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BACKGROUND: The efficacy of Vonoprazan-amoxicillin dual therapy (VAT) in the treatment of Helicobacter pylori (H. pylori) is controversial. AIM: To evaluate the efficacy of VAT in the Chinese population. METHODS: This prospective, multicenter, randomized, open-label, and two-stage study was conducted at 23 centers in Fujian, China (May 2021-April 2022). H. pylori-infected patients were randomized to bismuth quadruple therapy (BQT), BQT-Vonoprazan (BQT-V), seven-day VAT (VAT-7), ten-day VAT (VAT-10), and fourteen-day VAT (VAT-14) groups. The primary endpoint was the H. pylori eradication rate. The secondary endpoint was the frequency of adverse events. This study was registered with the Chinese Clinical Trial Registry, ChiCTR2100045778. RESULTS: In the first stage, VAT-7 and BQT-V groups were selected for early termination because less than 23 among 28 cases were eradicated. In the second stage, the eradication rates for BQT, VAT-10, and VA-14 were 80.2% [95% confidence interval (95%CI): 71.4%-86.8%], 93.2% (86.6%-96.7%), 92.2% (85.3%-96.0%) in the intention-to-treat (ITT) analysis, and 80.9% (95%CI: 71.7%-87.5%), 94.0% (87.5%-97.2%), and 93.9% (87.4%-97.2%) in the per-protocol analysis. The ITT analysis showed a higher eradication rate in the VAT-10 and VAT-14 groups than in the BQT group (P = 0.022 and P = 0.046, respectively). The incidence of adverse events in the VAT-10 and VAT-14 groups was lower than in the BQT group (25.27% and 13.73% vs 37.62%, respectively; P < 0.001). CONCLUSION: VAT with a duration of 10 or 14 days achieves a higher eradication rate than the BQT, with a more tolerable safety profile in H. pylori-infected patients in Fujian.
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Amoxicilina , Antibacterianos , Quimioterapia Combinada , Infecções por Helicobacter , Helicobacter pylori , Inibidores da Bomba de Prótons , Pirróis , Sulfonamidas , Humanos , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/diagnóstico , Pessoa de Meia-Idade , Masculino , Sulfonamidas/efeitos adversos , Sulfonamidas/administração & dosagem , Sulfonamidas/uso terapêutico , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/isolamento & purificação , Feminino , Estudos Prospectivos , Amoxicilina/administração & dosagem , Amoxicilina/efeitos adversos , Amoxicilina/uso terapêutico , China/epidemiologia , Quimioterapia Combinada/métodos , Pirróis/uso terapêutico , Pirróis/efeitos adversos , Pirróis/administração & dosagem , Resultado do Tratamento , Adulto , Inibidores da Bomba de Prótons/uso terapêutico , Inibidores da Bomba de Prótons/administração & dosagem , Inibidores da Bomba de Prótons/efeitos adversos , Antibacterianos/efeitos adversos , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Idoso , População do Leste AsiáticoRESUMO
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.
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Amoxicilina , Antibacterianos , Quimioterapia Combinada , Infecções por Helicobacter , Helicobacter pylori , Pirróis , Sulfonamidas , Humanos , Infecções por Helicobacter/tratamento farmacológico , Pirróis/uso terapêutico , Pirróis/administração & dosagem , Sulfonamidas/uso terapêutico , Sulfonamidas/administração & dosagem , Amoxicilina/uso terapêutico , Amoxicilina/administração & dosagem , Feminino , Pessoa de Meia-Idade , Masculino , Helicobacter pylori/efeitos dos fármacos , Antibacterianos/uso terapêutico , Antibacterianos/administração & dosagem , Adulto , Resultado do Tratamento , China , Idoso , Inibidores da Bomba de Prótons/uso terapêutico , Inibidores da Bomba de Prótons/administração & dosagemRESUMO
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.
