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Background and Aim Methods Results Conclusions Only a few studies have investigated the efficacy and safety of different durations of vonoprazan and amoxicillin (VA) high‐dose dual therapy for the eradication of Helicobacter pylori. We aimed to compare the efficacy and safety of 10 days versus 14 days of VA high‐dose dual therapy for H. pylori eradication.This study was conducted in 14 centers in China. A total of 250 patients infected with H. pylori were randomly assigned to Group VA‐10 or VA‐14. Both groups received the VA dual therapy (vonoprazan 20 mg twice daily + amoxicillin 1000 mg three times daily). The primary endpoint was the H. pylori eradication rate. Secondary endpoints included adverse events and patient compliance.Group VA‐10 achieved eradication rates of 89.60%, 91.06%, and 91.67% as determined by the intention‐to‐treat (ITT), modified intention‐to‐treat (MITT), and per‐protocol (PP) analysis, respectively. The eradication rates were similar to those in Group VA‐14: 91.20%, 93.44%, and 93.39%. The difference and 90% confidence interval boundary −1.60% (−7.73% to 4.53%) in the ITT analysis, −2.39% (−8.00% to 3.23%) in the MITT analysis, and −1.72% (−7.29% to 3.85%) in the PP analysis were greater than the predefined noninferiority margin of −10%, establishing a noninferiority of Group VA‐10 versus Group VA‐14 (noninferiority P = 0.001 in ITT analysis, P < 0.001 in MITT analysis, and P < 0.001 in PP analysis, respectively). No significant differences were observed in adverse events between the two groups.Ten‐day VA dual therapy achieves comparable efficacy and safety to the 14‐day regimen in Chinese population, providing patients with greater convenience and economic benefits. [ABSTRACT FROM AUTHOR]

Background: The latest guidelines discourage the use of long-acting beta2-agonists/inhaled corticosteroids (LABA/ICS) for chronic obstructive pulmonary disease (COPD). However, there is a lack of evidence regarding the optimal subsequent treatment after discontinuing LABA/ICS. Objectives: To compare the effectiveness and safety of switching from LABA/ICS to triple therapy (LABA/long-acting muscarinic antagonists (LAMA)/ICS) or to dual bronchodilators (LABA/LAMA) in COPD patients. Design: This was a new-user, active-comparator, and propensity score-matched cohort study analyzing the Taiwanese nationwide healthcare insurance claims. Methods: We recruited COPD patients switching from LABA/ICS to triple therapy or to dual bronchodilators from 2015 to 2019. The primary effectiveness outcome was the annual rate of exacerbations, and safety outcomes included severe pneumonia and all-cause mortality. Stratification by prior exacerbations was conducted. Results: After matching, each group comprised 1892 patients, 55% of whom experienced no exacerbations in the prior year. Treatment with LABA/LAMA/ICS versus LABA/LAMA showed comparable annual rate of moderate-to-severe exacerbations (incidence rate ratio, 1.04; 95% confidence interval (CI), 0.91–1.19). However, switching to LABA/LAMA/ICS was associated with increased risks of severe pneumonia (hazard ratio (HR), 1.65; 95% CI, 1.30–2.09) and all-cause death (HR, 1.39; 95% CI, 1.09–1.78). In patients with⩾2 prior exacerbations, LABA/LAMA/ICS versus LABA/LAMA was related to a 21% reduced rate of exacerbations but with a twofold increased pneumonia risk and a 49% elevated risk of all-cause mortality. Conclusion: Switching from LABA/ICS to triple therapy versus dual bronchodilators in COPD patients was associated with similar rates of annual exacerbations but was related to elevated risks of severe pneumonia and all-cause mortality. Among frequent exacerbators, triple therapy was associated with lower rates of exacerbation but was accompanied by increased risks of pneumonia and mortality compared to LABA/LAMA. Careful consideration of the examined safety events is necessary when switching from LABA/ICS to triple therapy in COPD management. [ABSTRACT FROM AUTHOR]

To assess the efficacy and safety of a two-drug regimen (2DR) with dolutegravir (DTG) and lamivudine (3TC) in maintaining viral suppression during pregnancy and breastfeeding, and to evaluate its potential as an alternative to the recommended three-drug regimen (3DR) in preventing mother-to-child transmission (MTCT) of HIV. We present a case of a 34-year-old pregnant woman who, after discontinuing 3DR due to side effects and poor adherence, was switched to DTG/3TC at gestational week 23. Maternal viral load (VL) and infant HIV status were monitored throughout pregnancy and a ten-month breastfeeding period. Data on pharmacokinetic changes in pregnancy and the risks associated with 2DR were reviewed. The patient's VL remained suppressed (<20 copies/mL) from gestational week 23 until the end of the breastfeeding period. A healthy HIV-negative baby was born at 39 weeks, and the child remained HIV-negative after ten months of breastfeeding. The 2DR was well-tolerated, improved adherence, and reduced fetal drug exposure. Despite limited experience with 2DR in pregnancy, no viral rebound occurred, and no adverse effects were observed. Although 3DR remains the preferred therapy during pregnancy and breastfeeding, this case indicates that DTG/3TC may be an effective alternative for patients experiencing intolerance or poor adherence to 3DR. Further studies are needed to explore the impact of pharmacokinetic changes in pregnancy on 2DR efficacy and to confirm its safety and role in preventing MTCT. [ABSTRACT FROM AUTHOR]

Background: Helicobacter pylori (H. pylori), prevalent in developing regions, is a key factor in gastrointestinal diseases. Despite the common use of bismuth-based quadruple therapy, its drawbacks have prompted the search for alternatives. Recently, vonoprazan, a novel acid suppressant, has shown promise in combination with antibiotics as a dual therapy for H. pylori eradication. This study aimed to assess the therapeutic outcomes and adverse events of vonoprazan-amoxicillin dual therapy compared to quadruple therapy. Methods: A randomized controlled trial (RCT) enrolled H. pylori-infected patients at Zhejiang Hospital. Participants were randomly assigned to dual and quadruple therapy groups. The primary endpoints were H. pylori eradication and adverse events. Results: Of the 400 patients studied from April 2022 to June 2023, In the intention-to-treat (ITT) analysis, the eradication rates of H. pylori in vonoprazan-amoxicillin dual therapy group and quadruple therapy group were 94.0% and 87.0%, respectively, p = 0.017. In the per-protocol (PP) analysis were 97.9% and 93.0%, p = 0.022. Additionally, the dual therapy group had a significantly lower incidence of adverse events (19%) compared to the quadruple therapy group (53%) (p < 0.001). Conclusion: Vonoprazan-amoxicillin dual therapy demonstrates superior eradication efficacy and reduced adverse events compared to quadruple therapy in H. pylori-infected patients, suggesting its potential for clinical application and promotion. [ABSTRACT FROM AUTHOR]

Helicobacter pylori infection is an important causative factor in a variety of gastrointestinal diseases, such as atrophic gastritis, peptic ulcer disease, and gastric cancer. Timely eradication treatment is conducive to maintaining the health of patients. With the increase of drug resistance in Helicobacter pylori, dual therapy with proton pump inhibitors combined with high-dose amoxicillin has gradually gained attention. Potassium- competitive acid blockers are new types of antacids that have a faster onset of action and a longer lasting acid suppression effect than traditional proton pump inhibitors, making it more suitable for dual therapy. In recent years, scholars have carried out a lot of exploration, improvement and verification of potassium-competitive acid blockers dual therapy, and this article reviews its research progress. [ABSTRACT FROM AUTHOR]

Abstract Background Antiretroviral therapy (ART) has transformed HIV management, with various regimens available. Dolutegravir (DTG) plus lamivudine (3TC) dual therapy is now the one of the first line regimens. Methods A retrospective, observational study included treatment naïve people living with HIV (PLWH) with baseline HIV RNA viral load (VL) greater than 500,000 copies/mL from March 2020 to June 2022. PLWH on DTG + 3TC were included in the 2DR group, while others on INSTI-based three-drug regimens were divided in the 3DR group. Viral suppression, immunological recovery, and safety were assessed. Results The study included 52 PLWH, with no significant baseline differences. Virologic suppression rates at weeks 24 and 48 were similar in both groups, even with baseline HIV RNA VL greater than 1,000,000 copies/mL. CD4 + T cell counts improved rapidly. No serious adverse effects were reported. Conclusions DTG + 3TC dual therapy demonstrates effectiveness in treatment naïve PLWH with high baseline HIV RNA VL, suggesting its potential as a first line regimen for all treatment naïve PLWH.

