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1.
J Investig Med High Impact Case Rep ; 10: 23247096221099893, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35593449

RESUMO

Several guidelines endorsed the indefinite use warfarin or heparin-containing products for acute venous thromboembolism (VTE) treatment and secondary prevention and discouraged the use of direct oral anticoagulants (DOAC) for patients diagnosed with antiphospholipid syndrome (APS). However, adequate anticoagulation despite warfarin therapy remains a challenge in APS patients. Using DOACs in APS patients is seen in clinical practice, despite the lack of evidence to support their use in this population. In this case series, we aim to evaluate the safety and effectiveness of apixaban use in nine patients with primary or secondary APS at King Abdulaziz Medical City (Riyadh, Saudi Arabia). All patients presented with APS and received apixaban with or without concomitant antiplatelet. Three patients had double positivity, and two patients had triple positivity of antiphospholipid antibodies (aPL). Some patients tolerated apixaban during the follow-up period, but recurrent VTE and stroke were reported in some of them. Bleeding complications were evident in some cases as well. In conclusion, warfarin remains the best choice to prevent VTE recurrence in patients with APS. On the other side, apixaban use in patients with APS may have some safety and effectiveness concerns evidenced by VTE recurrence and bleeding complications. The safety and effectiveness of utilizing apixaban in APS patients need to be assessed in well-controlled randomized trials.


Assuntos
Síndrome Antifosfolipídica , Tromboembolia Venosa , Anticoagulantes/efeitos adversos , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/tratamento farmacológico , Humanos , Pirazóis , Piridonas/efeitos adversos , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controle , Varfarina/efeitos adversos
2.
Zhonghua Jie He He Hu Xi Za Zhi ; 45(5): 493-497, 2022 May 12.
Artigo em Chinês | MEDLINE | ID: mdl-35527464

RESUMO

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease of unknown etiology, which was characterized by irreversible lung function decrease and high mortality. Up till now, only two drugs, i.e. Pirfenidone and Nintedanib,have been approved by Food and Drug Administration (FDA) for therapy of IPF, and the treatment is less effective. Therefore, it is urgent to develop new therapeutic drugs. In recent years, studies had paid attention to lipid metabolism in IPF. In this review, we discussed recent major advances of lipid metabolism, biomarkers and clinical trials in IPF.


Assuntos
Fibrose Pulmonar Idiopática , Humanos , Fibrose Pulmonar Idiopática/tratamento farmacológico , Metabolismo dos Lipídeos , Pulmão , Piridonas/uso terapêutico
4.
J Stroke Cerebrovasc Dis ; 31(7): 106520, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35523052

RESUMO

Background Selecting the appropriate direct oral anticoagulants (DOACs) for embolic ischemic stroke patients, especially on concurrent antiplatelet therapy, is important. However, a limited number of studies have reported on the pharmacological differences in platelet aggregation of each DOAC. We aimed to evaluate the antiplatelet effects of selected DOACs, by comparing dabigatran (a direct oral thrombin inhibitor) and factor Xa (FXa) inhibitors (apixaban and rivaroxaban) in patients who had suffered a cardioembolic stroke. Methods We retrospectively evaluated 12 patients diagnosed with a cardioembolic stroke who took any DOAC without an antiplatelet drug and underwent platelet aggregation tests within 60 days from the onset of symptoms. The platelet aggregation tests were analyzed by both light transmission aggregometry and VerifyNow®. Results Six patients (50%) took dabigatran, while the other six (50%) took an FXa inhibitor (n = 4 for apixaban and n = 2 for rivaroxaban). From the light transmission aggregometry analysis, it was found that the maximal extent of aggregation for adenosine diphosphate (ADP) was significantly higher with dabigatran than with FXa inhibitors, and the ED50 value of ADP on platelet aggregation was significantly lower with dabigatran than with FXa inhibitors. Moreover, the VerifyNow® analyses revealed that P2Y12 reaction units were significantly higher with dabigatran than with FXa inhibitors. Conclusions Dabigatran had little impact on platelet aggregation compared to FXa inhibitors in patients who had suffered a cardioembolic stroke with atrial fibrillation, and who took DOACs for secondary prevention within 60 days from the onset.