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Amoxicilina , Antibacterianos , Quimioterapia Combinada , Infecções por Helicobacter , Helicobacter pylori , Pirróis , Sulfonamidas , Humanos , Amoxicilina/administração & dosagem , Amoxicilina/uso terapêutico , Infecções por Helicobacter/tratamento farmacológico , Masculino , Sulfonamidas/administração & dosagem , Sulfonamidas/uso terapêutico , Sulfonamidas/efeitos adversos , Feminino , Pessoa de Meia-Idade , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Antibacterianos/efeitos adversos , Helicobacter pylori/efeitos dos fármacos , Pirróis/administração & dosagem , Pirróis/uso terapêutico , Resultado do Tratamento , Idoso , Adulto , Inibidores da Bomba de Prótons/administração & dosagem , Inibidores da Bomba de Prótons/uso terapêutico , Esquema de MedicaçãoRESUMO
Infectious diabetic wounds present a substantial challenge, characterized by inflammation, infection, and delayed wound healing, leading to elevated morbidity and mortality rates. In this work, we developed a multifunctional lipid nanoemulsion containing quercetin, chlorine e6, and rosemary oil (QCRLNEs) for dual anti-inflammatory and antibacterial photodynamic therapy (APDT) for treating infectious diabetic wounds. The QCRLNEs exhibited spherical morphology with a size of 51 nm with enhanced encapsulation efficiency, skin permeation, and localized delivery at the infected wound site. QCRLNEs with NIR irradiation have shown excellent wound closure and antimicrobial properties in vitro, mitigating the nonselective cytotoxic behavior of PDT. Also, excellent biocompatibility and anti-inflammatory and wound healing responses were observed in zebrafish models. The infected wound healing properties in S. aureus-infected diabetic rat models indicated re-epithelization and collagen deposition with no signs of inflammation. This multifaceted approach using QCRLNEs with NIR irradiation holds great promise for effectively combating oxidative stress and bacterial infections commonly associated with infected diabetic wounds, facilitating enhanced wound healing and improved clinical outcomes.
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Antibacterianos , Anti-Inflamatórios , Fotoquimioterapia , Cicatrização , Peixe-Zebra , Animais , Antibacterianos/farmacologia , Antibacterianos/química , Fotoquimioterapia/métodos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/administração & dosagem , Cicatrização/efeitos dos fármacos , Ratos , Infecção dos Ferimentos/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Nanopartículas/química , Infecções Estafilocócicas/tratamento farmacológico , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Humanos , Complicações do Diabetes/tratamento farmacológico , MasculinoRESUMO
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-1ß, IL-6, TNF-α, IFN-γ, IP-10, sTNFR-I/II, MIP-1α/ß, 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. Clinical trial registration: identifier NCT04076423.
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Biomarcadores , Infecções por HIV , Inibidores de Integrase de HIV , HIV-1 , Humanos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Infecções por HIV/virologia , Infecções por HIV/sangue , Masculino , HIV-1/efeitos dos fármacos , HIV-1/imunologia , Feminino , Biomarcadores/sangue , Adulto , Estudos Transversais , Inibidores de Integrase de HIV/uso terapêutico , Pessoa de Meia-Idade , Carga Viral , Inflamação/imunologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD4-Positivos/imunologia , Oxazinas/uso terapêuticoRESUMO
Inflammatory bowel disease (IBD) is entering a potentially new era of combined therapeutics. Triantafillidis et al provide an insightful review of the current state of combination therapy, with a focus on the use of a combined biologic and immunomodulator, as well as emerging data on the future potential of dual-biologic therapy (DBT). While current evidence for DBT is limited, encouraging safety profiles and ongoing trials suggest a brighter future for this approach. The importance of controlled trials should be stressed in establishing new treatment paradigms. Ongoing prospective randomized trials of DBT and perhaps future combinations of biologics and small molecule therapies will hopefully guide the next generation of IBD care.
