citrate 0.6 g bid) for 14 days. A 13 C-urea breath test ( 13 C-UBT) was performed at least 4 weeks after treatment. The eradication rate of H pylori, the incidence of side effects, and the cost-effectiveness of regimens were evaluated in this study., Results: The eradication frequencies were 86.67% for both groups in the intention-to-treat analysis, while the per-protocol eradication rates were 91% vs. 91.92% (p=0.817). The incidence of adverse events was higher in standard dose group (54.21% vs. 34.29%; p=0.004), especially bitter taste symptom. There was a higher level of costs per person associated with the standard-dose group as compared with half-dose group (￥804.3 vs ￥654.36). The cost-effectiveness ratio of the half dose was less than that of the standard dose (7.55 vs 9.16 CNY per percent)., Conclusions: A 14-day half-dose clarithromycin-containing bismuth quadruple regimen is as effective as the standard bismuth quadruple therapy at eradicating H pylori, which is better tolerated and more economical. (ChiCTR-ROC-15007406)., (© 2019 John Wiley & Sons Ltd.)

Objective: The main objective of this research is to formulate, optimize, and evaluate raft-forming chewable tablets of Nizatidine. Various raft-forming agents were used in preliminary screening. Sodium alginate showed maximum raft strength, so tablets were prepared using sodium alginate as the raft forming agent, along with calcium carbonate (CaCO 3 ) as antacid and raft strengthening agent, and sodium bicarbonate (NaHCO 3 ) as a gas generating agent., Research Design and Methods: Raft forming chewable tablets containing Nizatidine were prepared by direct compression and wet granulation methods, and evaluated for drug content, acid neutralization capacity, raft strength, and in-vitro drug release in 0.1 N HCl. Box-Behnken design was used for optimization., Results: Two optimized formulations were predicted from the design space. The first optimized recommended concentrations of the independent variables were predicted to be X 1  = 275.92 mg, X 2  = 28.60 mg, and X 3  = 202.14 mg for direct compression technique and the second optimized recommended concentrations were predicted to be X 1  = 253.62 mg, X 2  = 24.60 mg, and X 3  = 201.77 mg for wet granulation technique. Optimized formulations were stable at accelerated environmental testing for six months at 35 °C and 45 °C with 75% relative humidity. X-Ray showed that the raft floated immediately after ingestion and remained intact for ∼3 h., Conclusion: Raft was successfully formed and optimized. Upon chewing tablets, a raft is formed on stomach content. That results in rapid relief of acid burning symptoms and delivering the drug into systemic circulation with enhanced bioavailability.

Aim: To determine the incidence and types of complications associated with oesophageal foreign body (FB) removal in dogs, as well as to evaluate potential risk factors for the development of complications., Methods: Clinical records were searched within Animal Emergency Service and Veterinary Specialist Services databases between July 2001 and March 2017. Data were collected regarding signalment, FB type, method of removal, medical management and complications. Follow-up records from the referring veterinarian were then obtained by either phone call or email., Results: A total of 349 FB cases were reviewed. The majority of FBs were bones (77.4%), with Staffordshire Bull Terriers (12.3%) and West Highland White Terriers (9.8%) the most common breeds seen. Complications at the time of FB removal occurred in 20 cases (5.9%), with 14 cases of perforation. Persistent gastrointestinal signs were reported in 4.7% of cases within the initial 72-h period following FB removal and 11.9% cases outside this time period. Respiratory signs such as dyspnoea and coughing were also reported in 8 cases (2.3%), all of which occurred within 72 h after FB removal. Follow-up of at least 1 month was available in 151 cases. Delayed complications occurred in 11 cases (7.3%), with stricture occurring in 4 cases (2.6%); 16 animals were either euthanased (n = 14) or died (n = 2) post-FB removal, resulting in a case fatality rate of 4.6%., Conclusion: Use of antacid medications and FB type did not have a statistically significant relationship with complications following FB removal., (© 2019 Australian Veterinary Association.)