Assuntos
Fibrilação Atrial , AVC Embólico , Difosfato de Adenosina/farmacologia , Administração Oral , Anticoagulantes/uso terapêutico , Antitrombinas/uso terapêutico , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/tratamento farmacológico , Dabigatrana/uso terapêutico , Inibidores do Fator Xa/efeitos adversos , Humanos , Projetos Piloto , Agregação Plaquetária , Piridonas/efeitos adversos , Estudos Retrospectivos , Rivaroxabana/efeitos adversos
5.
BMC Infect Dis ; 22(1): 428, 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35508986

RESUMO

BACKGROUND: Efficacy and safety of long-acting cabotegravir (CAB) + rilpivirine (RPV) every 8 weeks (Q8W) versus daily oral standard of care (SoC) maintenance in treatment-experienced individuals with virologically suppressed human immunodeficiency virus type 1 (HIV-1) has not been directly compared in randomized clinical trials. This analysis aimed to indirectly compare these regimens. METHODS: An adjusted indirect treatment comparison of CAB + RPV Q8W with daily oral SoC was performed, using Phase 3 data from studies of CAB + RPV every 4 weeks (Q4W) vs SoC (ATLAS/FLAIR, n = 591 per group) and a Phase 3b trial of CAB + RPV Q8W vs Q4W (ATLAS-2M [excluding participants with prior CAB + RPV exposure]; n = 327 per group). Eligible participants were virologically suppressed (viral load < 50 HIV-1 ribonucleic acid (RNA) copies/mL), treatment-experienced individuals with HIV-1-infection. Treatment efficacy and safety assessments at Week 48 included virologic suppression and lack of virologic suppression (proportion of participants with plasma HIV-1 RNA < 50 copies/mL or ≥ 50 copies/mL, respectively; both as per FDA snapshot algorithm), CD4-cell count change from baseline, no virologic data, discontinuations due to adverse events (AEs), and overall AEs, serious AEs and Grade 3-5 AEs excluding injection-site reactions. A subgroup analysis stratified by baseline third active drug class was performed. RESULTS: Baseline characteristics between the Q4W arms of ATLAS/FLAIR and ATLAS-2M showed no significant differences or differences were not judged to be clinically relevant, apart from participants switching from a baseline third active drug class; more participants switched from integrase strand inhibitors in ATLAS/FLAIR, and from non-nucleoside reverse transcriptase inhibitors in ATLAS-2M. Injections of CAB + RPV Q8W showed no significant differences across efficacy and safety outcomes versus daily oral SoC. Univariate subgroup analysis found there were no significant differences on virologic suppression or lack of virologic suppression for any baseline third active drug class subgroup. These results suggest that CAB + RPV Q8W is non-inferior to daily oral SoC. CONCLUSIONS: This analysis supports the therapeutic potential of CAB + RPV Q8W for virologically suppressed people living with HIV-1 infection seeking an alternative maintenance treatment option to daily oral SoC. TRIAL REGISTRATION: NCT02938520, NCT02951052, NCT03299049.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , HIV-1 , Fármacos Anti-HIV/efeitos adversos , Antirretrovirais/uso terapêutico , Dicetopiperazinas , Infecções por HIV/tratamento farmacológico , HIV-1/genética , Humanos , Piridonas , RNA , Rilpivirina/efeitos adversos , Padrão de Cuidado , Carga Viral
6.
Lancet ; 399(10337): 1779-1789, 2022 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-35378077

