Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 218
Filtrar
1.
Artigo em Inglês | MEDLINE | ID: mdl-34632490

RESUMO

AIMS: The role of diuretics in patients with intermediate-risk pulmonary embolism (PE) is controversial. In this multicentre, double-blind trial, we randomly assigned normotensive patients with intermediate-risk PE to receive either a single 80 mg bolus of furosemide or a placebo. METHODS AND RESULTS: Eligible patients had at least a simplified PE Severity Index (sPESI) ≥1 with right ventricular dysfunction. The primary efficacy endpoint assessed 24 h after randomization included (i) absence of oligo-anuria and (ii) normalization of all sPESI items. Safety outcomes were worsening renal function and major adverse outcomes at 48 hours defined by death, cardiac arrest, mechanical ventilation, or need of catecholamine. A total of 276 patients underwent randomization; 135 were assigned to receive the diuretic, and 141 to receive the placebo. The primary outcome occurred in 68/132 patients (51.5%) in the diuretic and in 49/132 (37.1%) in the placebo group (relative risk = 1.30, 95% confidence interval 1.04-1.61; P = 0.021). Major adverse outcome at 48 h occurred in 1 (0.8%) patients in the diuretic group and 4 patients (2.9%) in the placebo group (P = 0.19). Increase in serum creatinine level was greater in diuretic than placebo group [+4 µM/L (-2; 14) vs. -1 µM/L (-11; 6), P < 0.001]. CONCLUSION: In normotensive patients with intermediate-risk PE, a single bolus of furosemide improved the primary efficacy outcome at 24 h and maintained stable renal function. In the furosemide group, urine output increased, without a demonstrable improvement in heart rate, systolic blood pressure, or arterial oxygenation.ClinicalTrials.gov identifier NCT02268903.

2.
Lancet Respir Med ; 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34506761

RESUMO

BACKGROUND: The use of cyclophosphamide in patients with acute exacerbation of idiopathic pulmonary fibrosis (IPF) is unknown. Our study was designed to evaluate the efficacy and safety of four cyclophosphamide pulses in addition to high-dose methylprednisolone in this population. METHODS: In this double-blind, placebo-controlled trial done in 35 departments across 31 hospitals in France, adult patients (≥18 years) with acute exacerbation of IPF and those with suspected acute exacerbation of IPF were randomly assigned in a 1:1 ratio using a web-based system to receive either intravenous pulses of cyclophosphamide (600 mg/m2) plus uromitexan as haemorrhagic cystitis prophylaxis (200 mg/m2) at the time of cyclophosphamide administration and then again, 4 h later, or placebo at days 0, 15, 30, and 60. Random assignment was stratified according to the severity of IPF and was block-balanced with variable block sizes of four or six patients. Patients receiving mechanical ventilation, with active infection, with active cancer, or who were registered on the lung transplant waiting list were excluded. All patients received standardised high-dose glucocorticoids. The investigators, patients, and the sponsor were masked to the treatment assignments. The primary endpoint was 3-month all-cause mortality, analysed by a χ2 test adhering to an intention-to-treat principle. The trial is now complete and registered with ClinicalTrials.gov, NCT02460588. FINDINGS: Between Jan 22, 2016, and July 19, 2018, 183 patients were assessed for eligibility, of whom 120 patients were randomly assigned and 119 patients (62 [52%] with severe IPF) received at least one dose of cyclophosphamide (n=60) or placebo (n=59), all of whom were included in the intention-to-treat analysis. The 3-month all-cause mortality was 45% (27/60) in patients given cyclophosphamide compared with 31% (18/59) in the placebo group (difference 14·5% [95% CI -3·1 to 31·6]; p=0·10). Similar results were found after adjustment by IPF severity (odds ratio [OR] 1·89 [95% CI 0·89-4·04]). The risk of death at 3 months, independent of the treatment received, was higher with severe than non-severe IPF (OR 2·62 [1·12-6·12]) and was lower with the use of antifibrotic therapy (OR 0·33 [0·13-0·82]). Adverse events were similar between groups by 6 months (25 [42%] in the cyclophosphamide group vs 30 [51%] in the placebo group) and their proportion, including infections, did not differ. Overall infection was the main adverse event and occurred in 20 (33%) of 60 patients in the cyclophosphamide group versus 21 (36%) of 59 patients in the placebo group. INTERPRETATION: In patients with acute exacerbation of IPF, adding intravenous cyclophosphamide pulses to glucocorticoids increased 3-month mortality. These findings provide evidence against the use of intravenous cyclophosphamide in such patients. FUNDING: Programme Hospitalier de Recherche Clinique of the French Ministry of Health (PHRC 2014-502), Roche Pharmaceuticals.