Fragile X syndrome (FXS) is the primary hereditary cause of intellectual disability and autism spectrum disorder. It is characterized by exacerbated neuronal excitability, and its correction is considered an objective measure of treatment response in animal models, a marker albeit rarely used in clinical trials. Here, we used an extensive transcranial magnetic stimulation (TMS) battery to assess the neurophysiological effects of a therapy combining two disease‐modifying drugs, lovastatin (40 mg) and minocycline (100 mg), administered alone for 8 weeks and in combination for 12 weeks, in 19 patients (mean age of 23.58 ± 1.51) with FXS taking part in the LOVAmix trial. The TMS battery, which included the resting motor threshold, short‐interval intracortical inhibition, long‐interval intracortical inhibition, corticospinal silent period, and intracortical facilitation, was completed at baseline after 8 weeks of monotherapy (visit 2 of the clinical trial) and after 12 weeks of dual therapy (visit 4 of the clinical trial). Repeated measure ANOVAs were performed between baseline and visit 2 (monotherapy) and visit 3 (dual therapy) with interactions for which monotherapy the participants received when they began the clinical trial. Results showed that dual therapy was associated with reduced cortical excitability after 20 weeks. This was reflected by a significant increase in the resting‐motor threshold after dual therapy compared to baseline. There was a tendency for enhanced short‐intracortical inhibition, a marker of GABAa‐mediated inhibition after 8 weeks of monotherapy compared to baseline. Together, these results suggest that a combined therapy of minocycline and lovastatin might act on the core neurophysiopathology of FXS. This trial was registered at clinicaltrials.gov (NCT02680379). Lay Summary: Individuals with fragile X syndrome (FXS), the primary hereditary cause of intellectual disability and autism spectrum disorder, often have overly excited brains, which is linked to their symptoms. In this study, we used noninvasive brain stimulation to understand how brain excitability changes with treatment in individuals with FXS while participating in the LOVAmix clinical trial (NCT02680379), which combined two disease‐modifying drugs. After 20 weeks of combined therapy, our participants showed signs of lower brain activity, suggesting that combining minocycline and lovastatin might act on the underlying biology that causes the symptoms experienced by individuals with FXS. [ABSTRACT FROM AUTHOR]

Objective: To compare the long-term effects on immune parameters, inflammation, and HIV-1 reservoir after switching to a two-drug (2DR) versus maintaining an integrase inhibitor (InSTI)-based three-drug regimen (3DR). Methods: Cross-sectional study in which HIV-1 treatment-naïve people started and maintained an InSTI-based 3DR or, at different times, switched to 2DR (dolutegravir or darunavir/cobicistat + lamivudine). CD4+ and CD8+ T-cell activation and exhaustion, plasma concentrations of hs-CRP, D-dimer, P-selectin, IL-1β, IL-6, TNF-α, IFN-γ, IP-10, sTNFR-I/II, MIP-1α/β, I-FABP, LBP, sCD14, sCD163, MCP-1, and cellular-associated HIV-1-DNA and -RNA were quantified by flow cytometry, different immunoassays, and droplet digital PCR, respectively. The U de Mann-Whitney test evaluated differences between 3DR and 2DR. Immune recovery was evaluated using a general linear model for repeated measures adjusted for different co-variables. Results: Fifty participants per group were included. The median time on 3DR was 82 months for the 3DR group and 30 months for the 2DR group, after which it switched to 2DR for a median of 57 months. We did not find differences between both groups in any of the parameters analyzed. Specifically, some values in 3DR and 2DR were hs-CRP, 0.92 mg/L (0.45–2.23) vs. 1.23 (0.61–2.38); D-dimer, 190.0 µg/L (150.0–370.0) vs. 190.0 (150.0–397.5); IL-6, 2.8 pg/mL (1.3–5.3) vs. 3.2 (2.1–4.7); sCD14, 4.5 ng/mL (3.3–6.2) vs. 5.0 (3.6–6.1), respectively, all p ≥ 0.399. Conclusion: In the long term, switching to 2DR does not negatively affect immunologic parameters, inflammatory markers, or HIV-1 reservoir. [ABSTRACT FROM AUTHOR]

Background: Antiretroviral therapy (ART) has transformed HIV management, with various regimens available. Dolutegravir (DTG) plus lamivudine (3TC) dual therapy is now the one of the first line regimens. Methods: A retrospective, observational study included treatment naïve people living with HIV (PLWH) with baseline HIV RNA viral load (VL) greater than 500,000 copies/mL from March 2020 to June 2022. PLWH on DTG + 3TC were included in the 2DR group, while others on INSTI-based three-drug regimens were divided in the 3DR group. Viral suppression, immunological recovery, and safety were assessed. Results: The study included 52 PLWH, with no significant baseline differences. Virologic suppression rates at weeks 24 and 48 were similar in both groups, even with baseline HIV RNA VL greater than 1,000,000 copies/mL. CD4 + T cell counts improved rapidly. No serious adverse effects were reported. Conclusions: DTG + 3TC dual therapy demonstrates effectiveness in treatment naïve PLWH with high baseline HIV RNA VL, suggesting its potential as a first line regimen for all treatment naïve PLWH. [ABSTRACT FROM AUTHOR]

Background: The effect of preprandial or postprandial administration of amoxicillin on the efficacy of vonoprazan–amoxicillin dual therapy (VA‐dual therapy) for Helicobacter pylori treatment has not been studied. It is also unclear whether amoxicillin dosing four times daily is more effective than three times daily. We aimed to investigate the effect of different amoxicillin administration regimens on the efficacy of VA‐dual therapy. Materials and Methods: H. pylori‐infected subjects were randomly assigned to three groups in a 1:1:1 ratio to receive a 14‐day dual therapy consisting of vonoprazan 20 mg twice daily + amoxicillin 1000 mg three times daily before meals (BM‐TID) or 1000 mg three times daily after meals (AM‐TID) or 750 mg four times daily after meals (AM‐QID). H. pylori eradication rates, adverse events rates, compliance, and antibiotic resistance were compared. Results: Between May 2021 to April 2023, 327 subjects were enrolled. The eradication rates of BM‐TID, AM‐TID, and AM‐QID dual therapy were 88.1%, 89.9%, and 93.6% in intention‐to‐treat (ITT) analysis, 90.6%, 94.2%, and 99.0% in modified ITT (MITT) analysis, and 90.4%, 94.1%, and 99.0% in per‐protocol (PP) analysis. Although there was non‐inferiority between BM‐TID and AM‐TID, as well as between AM‐TID and AM‐QID, AM‐QID was significantly more effective than BM‐TID. There were no significant differences in adverse event rates, compliance, and antibiotic resistance among the three groups. Conclusions: Postprandial administration and the increased frequency of administration of amoxicillin may contribute to a better efficacy of VA‐dual therapy, especially for rescue therapy. All VA‐dual therapy in our study could achieve good efficacy for first‐line treatment. Trial Registration:clinicaltrials.gov: NCT05901051. [ABSTRACT FROM AUTHOR]

Background: Antiretroviral drug simplification is a strategy to reduce drug exposure and improve treatment adherence. Nowadays, dolutegravir plus lamivudine is the most preferred regimen, which might lead in the future with problems related to drug resistance or drug intolerance. This meta-analysis aimed to assess the safety of HAART simplification without integrase inhibitors. Methods: We conducted a systematic review and meta-analysis using the Embase and Medline databases to include clinical trials and observational studies published between 2008 and March 2024. The studies focused on HIV-positive individuals with suppressed viral load who either simplified their treatment to dual therapy without integrase inhibitors or continued triple therapy. The primary outcome of interest was the likelihood of viral failure within 48 weeks. Results: Ten studies were included, with a total of 1,977 patients. Boosted Protease Inhibitors (PI) were the core of antiretroviral simplification therapy. The simplification group did not show an increased risk of virological failure, with a pooled RR in 48 weeks of 1.29 (0.61‒2.73, I² = 51 %) when compared to control group. Boosted protease inhibitors were preferred combined with lamivudine, nevirapine, efavirenz, and maraviroc). Only maraviroc plus boosted PI combination was associated with a higher risk of virological failure with an RR of 4.49 (1.99‒10.11). Conclusion: Simplification therapy with boosted PI plus lamivudine or non-nucleoside transcriptase reverse inhibitors was a safe strategy and not associated with a higher risk of virological failure. This approach might be an alternative to dolutegravir-based simplification regimens if needed.

Abstract Objective To compare the potential efficacy and safety of dual therapy and quadruple therapy with vonoprazan (VPZ) as well as the standard quadruple therapy of proton pump inhibitor (PPI) for the eradication of Helicobacter pylori (Hp) infection in Hainan province. Methods A single-centre, non-blinded, non-inferiority randomized controlled trial was conducted at the outpatient department of gastroenterology at the Second Affiliated Hospital of Hainan Medical University from June 2022 to February 2023. 135 patients aged 18–75 years with Hp infection were enrolled and randomized into three different groups (group V1: VPZ 20 mg twice a day and amoxicillin 1.0 g three times a day for 14 days V2: vonoprazan 20 mg, amoxicillin capsules 1.0 g, furazolidone 0.1 g and bismuth potassiulm citrate 240 mg, twice daily for 14 days;; group V3: ilaprazole 5 mg, Amoxicillin 1.0 g, Furazolidone 100 mg, bismuth potassiulm citrate 240 mg, twice a day for 14 days). Four weeks after the end of treatment, Hp eradication was confirmed by rechecking 13C-urea breath test (UBT). Results The eradication efficacy of V1 and V3 was non-inferior to that of V2, which is consistent with the results obtained from the Kruskal-Wallis H test. The eradication rate by intentional analysis was 84.4% (38/45, 95%CI 73.4%–95.5%, P>0.05) for all the three groups. If analyzed by per-protocol, the eradication rates were 88.4% (38/43, 95%CI 78.4%–98.4%), 92.7% (38/41, 95%CI 84.4%–101.0%),88.4% (38/43，95%CI 78.4%–98.4%) in groups V1, V2 and V3, respectively, which did not show a significant difference (P > 0.05). The incidence of adverse effects was significantly lower in VPZ dual therapy compared to the other two treatment regimens (P