RESUMO

BACKGROUND: Oral pre-exposure prophylaxis has been introduced in more than 70 countries, including many in sub-Saharan Africa, but women experience considerable barriers to daily pill-taking, such as stigma, judgement, and the fear of violence. Safe and effective long-acting agents for HIV prevention are needed for women. We aimed to evaluate the safety and efficacy of injectable cabotegravir compared with daily oral tenofovir diphosphate plus emtricitabine (TDF-FTC) for HIV prevention in HIV-uninfected women. METHODS: HPTN 084 was a phase 3, randomised, double-blind, double-dummy, active-controlled, superiority trial in 20 clinical research sites in seven countries in sub-Saharan Africa. Participants were eligible for enrolment if they were assigned female sex at birth, were aged 18-45 years, reported at least two episodes of vaginal intercourse in the previous 30 days, were at risk of HIV infection based on an HIV risk score, and agreed to use a long-acting reversible contraceptive method. Participants were randomly assigned (1:1) to either active cabotegravir with TDF-FTC placebo (cabotegravir group) or active TDF-FTC with cabotegravir placebo (TDF-FTC group). Study staff and participants were masked to study group allocation, with the exception of the site pharmacist who was responsible for study product preparation. Participants were prescribed 5 weeks of daily oral product followed by intramuscular injections every 8 weeks after an initial 4-week interval load, alongside daily oral pills. Participants who discontinued injections were offered open-label daily TDF-FTC for 48 weeks. The primary endpoints of the study were incident HIV infection in the intention-to-treat population, and clinical and laboratory events that were grade 2 or higher in all women who had received at least one dose of study product. This study is registered with ClinicalTrials.gov, NCT03164564. FINDINGS: From Nov 27, 2017, to Nov 4, 2020, we enrolled 3224 participants (1614 in the cabotegravir group and 1610 in the TDF-FTC group). Median age was 25 years (IQR 22-30); 1755 (54·7%) of 3209 had two or more partners in the preceding month. 40 incident infections were observed over 3898 person-years (HIV incidence 1·0% [95% CI 0·73-1·40]); four in the cabotegravir group (HIV incidence 0·2 cases per 100 person-years [0·06-0·52]) and 36 in the TDF-FTC group (1·85 cases per 100 person-years [1·3-2·57]; hazard ratio 0·12 [0·05-0·31]; p<0·0001; risk difference -1·6% [-1·0% to -2·3%]. In a random subset of 405 TDF-FTC participants, 812 (42·1%) of 1929 plasma samples had tenofovir concentrations consistent with daily use. Injection coverage was 93% of the total number of person-years. Adverse event rates were similar across both groups, apart from injection site reactions, which were more frequent in the cabotegravir group than in the TDF-FTC group (577 [38·0%] of 1519 vs 162 [10·7%] of 1516]) but did not result in injection discontinuation. Confirmed pregnancy incidence was 1·3 per 100 person-years (0·9-1·7); no congenital birth anomalies were reported. INTERPRETATION: Although both products for HIV prevention were generally safe, well tolerated, and effective, cabotegravir was superior to TDF-FTC in preventing HIV infection in women. FUNDING: National Institute of Allergy and Infectious Diseases, ViiV Healthcare, and the Bill & Melinda Gates Foundation. Additional support was provided through the National Institute of Mental Health, the National Institute on Drug Abuse, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development. ViiV Healthcare and Gilead Sciences provided pharmaceutical support.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Soropositividade para HIV , HIV-1 , Adulto , Criança , Dicetopiperazinas , Emtricitabina/uso terapêutico , Feminino , Infecções por HIV/induzido quimicamente , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Soropositividade para HIV/tratamento farmacológico , Humanos , Recém-Nascido , Gravidez , Piridonas/uso terapêutico
8.
Thromb Res ; 214: 47-52, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35487054

RESUMO

INTRODUCTION: Patients taking direct oral anticoagulants (DOACs) are increasingly managed in emergency departments (ED). It is unknown whether the risk of traumatic intracranial hemorrhage (ICH) after a head injury differs between DOACs. The objective of this study was to compare risk of ICH at the index ED visit among older adults presenting to the ED with a head injury prescribed different DOACs. METHODS: Retrospective cohort study using population-based administrative databases from Ontario, Canada between 2016 and 2018 of patients age 65 years and older prescribed DOACs who were seen in the ED with a head injury. Patients were matched on the propensity score to create three pairwise-matched cohorts based on the DOAC prescribed (dabigatran vs rivaroxaban; dabigatran vs apixaban; rivaroxaban vs apixaban). For each cohort, relative risk (RR) and 95% confidence intervals (CI) of ICH diagnosed at the index ED visit were calculated. RESULTS: We identified 9230 older adults presenting with a head injury prescribed a DOAC. There were 1274 (13.8%) patients with a prescription for dabigatran, 3136 (34.0%) patients with a prescription for rivaroxaban, and 4820 (52.2%) patients with a prescription for apixaban. Overall, 5.9% of patients had an ICH at the index ED visit. After matching, there were no significant differences in the risk of ICH between any matched DOAC cohorts. CONCLUSION: In patients aged 65 years and older with a prescription for a DOAC seen in the ED for a head injury, there were no differences in the risk of ICH between DOACs.