A physiologically-based pharmacokinetic (PBPK) model was developed for YH4808, a novel potassium-competitive acid blocker, using the SimCYP® Simulator based on the physicochemical, in vitro preclinical and clinical data of YH4808. The PBPK model was optimized using YH4808 concentrations obtained from the single-dose phase I clinical trial. Overall, the PBPK model adequately predicted the observed pharmacokinetic profiles of YH4808 in humans. The pharmacokinetic profiles of YH4808 after multiple oral administrations were predicted using a refined PBPK model. The ratios of model-predicted to observed C max , AUC inf and AUC τ values on Day 1 and Day 7 at 100 mg were 0.7-1.0. However, the model failed to predict a decreased exposure after multiple oral administration particularly at higher doses of 200 and 400 mg. The reduced solubility of YH4808 at higher pH was hypothesized as the main cause of the reduction in exposure such that absorption was decreased as pH was increased. This hypothesis was confirmed by PBPK modeling and simulation, where intragastric pH was increased by YH4808., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Chronic reflux patients with long-term PPI therapy frequently have persistent symptoms. A critical source of the persistent acid reflux is the acid pocket, which can be treated effectively by the non-systemic reflux suppressing action of alginates., Methods: GERD patients with at least one year of PPI long-term therapy, who were dissatisfied with their therapy, were treated over a period of 14 days with alginate as add-on and when required (up to 4 times daily) in a prospective, multi-centre, non-randomised, non-interventional and uncontrolled study in GP practices. The frequency of symptoms in the week before treatment was recorded, as well as in the second week of the study phase and the consumption of alginate. The validated GERD Q score was also applied. The patients assessed satisfaction with the therapy on a five-point Likert scale (very unhappy - happy) before the beginning and at the end of the study. The primary endpoint of the study was improvement in satisfaction with the therapy by ≥ 1 point., Results: 155 patients (54 % women, median age 57 (18 - 85) years) entered the study. Six patients had to be excluded from the final efficacy analysis (no intake of study drug, lost to follow-up). The median duration of GORD was 8 (1 - 50) years and the median time on PPI therapy was 6 years. On average the patients took 3 sachets of alginate per day. The alginate therapy led to an improvement by at least 1 point on the Likert scale in 72 % of patients (1 step n = 45, 2 steps n = 41, 3 steps n = 16, 4 steps n = 5). Patients with a Gerd Q score > 8 showed a higher response rate at 81 %. There was improvement in all typical reflux symptoms and sleep disorders. The treatment was generally well-tolerated., Conclusions: A reflux blocking alginate taken on demand is an effective and safe option for the treatment of breakthrough symptoms in GERD patients on PPI., Competing Interests: JL: Beratungs- und Vortragstätigkeit für Reckitt BenckiserGL: Vortragstätigkeit für Reckitt BenckiserMM und DB: keine Interessenkonflikte, (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: The alginate-antacid Gaviscon Double Action (Gaviscon DA) has a combined acid-neutralizing and reflux-suppressing action. Response to treatment in a symptomatic gastro-oesophageal reflux disease (GERD) population has not yet been tested in a large-scale clinical study., Aim: The aim of this study was to assess the efficacy and safety of Gaviscon DA compared with matched placebo tablets in the reduction of upper gastrointestinal symptoms in patients with GERD., Participants and Methods: In this multicentre, randomized, double-blind, placebo-controlled study, adults with GERD symptoms (N=424) received Gaviscon DA or placebo tablets for 7 days. The primary endpoint was a clinically important reduction of at least 1.5 points in the Reflux Disease Questionnaire (RDQ) GERD dimension (combined heartburn/regurgitation) between baseline and the end of the treatment. Secondary endpoints included the change in RDQ score from baseline for individual RDQ dimensions and Overall Treatment Evaluation., Results: A significantly greater proportion of patients treated with Gaviscon DA met the primary endpoint compared with placebo (47.8 vs. 33.2%, respectively, P=0.0031; odds ratio: 1.85, 95% confidence interval: 1.23-2.78). A significant treatment effect was also observed for heartburn, regurgitation and dyspepsia individually. Patients in the Gaviscon DA group rated their overall treatment response greater than patients in the placebo group [mean Overall Treatment Evaluation (SD): 3.2 (3.08) vs. 2.2 (3.34); P<0.001]. No notable differences in the incidence of adverse events were observed between treatments., Conclusion: The alginate-antacid combination, Gaviscon DA, is an effective and well-tolerated treatment to reduce reflux symptoms and associated dyspepsia in symptomatic GERD patients.