Bacterial infections are a global health concern, particularly due to the increasing resistance of bacteria to antibiotics. Multi-drug resistance (MDR) is a considerable challenge, and novel approaches are needed to treat bacterial infections. Photodynamic inactivation (PDI) of microorganisms is increasingly recognized as an effective method to inactivate a broad spectrum of bacteria and overcome resistance mechanisms. This study presents the synthesis of a new cationic 5,15-di-imidazolyl porphyrin derivative and the impact of n-octanol/water partition coefficient (logP) values of this class of photosensitizers on PDI efficacy of Escherichia coli. The derivative with logP = –0.5, IP-H-OH2+, achieved a remarkable 3 log CFU reduction of E. coli at 100 nM with only 1.36 J/cm2 light dose at 415 nm, twice as effective as the second-best porphyrin IP-H-Me2+, of logP = –1.35. We relate the rapid uptake of IP-H-OH2+ by E. coli to improved PDI and the very low uptake of a fluorinated derivative, IP-H-CF32+, logP ≈ 1, to its poor performance. Combination of PDI with cinnamaldehyde, a major component of the cinnamon plant known to alter bacteria cell membranes, offered synergic inactivation of E. coli (7 log CFU reduction), using 50 nM of IP-H-OH2+ and just 1.36 J/cm2 light dose. The success of combining PDI with this natural compound broadens the scope of therapies for MDR infections that do not add drug resistance. In vivo studies on a mouse model of wound infection showed the potential of cationic 5,15-di-imidazolyl porphyrins to treat clinically relevant infected wounds. [ABSTRACT FROM AUTHOR]

Background: This study aims to evaluate the efficacy and safety of vonoprazan‐amoxicillin (VA), vonoprazan‐amoxicillin‐clarithromycin (VAC), vonoprazan‐based bismuth‐containing quadruple therapy (VBQT), and PPI‐based triple (PAC) or quadruple therapy (PBQT) for H. pylori infection with the consideration of duration of therapy and amoxicillin dose (H: high; L: low). Materials and Methods: PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched for eligible randomized controlled trials (RCTs) up to December 15, 2023. The efficacy outcome was eradication rate, and safety outcomes included the rates of adverse events and treatment discontinuation. Results: Twenty‐seven RCTs were included. The pooled eradication rates were 82.8% for VA, 89.1% for VAC, and 91.8% for VBQT, which increased with the higher amoxicillin frequency of administration and extended duration of therapy within each regimen. There were no significant differences in eradication rate when comparing 7‐VA versus 7‐VAC and 14‐VA versus 14‐VAC. VA was at least comparable to PAC. The eradication rate did not differ significantly between 10‐H‐VA or 14‐H‐VA versus 14‐PBQT. 7‐L‐VAC demonstrated higher eradication rate versus 7‐PAC and comparable rate to 14‐PAC. 14‐VBQT showed higher eradication rates versus 14‐PBQT. The adverse events rate was 19.3% for VA, 30.6% for VAC, and 38.4% for VBQT. VA had similar risk of adverse events versus VAC and significantly fewer adverse events compared to PBQT. The treatment discontinuation rate did not differ significantly between treatments. Conclusions: The eradication rate of VBQT was the highest at above 90% followed by VAC and VA. VA was as effective as VAC and superior to PPI‐based therapies with favorable safety, highlighting the potential of VA therapy as a promising alternative to traditional PPI‐based therapies. VPZ‐based triple or quadruple therapies was more effective than PPI‐based therapies. Further studies are needed to establish the optimal treatment regimen especially in the western countries. [ABSTRACT FROM AUTHOR]

The beneficial role of dual anti-platelet therapy (DAPT) in coronary artery disease is well established. However, there is limited data describing the effects of DAPT in patients with atherosclerotic peripheral artery disease (PAD). The aim of this meta-analysis is to compare clinical outcomes associated with DAPT versus single anti-platelet therapy (SAPT) in patients with symptomatic PAD. We performed a literature search for studies assessing the risk of adverse cardiovascular and limb events in cohorts receiving either DAPT or SAPT. The primary endpoint was all cause mortality. The secondary endpoints included graft failure, amputation, total bleeding, severe bleeding and fatal bleeding. The search included the following databases: Ovid MEDLINE, EMBASE, Web of Science, and Google Scholar. The search was not restricted to time or publication status. A total of 11 studies with 54,331 participants (24,449 on SAPT and 29,882 on DAPT) were included. Patients with PAD treated with SAPT had higher all-cause mortality compared to patients treated with DAPT (OR 1.37, 95 % CI 1.09–1.74; p < 0.01). There was no difference in risk of graft failure or amputation between patients treated with SAPT or DAPT (OR 0.9, 95 % CI 0.77–1.06; p = 0.19; OR 1.11, 95 % CI 0.88–1.41; p = 0.37). Patients treated with SAPT had lower total bleeds compared to patients treated with DAPT (OR 0.53, 95 % CI 0.36–0.77; p < 0.01). However, For SAPT plus AC vs SAPT, a total of 8 studies with 17,100 participants (3447 with SAPT plus AC and 8619 with only SAPT) were included. Patients on SAPT plus AC did not have a statistically significant difference in risk for all-cause mortality, (OR 0.91, 95 % CI 0.67–1.24; p = 0.56). SAPT plus AC had significantly lower risk of MI (OR 0.82, 95 % CI 0.69–0.97; p = 0.02), amputation (OR 0.72, 95 % CI 0.53–0.97; p = 0.03), and graft failure (OR 0.66, 95 % CI 0.48–0.93; p = 0.02). There was no significant different in risk of fatal bleeding be-tween the two groups (OR 1.60, 95 % CI 0.76–3.35; p = 0.22). In patients with symptomatic PAD, a strategy of DAPT may confer a mortality benefit when compared to SAPT without significantly increasing the risk of serious bleeding events. • In patients with symptomatic PAD, a strategy of DAPT may confer a mortality benefit when compared to SAPT without significantly increasing the risk of serious bleeding events. • SAPT with AC maybe associated with lower risk of MI, amputation and graft failure without incraese risk of fatal bleeds. • Further randomised trials are needed to confirm such findings. [ABSTRACT FROM AUTHOR]

In recent decades, peptide amphiphiles (PAs) have established themselves as promising self-assembling bioinspired materials in a wide range of medical fields. Herein, we report a dual-therapeutic system constituted by an antimicrobial PA and a cylindrical protease inhibitor (LJC) to achieve broad antimicrobial spectrum and to enhance therapeutic efficacy. We studied two strategies: PA-LJC nanostructures (Encapsulation) and PA nanostructures + free LJC (Combination). Computational modeling using a molecular theory for amphiphile self-assembly captures and explains the morphology of PA-LJC nanostructures and the location of encapsulated LJC in agreement with transmission electron microscopy and two-dimensional (2D) NMR observations. The morphology and release profile of PA-LJC assemblies are strongly correlated to the PA:LJC ratio: high LJC loading induces an initial burst release. We then evaluated the antimicrobial activity of our nanosystems toward gram-positive and gram-negative bacteria. We found that the Combination broadens the spectrum of LJC, reduces the therapeutic concentrations of both agents, and is not impacted by the inoculum effect. Further, the Encapsulation provides additional benefits including bypassing water solubility limitations of LJC and modulating the release of this molecule. The different properties of PA-LJC nanostructures results in different killing profiles, and reduced cytotoxicity and hemolytic activity. Meanwhile, details in membrane alterations caused by each strategy were revealed by various microscopy and fluorescent techniques. Last, in vivo studies in larvae treated by the Encapsulation strategy showed better antimicrobial efficacy than polymyxin B. Collectively, this study established a multifunctional platform using a versatile PA to act as an antibiotic, membrane-penetrating assistant, and slow-release delivery vehicle. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Whether 10-day short-course vonoprazan-amoxicillin dual therapy (VA-dual) is noninferior to the standard 14-day bismuth-based quadruple therapy (B-quadruple) against Helicobacter pylori eradication has not been determined. This trial aimed to compare the eradication rate, adverse events, and compliance of 10-day VA-dual regimen with standard 14-day B-quadruple regimen as first-line H. pylori treatment. METHODS: This prospective randomized clinical trial was performed at 3 institutions in eastern China. A total of 314 treatment-naive, H. pylori-infected patients were randomly assigned in a 1:1 ratio to either 10-day VA-dual group or 14-day B-quadruple group. Eradication success was determined by 13C-urea breath test at least 4 weeks after treatment. Eradication rates, adverse events, and compliance were compared between groups. RESULTS: Eradication rates of VA-dual and B-quadruple groups were 86.0% and 89.2% (P 5 0.389), respectively, by intention-to-treat (ITT) analysis; 88.2% and 91.5% (P 5 0.338), respectively, by modified ITT analysis; and 90.8% and 91.3%(P50.884), respectively, by per-protocol (PP) analysis. The efficacy of the VA-dual remained noninferior to B-quadruple therapy in all ITT, modified ITT, and PP analyses. The incidence of adverse events in the VA-dual group was significantly lower compared with that in the B-quadruple group (P < 0.001). Poor compliance contributed to eradication failure in the VAdual group (P < 0.001), while not in the B-quadruple group (P 5 0.110). DISCUSSION: The 10-day VA-dual therapy provided satisfactory eradication rates of >90% (PP analysis) and lower rates of adverse events compared with standard 14-day B-quadruple therapy as first-line H. pylori therapy. [ABSTRACT FROM AUTHOR]

ObjectiveTo compare the long-term effects on immune parameters, inflammation, and HIV-1 reservoir after switching to a two-drug (2DR) versus maintaining an integrase inhibitor (InSTI)-based three-drug regimen (3DR).MethodsCross-sectional study in which HIV-1 treatment-naïve people started and maintained an InSTI-based 3DR or, at different times, switched to 2DR (dolutegravir or darunavir/cobicistat + lamivudine). CD4+ and CD8+ T-cell activation and exhaustion, plasma concentrations of hs-CRP, D-dimer, P-selectin, IL-1β, IL-6, TNF-α, IFN-γ, IP-10, sTNFR-I/II, MIP-1α/β, I-FABP, LBP, sCD14, sCD163, MCP-1, and cellular-associated HIV-1-DNA and -RNA were quantified by flow cytometry, different immunoassays, and droplet digital PCR, respectively. The U de Mann-Whitney test evaluated differences between 3DR and 2DR. Immune recovery was evaluated using a general linear model for repeated measures adjusted for different co-variables.ResultsFifty participants per group were included. The median time on 3DR was 82 months for the 3DR group and 30 months for the 2DR group, after which it switched to 2DR for a median of 57 months. We did not find differences between both groups in any of the parameters analyzed. Specifically, some values in 3DR and 2DR were hs-CRP, 0.92 mg/L (0.45–2.23) vs. 1.23 (0.61–2.38); D-dimer, 190.0 µg/L (150.0–370.0) vs. 190.0 (150.0–397.5); IL-6, 2.8 pg/mL (1.3–5.3) vs. 3.2 (2.1–4.7); sCD14, 4.5 ng/mL (3.3–6.2) vs. 5.0 (3.6–6.1), respectively, all p ≥ 0.399.ConclusionIn the long term, switching to 2DR does not negatively affect immunologic parameters, inflammatory markers, or HIV-1 reservoir.Clinical trial registrationidentifier NCT04076423.