Assuntos
Fibrilação Atrial , Traumatismos Craniocerebrais , Administração Oral , Idoso , Anticoagulantes/efeitos adversos , Fibrilação Atrial/tratamento farmacológico , Estudos de Coortes , Traumatismos Craniocerebrais/complicações , Dabigatrana/efeitos adversos , Serviço Hospitalar de Emergência , Humanos , Hemorragias Intracranianas/induzido quimicamente , Ontário/epidemiologia , Piridonas/efeitos adversos , Estudos Retrospectivos , Rivaroxabana/efeitos adversos
9.
BMJ Case Rep ; 15(4)2022 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-35396243

RESUMO

BRAF V600E mutations are detected in 3%-10% of patients with multiple myeloma (MM) and are associated with more aggressive disease, higher frequency of extramedullary growth and shorter survival. Monotherapy with the BRAF inhibitor vemurafenib has been disappointing in MM. In patients with BRAF-mutated melanoma, MEK and BRAF inhibition has been a successful approach. Here we describe a very good partial response and possible mechanisms of resistance to a combination of the BRAF inhibitor dabrafenib and the MEK inhibitor trametinib in a patient with BRAF V600E-mutant refractory MM.


Assuntos
Mieloma Múltiplo , Proteínas Proto-Oncogênicas B-raf , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Humanos , Imidazóis , Quinases de Proteína Quinase Ativadas por Mitógeno , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/genética , Mutação , Oximas , Inibidores de Proteínas Quinases , Proteínas Proto-Oncogênicas B-raf/genética , Piridonas , Pirimidinonas
10.
Drug Des Devel Ther ; 16: 973-979, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35386852

RESUMO

Objective: Fluorofenidone (AKF-PD) is a novel antifibrotic small-molecule compound. The purpose of this study was to investigate the metabolic and excretory pathways of AKF-PD in rats. Methods: High-performance liquid chromatography with mass spectrometric (HPLC-MS) detection was used to analyze the metabolites in rat urine. The metabolites were separated by chromatography and their structure was confirmed. HPLC was used to determine the contents of the parent compound and its metabolites in feces and urine after quantitative administration to study the excretion pathway. Results: AKF-PD was mainly oxidized to the carboxyl group after methyl hydroxylation. After oral administration, the total amount of the prototype drug and its hydroxylated metabolites and carboxylated metabolites excreted from the urine and feces of rats was 87%. However, most of them are excreted in urine and feces in the form of carboxylated metabolites, and rarely excreted in the form of prototype drugs and hydroxylated metabolites. Which is that the urinary discharge of hydroxylated metabolites, fluorine ketones, and carboxylated metabolites were 0.2%, 1.1%, and 75.2%, respectively, while the fecal discharge were 0.2%, 0.3%, and 10.1%, respectively. Conclusion: AKF-PD is mainly oxidized into 2-hydroxymethyl and 5-carboxyl AKF-PD through the Phase I metabolic reaction in rats. AKF-PD is a highly permeable compound classified by biopharmaceutics and is mainly excreted from the urine in the form of metabolites.


Assuntos
Piridonas , Administração Oral , Animais , Cromatografia Líquida de Alta Pressão , Preparações Farmacêuticas , Ratos
11.
Int J Mol Sci ; 23(7)2022 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-35408988