3.
Int J Cardiol ; 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34534607

RESUMO

INTRODUCTION: Triggering receptor expressing on myeloid cells (TREM)-1 is involved in the pathophysiology of ischemic heart disease. Plasma soluble TREM-1 levels (sTREM-1) has been associated with increased risk of major adverse cardiovascular events (MACE) in acute myocardial infarction (AMI) patients. However, the causative link between TREM-1 and MACE remains unknown and requires further investigation before developing potential therapeutic approaches. METHODS AND RESULTS: Using the serum and DNA data bank from the prospective, nationwide French registry of Acute ST-elevation and non-ST-elevation Myocardial Infarction (FAST-MI 2010, N = 1293), we studied the association of plasma levels of sTREM-1 with 9 common genetic variants at the TREM1 locus and their relationship with recurrent MACE over a 3-year follow up. Plasma levels of sTREM-1 were associated with an increased risk of MACEs (death, recurrent MI or stroke) (adjusted HR = 1.86, 95%CI = 1.06-3.26 and HR = 1.11, 95%CI = 0.61-2.02 respectively for tertiles 3 and 2 versus tertile 1, P < 0.001). The study of common variants identified two major genetic determinants of sTREM-1 (rs4714449: beta = -0.11, Padd = 7.85 × 10-5 and rs3804276: beta = 0.18, Padd = 2.65 × 10-11) with a potential role on maintenance and/or differentiation of hematopoietic stem cells. However, associated variants only explained 4% of sTREM-1 variance (P = 2.74 × 10-14). Moreover, the rs4714449 variant, individually and in haplotype, was not significantly associated with MACE (HR = 0.61, 95%CI: 0.35-1.05, P = 0.07). CONCLUSIONS: Despite its relationship with increased risk of death, recurrent MI and stroke, genetic determinants of plasma levels of sTREM-1 were not found to be causal prognostic factors in patients with acute myocardial infarction.

4.
J Am Coll Cardiol ; 78(13): 1291-1305, 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34556314

RESUMO

BACKGROUND: The optimal management of patients with ST-segment elevation myocardial infarction (STEMI) presenting late->12 hours following symptom onset-is still under debate. OBJECTIVES: The purpose of this study was to describe characteristics, temporal trends, and impact of revascularization in a large population of latecomer STEMI patients. METHODS: The authors analyzed the data of 3 nationwide observational studies from the FAST-MI (French Registry of Acute ST-elevation and non-ST-elevation Myocardial Infarction) program, conducted over a 1-month period in 2005, 2010, and 2015. Patients presenting between 12 and 48 hours after symptom onset were classified as latecomers. RESULTS: A total of 6,273 STEMI patients were included in the 3 cohorts, 1,169 (18.6%) of whom were latecomers. After exclusion of patients treated with fibrinolysis and patients deceased within 2 days after admission, 1,077 patients were analyzed, of whom 729 (67.7%) were revascularized within 48 hours after hospital admission. At 30-day follow-up, all-cause death rate was significantly lower among revascularized latecomers (2.1% vs 7.2%; P < 0.001). After a median follow-up of 58 months, the rate of all-cause death was 30.4 (95% CI: 25.7-35.9) per 1,000 patient-years in the revascularized latecomers group vs 78.7 (95% CI: 67.2-92.3) per 1,000 patient-years in the nonrevascularized latecomers group (P < 0.001). In multivariate analysis, revascularization of latecomer STEMI patients was independently associated with a significant reduction of mortality occurrence during follow-up (HR: 0.65 [95% CI: 0.50-0.84]; P = 0.001). CONCLUSIONS: Coronary revascularization of latecomer STEMI patients is associated with better short and long-term clinical outcomes.