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Produtos Biológicos , Quimioterapia Combinada , Doenças Inflamatórias Intestinais , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/terapia , Doenças Inflamatórias Intestinais/imunologia , Quimioterapia Combinada/métodos , Produtos Biológicos/uso terapêutico , Produtos Biológicos/administração & dosagem , Resultado do Tratamento , Agentes de Imunomodulação/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
AIMS: Guidelines recommend initiation of dual combination antihypertensive therapy, preferably single-pill combination (SPC), in most patients with hypertension. Evidence on narrowing gaps in clinical practice relative to guidelines is limited. METHODS AND RESULTS: Monte Carlo simulation was applied to 1.1 million patients qualifying for dual combination therapy from a previously conducted retrospective analysis of clinical practice, hospital statistics, and national statistics in the UK. We provide 10-year Kaplan-Meier event rates for the primary endpoint representing a composite of nonfatal myocardial infarction, nonfatal stroke (ischemic or hemorrhagic), nonfatal heart failure hospitalization or cardiovascular death. Cox model results from a previously conducted study were utilized to estimate baseline risk, together with evidence on risk reduction from the Blood Pressure Lowering Treatment Trialists' Collaboration (BPLTTC) meta-analysis and published evidence on BP-lowering efficacy of antihypertensive therapies. In the overall population, estimated 10-year event rates for the primary endpoint in patients with 100% persistence in monotherapy were 17.0% for irbesartan (I) and 17.6% for ramipril (R). These rates were only modestly better than that observed in clinical practice (17.8%). In patients with 100% persistence in dual therapy, estimated event rates were 13.6% for combinations of Irbesartan + Amlodipine (ARR = 8.7% compared to untreated) and 14.3% for Ramipril + Amlodipine (ARR = 8.0% compared to untreated). The absolute risk of the primary endpoint was reduced by 15.9% in patients with ASCVD and 6.6% in those without ASCVD. Similarly, the absolute risk was reduced by 11.7% in diabetics and 7.8% in those without diabetes. CONCLUSION: This study represents the first to investigate guidelines-based treatment in hypertensive patients and demonstrates the opportunity for considerable risk reduction by ensuring recommended dual therapy in clinical practice, particularly in the form of SPC with high persistence, relative to no treatment or monotherapy.
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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.
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Fármacos Anti-HIV , Infecções por HIV , Compostos Heterocíclicos com 3 Anéis , Lamivudina , Oxazinas , Piridonas , Carga Viral , Humanos , Estudos Retrospectivos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Carga Viral/efeitos dos fármacos , Feminino , Masculino , Piridonas/uso terapêutico , Lamivudina/uso terapêutico , Lamivudina/administração & dosagem , Adulto , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Oxazinas/uso terapêutico , Pessoa de Meia-Idade , Contagem de Linfócito CD4 , Fármacos Anti-HIV/uso terapêutico , Fármacos Anti-HIV/administração & dosagem , Piperazinas/uso terapêutico , HIV-1/efeitos dos fármacos , Quimioterapia Combinada , RNA Viral/sangue , Resultado do TratamentoRESUMO
BACKGROUND: Helicobacter pylori (H. pylori) eradication rates have fallen globally, likely in large part due to increasing antibiotic resistance to traditional therapy. In areas of high clarithromycin and metronidazole resistance such as ours, Maastricht VI guidelines suggest high dose amoxicillin dual therapy (HDADT) can be considered, subject to evidence for local efficacy. In this study we assess efficacy of HDADT therapy for H. pylori eradication in an Irish cohort. AIM: To assess the efficacy of HDADT therapy for H. pylori eradication in an Irish cohort as both first line, and subsequent therapy for patients diagnosed with H. pylori. METHODS: All patients testing positive for H. pylori in a tertiary centre were treated prospectively with HDADT (amoxicillin 1 g tid and esomeprazole 40 mg bid × 14 d) over a period of 8 months. Eradication was confirmed with Urea Breath Test at least 4 wk after cessation of therapy. A delta-over-baseline > 4% was considered positive. Patient demographics and treatment outcomes were recorded, analysed and controlled for basic demographics and prior H. pylori treatment. RESULTS: One hundred and ninety-eight patients were identified with H. pylori infection, 10 patients were excluded due to penicillin allergy and 38 patients refused follow up testing. In all 139 were included in the analysis, 55% (n = 76) were female, mean age was 46.6 years. Overall, 93 (67%) of patients were treatment-naïve and 46 (33%) had received at least one previous course of treatment. The groups were statistically similar. Self-reported compliance with HDADT was 97%, mild side-effects occurred in 7%. There were no serious adverse drug reactions. Overall the eradication rate for our cohort was 56% (78/139). Eradication rates were worse for those with previous treatment [43% (20/46) vs 62% (58/93), P = 0.0458, odds ratio = 2.15]. Age and Gender had no effect on eradication status. CONCLUSION: Overall eradication rates with HDADT were disappointing. Despite being a simple and possibly better tolerated regime, these results do not support its routine use in a high dual resistance country. Further investigation of other regimens to achieve the > 90% eradication target is needed.