RESUMO

Pirfenidone, an antifibrotic drug, has antitumor potential against different types of cancers. Our work explored whether pirfenidone sensitizes non-small cell lung cancer (NSCLC) cell lines to chemotherapeutic treatments. The cytotoxic effect of paclitaxel in combination with pirfenidone against three NSCLC cell lines (A549, NCI-H322 and NCI-H460) was evaluated using the sulforhodamine B assay. The effects of this combination on cell viability (trypan blue exclusion assay), proliferation (BrdU incorporation assay), cell cycle (flow cytometry following PI staining) and cell death (Annexin V-FITC detection assay and Western blot) were analyzed on the most sensitive cell line (NCI-H460). The cytotoxic effect of this drug combination was also evaluated against two non-tumorigenic cell lines (MCF-10A and MCF-12A). Finally, the ability of pirfenidone to sensitize NCI-H460 cells to a combination of paclitaxel plus carboplatin was assessed. The results demonstrated that pirfenidone sensitized NCI-H460 cells to paclitaxel treatment, reducing cell growth, viability and proliferation, inducing alterations in the cell cycle profile and causing an increase in the % of cell death. Remarkably, this combination did not increase cytotoxicity in non-tumorigenic cells. Importantly, pirfenidone also sensitized NCI-H460 cells to paclitaxel plus carboplatin. This work highlights the possibility of repurposing pirfenidone in combination with chemotherapy for the treatment of NSCLC.


Assuntos
Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Antineoplásicos/farmacologia , Apoptose , Carboplatina/farmacologia , Carboplatina/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Neoplasias Pulmonares/metabolismo , Paclitaxel , Piridonas
13.
Kardiologiia ; 62(3): 4-15, 2022 Mar 31.
Artigo em Russo, Inglês | MEDLINE | ID: mdl-35414354

RESUMO

Background    Venous thromboembolic complications (VTEC) are a major non-oncological cause of death of patients with malignant neoplasm (MNP). This determines the high significance of antithrombotic therapy for the treatment and secondary prevention of VTEC in this population. During recent years, low-molecular weight heparins (LMWH) have been a "gold standard" for the treatment of cancer-associated venous thrombosis (CAVT). In the recent decade, direct oral anticoagulants (DOACs) have become extensively used for the treatment and prevention of VTEC relapse in non-oncological patients and also for primary prevention of VTEC following orthopedic surgery. Taking into account the oral route of administration, the predictable and convenient pharmacokinetic profile, and the absence of need for coagulation monitoring, it seems possible to use DOACs for the treatment and secondary prevention of VTEС in oncological patients. A meta-analysis of 4 randomized clinical trials (RCTs) showed a higher efficacy of DOACs compared to LMWHs, however, with a greater risk of bleedings in CAVT. In two of four studies using apixaban (more than 40% of weight in meta-analysis), no increase in bleedings was noted.Aim    The aim of this study was to perform a systematic search for comparative clinical studies with apixaban and to perform a meta-analysis to answer the question on clinical efficacy and safety of apixaban in the treatment and secondary prevention of recurrent VTEC in patients with CAVT.Material and methods    The systematic search was performed in three reference databases, Medline (PubMed), Cochrane Library (CENTRAL), and eLibrary. The search was aimed at publications containing results of RCTs using apixaban for the treatment and prevention of VTEC in patients with MNP. A totality of 678 titles was found; 15 articles were selected for detailed studying, and 4 RCTs were included into the final analysis. The meta-analysis was performed according to the criteria of PRISMA guidelines. Relative risk (RR) was used as a measure of the effect. The meta-analysis was performed by the Mantel-Haenszel method using the R software. Statistical heterogeneity was evaluated with the Cochran criterion (I2); heterogeneity was considered significant at I2 ≥50 %, which was a reason for performing a random-effects meta-analysis. For this meta-analysis, the primary outcome measure was new VTECs (symptomatic or detected proximal deep vein thrombosis and/or symptomatic, detected or fatal pulmonary thromboembolism plus symptomatic upper extremity thromboses, celiac veinous thromboses, and cerebral veinous thromboses if they were included into the efficacy endpoint of the primary studies). The primary safety measure was major bleeding according to ISTH criteria. Other variables included major and clinically significant minor bleedings as well as overall death rate.Results    During the systematic search, 4 RCTs were selected. The meta-analysis of the treatment and secondary prevention of VTEC in patients with MNP showed that apixaban was more effective than the active control (88% of LMWHs) in prevention of VTEC relapse. The RR was 0.59; 95 % confidence interval (CI): 0.40-0.86 in the absence of statistically significant differences from the control in the risk of major bleedings (statistically non-significant decrease by 21%), the sum of major and clinically significant minor bleedings, and overall death rate.Conclusion    According to the results of the meta-analysis, the DOAC apixaban may be a drug of choice for the treatment and prevention of VTEC relapse in patients with MNO.