5.
BMJ Open ; 11(8): e048187, 2021 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-34408046

RESUMO

INTRODUCTION: At the time of the worrying emergence and spread of bacterial resistance, reducing the selection pressure by reducing the exposure to antibiotics in patients with community-acquired pneumonia (CAP) is a public health issue. In this context, the combined use of molecular tests and biomarkers for guiding antibiotics discontinuation is attractive. Therefore, we have designed a trial comparing an integrated approach of diagnosis and treatment of severe CAP to usual care. METHODS AND ANALYSIS: The multiplex PCR and procalcitonin to reduce duration of antibiotics exposure in patients with severe-CAP (MULTI-CAP) trial is a multicentre (n=20), parallel-group, superiority, open-label, randomised trial. Patients are included if adult admitted to intensive care unit for a CAP. Diagnosis of pneumonia is based on clinical criteria and a newly appeared parenchymal infiltrate. Immunocompromised patients are excluded. Subjects are randomised (1:1 ratio) to either the intervention arm (experimental strategy) or the control arm (usual strategy). In the intervention arm, the microbiological diagnosis combines a respiratory multiplex PCR (mPCR) and conventional microbiological investigations. An algorithm of early antibiotic de-escalation or discontinuation is recommended, based on mPCR results and the procalcitonin value. In the control arm, only conventional microbiological investigations are performed and antibiotics de-escalation remains at the clinician's discretion. The primary endpoint is the number of days alive without any antibiotic from the randomisation to day 28. Based on our hypothesis of 2 days gain in the intervention arm, we aim to enrol a total of 450 patients over a 30-month period. ETHICS AND DISSEMINATION: The MULTI-CAP trial is conducted according to the principles of the Declaration of Helsinki, is registered in Clinical Trials and has been approved by the Committee for Protection of Persons and the National French Drug Safety Agency. Written informed consents are obtained from all the patients (or representatives). The results will be disseminated through educational institutions, submitted to peer-reviewed journals for publication and presented at medical congresses. TRIAL REGISTRATION NUMBER: NCT03452826; Pre-results.


Assuntos
COVID-19 , Pneumonia , Adulto , Antibacterianos/uso terapêutico , Humanos , Unidades de Terapia Intensiva , Reação em Cadeia da Polimerase Multiplex , Pneumonia/tratamento farmacológico , Pró-Calcitonina
6.
iScience ; : 103040, 2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34462732

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic remains a source of considerable morbidity and mortality throughout the world. Therapeutic options to reduce symptoms, inflammatory response, or disease progression are limited. This randomized open-label trial enrolled 100 ambulatory patients with symptomatic COVID-19 in Toronto, Canada. Results indicate that icosapent ethyl (8g daily for 3 days followed by 4g daily for 11 days) significantly reduced high-sensitivity C-reactive protein (hs-CRP) and improved symptomatology compared with patients assigned to usual care. Specifically, the primary biomarker endpoint, change in hs-CRP, was significantly reduced by 25% among treated patients (-0.5mg/L, IQR[-6.9,0.4], within-group P=0.011). Conversely, a non-significant 5.6% reduction was observed among usual care patients (-0.1mg/L, IQR[-3.2,1.7], within-group P=0.51). An unadjusted between-group primary biomarker analysis was non-significant (P=0.082). Overall, this report provides evidence of an early anti-inflammatory effect of icosapent ethyl in a modest sample, including an initial well-tolerated loading dose, in symptomatic COVID-19 outpatients. ClinicalTrials.gov Identifier: NCT04412018.

7.
Artigo em Inglês | MEDLINE | ID: mdl-34420366

RESUMO

Background: In patients with ST-elevation myocardial infarction (STEMI) and multivessel disease, percutaneous coronary intervention (PCI) for non-culprit lesions guided by FFR is superior to treatment of the culprit lesion alone. Whether deferring non-culprit PCI is safe in this specific context is questionable. We aimed to assess clinical outcomes at one-year in STEMI patients with multivessel coronary artery disease and an FFR-guided strategy for non-culprit lesions, according to whether or not ≥1 PCI was performed. Methods: Outcomes were analyzed in patients of the randomized FLOWER MI (Flow Evaluation to Guide Revascularization in Multivessel ST-Elevation Myocardial Infarction) trial in whom, after successful primary PCI, non-culprit lesions were assessed using FFR. The primary outcome was a composite of all-cause death, non-fatal MI, and unplanned hospitalization with urgent revascularization at one year. Results: Among 1,171 patients enrolled in this study, 586 were assigned to the FFR-guided group: 388 (66%) of them had ≥1 PCI and 198 (34%) had no PCI. Mean FFR before decision (i.e., PCI or not) of non-culprit lesions were 0.75±0.10 and 0.88±0.06, respectively. During follow-up, a primary outcome event occurred in 16 of 388 patients (4.1%) in patients with PCI and in 16 of 198 patients (8.1%) in patients without PCI (adjusted hazard ratio, 0.42; 95% confidence interval, 0.20 to 0.88; P = 0.02). Conclusions: In patients with STEMI undergoing complete revascularization guided by FFR measurement, those with ≥1 PCI had lower event rates at 1 year, compared with patients with deferred PCI, suggesting that deferring lesions judged relevant by visual estimation but with FFR >0.80 may not be optimal in this context. Future randomized studies are needed to confirm this data.

