Effect of Food, Crushing of Tablets, and Antacid Coadministration on Maribavir Pharmacokinetics in Healthy Adult Participants: Results From 2 Phase 1, Open-Label, Randomized, Crossover Studies.

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 (Cmax) 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 Cmax were within 80%-125% for crushed versus whole tablet. Maribavir median time to Cmax 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 Cmax, findings suggest that maribavir can be administered with food or antacids or as a crushed tablet.

Together or Apart? Revealing the Impact of Dietary Interventions on Bioavailability of Quinolones: A Systematic Review with Meta-analyses.

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 Cmax increased by > 45%), whereas, for all the remaining drugs, postprandial absorption was lower. The most significant negative influence of food (AUC or Cmax decreased by > 40%) occurred for delafloxacin capsules and norfloxacin, whereas the moderate influence (AUC or Cmax 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.

Two Different 1-Week Quadruple Therapies Given Back-to-Back Consecutive Therapy for Difficult-to-Treat Helicobacter pylori Infection: A Pilot Study.

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.

Neutralization of Acidic Tumor Microenvironment (TME) with Daily Oral Dosing of Sodium Potassium Citrate (K/Na Citrate) Increases Therapeutic Effect of Anti-cancer Agent in Pancreatic Cancer Xenograft Mice Model.

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 HCO3- concentrations, corresponding to increase of HCO3- concentrations and pHs in urine, and neutralized the tumor pHe. Neutralization of acidic TME by alkaline substance like HCO3-, 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.

Over-the-counter antacids linked to severe hypokalaemia in the context of threatened preterm labour.

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.

High prevalence of comorbidities and use of concomitant medication in treated people living with HIV in Germany - results of the BESIDE study.

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.

Effect of meal timing on pharmacokinetics and pharmacodynamics of tegoprazan in healthy male volunteers.

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.

Lack of almagate interference in breath test results for Helicobacter pylori diagnosis (Almatest study). / Ausencia de interferencia de almagato en los resultados de la prueba de aliento para el diagnóstico de Helicobacter pylori (estudio Almatest).

OBJECTIVE: The 13C-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.

Gastroprotective Therapy.

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.

The efficacy of first-line tyrosine kinase inhibitors combined with co-medications in Asian patients with EGFR mutation non-small cell lung cancer.

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.

Symptomatic response to GERDOFF® in patients with gastro-esophageal reflux disease and poor response to alginates: an exploratory, post-market, open-label study.

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_15143752.

Potential Implications of Gut Microbiota in Drug Pharmacokinetics and Bioavailability.

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.

Chewable Antacid Tablets: Are Disintegration Tests Relevant?

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.

Reno-protective effects of oral alkalizing agents in chronic kidney disease with aciduria: protocol for a randomized cohort study.

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.

Effect of an Al/Mg Hydroxide Antacid and Food on the Pharmacokinetics of Dexibuprofen.

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 Cmax values showed a significant (p value 0.035) decrease from 44.14±2.3 to 33.1±0.8 µg/mL. Tmax, Area under curve, t1/2, Cl, Vd and Ke 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. t1/2 increased significantly from 4.505±0.19 hrs to 6.216±0.36 hrs whereas Ke reduced from 0.159±0.00 to 0.116±0.006 hrs-1. Cmax 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.

Randomised trial of acid inhibition by vonoprazan 10/20 mg once daily vs rabeprazole 10/20 mg twice daily in healthy Japanese volunteers (SAMURAI pH study).

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).

Alkalinizing Agents: A Review of Prescription, Over-the-Counter, and Medical Food Supplements.

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.

A Potassium-Competitive Acid Blocker-Based Regimen as Second-Line Therapy Improves Helicobacter pylori Eradication.

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.

Quality of life and gastric acid-suppression medication 20 years after laparoscopic fundoplication.

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.