Assuntos
Neoplasias , Tromboembolia Venosa , Trombose Venosa , Anticoagulantes/uso terapêutico , Hemorragia/induzido quimicamente , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Pirazóis , Piridonas , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controle , Trombose Venosa/induzido quimicamente , Trombose Venosa/prevenção & controle
14.
PLoS One ; 17(4): e0266011, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35390010

RESUMO

OBJECTIVE: Few studies have compared the frequency of hemorrhages after tooth extraction between patients taking direct oral anticoagulants (DOACs) and those taking warfarin or no anticoagulants. Further, the effects of the timing of DOAC administration and tooth extraction on the frequency of post-extraction hemorrhage have not been demonstrated. Therefore, we compared the frequency of post-extraction hemorrhages in patients in these different conditions and examined the effects of the timing of DOAC administration and tooth extraction on the frequency. DESIGN: Prospective multicenter study. SETTING: Eighty-six Japanese hospitals. PARTICIPANTS: In total, 182 teeth extracted from 145 individuals (119 teeth from adult males) receiving dabigatran and 88 teeth from individuals (62 teeth from adult males) receiving rivaroxaban were included. INTERVENTION: Tooth extraction was followed by a 7-day observational period between November 1, 2008 and December 31, 2015. Dabigatran was administered twice daily; rivaroxaban was administered once a day. PRIMARY OUTCOME MEASURE: Hemorrhage after tooth extraction. RESULTS: The frequency of hemorrhage after tooth extraction was 1.65%, 3.41%, and 3.63% in those treated with dabigatran, rivaroxaban, and warfarin, respectively, and 0.39% in those who did not receive anticoagulants. Hemorrhages after tooth extraction were significantly higher in the rivaroxaban group than in patients who did not receive anticoagulants (P = 0.008). These frequencies did not differ significantly in the dabigatran and rivaroxaban groups compared to the warfarin group (P = 0.221 and P = 1.000, respectively). CONCLUSIONS: The frequency of hemorrhaging after tooth extraction appeared to be similar in patients receiving continuous dabigatran or rivaroxaban and in those receiving continuous warfarin.


Assuntos
Fibrilação Atrial , Dabigatrana , Administração Oral , Adulto , Anticoagulantes/efeitos adversos , Fibrilação Atrial/tratamento farmacológico , Estudos Transversais , Dabigatrana/efeitos adversos , Hemorragia/induzido quimicamente , Hemorragia/tratamento farmacológico , Humanos , Masculino , Estudos Prospectivos , Piridonas/uso terapêutico , Rivaroxabana/efeitos adversos , Extração Dentária/efeitos adversos , Varfarina/efeitos adversos
15.
Am J Manag Care ; 28(3): e88-e95, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-35404552

RESUMO

OBJECTIVES: To determine whether baloxavir use is associated with lower health care resource utilization (HCRU) and costs for secondary influenza complications post treatment compared with oseltamivir. STUDY DESIGN: Retrospective cohort study. METHODS: Patients filling a prescription for baloxavir or oseltamivir within 48 hours following an influenza-related outpatient visit were identified in the 2018-2019 influenza season from the US Truven MarketScan Research Databases and propensity matched 1:2 (baloxavir:oseltamivir). Outcomes were assessed 15 and 30 days after antiviral treatment and included all-cause, all respiratory-related, and select respiratory-related (influenza, asthma, chronic obstructive pulmonary disease, or infection) HCRU and costs. RESULTS: The study included 5080 baloxavir-treated and 10,160 matched oseltamivir-treated patients. All-cause emergency department (ED) visits and inpatient hospitalizations were lower in baloxavir-treated patients, with a statistically significant difference in the percentage hospitalized at 30 days (0.3% vs 0.5%; P = .04). ED visits for all or select respiratory-related conditions were significantly reduced with baloxavir (P < .01 for all comparisons). Mean per-patient cost savings at day 30 for all-cause, all respiratory-related, and select respiratory-related conditions were $79, $50, and $51, respectively, despite slightly higher prescription costs for baloxavir. In high-risk patients (baloxavir: n = 1958; oseltamivir: n = 3949), the incidence of ED visits was significantly lower for all respiratory-related and select respiratory-related conditions (P < .01); cost savings with baloxavir in the high-risk cohort were substantially greater than in the overall cohort. CONCLUSIONS: Treatment of patients with influenza with single-dose baloxavir was generally associated with lower HCRU and costs post treatment compared with oseltamivir, particularly in high-risk patients.