8.
Nature ; 597(7874): 92-96, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34433968

RESUMO

Atherosclerotic cardiovascular disease causes heart attacks and strokes, which are the leading causes of mortality worldwide1. The formation of atherosclerotic plaques is initiated when low-density lipoproteins bind to heparan-sulfate proteoglycans (HSPGs)2 and become trapped in the subendothelial space of large and medium size arteries, which leads to chronic inflammation and remodelling of the artery wall2. A proliferation-inducing ligand (APRIL) is a cytokine that binds to HSPGs3, but the physiology of this interaction is largely unknown. Here we show that genetic ablation or antibody-mediated depletion of APRIL aggravates atherosclerosis in mice. Mechanistically, we demonstrate that APRIL confers atheroprotection by binding to heparan sulfate chains of heparan-sulfate proteoglycan 2 (HSPG2), which limits the retention of low-density lipoproteins, accumulation of macrophages and formation of necrotic cores. Indeed, antibody-mediated depletion of APRIL in mice expressing heparan sulfate-deficient HSPG2 had no effect on the development of atherosclerosis. Treatment with a specific anti-APRIL antibody that promotes the binding of APRIL to HSPGs reduced experimental atherosclerosis. Furthermore, the serum levels of a form of human APRIL protein that binds to HSPGs, which we termed non-canonical APRIL (nc-APRIL), are associated independently of traditional risk factors with long-term cardiovascular mortality in patients with atherosclerosis. Our data reveal properties of APRIL that have broad pathophysiological implications for vascular homeostasis.


Assuntos
Aterosclerose/metabolismo , Aterosclerose/prevenção & controle , Proteoglicanas de Heparan Sulfato/metabolismo , Membro 13 da Superfamília de Ligantes de Fatores de Necrose Tumoral/metabolismo , Animais , Antígeno de Maturação de Linfócitos B/metabolismo , Sítios de Ligação , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/mortalidade , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ligação Proteica , Proteína Transmembrana Ativadora e Interagente do CAML/metabolismo , Membro 13 da Superfamília de Ligantes de Fatores de Necrose Tumoral/sangue , Membro 13 da Superfamília de Ligantes de Fatores de Necrose Tumoral/deficiência
9.
Diabetes Metab ; : 101265, 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34224895

RESUMO

AIM: . - We attempted to describe the risk of heart failure (HF) occurrence according to diabetes mellitus (DM) status in patients with coronary artery disease (CAD) over time, from acute myocardial infarction (MI) to the chronic stable phase. METHODS: . - For the acute and subacute MI phases, we analysed the FAST-MI cohort restricted to patients without history of HF (n=12,473). The analysis on 1-year outcomes after MI was further restricted to patients who were discharged alive and without history of HF and/or HF symptoms during the index hospitalisation for MI (n=9,181). To analyse the chronic phase, we analysed the CORONOR cohort restricted to patients without history of HF (n=3,871). The primary endpoint was HF occurrence according to DM status. We also analysed the composite of all-cause death or HF. RESULTS: . - Killip-Kimball class ≥II during the index MI hospitalisation was more frequent in DM patients compared to non-DM patients (29% vs. 15.3%, adjusted OR=1.60). At one year after MI, hospitalisation for HF was more frequent in DM patients (3.3% vs. 1.2%, adjusted HR=1.73). At the chronic phase (5-year outcomes), hospitalisation for HF was more frequent in DM patients (8.5% vs. 4.3%, adjusted HR=1.70). Results focusing on the composite endpoint (all-cause death or HF) were consistent. CONCLUSION: . - DM was associated with a very constant near 2-fold increase in the risk of HF whatever the presentation of CAD. Avoiding the risk of HF occurrence in CAD patients with DM is critical in daily practice and should be a constant life-long endeavour.