Objective To evaluate clinical efficacy of the combination of Vonoprazan and high-dose Amoxicillin in the initial eradication treatment of Helicobacter pylori （Hp）. Methods Select 200 patients with Hp infection who have not undergone Hp eradication treatment in the past as the research subjects. All patients were randomly divided into the observation group （n = 100） and control group （n = 100） using random number table method. In the observation group， a combination regimen of Vonoprazan （20 mg twice a day） and Amoxicillin （1 g three times a day） was given for 14 days. In the control group， a bismuth quadruple therapy was delivered for 14 days， which included Esomeprazole （20 mg twice a day）， Bismuth Potassium Citrate （220 mg twice a day）， Amoxicillin （1 g twice a day） and Clarithromycin （0.5 g twice a day）. The Hp eradication rate and incidence of adverse reactions after medication were compared between two groups. Results Of 200 patients， 11 patients were excluded from subsequent analysis， including 8 cases lost to follow-up and 3 cases with poor compliance of medication. The remaining 189 patients （96 in the observation group and 93 in the control group） completed the entire procedure. According to intention-to-treat （ITT） and per-protocol （PP） set analyses， the Hp eradication rate in the observation group was significantly higher than that in the control group （91.0% vs. 79.0%， PITT =0.017； 94.8% vs. 84.9%， PPP= 0.024）. The incidence of adverse reactions did not significantly differ between two groups （4% vs. 5%，χ 2 < 0.001，P > 0.999）. Conclusion The combination therapy of Vonoprazan and high-dose Amoxicillin is an efficacious and safe therapeutic option for patients with initial Hp infection， which is worthy of promotion in grassroot-level hospitals.

Introduction: The preference for using transradial access (TRA) over transfemoral access (TFA) in patients requiring percutaneous coronary intervention (PCI) is based on evidence suggesting that TRA is associated with less bleeding and fewer vascular complications, shorter hospital stays, improved quality of life, and a potential beneficial effect on mortality. We have limited study data comparing the two access routes in a patient population with atrial fibrillation (AF) undergoing PCI, who have a particular increased risk of bleeding, while AF itself is associated with an increased risk of thromboembolism. Methods: Using data from the RIVA-PCI registry, which includes patients with AF undergoing PCI, we analyzed a high-bleeding-risk (HBR) cohort. These patients were predominantly on oral anticoagulants (OAC) for AF, and the PCI was performed via radial or femoral access. Endpoints examined were in-hospital bleeding (BARC 2–5), cerebral events (TIA, hemorrhagic or ischemic stroke) and coronary events (stent thrombosis and myocardial infarction). Results: Out of 1636 patients, 854 (52.2%) underwent TFA, while 782 (47.8%) underwent the procedure via TRA, including nine patients with brachial artery puncture. The mean age was 75.5 years. Groups were similar in terms of age, sex distribution, AF type, cardiovascular history, risk factors, and comorbidities, except for a higher incidence of previous bypass surgeries, heart failure, hyperlipidemia, and chronic kidney disease (CKD) with a glomerular filtration rate (GFR) < 60 ml/min in the TFA group. No clinically relevant differences in antithrombotic therapy and combinations were present at the time of PCI. However, upon discharge, transradial PCI patients had a higher rate of triple therapy, while dual therapy was preferred after transfemoral procedures. Radial access was more frequently chosen for non-ST-segment elevation myocardial infarction (NSTEMI) and unstable angina pectoris (UAP) cases (NSTEMI 26.6% vs. 17.0%, p < 0.0001; UAP 21.5% vs. 14.5%, p < 0.001), while femoral access was more common for elective PCI (60.3% vs. 44.1%, p < 0.0001). No differences were observed for ST-segment elevation myocardial infarction (STEMI). Both groups had similar rates of cerebral events (TFA 0.2% vs. TRA 0.3%, p = 0.93), but the TFA group had a higher incidence of bleeding (BARC 2–5) (4.2% vs. 1.5%, p < 0.01), mainly driven by BARC 3 bleeding (1.5% vs. 0.4%, p < 0.05). No significant differences were found for stent thrombosis and myocardial infarction (TFA 0.2% vs. TRA 0.3%, p = 0.93; TFA 0.4% vs. TRA 0.1%, p = 0.36). Conclusions: In HBR patients with AF undergoing PCI for acute or chronic coronary syndrome, the use of TRA might be associated with a decrease in in-hospital bleeding, while not increasing the risk of embolic or ischemic events compared to femoral access. Further studies are required to confirm these preliminary findings. [ABSTRACT FROM AUTHOR]

Vonoprazan holds significant research promise for Helicobacter pylori eradication, with the goal of determining the most effective drug regimen. In this study, H. pylori patients (426) were enrolled and randomized into 3 groups: an EA14 group (20 mg of esomeprazole qid and 1000 mg of amoxicillin tid for 14 days), a VA14 group (20 mg of vonoprazan bid and 750 mg of amoxicillin qid for 14 days), and a VA10 group (20 mg of vonoprazan bid and 1000 mg of amoxicillin tid for 10 days). Key outcomes encompassed the H. pylori eradication rate, patient adverse effects, and compliance. In the EA14, VA14, and VA10 groups, H. pylori eradication rates were 89.4%, 90.1%, and 88.7% in intention‐to‐treat analysis, and 94.2%, 94.4%, and 94.6% in per‐protocol analysis, respectively. Adverse events incidences were 14.8%, 12.7%, and 5.6%, while compliance rates were 88.7%, 90.9%, and 95.8%, respectively. Notably, the VA10 regimen demonstrated comparable H. pylori eradication rates, adverse effect incidences, and compliance levels to the EA14 and VA14 regimens. [ABSTRACT FROM AUTHOR]

Objective To evaluate clinical efficacy of the combination of Vonoprazan and high-dose Amoxicillin in the initial eradication treatment of Helicobacter pylori(Hp). Methods Select 200 patients with Hp infection who have not undergone Hp eradication treatment in the past as the research subjects. All patients were randomly divided into the observation group (n = 100) and control group (n = 100) using random number table method. In the observation group, a combination regimen of Vonoprazan (20 mg twice a day) and Amoxicillin (1 g three times a day) was given for 14 days. In the control group, a bismuth quadruple therapy was delivered for 14 days, which included Esomeprazole (20 mg twice a day), Bismuth Potassium Citrate (220 mg twice a day), Amoxicillin (1 g twice a day) and Clarithromycin (0.5 g twice a day). The Hp eradication rate and incidence of adverse reactions after medication were compared between two groups. Results Of 200 patients, 11 patients were excluded from subsequent analysis, including 8 cases lost to follow-up and 3 cases with poor compliance of medication. The remaining 189 patients (96 in the observation group and 93 in the control group) completed the entire procedure. According to intention-to-treat (ITT) and per-protocol (PP) set analyses, the Hp eradication rate in the observation group was significantly higher than that in the control group (91.0% vs. 79.0%,PITT = 0.017; 94.8% vs. 84.9%,PPP = 0.024). The incidence of adverse reactions did not significantly differ between two groups (4% vs. 5%, χ2 < 0.001,P > 0.999). Conclusion The combination therapy of Vonoprazan and high-dose Amoxicillin is an efficacious and safe therapeutic option for patients with initial Hp infection, which is worthy of promotion in grassroot-level hospitals. [ABSTRACT FROM AUTHOR]

Introduction: Triple therapy (fluticasone furoate/umeclidinium/vilanterol; FF/UMEC/VI) has been shown to improve symptoms and reduce exacerbations in patients with chronic obstructive pulmonary disease (COPD) and a history of exacerbations. This real-world study compared exacerbation rates and healthcare resource utilization (HCRU) before and after initiation of FF/UMEC/VI in patients with COPD previously treated with inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA). Methods: This retrospective cohort study included commercial and Medicare Advantage with Part D administrative claims data from September 01, 2016, to March 31, 2020, of patients diagnosed with COPD. The index date was the date of the first FF/UMEC/VI claim (September 2017–March 2019). The 12 months prior to index (baseline) were used to assess patient characteristics and outcomes; the 12 months following index (follow-up) were used to assess study outcomes. All patients had ≥ 30 consecutive days' supply of any ICS/LABA dual therapy during the 12 months prior to FF/UMEC/VI initiation. Subgroup analyses included patients with ≥ 30 consecutive days' supply of budesonide/formoterol (BUD/FORM) during baseline. Analyses of patients with ≥ 1 COPD exacerbation during baseline were reported as well. Results: The overall population included 1449 patients (mean age 70.75 years; 54.18% female), of whom 540 were patients in the BUD/FORM subgroup. Significantly fewer patients experienced any exacerbation during follow-up versus baseline (overall population 53.49% vs 62.59%; p < 0.001; BUD/FORM subgroup 55.00% vs 62.41%; p = 0.004). Effects on exacerbation reduction were more pronounced among patients with ≥ 1 exacerbation during baseline. Lower COPD-related HCRU was observed during the follow-up compared with baseline for both the overall population and the BUD/FORM subgroup. Conclusion: Patients with COPD treated with ICS/LABA during baseline, including patients specifically treated with BUD/FORM and those with a history of ≥ 1 exacerbation, had fewer COPD exacerbations and lower COPD-related HCRU after initiating FF/UMEC/VI. [ABSTRACT FROM AUTHOR]