Assuntos
Influenza Humana , Oseltamivir , Antivirais/uso terapêutico , Dibenzotiepinas , Humanos , Influenza Humana/tratamento farmacológico , Morfolinas/uso terapêutico , Oseltamivir/uso terapêutico , Piridonas/uso terapêutico , Estudos Retrospectivos , Triazinas/uso terapêutico
17.
Artigo em Inglês | MEDLINE | ID: mdl-35457498

RESUMO

This study aimed to examine the incidence and predictors of loss to follow up (LTFU) in the context of ongoing atrocities caused by armed conflict, where HIV treatment programs and HIV-infected patients may face unique challenges in terms of ART adherence and retention in care. We conducted an observational prospective cohort study of 468 patients living with HIV (PLWHIV) under dolutegravir (DTG) in all health facilities in Bunia between July 2019 and July 2021. Kaplan-Meier plots were used to determine the probability of LTFU as a function of time as inclusive of the cohort. The main outcome variable was LTFU, defined as not taking an ART refill for a period of 3 months or longer from the last attendance for refill, and not yet classified as 'dead' or 'transferred-out.' The log-rank test was used to compare survival curves based on predictors. Cox proportional hazard modeling was used to measure predictors of LTFU from the baseline until 31 July 2021 (the endpoint). A total of 3435.22 person-months (p-m) were involved in follow up, with an overall incidence rate of 33.48 LTFU per 1000 p-m. Patients who had less experience with ART at enrolment and the ethnically Sudanese, had a higher hazard of being LTFU compared to their reference groups. This study reports a high LTFU rate in this conflict setting. An ART program in such a setting should pay more attention to naive patients and other particularly vulnerable patients such as Sudanese during the pre-ART phase. The study implies the implementation of innovative strategies to address this high risk of being LTFU, reducing either the cost or the distance to the health facility.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Fármacos Anti-HIV/uso terapêutico , Estudos de Coortes , República Democrática do Congo , Seguimentos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Compostos Heterocíclicos com 3 Anéis , Humanos , Incidência , Perda de Seguimento , Oxazinas , Piperazinas , Modelos de Riscos Proporcionais , Estudos Prospectivos , Piridonas , Estudos Retrospectivos
18.
Curr Opin HIV AIDS ; 17(3): 121-126, 2022 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-35439786

RESUMO

PURPOSE OF REVIEW: Long-acting antiretroviral therapy (LA-ART) brings a paradigm shift to HIV care with injectable cabotegravir/rilpivirine (IM-CAB/RPV) in current or imminent use in several countries. This brings the usual opportunities and challenges of a new therapy, plus requirements to adapt services to reliably deliver injections and ensure patients understand advantages and limitations. We summarise key considerations for implementation in high-income countries. RECENT FINDINGS: Monthly IM-CAB/RPV is noninferior to oral ART and monthly IM-CAB/RPV to 1-monthly in carefully selected virally suppressed people. The numerically higher virological failure rate on two-monthly IM-CAB/RPV warrants close attention and careful monitoring. Implementation projects report positive experiences for patients and staff, but also barriers. Data is needed in younger people, pregnancy/breastfeeding, and in those with detectable viraemia secondary to suboptimal adherence. SUMMARY: We highlight a paucity of real-world data and key unanswered questions. Existing data on injection techniques may have implications for training; monitoring of outcomes is crucial to ensure clinical trial results are replicated in real-life. Better understanding of treatment failure, and individualised therapy, is crucial, and it is important to repeat patient preference surveys as new data emerges to ensure decisions are based on the most recent evidence of benefit vs risk.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Fármacos Anti-HIV/uso terapêutico , Antirretrovirais/uso terapêutico , Países Desenvolvidos , Infecções por HIV/tratamento farmacológico , Humanos , Piridonas , Rilpivirina
19.
Future Cardiol ; 18(5): 393-405, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35360925