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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.
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Amoxicilina , Antibacterianos , Quimioterapia Combinada , Infecções por Helicobacter , Helicobacter pylori , Pirróis , Sulfonamidas , Amoxicilina/administração & dosagem , Amoxicilina/uso terapêutico , Humanos , Infecções por Helicobacter/tratamento farmacológico , Sulfonamidas/administração & dosagem , Sulfonamidas/uso terapêutico , Sulfonamidas/efeitos adversos , Pirróis/administração & dosagem , Pirróis/uso terapêutico , Pirróis/efeitos adversos , Helicobacter pylori/efeitos dos fármacos , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Antibacterianos/efeitos adversos , Resultado do Tratamento , Inibidores da Bomba de Prótons/administração & dosagem , Inibidores da Bomba de Prótons/uso terapêutico , Inibidores da Bomba de Prótons/efeitos adversosRESUMO
Three manufacturers sell artificial pancreas systems in the United States for management of Type 1 Diabetes. Given the life-saving task required of an artificial pancreas there needs to be a high level of trust and safety in the devices. This evaluation sought to find the adjusted safety event reporting rate and themes along with device-associated risk in events reported utilizing the MAUDE database. We searched device names in the MAUDE database over the period from 2016 until August 2023 (the date of retrieval). Thematic analysis was performed using dual-reviewer examination with a 96% concurrence. Relative risk (RR) was calculated for injury, malfunction, and overall, for each manufacturer, as well as adjusted event rate per manufacturer. Most events reported related to defects in the manufacturing of the casing materials which resulted in non-delivery of therapy. Tandem Diabetes Care, Inc. had an adjusted event rate of 50 per 100,000 units and RR of 0.0225. Insulet had an adjusted event rate of 300 per 100,000 units and RR of 0.1684. Medtronic has an adjusted event rate of 2771.43 per 100,000 units and RR of 20.7857. The newer Medtronic devices show improvements in likely event rate. While the artificial pancreas is still in its infancy, these event rates are not at an acceptable level for a device which can precipitate death from malfunctions. Further exploration into safety events and much more research and development is needed for devices to reduce the event rates. Improved manufacturing practices, especially the casing materials, are highly recommended. The artificial pancreas holds promise for millions but must be improved before it becomes a true life-saving device that it has the potential to become.
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Pâncreas Artificial , Pâncreas Artificial/efeitos adversos , Humanos , Estados Unidos , Diabetes Mellitus Tipo 1 , Bases de Dados Factuais , Falha de EquipamentoRESUMO
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.
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Amoxicilina , Antibacterianos , Infecções por Helicobacter , Helicobacter pylori , Inibidores da Bomba de Prótons , Pirróis , Sulfonamidas , Humanos , Amoxicilina/uso terapêutico , Amoxicilina/administração & dosagem , Amoxicilina/efeitos adversos , Antibacterianos/uso terapêutico , Antibacterianos/efeitos adversos , Antibacterianos/administração & dosagem , Claritromicina/uso terapêutico , Claritromicina/efeitos adversos , Quimioterapia Combinada , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Inibidores da Bomba de Prótons/uso terapêutico , Inibidores da Bomba de Prótons/efeitos adversos , Inibidores da Bomba de Prótons/administração & dosagem , Pirróis/uso terapêutico , Pirróis/administração & dosagem , Pirróis/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Sulfonamidas/uso terapêutico , Sulfonamidas/efeitos adversos , Sulfonamidas/administração & dosagem , Resultado do TratamentoRESUMO
Background: Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is a serious clinical infection associated with a high risk of mortality. Dual therapy is often used in patients with persistent bacteremia. Objective: This study aimed to compare the outcomes of vancomycin or daptomycin monotherapy with those of dual therapy with ceftaroline in high-grade or persistent MRSA bacteremia. Methods: We conducted a retrospective cohort study at a university teaching hospital between January 2014 and June 2021, involving adults initially treated with vancomycin or daptomycin. Patients were categorized into monotherapy and dual therapy groups. The primary outcome was 30-day mortality. Secondary outcomes included microbiological relapse and antibiotic-related adverse events. Results: In a group of 155 patients, 30-day mortality rates were similar between the monotherapy (23.4%) and dual therapy (22.6%) groups, with comparable microbiological relapse rates (6.5%). In inverse probability of treatment weighting analysis, we found no significant association between dual therapy and mortality (adjusted risk ratio [ARR] 1.38, 95% CI 0.64-2.41, P = 0.38) or microbiological relapse (ARR 0.95, 95% CI 0.31-2.73, P = 0.93). Dual therapy was associated with a lower risk of antibiotic-related adverse events (ARR 0.45, 95% CI 0.21-0.89, P = 0.02). Infectious diseases (ID) consultation was associated with a reduced mortality risk (ARR 0.27, 95% CI 0.07-0.95, P = 0.04). Conclusions: Dual therapy with ceftaroline did not reduce mortality risk compared with monotherapy in patients with MRSA bacteremia. However, patients with ID consultations showed a 73% reduction in mortality rates. Large-scale, prospective, and randomized controlled trials are needed to provide conclusive evidence regarding the potential benefits of dual therapy with ceftaroline for MRSA bacteremia.