Clinical trials of dual regimen dolutegravir/lamivudine (DOL/3TC) demonstrated potent efficacy and favorable safety in both antiretroviral therapy-naïve and -experienced patients, but data on older people are lacking. We aimed to evaluate virological efficacy and safety of DOL/3TC in suppressed older patients over a 12-month period. We performed a retrospective cohort study evaluating people living with HIV (PLWHIV) aged ≥65 years at our HIV Clinic who were switched to DOL/3TC. Eligible patients had baseline HIV-1 RNA <20 copies/mL, and no previous virological failures or known resistance mutations for lamivudine or dolutegravir. Inclusion criteria were met by 72 patients: 59 were men, median age was 69.2 years, and one or more comorbidities were present in 89% of patients. The most common reason for switch was simplification, followed by drug–drug interactions (DDIs) and toxicities. After 12 months, 64 (88.9%, by the intention-to-treat analysis) patients maintained HIV-1 RNA <20 copies/mL, and reasons for treatment failure were virological failure in three cases, adverse events in three, and missing data in two. Genotype resistance testing showed no resistance mutations for lamivudine or dolutegravir in subjects with virological failure. The number of potential DDIs decreased from 92 to 12 after switching to DOL/3TC, and a significant reduction in median total and low-density lipoprotein cholesterol was reported, while median change in body weight was not significant. In this real-life cohort, switching to DOL/3TC was associated with maintenance of virological control and good tolerability among persons aged >65 years, supporting use of this dual regimen in older PLWHIV. [ABSTRACT FROM AUTHOR]

Background: The amoxicillin dose used in dual therapy to eradicate Helicobacter pylori varies across studies and the optimal amoxicillin dose for vonoprazan‐based dual therapies remains unclear. We aimed to investigate the efficacy and safety of low‐ and high‐dose amoxicillin in vonoprazan–amoxicillin dual therapy. Materials and Methods: A comprehensive systematic review was conducted by searching databases from inception to October 2023. All trials that evaluated the effectiveness and safety of vonoprazan–amoxicillin dual therapy for eradicating H. pylori were included. Pooled eradication rate, incidence of adverse events, relative risks, and 95% confidence intervals are presented. Results: Eighteen studies with 12 low‐dose amoxicillin (VLA) and 13 high‐dose amoxicillin (VHA) arms were included. The pooled eradication rates were 82.4% and 86.8% for VLA therapy, and 86.0% and 90.9% for VHA therapy by the intention‐to‐treat and per‐protocol analyses, respectively. In the subgroup analysis stratified by duration, the eradication rates achieved in 7 days, 10 days, and 14 days treatments with VLA and VHA dual therapies were 80.8%, 84.2%, 83.1%, and 67.3%, 88.8%, 87.5%, respectively. In the four randomized controlled trials that directly compared VLA and VHA dual therapies, the efficacy was not statistically different in the intention‐to‐treat (76.9% vs 81.4%, p = 0.337) and per‐protocol (81.6% vs 84.0%, p = 0.166) analyses. Additionally, the incidence of adverse events (p = 0.965) and compliance (p = 0.994) were similar in both groups. Conclusion: VLA therapy demonstrated comparable efficacy and safety to VHA therapy, along with regional differences. An appropriately extended treatment duration may be critical for therapeutic optimization of vonoprazan–amoxicillin treatment. [ABSTRACT FROM AUTHOR]

Background: We previously optimized the duration and dose of vonoprazan and amoxicillin dual therapy in China. The efficacy of vonoprazan with b.i.d. amoxicillin in comparison with vonoprazan‐containing quadruple therapy as the first‐line treatment of Helicobacter pylori infection has not been adequately evaluated. Methods: In a non‐inferiority, randomized clinical trial, H. pylori infected and treatment‐naïve patients were randomly assigned to receive 14 days of either vonoprazan dual (vonoprazan 20 mg and amoxicillin 1 g twice daily) or quadruple therapy (vonoprazan 20 mg + amoxicillin 1 g + furazolidone 100 mg + bismuth potassium citrate 600 mg twice daily). H. pylori status was confirmed using 13C‐urea breath tests or fecal antigen test. The primary outcome was the H. pylori eradication rate following vonoprazan dual and quadruple therapy at 4–12 weeks. We also compared drug compliance to either regimen and documented their side effect. Results: A total of 190 subjects were randomized. The eradication rate of vonoprazan dual and quadruple therapy were 87.4% and 92.6% (p = 0.23) by intention‐to‐treat analysis, respectively, and 96.5% and 97.7% (p = 0.63) by per‐protocol analysis, respectively. The efficacy of vonoprazan dual therapy was non‐inferior to vonoprazan‐containing quadruple therapy in per‐protocol analysis (p < 0.001; difference: −1.2%; 90% confidence interval: −5.4% to 3.0%). Conclusion: Vonoprazan with b.i.d. amoxicillin for 14 days provided similar satisfactory efficacy with vonoprazan‐containing quadruple therapy as a first‐line H. pylori treatment in China. [ABSTRACT FROM AUTHOR]

Background and Objective: Recently, vonoprazan‐amoxicillin (VA) dual therapy has been reported as a promising approach for Helicobacter pylori (H. pylori) eradication. However, the effects of VA therapy versus bismuth‐containing quadruple therapy (BQT) on H. pylori eradication remains unclear. The objective of this meta‐analysis was to compare the effects of VA dual therapy with BQT for H. pylori eradication. Methods: A comprehensive search of the literature was conducted from the beginning to September 2023, utilizing PubMed, Embase, the Cochrane Library and Web of Science database. A random‐effects model was used to perform a meta‐analysis to determine the pooled relative risk (RR) with 95% confidence intervals (CIs). Moreover, trial sequential analysis (TSA) was conducted to evaluate the conclusiveness of the H. pylori eradication rate. Results: Six randomized controlled trials (RCTs) with 1233 patients were included. The VA therapy has similar eradication rate (ITT analysis: 87% vs. 85.7%, RR = 1.01, 95% CI: 0.93–1.09, p = 0.84; PP analysis: 92.5% vs. 93.2%, RR = 1.00, 95% CI: 0.94–1.06, p = 0.97) and compliance (RR = 1.01, 95% CI: 0.99–1.03, p = 0.32) compared to BQT. The VA therapy group had a significantly lower incidence of total adverse events than the BQT group (16.3% vs. 40.0%, RR = 0.45, 95% CI: 0.37–0.55, p < 0.00001). The TSA result showed that the effect was conclusive. Conclusions: Current evidence indicated that VA therapy is just as successful as BQT in eliminating H. pylori, yet it has fewer adverse events and similar compliance. [ABSTRACT FROM AUTHOR]

Background: Recent clinical trials have evaluated the efficacy of vonoprazan‐amoxicillin (VA) dual therapy as the first‐line treatment for Helicobacter pylori infection in different regions with inconsistent results reported. In this systematic review and meta‐analysis, we aimed to evaluate the efficacy of VA dual therapy compared to the currently recommended therapy for eradicating H. pylori. Materials and Methods: A comprehensive search of the PubMed, Cochrane, and Embase databases was performed using the following search terms: ("Helicobacter" OR "H. pylori" OR "Hp") AND ("vonoprazan" OR "potassium‐competitive acid blocker" OR "P‐CAB") AND ("amoxicillin" OR "penicillin") AND ("dual"). The primary outcome was to evaluate the eradication rate according to intention‐to‐treat and per‐protocol analysis. The secondary outcomes were adverse events and compliance. Results: A total of 15 studies involving 4, 568 patients were included. The pooled eradication rate of VA dual therapy was 85.0% and 90.0% by intention‐to‐treat and per‐protocol analysis, respectively. The adverse events rate and compliance of VA dual therapy were 17.5% and 96%, respectively. The efficacy of VA dual therapy was superior to proton pump inhibitors‐based triple therapy (82.0% vs. 71.4%, p < 0.01) but lower than vonoprazan‐containing quadruple therapy (83.1% vs. 93.3%, p = 0.02). 7‐day VA dual therapy showed lower eradication rates than 10‐day (χ2 = 24.09, p < 0.01) and 14‐day VA dual therapy (χ2 = 11.87, p < 0.01). The adverse events rate of VA dual therapy was lower than vonoprazan triple therapy (24.6% vs. 30.9%, p = 0.01) and bismuth‐containing quadruple therapy (20.5% vs. 47.9%, p < 0.01). No significant difference of compliance was observed between VA dual therapy and each subgroup. Conclusion: VA dual therapy, a novel regimen, showed high efficacy as the first‐line treatment for H. pylori eradication, which should be optimized before application in different regions. [ABSTRACT FROM AUTHOR]

