Deprescribing antacids after the diagnosis of Clostridioides difficile infection: A single-center observational study.

Overuse of antacids is associated with the development and recurrence of Clostridioides difficile infection (CDI). Discontinuation of unnecessary antacids for CDI management is advocated; however, the clinical pervasiveness on the discontinuation of antacids remains unclear. We conducted a single-center retrospective observational study to determine the rate of antacid discontinuation following CDI diagnosis. Among 51 patients (58 infections; median age 76.5 years, range 69-82; 53.5% women) treated with antimicrobials against C. difficile, 41 had been treated with antacids, and of these, 18 exhibited no indication for antacid administration. However, none had discontinued antacid use. While CDI provides an opportunity for antacid stewardship, it is not implemented in clinical practice. In addition to the efforts of individual clinicians, the dissemination of knowledge of the indications and side effects of antacids, establishment of a multidisciplinary support system, and creation and implementation of a clinical stewardship pathway are necessary to increase the deprescription of antacids in patients with CDI.

Autoimmune and immune-mediated inflammatory diseases after exposure to acid-suppressive medication: A systematic review and meta-analysis.

BACKGROUND: Pharmacovigilance risk signals have proposed a relationship between the use of acid-suppressive medications and the development of certain autoimmune and immune-mediated inflammatory diseases. OBJECTIVE: A systematic review and a meta-analysis was performed. METHODS: We reviewed MEDLINE (Ovid) and Scopus for comparative observational studies between these diseases and previous exposure to proton-pump inhibitors (PPI), H2-receptor antagonists (H2RA), and antacids. The protocol was registered on the PROSPERO database (CRD42020192715). RESULTS: From 3,191 citations, 25 articles were eligible and covered 16 diseases. Microscopic colitis (MC) was studied the most (7 studies). In a random-effects meta-analysis, there was low certainty evidence (GRADE approach) of a non-significant relationship between exposure to any PPIs and MC (meta-OR 3.28, 95% CI 0.98-11.0, I2 98.2%, six studies, 4,436 PPI-exposed MC patients). Moderate certainty evidence pointed towards large odds of collagenous colitis after exposure to lansoprazole (meta-OR 14.5, 95% CI 9.37-22.3, I2 10.2%, three studies, 1,725 lansoprazole-exposed patients). After PPI exposure, the risk of rheumatoid arthritis was slightly increased based on low certainty evidence from two cohort studies totaling 475 diagnoses (meta-RR 1.62, 95% CI 1.12-2.34, I2 34.5%). CONCLUSIONS: In patients with MC, it would be reasonable to carefully review the indication of PPI, especially in CC patients using lansoprazole.

Effect of Antacid Use on Immune Checkpoint Inhibitors in Advanced Solid Cancer Patients: A Systematic Review and Meta-analysis.

The influence of antacids use on immune checkpoint inhibitor (ICI) efficacy remains unclear. A systematic review and meta-analysis was performed to evaluate the effect of proton pump inhibitors (PPIs) and histamine-2-receptor antagonists (H2RAs) on ICI efficacy in advanced solid cancer patients. A systematic literature search in PubMed, EMBASE, and Web of Science was performed to retrieve studies investigating the effect of antacid use on ICI efficacy. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and immune-related adverse events were measured using hazard ratios (HRs) or odds ratios (ORs). Thirty studies enrolling 16,147 advanced cancer patients receiving ICI treatment were included. The pooled analysis indicated that PPI use was associated with shorter OS (HR=1.40, 95% CI, 1.25-1.57) and PFS (HR=1.34, 95% CI, 1.19-1.52) in advanced cancer patients treated with ICIs. PPI use did not show effect on ORR or immune-related adverse event of advanced cancer patients receiving ICI treatment. OS, PFS, and ORR did not differ between H2RA users and non-H2RA users. In subgroup analyses, PPI use was associated with shorter OS and PFS in NSCLC and urothelial carcinoma patients and in patients treated with anti-programmed cell death 1 or anti-programmed cell death ligand 1 monotherapy. In addition, ICI efficacy was different in the antacid exposure time frame subgroups. In conclusion, PPI use has a negative effect on OS and PFS among advanced cancer patients receiving ICI treatment. PPIs should be cautiously administered among advanced cancer patients treated with ICI. The safety of H2RAs and the influence of H2RAs on ICI efficacy need further investigation.