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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.
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Acroleína , Antibacterianos , Escherichia coli , Imidazóis , Fármacos Fotossensibilizantes , Porfirinas , Escherichia coli/efeitos dos fármacos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/síntese química , Porfirinas/farmacologia , Porfirinas/química , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Acroleína/análogos & derivados , Acroleína/farmacologia , Acroleína/química , Imidazóis/química , Imidazóis/farmacologia , Imidazóis/síntese química , Cátions/química , Cátions/farmacologia , Testes de Sensibilidade Microbiana , Animais , Camundongos , Sinergismo Farmacológico , FotoquimioterapiaRESUMO
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% (38/43ï¼95%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 < 0.05). VPZ dual therapy or quadruple therapy was also relatively less costly than standard quadruple therapy. CONCLUSION: VPZ dual therapy and quadruple therapy shows promise of not being worse than the standard quadruple therapy by a clinically relevant margin. More studies might be needed to definitively determine if the new therapy is equally effective or even superior.
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Infecções por Helicobacter , Helicobacter pylori , Pirróis , Sulfonamidas , Humanos , Infecções por Helicobacter/tratamento farmacológico , Bismuto/uso terapêutico , Furazolidona/uso terapêutico , Amoxicilina/uso terapêutico , CitratosRESUMO
Background/Aims: Helicobacter pylori (H. pylori) is the most prevalent infection in the world and is strongly associated with gastric adenocarcinoma, lymphoma and gastric or duodenal ulcers. Different regimens have been used for H. pylori eradication. We aimed to compare the efficacy of two different regimens as first-line H. pylori eradication regimens, in an area with high antibiotic resistance. Methods: In this RCT, we assigned 223 patients with H. pylori infection, who were naïve to treatment. They were randomly divided into two groups to receive either 12-day concomitant quadruple therapy (consisting of pantoprazole 40 mg, amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg every 12 hours) or 14-day high dose dual therapy (consisting of esomeprazole 40 mg and amoxicillin 1 g TDS). H. pylori eradication was assessed eight weeks after the end of treatment. Results: H. pylori eradication rate by PP analysis for 12-day concomitant quadruple therapy and 14-day high dose dual therapy were 90.4% and 79.1%, respectively (p=0.02). According to ITT analysis, the eradication rates were 86.2% and 76.3%, respectively (p=0.06). Adverse drug reactions were 12.3% in high dose dual therapy and 36.8% in concomitant quadruple therapy (p<0.001). Conclusions: Twelve-day concomitant therapy seems to be an acceptable regimen for first-line H. pylori eradication in Iran, a country with a high rate of antibiotic resistance. Although, high dose dual therapy did not result in an ideal eradication rate, but it had fewer drug side effects than the 12-day concomitant regimen.
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Amoxicilina , Antibacterianos , Claritromicina , Quimioterapia Combinada , Esomeprazol , Infecções por Helicobacter , Helicobacter pylori , Metronidazol , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Amoxicilina/uso terapêutico , Antibacterianos/uso terapêutico , Claritromicina/uso terapêutico , Claritromicina/administração & dosagem , Esquema de Medicação , Esomeprazol/uso terapêutico , Esomeprazol/administração & dosagem , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Metronidazol/uso terapêutico , Pantoprazol/uso terapêutico , Inibidores da Bomba de Prótons/uso terapêutico , Resultado do TratamentoRESUMO
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.