Purpose: YH4808 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., Methods: The 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., Results: After 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., Conclusions: As 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 Registration: ClinicalTrials.gov registry no.: NCT01520012.

Objectives: Management of laryngopharyngeal reflux (LPR) typically comprises alginates and proton pump inhibitors (PPIs) alone or in combination, yet evidence to support any particular treatment regimen is lacking. We sought to evaluate the efficacy of Gaviscon® Advance alone versus co-prescription with a PPI in treating LPR., Methods: One hundred consecutive LPR patients with a reflux symptom index (RSI) score > 10 attending our joint voice clinic (JVC) were studied prospectively. All were treated with Gaviscon® Advance four times daily. If patients had been started on a PPI prior to their JVC attendance, this was optimised to a twice-daily dosing regimen and continued. RSI scores were recorded at first attendance and 3 months post-treatment via postal questionnaire. Scores were analysed using t tests and Levene's test for equality of variances., Results: Follow-up RSI scores were returned by 72 patients, 39 of whom were treated with Gaviscon® Advance only (group A) and 33 with Gaviscon® Advance + PPI (group B). Mean pre-treatment RSI scores were similar between groups [group A: 19.2, 95% confidence interval (CI) ± 2.4; group B: 21.3, 95% CI ± 3.2 (p = 0.65)]. No significant differences were observed with respect to 3-month post-treatment RSI scores [group A: 9.9, 95% CI ± 2.8; group B: 12.6, 95% CI ± 4.2 (p = 0.82)] and change in RSI scores [group A: 9.3, 95% CI ± 3.0; group B: 8.7, 95% CI ± 2.9 [p = 0.75])., Conclusions: Gaviscon® Advance alone is effective in treating symptoms of LPR, while co-prescription with a high-dose PPI offers no additional benefit.

Background: Whether extending the treatment length and the use of high-dose esomeprazole may optimize the efficacy of Helicobacter pylori eradication remains unknown., Objectives: To compare the efficacy and tolerability of optimized 14 day sequential therapy and 10 day bismuth quadruple therapy containing high-dose esomeprazole in first-line therapy., Methods: We recruited 620 adult patients (≥20 years of age) with H. pylori infection naive to treatment in this multicentre, open-label, randomized trial. Patients were randomly assigned to receive 14 day sequential therapy or 10 day bismuth quadruple therapy, both containing esomeprazole 40 mg twice daily. Those who failed after 14 day sequential therapy received rescue therapy with 10 day bismuth quadruple therapy and vice versa. Our primary outcome was the eradication rate in the first-line therapy. Antibiotic susceptibility was determined. ClinicalTrials.gov: NCT03156855., Results: The eradication rates of 14 day sequential therapy and 10 day bismuth quadruple therapy were 91.3% (283 of 310, 95% CI 87.4%-94.1%) and 91.6% (284 of 310, 95% CI 87.8%-94.3%) in the ITT analysis, respectively (difference -0.3%, 95% CI -4.7% to 4.4%, P = 0.886). However, the frequencies of adverse effects were significantly higher in patients treated with 10 day bismuth quadruple therapy than those treated with 14 day sequential therapy (74.4% versus 36.7% P < 0.0001). The eradication rate of 14 day sequential therapy in strains with and without 23S ribosomal RNA mutation was 80% (24 of 30) and 99% (193 of 195), respectively (P < 0.0001)., Conclusions: Optimized 14 day sequential therapy was non-inferior to, but better tolerated than 10 day bismuth quadruple therapy and both may be used in first-line treatment in populations with low to intermediate clarithromycin resistance.