Use of food and food-derived products in the treatment of gastritis: A systematic review.

Gastritis is the acute or chronic inflammation of gastric mucosa and is triggered by diverse factors. Treatments used for non-bacterial gastritis include proton pump inhibitors, histamine H2 receptor inhibitors, and antacids, and their use is linked to various side effects. Research on alternative therapeutics using food or food-based products is extensive, mostly in preclinical research. We aimed at documenting the clinical advances in food-based therapies as alternative therapeutics for gastritis. Articles with information on the treatment of gastritis with food or food-based products published until December 1, 2020 were identified through a systematic search in PubMed Medline Database. Additionally, references of retrieved articles were screened for relevant reviews and meta-analyses. Two investigators independently selected and reviewed the titles and abstracts of articles and extracted the study characteristics (PICO framework) and key findings. Dual quality assessment and data extraction were performed. We found 28 clinical studies evaluating garlic, turmeric, red peppers, broccoli sprouts, cranberry juice, honey, oils, and probiotics contained in different foods, such as juices, yogurt, and cheese. The existing literature presents a high risk of bias, and results of the same should be evaluated and replicated with precaution; more rigorous clinical studies are lacking.

Association between use of antacid medications (proton pump inhibitors and histamine-2 receptor antagonists) and the incidence of lung cancer: A population-based cohort analysis.

This study investigated the association between antacid administration and lung cancer incidence in a real-world setting. This was a nationwide, retrospective cohort study. The cohort comprised random samples (n = 1,031,392) from the entire South Korean population in 2002. The duration of antacid administration between January 2006 and December 2010 was recorded for each participant. Newly developed lung cancers were counted during the 5-year observation period (January 1, 2006 to December 31, 2010). A total of 437,370 participants aged ≥ 40 years were included, of whom 301,201 (68.9%) had antacid exposure before the diagnosis of lung cancer. A total of 1230 (0.28%) antacid-exposed patients developed lung cancer. Among patients with no antacid exposure or underexposure (n = 136,171), 597 (0.44%) developed lung cancer. In the multivariable analysis, antacid exposure before the diagnosis of lung cancer was independently associated with a reduced incidence of lung cancer (hazard ratio: 0.64; 95% confidence interval: 0.55-0.74; P < .001). Antacid use might be independently associated with a decreased risk of lung cancer development in this cohort study.

Magnesium exposure increases hip fracture risks in patients with chronic kidney disease: a population-based nested case-control study.

This population-based study demonstrates a strong link between Mg-containing antacid exposure and hip fracture risk in nondialysis CKD and dialysis patients. As an Mg-containing antacid, MgO is also commonly used as a stool softener, which can be effortlessly replaced by other laxatives in CKD patients to maintain bone health. PURPOSE: Bone fracture is a severe complication in chronic kidney disease (CKD) patients, leading to disability and reduced survival. In CKD patients, blood magnesium (Mg) concentrations are usually above the normal range due to reduced kidney excretion of Mg. The present study examines the association between Mg-containing antacid exposure and the risk of hip fracture of CKD patients. METHODS: In this nationwide nested case-control study, we enrolled 44,062 CKD patients with hip fracture and 44,062 CKD matched controls, among which the mean age was 77.1 years old, and 87.9% was nondialysis CKD. RESULTS: As compared to non-users, Mg-containing antacid users were significantly more likely to experience hip fracture (adjusted odds ratio (OR) 1.36, 95% CI, 1.32 to 1.41; p < 0.001). Subgroup analysis showed that such risk exists in both nondialysis CKD patients and long-term dialysis patients. In contrast, aluminum or calcium-containing-antacid use did not reveal such association. Next, we examined the influence of Mg-containing antacid dosage on hip fracture risk, the adjusted ORs in the first quartile (Q1), Q2, Q3, and Q4 were 1.20 (95% CI, 1.15 to 1.25; p < 0.001), 1.35 (95% CI, 1.30 to 1.41; p < 0.001), 1.49 (95% CI, 1.43 to 1.56; p < 0.001), and 1.54 (95% CI, 1.47 to 1.61; p < 0.001), respectively, showing that such risk exists regardless of the antacid dosage. A receiver operating characteristic curve analysis demonstrated that the best cutoff value of the exposed Mg dose to discriminate the hip fracture is 532 mEq during the follow-up period. CONCLUSION: This population-based study demonstrates a strong link between Mg-containing antacid exposure and the hip fracture risk in both nondialysis CKD and dialysis patients.