Abstract Introduction The preference for using transradial access (TRA) over transfemoral access (TFA) in patients requiring percutaneous coronary intervention (PCI) is based on evidence suggesting that TRA is associated with less bleeding and fewer vascular complications, shorter hospital stays, improved quality of life, and a potential beneficial effect on mortality. We have limited study data comparing the two access routes in a patient population with atrial fibrillation (AF) undergoing PCI, who have a particular increased risk of bleeding, while AF itself is associated with an increased risk of thromboembolism. Methods Using data from the RIVA-PCI registry, which includes patients with AF undergoing PCI, we analyzed a high-bleeding-risk (HBR) cohort. These patients were predominantly on oral anticoagulants (OAC) for AF, and the PCI was performed via radial or femoral access. Endpoints examined were in-hospital bleeding (BARC 2–5), cerebral events (TIA, hemorrhagic or ischemic stroke) and coronary events (stent thrombosis and myocardial infarction). Results Out of 1636 patients, 854 (52.2%) underwent TFA, while 782 (47.8%) underwent the procedure via TRA, including nine patients with brachial artery puncture. The mean age was 75.5 years. Groups were similar in terms of age, sex distribution, AF type, cardiovascular history, risk factors, and comorbidities, except for a higher incidence of previous bypass surgeries, heart failure, hyperlipidemia, and chronic kidney disease (CKD) with a glomerular filtration rate (GFR)

Abstract Background Diabetes is one of the world’s most widespread conditions, and diabetic patients are among the most likely to engage in fierce battles with this chronic disease. Which group should be added-on as a dual therapy for Egyptian patients with type 2 diabetes and inadequate glycemic management, HbA1c ≥ 7.0% and ≤ 10% (≥ 53 and ≤ 86 mmol/mol), following not less than 3 months of metformin and diet therapy, is still up for debate. Based on this ambiguity, we designed our study to compare the safety and efficacy of sitagliptin 50 mg (n = 85) with empagliflozin 12.5 mg (n = 85) twice daily as an adjunctive therapy to metformin and diet for a further 12 weeks. HbA1c after 12 weeks of open-label therapy was the major outcome measure. Results After 12 weeks of treatment, empagliflozin drastically lowered HbA1c, FPG, PP, body weight, and triglycerides from baseline while significantly increasing LDL, total cholesterol, and HDL. On the other hand, sitagliptin significantly reduced FPG, PP (with a no discernable alteration in HbA1c), body weight, and triglycerides while significantly increasing HDL (P ≤ 0.001 for all comparisons). Comparing the two groups, empagliflozin significantly reduced HbA1c, FPG, and PP while significantly increasing LDL and triglycerides than sitagliptin (P

Background. Initial dual antihypertensive therapy is currently considered as the first management step for the majority of patients with arterial hypertension. However, it often fails to achieve the target blood pressure levels. An approved algorithm for predicting the failure of dual antihypertensive therapy is still to be developed. Objectives. To establish predictors of dual antihypertensive therapy failure in patients with high and very high cardiovascular risk and to create a model for predicting negative outcome of dual antihypertensive therapy. Methods. The paper presents a prospective comparative non-randomized clinical trial. The recruiting of participants and recording of results were carried out in March–December 2019 with 3 months of the follow-up period. The trial involved examination of 88 patients with poor blood pressure control, stage II and III arterial hypertension, high and very high cardiovascular risk of stages 1–3. Clinical and laboratory examination was carried out in compliance with the current regulatory documents. Additional examination included tests for uric acid, high-sensitivity C-reactive protein, as well as respiratory polygraphy and computerized capillaroscopy. All patients were prescribed dual antihypertensive therapy. The primary search for predictors was performed using the binary logistic regression. The predictive model was developed by stepwise variable selection. The diagnostic significance of the binary classifier was assessed by means of ROC-curve analysis; the calculation was performed using MedCalc 20.218 software (MedCalc Software Ltd., Belgium). Results. Administration of two hypotensive drugs appears to be effective in 33% of patients. The final model for predicting negative outcomes of dual antihypertensive therapy included such independent predictors as interventricular septal thickness, daily mean systolic blood pressure, and area density of the capillary network. The odds ratio accounted for 9.1 (95% confidence interval 3.12; 26.82). The area under the ROC curve based on the multiple binary logistic regression model comprised 0.805±0.05 with 95% confidence interval: 0.707-0.882 (p

Abstract Aim To evaluate the efficacy and safety of vonoprazan–amoxicillin (VA) dual therapy for radically eradicating Helicobacter pylori (H. pylori). Methods The PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI) and Wanfang databases were searched up to July 7, 2022, to identify clinical trials comparing the efficacy of VA dual therapy and triple therapy for H. pylori eradication. After evaluating the quality of the included studies, random effects models were conducted, and risk ratios (RRs) with 95% confidence intervals (CIs) were calculated to estimate the efficacy and safety of each approach. Results Six publications (including four randomized controlled trials) involving 2019 patients were included in this meta-analysis. Overall, the eradication rate for VA dual therapy was 89.9%, while it was 85.2% for triple therapy based on other acid inhibitors. The eradication rate of H. pylori in the VA dual regimen group was higher than that in the PPI-based (omeprazole or lansoprazole) triple therapy group (RR = 1.15, 95% CI 1.07–1.23, p

Abstract Objectives This study aimed to evaluate the efficacy, adverse events, patient compliance, and cost of dual therapy with Ilaprazole-amoxicillin (IA) at high dose versus Ilaprazole-amoxicillin-furazolidone-bismuth (IAFB) quadruple therapy for the Helicobacter pylori (H.pylori) infection among Chinese patients. Methods 200 patients who had tested positive for H. pylori and undergoing upper gastrointestinal endoscopy after being diagnosed with chronic gastritis participated in this open-label randomized controlled clinical trial. Patients were randomized to Group A and Group B: the 14-day IA dual treatment group (101) and IAFB quadruple treatment group (99). The 13 C urea breath test was conducted to determine whether H. pylori had been eliminated 4–6 weeks after the treatment. Eradication rates, drug-related adverse events, patient compliance, and drug costs were compared between the two treatment groups. Results Eradication rates in group A were 92.1% and 94.9%, depending on the intention-to-treat (ITT), per-protocol (PP), respectively, which was similar to group B (91.9% and 93.6%). There was no significant difference observed in adverse events between the two groups (P = 0.518). Interestingly, compliance was significantly higher in group A compared to the group B (P = 0.031). In addition, drug costs were significantly lower for group A in comparison to the group B. Conclusions IA dual therapy was found to be equally effective, safer and less costly than IAFB quadruple therapy. Therefore, these therapies can be potentially considered as first-line regimens for empirical treatment.

Background: The application of vonoprazan significantly improved the eradication rate of Helicobacter pylori (H. pylori). This study aimed to compare efficacy and safety of the 10-day vonoprazan–amoxicillin (VA) and 14-day rabeprazole–amoxicillin (RA) dual therapy, and to provide a more efficient, safer, and convenient dual regimen for H. pylori infection. Methods: This was a prospective, open-label, multi-center, randomized controlled study of treatment-naive patients with H. pylori infection. The participants were randomly assigned to the 10-day VA group with vonoprazan 20 mg Bid plus amoxicillin 1 g Tid or the 14-day RA group with rabeprazole 10 mg Tid plus amoxicillin 1 g Tid. The effectiveness, the adverse events, and the patient compliance of the two groups were compared. Results: A total of 690 patients were enrolled. The eradication rates of 10-day VA and 14-day RA dual therapy were 89.3% and 84.9% in intention-to-treat (ITT) analysis (P = 0.088); 90.6% and 85.9% by modified intention-to-treat (mITT) analysis (P = 0.059); 91.4% and 86.6% by per-protocol (PP) analysis (P = 0.047). Non-inferiority was confirmed between the two groups (all P < 0.001). No discernible differences were observed in adverse effects and compliance between groups. Poor compliance reduced the eradication efficacy (P < 0.05). Conclusions: The 10-day VA dual therapy was non-inferior to the 14-day RA dual therapy for H. pylori treatment-naive patients, which should be given priority in the first-line treatment. The application of vonoprazan reduced treatment course and antibiotic use. Patients' adherence was crucial for the success of eradication. [ABSTRACT FROM AUTHOR]

Background Currently, two-drug antiretroviral regimens are emerging fields in life-long treatment in people living with HIV. Objectives This randomized non-inferiority open-label controlled trial was designed to compare the 48-week efficacy and safety of tenofovir alafenamide plus dolutegravir versus the standard triple therapy in virologically suppressed people living with HIV. To the best of our knowledge this combination has not been studied before. Methods This open-label randomized controlled trial was conducted in treatment-experienced people with HIV who had HIV-RNA < 47 copies/mL for at least two years. Patients received either tenofovir alafenamide plus dolutegravir combination (26 patients) or a standard three-drug regimen (29 patients). The primary outcome was the proportion of patients maintaining HIV-RNA < 47 copies/mL during 48 weeks, and the secondary outcomes were CD4 cell count changes, the adherence rate, and adverse drug reactions, all over 48 weeks of study. Results HIV viral load remained undetectable (HIV-RNA < 47 copies/mL) during the 48 weeks of the study in both arms. The absolute CD4 cell count change was not significant between the two groups. The overall proportion of adverse effects in each group was comparable. The rate of adherence to treatment was acceptable in both groups, and no significant difference was observed. Conclusions Treatment simplification with tenofovir alafenamide plus dolutegravir regimen as maintenance therapy was non-inferior in terms of efficacy and safety compared to the standard triple therapy. [ABSTRACT FROM AUTHOR]