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Anti-Infecciosos , Nanoestruturas , Antibacterianos/farmacologia , Antibacterianos/química , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Nanoestruturas/químicaRESUMO
BACKGROUND: A novel regimen with high-dose dual therapy (HDDT) has emerged, but its impact on the gut microbiota is not well understood. This study aimed to evaluate the impact of HDDT on the gut microbiota and compare it with that of bismuth quadruple therapy (BQT). METHODS: We enrolled outpatients (18-70 years) diagnosed with Helicobacter pylori infection by either histology or a positive 13C-urea breath test (13C-UBT) and randomly assigned to either the BQT or HDDT group. Subjects consented to provide fecal samples which were collected at baseline, Week 2, and Week 14. Amplification of the V1 and V9 regions of the 16S rRNA was conducted followed by high-throughput sequencing. RESULTS: Ultimately, 78 patients (41 patients in the HDDT group and 37 in the BQT group) were enrolled in this study. Eradication therapy significantly altered the diversity of the gut microbiota. However, the alpha diversity rebounded only in the HDDT group at 12 weeks post-eradication. Immediately following eradication, the predominance of Proteobacteria, replacing commensal Firmicutes and Bacteroidetes, did not recover after 12 weeks. Species-level analysis showed that the relative abundances of Klebsiella pneumoniae and Escherichia fergusonii significantly increased in both groups at Week 2. Enterococcus faecium and Enterococcus faecalis significantly increased in the BQT group, with no significant difference observed in the HDDT group. After 12 weeks of treatment, the relative abundance of more species in the HDDT group returned to baseline levels. CONCLUSION: Eradication of H. pylori can lead to an imbalance in gut microbiota. Compared to BQT, the HDDT is a regimen with milder impact on gut microbiota.
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Antibacterianos , Bismuto , Quimioterapia Combinada , Microbioma Gastrointestinal , Infecções por Helicobacter , Helicobacter pylori , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Antibacterianos/uso terapêutico , Antibacterianos/administração & dosagem , Bactérias/classificação , Bactérias/genética , Bactérias/efeitos dos fármacos , Bactérias/isolamento & purificação , Bismuto/uso terapêutico , Bismuto/administração & dosagem , Fezes/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/microbiologia , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/fisiologia , Inibidores da Bomba de Prótons/uso terapêutico , Inibidores da Bomba de Prótons/administração & dosagem , RNA Ribossômico 16S/genéticaRESUMO
INTRODUCTION: Despite adherence to inhaled corticosteroid/long-acting ß2-agonist (ICS/LABA) therapy, many patients with asthma experience moderate exacerbations. Data on the impact of moderate exacerbations on the healthcare system are limited. This study assessed the frequency and economic burden of moderate exacerbations in patients receiving ICS/LABA. METHODS: Retrospective, longitudinal study analyzed data from Optum's de-identified Clinformatics® Data Mart Database recorded between October 1, 2015, and December 31, 2019. Eligibility criteria included patients ≥18 years of age with ≥1 ICS/LABA claim and ≥1 medical claim for asthma in the 12 months pre-index (first ICS/LABA claim). Primary objectives included describing moderate exacerbation frequency, and associated healthcare resource utilization (HRU) and costs. A secondary objective was assessing the relationship between moderate exacerbations and subsequent risk of severe exacerbations. Patients were stratified by moderate exacerbation frequency in the 12 months post index. Moderate exacerbations were identified using a newly developed algorithm. RESULTS: In the first 12 months post index 61.6% of patients experienced ≥1 moderate exacerbation. Mean number of asthma-related visits was 4.1 per person/year and median total asthma-related costs was $3544. HRU and costs increased with increasing exacerbation frequency. Outpatient and inpatient visits accounted for a similar proportion of these costs. Moderate exacerbations were associated with an increased rate and risk of future severe exacerbations (incidence rate ratio, 1.56; hazard ratio, 1.51 [both p < 0.001]). CONCLUSIONS: This study highlighted that a high proportion of patients continue to experience moderate exacerbations despite ICS/LABA therapy and subsequently experience increased economic burden and risk of future severe exacerbations.