Sodium Bicarbonate Prescription and Extracellular Volume Increase: Real-world Data Results from the AlcalUN Study.

Oral alkalization with sodium bicarbonate (NaHCO3 ) or citrate is prescribed for conditions ranging from metabolic acidosis to nephrolithiasis. Although most nephrologists/urologists use this method routinely, extracellular volume (ECV) increase is the main feared adverse event reported for NaHCO3 . Thus far, no trial has specifically studied this issue in a real-world setting. AlcalUN (NCT03035812) is a multicentric, prospective, open-label cohort study with nationwide (France) enrollment in 18 (public and private) nephrology/urology units. Participants were adult outpatients requiring chronic (>1 month) oral alkalization by either NaHCO3 -containing or no-NaHCO3 -containing agents. The ECV increase (primary outcome) was judged based on body weight increase (ΔBW), blood pressure increase (ΔBP), and/or new-onset edema at the first follow-up visit (V1). From February 2017 to February 2020, 156 patients were enrolled. After a median 106 days of treatment, 91 (72%) patients reached the primary outcome. They had lower systolic (135 (125, 141) vs. 141 (130, 150), P = 0.02) and diastolic (77 (67, 85) vs. 85 (73, 90), P = 0.03) BP values, a higher plasma chloride (106.0 (105.0, 109.0) vs. 105.0 (102.0, 107.0), P = 0.02) at baseline, and a less frequent history of nephrolithiasis (32 vs. 56%, P = 0.02). Patients experienced mainly slight ΔBP (< 10 mmHg). The primary outcome was not associated (P = 0.79) with the study treatment (129 received NaHCO3 and 27 received citrate). We subsequently developed three different models of propensity score matching; each confirmed our results. Chronic oral alkalization with NaHCO3 is no longer associated with an ECV increase compared to citrate in real-life settings.

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.

Impact of pharmacy-supported interventions on proportion of patients receiving non-indicated acid suppressive therapy upon discharge: A systematic review and meta-analysis.

OBJECTIVE: Conduct a systematic review and meta-analysis to estimate the impact of pharmacy-supported interventions on the proportion of patients discharged from the hospital on inappropriate acid suppressive therapy (AST). METHODS: To identify studies, the following databases were systematically searched on October 14th, 2018 and repeated on September 12th, 2019: Ovid MEDLINE(R) and In-Process & Other Non-Indexed Citations and Daily, Embase.com, CINAHL, Web of Science, Cochrane CENTRAL (EBSCO), and ClinicalTrials.gov. Eligible studies consisted of adults, intervention and historical/usual care groups, description of active pharmacy-supported intervention, and proportion of patients discharged on inappropriate AST. Qualitative assessments and quantitative analyses were performed. Modified funnel plot analysis assessed heterogeneity. Preferred reporting items of systematic reviews and meta-analyses (PRISMA) methodology was used to evaluate studies in this review. RESULTS: Seventeen publications resulting in 16 studies were included in the review. Using random effects model, meta-analysis showed a significant reduction in the odds of being discharged on inappropriate AST from the hospital in the pharmacist-supported intervention arm versus comparator (Odds Ratio 0.33 [95%CI 0.20 to 0.53]), with significant heterogeneity (I2 = 86%). Eleven studies favored pharmacy-supported interventions, four were inconclusive and one favored usual care. Using modified funnel plot analysis, our final evaluation was distilled to 11 studies and revealed a similar outcome (OR 0.36 [95%CI 0.27 to 0.48]), but with less heterogeneity (I2 = 36%). CONCLUSION: This systematic review and meta-analysis showed that pharmacy-supported interventions were associated with a significantly reduced probability of patients discharged on inappropriate AST. However, heterogeneity was high and may affect interpretation of results. Using funnel plot optimization method, three positive and two negative studies were objectively removed from analyses, resulting in a similar effect size, but with less heterogeneity. To improve study quality, future researchers should consider utilizing a pre-post, multi-arm, prospective design with sampling randomization, training of data extractors (preferably two extractors), re-evaluating a small dataset to check for agreement and providing a comprehensive methodology in subsequent publications.