Purpose of the review to present up-to-date data on the causes, methods of diagnosis and treatment of the refractory form of gastroesophageal reflux disease (GERD). Refractory GERD is the preservation of typical symptoms of the disease and/or incomplete healing of the esophageal mucosa against the background of taking a standard dose of proton pump inhibitors (PPI) once a day for 8 weeks. The reasons for the lack of response to the treatment are divided into related to the patient, related to therapy, and not related to GERD. Diagnostic approaches include x-ray examination of the esophagus and stomach, endoscopy with biopsy, 24-hour Impedance-pH monitoring, esophageal manometry. Depending on the reasons for the lack of response to the therapy, treatment may include lifestyle changes, doubling the dose of PPI, replacing PPI with another, adding H2-receptor antagonists, prokinetics, antacids, alginates and adsorbents. If conservative treatment is ineffective, it is possible to consider alternative methods, such as surgical treatment. Refractory GERD is a serious clinical problem. The absence of an answer to 8-week therapy with PPI requires a thorough differential diagnosis using additional examination methods. The identification of the causes of refractory to the therapy allows to optimize the approaches to its overcoming and to choose the optimal treatment.

Aim: The aim is to conduct a comprehensive comparative study of the efficacy and safety of the hybrid scheme of eradication therapy (ET) in patients with peptic ulcer of the stomach or duodenum associated with Helicobacter pylori., Materials and Methods: Materials and methods. In a prospective, randomized comparative study, 180 patients were divided into three equal groups of 60 people, depending on the prescribed 10-day ET regimen. Group 1 - the standard triple scheme (omeprazole, amoxicillin and clarithromycin); group 2 - four-component therapy with preparations of bismuth (omeprazole, tetracycline, metronidazole, bismuth tricalium dicitrate); group 3 - hybrid scheme (first 5 days: omeprazole and amoxicillin, the next 5 days: omeprazole, amoxicillin, clarithromycin, metronidazole). The effectiveness of ET was determined with the help of a breath test a month after the end of therapy. Adverse events were recorded by patients in specially developed diaries. Pharmacoeconomic analysis was carried out using the &quot;cost-effectiveness&quot; method with calculation of the CER coefficient., Results: Results and discussion. The effectiveness of standard triple therapy was 73.3% (ITT), 75.9% (PP); four-component therapy with bismuth preparations - 78.3% (ITT), 82.4% (PP); hybrid scheme - 85% (ITT), 91% (PP). Hybrid therapy proved to be significantly more effective than standard triple therapy with a odds ratio (OR) of 3.25; 95% confidence interval (CI) 1.08-9.73 (p=0.043, χ2=4.75, p-level=0.029298). The incidence of adverse events with the use of triple, four-component and hybrid ET regimens was 15; 18.3 and 28.3% respectively. The OR of at least one adverse event in patients receiving a hybrid ET regimen compared with triple therapy was 2.24 (95% CI 0.91-5.53, p=0.0823, χ2=3.14, p-level=0.076394), and compared with the four-component therapy - 1.76 (95% CI 0.74-4.17, p=0.2804, χ2=1.68, p-level=0.194924). According to the results of the pharmacoeconomic analysis, the most profitable from an economic point of view was a hybrid ET scheme with a CER of 20.1., Conclusion: The conclusion. Hybrid therapy showed the greatest effectiveness in comparison with the triple and four-component ET regimens, however, the incidence of side effects in patients receiving the hybrid ET scheme was higher, although it remained within the acceptable level for use in clinical practice. Pharmacoeconomic analysis also showed the advisability of designating a hybrid ET scheme. The obtained data allow to draw a conclusion about the necessity of further study of the efficiency and safety of the hybrid ET scheme.