RESUMO

Aim: To compare real-world effectiveness/safety of non-vitamin K antagonist oral anticoagulants and vitamin K antagonists among patients with non-valvular atrial fibrillation. Materials & methods: A systematic review of electronic databases yielded 7661 citations published from January 2013 to January 2020. Fifty-five studies were included in Bayesian network meta-analyses of hazard ratios. Results & conclusion: In comparison with vitamin K antagonists, apixaban, dabigatran and rivaroxaban were associated with a reduced risk of stroke or systemic embolism, ischemic stroke, intracranial hemorrhage and all-cause mortality. Apixaban, dabigatran and edoxaban, but not rivaroxaban, were associated with a reduced risk of major bleeding. This study confirmed the effectiveness and safety of non-vitamin K antagonist oral anticoagulants for the treatment of non-valvular atrial fibrillation in real-world settings, consistent with clinical trial evidence.


This study aimed to compare real-world effectiveness/safety of non-vitamin K antagonist oral anticoagulants and vitamin K antagonists among patients with non-valvular atrial fibrillation. A systematic review was conducted from January 2013 to January 2020, and a total of 7661 references were assessed for relevance. Fifty-five studies were combined in the analysis; in comparison with vitamin K antagonists, apixaban, dabigatran and rivaroxaban were associated with a reduced risk of stroke or systemic embolism, ischemic stroke, intracranial hemorrhage and all-cause mortality. Apixaban, dabigatran and edoxaban, but not rivaroxaban, were associated with a reduced risk of major bleeding. This study confirmed the effectiveness and safety of non-vitamin K antagonist oral anticoagulants for the treatment of non-valvular atrial fibrillation in real-world settings, consistent with clinical trial evidence.


Assuntos
Fibrilação Atrial , Acidente Vascular Cerebral , Administração Oral , Anticoagulantes/uso terapêutico , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Teorema de Bayes , Dabigatrana/uso terapêutico , Fibrinolíticos/uso terapêutico , Humanos , Metanálise em Rede , Piridonas/uso terapêutico , Rivaroxabana/uso terapêutico , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Vitamina K
20.
PLoS One ; 17(4): e0266658, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35443000

RESUMO

AIMS: A Markov model was adapted to assess the real-world cost-effectiveness of rivaroxaban, dabigatran and apixaban. Each of these non-vitamin K antagonist oral anticoagulants was compared with vitamin K antagonist for stroke prevention in patients with non-valvular atrial fibrillation in Spain. METHODS: All inputs were derived from real-world studies: baseline patient characteristics, clinical event rates, as well as persistence rates for the vitamin K antagonist treatment option. A meta-analysis of real-world studies provided treatment effect and persistence data for rivaroxaban, dabigatran and apixaban, each compared with vitamin K antagonist therapy. The model considered 3-month cycles over a lifetime horizon. The model outcomes included different costs, quality-adjusted life years and life-years gained. Sensitivity analyses were performed to test the robustness of the model. RESULTS: When compared with vitamin K antagonist, rivaroxaban incurred incremental costs of €77 and resulted in incremental quality-adjusted life years of 0.08. The incremental cost per quality-adjusted life year was €952. For the same comparison, the incremental cost per quality-adjusted life year for dabigatran was €4,612. Finally, compared with vitamin K antagonist, the incremental cost per quality-adjusted life year for apixaban was €32,015. The sensitivity analyses confirmed the robustness of the base case results. The probabilities to be cost-effective versus vitamin K antagonist were 94%, 86% and 35%, respectively, for rivaroxaban, dabigatran and apixaban, considering a willingness-to-pay threshold of €22,000 per quality-adjusted life year gained, based on a cost-effectiveness study of the Spanish National Health System. CONCLUSION: These results suggest that rivaroxaban and dabigatran are cost-effective versus vitamin K antagonist for stroke prevention in non-valvular atrial fibrillation, from the Spanish National Health System perspective.


Assuntos
Fibrilação Atrial , Acidente Vascular Cerebral , Administração Oral , Anticoagulantes , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Análise Custo-Benefício , Dabigatrana/uso terapêutico , Humanos , Piridonas , Rivaroxabana/uso terapêutico , Espanha/epidemiologia , Acidente Vascular Cerebral/tratamento farmacológico , Vitamina K
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