Background: Vonoprazan‐containing Helicobacter pylori eradication is reliably effective in Japan. Its effectiveness in other countries remains unclear. Here, we examined vonoprazan‐H. pylori therapies in Thailand. Materials and Methods: This was pilot study of four different vonoprazan containing therapies. Subjects were randomized to: 14‐day dual therapy (500 mg amoxicillin q.i.d. plus 20 mg vonoprazan b.i.d.), 14‐day triple therapy (amoxicillin 1 g b.i.d., slow release clarithromycin‐MR, 1 g daily plus vonoprazan 20 mg b.i.d.), 7‐day high‐dose vonoprazan triple therapy (amoxicillin 1 g b.i.d., clarithromycin‐MR 1 g daily and 60 mg vonoprazan once daily), and 14‐day vonoprazan triple therapy plus bismuth (amoxicillin 1 g b.i.d., clarithromycin‐MR 1 g daily, vonoprazan 20 mg b.i.d., and bismuth subsalicylate 1048 mg b.i.d.). Eradication was confirmed 4 weeks after therapy. Antimicrobial susceptibility and CYP3A4/5 genotyping were performed. Results: One hundred H. pylori‐infected patients (mean age 54.3 ± 13 years, 51% men) were randomized. All were CYP3A4 extensive metabolizers. Cure rates with both 14‐day vonoprazan dual therapy and 14‐day triple therapy were low: 66.7%; 95% CI = 43–85% (14/21), and 59.3%; 95% CI = 39–78%) (16/27), respectively. In contrast, 7‐day high‐dose vonoprazan triple therapy and 14‐day vonoprazan triple plus bismuth proved effective 92.3%; 95% CI = 75%–99% (24/26) and 96.2%; 95% CI = 80%–100% (25/26), respectively. Conclusion: Both 14‐day vonoprazan dual and triple therapy were ineffective for H. pylori eradication in Thailand. Higher dosage of vonoprazan, and/or the addition of bismuth may be required to achieve high H. pylori eradication rates. High‐dose vonoprazan triple therapy and vonoprazan triple therapy adding bismuth might be used as first‐line treatments in some regions with high efficacy irrespective of CYP3A4/5 genotype and clarithromycin resistance. [ABSTRACT FROM AUTHOR]

Background: Until now, there have been no randomized controlled trials directly evaluating the efficacy of high-dose ilaprazole-amoxicillin dual therapy (HT) in comparison to other standard treatments for H. pylori (Helicobacter pylori) infection. This study aimed to compare the effectiveness and safety of HT with bismuth quadruple therapy (BQT) as an initial treatment for H. pylori. Methods: This single-center, prospective, randomized clinical controlled trial recruited 225 consecutive patients. They were assigned to either HT group (ilaprazole, 10 mg, twice daily; amoxicillin 1,000 mg, three times daily) or BQT group (compound bismuth aluminate granules, 2.6 g, three times daily; ilaprazole, 5 mg, twice daily; amoxicillin, 1,000 mg, twice daily; clarithromycin, 500 mg, twice daily) for 14 days. The 13C-urea breath test assessed eradication success 4 weeks after treatment. The primary outcome focused on the eradication rate, with secondary outcomes including safety and compliance. Results: From February 2023 to March 2023, 228 subjects were screened, and 225 were randomized. The HT and BQT groups showed eradication rates of 76.3% and 61.3% (p = 0.015) both by intention-to-treat (ITT) analysis and per-protocol (PP) analysis. HT was associated with fewer adverse events than BQT (27.2% vs. 81.8%, p = 0.002). The most commonly reported adverse events was bitter taste of mouth (3.5% vs. 60.4%, p < 0.001). There was no significant difference in compliance between the two groups (89.5% vs. 92.8%, p = 0.264). Conclusion: The 14-day HT treatment demonstrates better efficacy in H. pylori eradication treatment and improved safety and compliance compared to BQT. The results provide supporting evidence for 14-day HT can be potentially considered as a first-line regimen for empirical treatment. [ABSTRACT FROM AUTHOR]

Background: Diabetes is one of the world's most widespread conditions, and diabetic patients are among the most likely to engage in fierce battles with this chronic disease. Which group should be added-on as a dual therapy for Egyptian patients with type 2 diabetes and inadequate glycemic management, HbA1c ≥ 7.0% and ≤ 10% (≥ 53 and ≤ 86 mmol/mol), following not less than 3 months of metformin and diet therapy, is still up for debate. Based on this ambiguity, we designed our study to compare the safety and efficacy of sitagliptin 50 mg (n = 85) with empagliflozin 12.5 mg (n = 85) twice daily as an adjunctive therapy to metformin and diet for a further 12 weeks. HbA1c after 12 weeks of open-label therapy was the major outcome measure. Results: After 12 weeks of treatment, empagliflozin drastically lowered HbA1c, FPG, PP, body weight, and triglycerides from baseline while significantly increasing LDL, total cholesterol, and HDL. On the other hand, sitagliptin significantly reduced FPG, PP (with a no discernable alteration in HbA1c), body weight, and triglycerides while significantly increasing HDL (P ≤ 0.001 for all comparisons). Comparing the two groups, empagliflozin significantly reduced HbA1c, FPG, and PP while significantly increasing LDL and triglycerides than sitagliptin (P < 0.001 for all except FPG, P = 0.005). More patients receiving empagliflozin 12.5 mg than sitagliptin 50 mg twice daily reported adverse events during open-label treatment (11.8% vs. 8.2%, respectively). Conclusions: In type 2 diabetic Egyptian patients uncontrolled with metformin and diet, empagliflozin was superior to sitagliptin as regards glycemic control, weight, and SBP/DBP reduction. [ABSTRACT FROM AUTHOR]

Introduction: Adding LAMA to LABA/ICS is recommended to improve control in patients with persistent asthma. Methods: This observational, retrospective, before-and-after study considered patients diagnosed with asthma who started LABA/ICS + LAMA treatment (triple therapy, TT) between 1 January 2017 and 31 December 2018 and had been treated with LABA/ICS (dual therapy, DT) in the year before. Changes in lung function and exacerbation rates, healthcare resource utilization, and healthcare and non-healthcare costs (€2019) were estimated in patients with asthma in clinical practices in Spain. Data from computerized medical records from seven Spanish regions were collected ±1 year of LAMA addition. Results: 4740 patients (64.1 years old [SD: 16.3]) were included. TT reduced the incidence of exacerbations by 16.7% (p < 0.044) and the number of patients with exacerbations by 8.5% (p < 0.001) compared to previous DT. The rate of patients with severe exacerbations requiring systemic corticosteroids and their hospitalization rates significantly decreased by 22.5% and 29.5%. TT significantly improved FEV1, FVC, and FEV1/FVC, saving €571/patient for society. Younger patients with asthma (18–44 years old) and patients with severe asthma (FEV1 < 60%) performed better upon the initiation of TT. Conclusions: TT reduced asthma exacerbations, improved lung function and reduced healthcare costs vs. DT, particularly in patients requiring systemic corticosteroids to treat severe exacerbations. [ABSTRACT FROM AUTHOR]

Background: Vonoprazan-amoxicillin (VA) dual therapy has recently been proposed to eradicate Helicobacter pylori (H. pylori) with controversial results. We, therefore, conducted a meta-analysis to assess the effect of this therapy for H. pylori eradication. Methods: We searched PubMed, Embase, Cochrane Library, and Web of Science database from inception until November 2022, collecting randomized controlled trials (RCTs) comparing VA dual therapy with other regimens for H. pylori eradication. Pooled relative risks (RRs) were calculated using random effects model. Results: Five RCTs were ultimately included. Compared with the vonoprazan-amoxicillin-clarithromycin (VAC) triple therapy, the eradication rate of VA dual therapy was lower in intention-to-treat (ITT) analysis (n = 3 RCTs, RR = 0.94, 95% CI: 0.88–0.99, P = 0.03), but there was no significant difference between them in the per-protocol (PP) analysis (RR = 0.96, 95% CI: 0.91–1.01, P = 0.11). For clarithromycin-resistant H. pylori strains, the eradication rate of VA dual therapy was significantly higher than that of the VAC triple therapy (n = 2 RCTs, RR = 1.20, 95% CI: 1.03–1.39, P = 0.02). Compared with the PPI-based triple therapy (PAC), VA dual therapy had a superior eradication rate (n = 2 RCTs, ITT analysis: RR = 1.13, 95% CI: 1.04–1.23, P = 0.003; PP analysis: pooled RR = 1.14, 95% CI: 1.06–1.22, P = 0.0004). Compared with VAC or PAC triple therapy, VA dual therapy has a similar incidence of total adverse events and compliance. Conclusions: VA dual therapy had a similar effect compared to VAC triple therapy and was superior to PAC triple therapy. Future RCTs are needed to ascertain the optimal dosage and duration of vonoprazan and amoxicillin, and the effect of VA dual therapy compared with the mainstream regimens recommended by current guidelines. [ABSTRACT FROM AUTHOR]

Background: Helicobacter pylori infection and eradication have been reported to cause dysbiosis of the oral microbiota. Probiotics are increasingly being used to maintain the balance of the oral microbiota. We aimed to investigate the effects of H. pylori infection, H. pylori eradication with vonoprazan-amoxicillin dual therapy, and probiotics supplementation on the oral microbiota. Methods: H. pylori positive patients were randomly assigned to a vonoprazanamoxicillin regimen plus probiotics (BtT group) or the placebo (PT group) for 14 days. H. pylori negative population served as normal controls. Tongue coating samples were collected from 60 H. pylori positive patients at three time points (before H. pylori eradication, after H. pylori eradication, and at confirmation of H. pylori infection cure) and 20 H. pylori negative subjects. 16S rRNA gene sequencing was used to analyze the oral microbiota. Results: H. pylori was detected in the oral cavity in positive (34/60), negative (7/20), and eradicated (1/60) subjects using high-throughput sequencing. Compared with normal controls, H. pylori positive patients exhibited higher richness (p = 0.012) and comparable diversity (p = 0.075) of oral microbiota. Beta diversity and KEGG analysis showed oral flora composition and function differences in H. pylori positive and negative subjects. Alpha diversity dramatically decreased after H. pylori eradication and modestly increased with confirmation of H. pylori eradication. Beta diversity and LEfSe analysis revealed distinct structures, and KEGG analysis showed distinct signaling pathways of tongue coating flora at three time points. There was a significant reduction of Firmicutes and Lactobacillus after H. pylori erdication. The PT group and BtT group had identical compositional and functional differences of oral microbiota at three time points. Conclusion: No substantial link existed between oral and stomach H. pylori, while removing gastric H. pylori helped eliminate oral H. pylori. H. pylori infection and vonoprazan-amoxicillin dual therapy affected oral microbiota diversity, structure, and function. H. pylori eradication demonstrated a suppressive impact on the proliferation of oral pathogens, specifically Firmicutes and Lactobacillus. Nevertheless, probiotics supplementation did not reduce the oral microbial disturbance caused by H. pylori eradication. [ABSTRACT FROM AUTHOR]