Efficacy and safety of traditional Chinese herbal formula combined with western medicine for gastroesophageal reflux disease: A protocol for systematic review and meta-analysis.

BACKGROUND: The combined therapy of Chinese herbal formula and western medicine against gastroesophageal reflux disease (GERD) could significantly improve the clinical effect, reduce the recurrence rate and the side effects of western medicine, and even reduce the dosage and course of treatment of western medicine. This study tried to systematically evaluate the efficacy and safety traditional Chinese herbal formula combined with western medicine in the treatment of GERD. METHODS: Randomized controlled trials of traditional Chinese herbal formula combined with western medicine for GERD patients will be systematically searched using the PubMed, Embase, Medline, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang database, Chongqing VIP Chinese Science and Technology Periodical Database, and Chinese Biological and Medical database (CMB) until Aug. 28, 2020. Two researchers will perform data extraction and risk of bias assessment independently. Statistical analysis will be conducted in RevMan 5.3. RESULTS: This study will summarize the present evidence by exploring the efficacy and safety of traditional Chinese herbal formula combined with western medicine in the treatment of GERD. CONCLUSIONS: The findings of the study will help to determine potential benefits of traditional Chinese herbal formula combined with western medicine against GERD. ETHICS AND DISSEMINATION: The private information from individuals will not be published. This systematic review also will not involve endangering participant rights. Ethical approval is not required. The results may be published in a peer-reviewed journal or disseminated in relevant conferences. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/RSAVF.

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.

Lessons of the month: Over-the-counter antacids causing hypercalcaemia: The emergence of calcium-alkali syndrome.

We present the case of a woman who was found to have severe hypercalcaemia, staghorn calculus formation and renal impairment from the long-standing ingestion of calcium carbonate antacids from a supermarket outlet. The dosage was reported to be approximately 1,800 mg of elemental calcium each day which would constitute only a marginal increase on the recommended intake for daily elemental calcium. Furthermore, she was concomitantly taking a prescribed anti-hypertensive medication that may have exacerbated the hypercalcaemia and subsequent renal calcification. While calcium-alkali syndrome is well documented, it can be overlooked by clinicians as the predominant cause of hypercalcaemia, especially if a thorough drug history is not actively sought. This is particularly important as calcium carbonate products are increasingly being purchased as over-the-counter remedies for dyspepsia management as well as osteoporosis prevention. Explicit product labelling regarding limiting duration usage, potential drug interactions and risk of calcification is therefore recommended.

Riesgo de fractura e inhibidores de la bomba de protones: otra razón para un uso adecuado / Proton pump inhibitors and increased fracture hazard. Another reason for an appropriate prescription of these drugs

CONCLUSIONES DE LOS AUTORES DEL ESTUDIO: el uso de tratamiento antisecretor en el primer año de vida, inhibidores de bomba de protones solos o en combinación con antagonistas de receptores H2, está asociado con un incremento del riesgo de fracturas en niños. Este riesgo puede ser mayor si el tratamiento se inicia en los primeros meses de vida y es de mayor duración. COMENTARIO DE LOS REVISORES: el aumento del riesgo de fracturas asociado al tratamiento antisecretor durante el primer año es un argumento más para valorar cuidadosamente la indicación de estos fármacos, especialmente los inhibidores de la bomba de protones, sobre todo en tratamientos precoces o prolongados

AUTHORS' CONCLUSIONS: infant proton pump inhibitors alone or together with H2 receptor antagonists is associated with an increased childhood fracture risk. This risk appears amplified by duration or early initiation of the therapy. REVIEWERS' COMMENTARY: the increased risk of fractures associated with antisecretory treatment during the first year of life another argument to carefully assess the indication of these drugs, especially proton pump inhibitors, particularly in treatments at an early age or long-term treatments

Impact of intestinal dysbiosis-related drugs on the efficacy of immune checkpoint inhibitors in clinical practice.