The challenge in HER2-overexpressing breast cancer therapy lies in creating an effective target therapy to overcome treatment resistance. Monoclonal antibodies and target gene silencing by siRNA are two potential strategies that have been widely developed for treating HER2-positive breast cancer. The siRNA delivery system is a crucial factor that influences siRNA therapy's success. In this study, lipid-based nanoparticles (cationic niosomes) composed of different cholesterol-based cationic lipids were formulated and characterized for delivering siRNA into HER2-overexpressing breast cancer cells. Niosomes containing a trimethylammonium headgroup showed the highest siRNA delivery efficiency with low toxicity. The myeloid cell leukemia-1 (Mcl-1) siRNA nioplex treatment significantly decreased mRNA expression and breast cancer cell growth. Dual-targeted therapy, consisting of treatment with an Mcl-1 siRNA nioplex and trastuzumab (TZ) solution, noticeably promoted cell-growth inhibition and apoptosis. The synergistic effect of dual therapy was also demonstrated by computer modeling software (CompuSyn version 1.0). These findings suggest that the developed cationic niosomes were effective nanocarriers for siRNA delivery in breast cancer cells. Furthermore, the Mcl-1 nioplex/TZ dual treatment establishes a synergistic outcome that may have the potential to treat HER2-overexpressing breast cancer. [ABSTRACT FROM AUTHOR]

BackgroundPrevious trials investigating antithrombotic therapy with a direct oral anticoagulant (DOAC) and a P2Y12 inhibitor after percutaneous coronary intervention (PCI), termed dual therapy, allowed a short period of triple therapy including a DOAC, a P2Y12 inhibitor, and aspirin.AimsThis study aimed to determine whether discontinuation of aspirin on the first post-procedural day is safe or causes ischemic events.MethodsIschemic and bleeding events during hospitalization were investigated retrospectively in all patients treated with dual therapy (DOAC + P2Y12 inhibitor, designated as group 1) or triple therapy (DOAC + P2Y12 inhibitor+aspirin, designated as group 2) from day 1 after PCI at our center.ResultsOf 4,564 consecutive PCI procedures, 1,059 (23.2%) had an indication for OAC. Of these, 322 met the inclusion criteria for group 1 and 62 for group 2. Baseline characteristics, CHA2DS2-VASc and HAS-BLED scores showed no relevant differences between the two groups, and the main indication for DOAC therapy was atrial fibrillation in both groups. Approximately ¼ of patients were treated for acute coronary syndrome. The mean length of post-procedural hospitalization was 2.1 ± 2.5 and 2.2 ± 3.0 days in group 1 and 2, respectively (p = 0.305). One patient per group suffered a TIA (p = 0.297). There were no other ischemic events and no statistically significant differences in bleeding events. A subgroup analysis of cases hospitalized for ≥2 post-procedural days (group 1: 100 cases, mean 4.4 ± 3.4 days vs. group 2: 25 cases, mean 4.0 ± 4.1 days) confirmed these results.ConclusionThe initiation of dual therapy and thus discontinuation of aspirin on the first postprocedural day appears to be safe with respect to short-term ischemic events in a real-world population. Almost ¼ of patients undergoing PCI have an indication for OAC, highlighting the relevance of this issue.

OBJECTIVE We estimated the effect of early initiation of dual therapy vs monotherapy on drug administration and related outcomes in mechanically ventilated, critically ill children. METHODS We used the electronic medical record at a single tertiary medical center to conduct an active comparator, new user cohort study. We included children <18 years of age who were exposed to a sedative or analgesic within 6 hours of intubation. We used stabilized inverse probability of treatment weighting to account for confounding at baseline. We estimated the average effect of initial dual therapy vs monotherapy on outcomes including cumulative opioid, benzodiazepine, and dexmedetomidine dosing; sedation scores; time to double the opioid or benzodiazepine infusion rate; initiation of neuromuscular blockade within the first 7 days of follow-up; time to extubation; and 7-day all-cause in-hospital death. RESULTS The cohort included 640 patients. Children receiving dual therapy received 0.03 mg/kg (95% CI, 0.02-0.04) more dexmedetomidine over the first 7 days after initiation of mechanical ventilation than did monotherapy patients. Dual therapy patients had similar sedation scores, time to double therapy, initiation of neuromuscular blockade, and time to extubation as monotherapy patients. Dual therapy patients had a lower incidence of death. CONCLUSIONS In this study, initial dual therapy compared with monotherapy does not reduce overall drug administration during mechanical ventilation. The identified effect of dual therapy on mortality deserves further investigation. [ABSTRACT FROM AUTHOR]

Background/aim: People living with human immunodeficiency virus (PLWH) are getting older. Age-related comorbidities in PLWH result in polypharmacy and increase the risk for potential drug-drug interactions (pDDIs). This study aimed to evaluate how the rate of pDDIs would change if the treatment of patients receiving different combined antiretroviral therapies (ARTs) were theoretically changed with dolutegravir/lamivudine (DTG+3TC) or cabotegravir/rilpivirine (CAB+RPV). Materials and methods: This study was conducted at the infectious disease outpatient clinic of a university hospital as a follow-up of a previous study. The data of PLWH receiving at least 1 comedication other than antiretrovirals (ARVs) were retrospectively reviewed and analyzed. The Drugs.com/Drug Interactions Checker and University of Liverpool HIV Drug Interactions Checker databases were used to identify pDDIs and their severities. Results: A total of 75 PLWH, of whom 83% were male, with a mean age (± standard deviation) of 46.5 (±12.98) years were included. Polypharmacy was observed in 59 (79%) of the participants; however, with dual ARV options, the probability of polypharmacy was 35 (47%) (p < 0.001). In the Drugs.com database, no significant difference was found in terms of pDDIs between the treatment of current ARTs (64%) and DTG/3TC (%44) (p = 0.06) or CAB/RPV (%64) (p = 0.521). However, in the University of Liverpool database, the current rate of pDDIs (55%) was significantly higher compared to the theoretical treatment of DTG/3TC (40%) (p = 0.029), oral CAB/RPV (48%) (p = 0.003), and injectable CAB/RPV (31%) use (p = 0.006). Conclusion: The results suggest that dual treatment regimens can reduce pDDIs, resulting in better tolerance and probably higher quality of life among PLWH. [ABSTRACT FROM AUTHOR]

Objective: To describe and review the published evidence on use of multiple biologics within specialty pharmacy practice. Data Sources: A search of PubMed and Embase was conducted from October 2021 through September 2022. Keywords included biologics for immune-mediated conditions along with the terms "dual," "add-on," and "combination." Study Selection and Data Extraction: All human studies in the English language were considered. Published abstracts, case reports, case series, randomized controlled trials, systematic reviews, and meta-analyses were included. Data Synthesis: Although evidence is limited, there are published meta-analyses of combined biologic use within gastroenterology and rheumatology. There are also numerous case reports within dermatology. Clinical trials of dual biologics for severe rheumatologic conditions and inflammatory bowel disease are in progress. Existing evidence for use in pulmonology and allergy suggest dual biologic therapy can be safe and effective, but data are limited. Literature describing use of monoclonal antibodies for other overlapping conditions is lacking. Relevance to Patient Care and Clinical Practice: This article reviews the evidence describing combination biologic use and outlines remaining knowledge gaps. It also describes the essential role that specialty pharmacists play in managing therapeutic mAbs. Conclusions: High-quality evidence describing combination biologic use is limited and long-term safety data are lacking. Pharmacists should utilize their specialized training to assess appropriateness of therapy, provide patient counseling and monitor for safety and efficacy. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the efficacy and safety of vonoprazan–amoxicillin (VA) dual therapy for radically eradicating Helicobacter pylori (H. pylori). Methods: The PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI) and Wanfang databases were searched up to July 7, 2022, to identify clinical trials comparing the efficacy of VA dual therapy and triple therapy for H. pylori eradication. After evaluating the quality of the included studies, random effects models were conducted, and risk ratios (RRs) with 95% confidence intervals (CIs) were calculated to estimate the efficacy and safety of each approach. Results: Six publications (including four randomized controlled trials) involving 2019 patients were included in this meta-analysis. Overall, the eradication rate for VA dual therapy was 89.9%, while it was 85.2% for triple therapy based on other acid inhibitors. The eradication rate of H. pylori in the VA dual regimen group was higher than that in the PPI-based (omeprazole or lansoprazole) triple therapy group (RR = 1.15, 95% CI 1.07–1.23, p < 0.0001). However, the efficacy of VA dual therapy was comparable with VA–Clarithromycin (VAC) triple therapy (RR = 0.97, 95% CI 0.93–1.02). Besides, the incidence of adverse reactions in VA dual therapy was also lower than that in triple therapy (RR = 0.80, 95% CI 0.70–0.91, p = 0.0009). Conclusion: Compared with PPI-based triple therapy, VA dual therapy showed a better therapeutic effect, safety and patient compliance rate for eradicating H. pylori, which should be used as a novel curative strategy in the future. [ABSTRACT FROM AUTHOR]