PURPOSE: Intestinal dysbiosis has emerged as a biomarker of response to immune checkpoint inhibitors (ICIs). It can be caused by antibiotics, although it may also result from the use of other drugs that have been studied to a lesser extent. The objective of our study was to analyze the association between the use of potentially dysbiosis-related drugs and survival in patients treated with ICIs in the clinical practice. MATERIALS AND METHODS: A retrospective, multicenter, cohort study was conducted. Clinicopathological variables were collected and the concomitant use of drugs was analyzed. A descriptive analysis of variables and overall survival, estimated by the Kaplan-Meier method, was performed, and association with various independent variables was assessed using Cox regression. RESULTS: We included 253 patients, mainly with non-small cell lung cancer and melanoma. The most commonly used drugs were acid reducers, prescribed to 55.3% of patients, followed by corticosteroids (37.9%), anxiolytic drugs (35.6%), and antibiotics (20.5%). The use of acid reducers (9 vs. 18 months, P < .0001), antibiotics (7 vs. 15 months, P < .017), anxiolytic drugs (8 vs. 16 months, P < .015), and corticosteroids (6 vs. 19 months, P < .00001) was associated with poorer overall survival. Furthermore, the greater the number of drugs used concomitantly with ICIs, the higher the risk of death (1 drug: hazard ratio, 1.88; CI 95%, 1.07-3.30; 4 drugs: hazard ratio, 4.19; CI9 5%, 1.77-9.92; P < .001). CONCLUSION: Response to ICIs may be influenced by the use of drugs that lead to intestinal dysbiosis. Although a confirmatory prospective controlled study is required, our findings should be taken into account when analyzing ICI efficacy.

Pharmacologic Prophylaxis of Stress Ulcer in Non-ICU Patients: A Systematic Review and Network Meta-analysis of Randomized Controlled Trials.

PURPOSE: Acid-suppressive medications are widely used in non-intensive care unit (non-ICU) patients for stress ulcer (SU) prophylaxis. However, SU prophylaxis in this population is still controversial. The purpose of this study was to systematically evaluate the efficacy and tolerability of these agents for SU prophylaxis in non-ICU patients. METHODS: Electronic databases including Cochrane, ClinicalTrials.gov, Ovid-Medline, Embase, Chinese CNKI, and Wanfang Data were systematically searched on July 10, 2019, for randomized controlled trials (RCTs) that evaluated acid-suppressive medications in non-ICU patients. Network meta-analysis and pairwise meta-analysis were performed to calculate odds ratios (ORs) and 95% CIs. A random-effects model was used for generating pooled estimates. The primary outcome was occurrence of SU bleeding, and the adverse drug events (ADEs) were described as the secondary outcome. FINDINGS: A total of 17 RCTs involving 1985 patients were eligible. Meta-analysis results indicated that the occurrence of SU bleeding was significantly decreased with all acid-suppressive medications compared with placebos (gastric mucosa protectants, OR = 0.29 [95% CI, 0.14-0.61]; H2-receptor antagonists, OR = 0.3 [95% CI, 0.18-0.50]; proton pump inhibitors [PPIs]: OR = 0.08 [95% CI, 0.04-0.16]). The occurrence of SU bleeding was significantly decreased with PPIs compared with gastric mucosa protectants (OR = 0.29; 95% CI, 0.12-0.72) and H2-receptor antagonists (OR = 0.28; 95% CI, 0.16-0.48). There was no significant difference between any 2 classes of PPIs on SU bleeding or any 2 acid-suppressive medications on ADEs. IMPLICATIONS: PPIs could significantly decrease SU bleeding risk without increasing ADEs than other acid-suppressive medications for SU prophylaxis in non-ICU patients. However, RCTs of high quality were required to confirm the findings of this investigation.

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).

Drug-Drug Interactions Potential of Direct-Acting Antivirals for the treatment of Chronic Hepatitis C Virus infection.

The advent of direct-acting antiviral agents (DAAs) has transformed the hepatitis C virus (HCV) therapeutic landscape in terms of efficacy and safety, with a cure rate of more than 90%. However, an important potential for drug-drug interactions (DDIs) is expected with these combinations, particularly in patients with other comorbidities (e.g. HIV co-infection, cardiovascular diseases). Each DAA can be a substrate, an inhibitor and/or an inducer of metabolic enzymes and drug efflux transporters. DAAs can act as both victims and perpetrators of DDIs and can sometimes increase the risk and/or intensity of side effects or limit the efficacy of treatment. Therefore, knowledge and management of DDIs with DAAs should be considered a key issue of HCV therapy. This review describes the pharmacokinetic profile of currently used and recommended DAA regimens and summarizes available data regarding DDIs to optimize HCV treatment in clinical practice.

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.

Allicin as add-on therapy for Helicobacter pylori infection: A systematic review and meta-analysis.

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.