10.
Nurs Res ; 70(5): 354-365, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34173380

RESUMO

BACKGROUND: Optimizing care continuum entry interventions is key to ending the HIV epidemic. Offering HIV screening to key populations in emergency departments (EDs) is a strategy that has been demonstrated to be effective. Analyzing patient and provider perceptions of such screening can help identify implementation facilitators and barriers. OBJECTIVES: The aim of this study was to investigate the acceptability of offering nurse-driven HIV screening to key populations based on data collected from patients, nurses, and other service providers. METHODS: This convergent mixed-methods study was a substudy of a cluster-randomized two-period crossover trial conducted in eight EDs to evaluate the effectiveness of the screening strategy. During the DICI-VIH (Dépistage Infirmier CIblé du VIH) trial, questionnaires were distributed to patients aged 18-64 years. Based on their responses, nurses offered screening to members of key populations.Over 5 days during the intervention period in four EDs, 218 patients were secondarily questioned about the acceptability of screening. Nurses completed 271 questionnaires pre- and posttrial regarding acceptability in all eight EDs. Descriptive analyses were conducted on these quantitative data. Convenience and purposeful sampling was used to recruit 53 providers to be interviewed posttrial. Two coders conducted a directed qualitative content analysis of the interview transcripts independently. RESULTS: The vast majority of patients (95%) were comfortable with questions asked to determine membership in key populations and agreed (89%) that screening should be offered to key populations in EDs. Nurses mostly agreed that offering screening to key populations was well accepted by patients (62.2% pretrial and 71.4% posttrial), was easy to implement, and fell within the nursing sphere of competence. Pretrial, 73% of the nurses felt that such screening could be implemented in EDs. Posttrial, the proportion was 41%. Three themes emerged from the interviews: preference for targeted screening and a written questionnaire to identify key populations, facilitators of long-term implementation, and implementation barriers. Nurses were favorable to such screening provided specific conditions were met regarding training, support, collective involvement, and flexibility of application to overcome organizational and individual barriers. DISCUSSION: Screening for key populations was perceived as acceptable and beneficial by patients and providers. Addressing the identified facilitators and barriers would help increase screening implementation in EDs.


Assuntos
Infecções por HIV/diagnóstico , Programas de Rastreamento/normas , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Adolescente , Adulto , Serviço Hospitalar de Emergência/organização & administração , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Infecções por HIV/psicologia , Humanos , Masculino , Programas de Rastreamento/métodos , Programas de Rastreamento/psicologia , Pessoa de Meia-Idade , Paris , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Pesquisa Qualitativa , Inquéritos e Questionários
11.
J Am Coll Cardiol ; 77(23): 2960-2972, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-34112322

RESUMO

Women are under-represented as leaders of cardiovascular randomized controlled trials, representing 1 in 10 lead authors of cardiovascular trials published in high-impact journals. Although the proportion of cardiovascular specialists who are women has increased in recent years, the proportion of cardiovascular clinical trialists who are women has not. This gap, underpinned by systemic sexism, has not been adequately addressed. The benefits of diverse randomized controlled trial leadership extend to patients and professionals. In this position statement, we present strategies adopted by some organizations to end gender inequality in research leadership. We offer an actionable roadmap for early-career researchers, scientists, academic institutions, professional societies, trial sponsors, and journals to follow, with the goal of harnessing the strength of women and under-represented groups as research leaders and facilitating a just culture in the cardiovascular clinical trial enterprise.

12.
BMJ Open Respir Res ; 8(1)2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34088727

RESUMO

BACKGROUND: Whereas first-line bronchial artery embolisation (BAE) is considered standard of care for the management of severe haemoptysis, it is unknown whether this approach is warranted for non-severe haemoptysis. RESEARCH QUESTION: To assess the efficacy on bleeding control and the safety of first-line BAE in non-severe haemoptysis of mild abundance. STUDY DESIGN AND METHODS: This multicentre, randomised controlled open-label trial enrolled adult patients without major comorbid condition and having mild haemoptysis (onset <72 hours, 100-200 mL estimated bleeding amount), related to a systemic arterial mechanism. Patients were randomly assigned (1:1) to BAE associated with medical therapy or to medical therapy alone. RESULTS: Bleeding recurrence at day 30 after randomisation (primary outcome) occurred in 4 (11.8%) of 34 patients in the BAE strategy and 17 (44.7%) of 38 patients in the medical strategy (difference -33%; 95% CI -13.8% to -52.1%, p=0.002). The 90-day bleeding recurrence-free survival rates were 91.2% (95% CI 75.1% to 97.1%) and 60.2% (95% CI 42.9% to 73.8%), respectively (HR=0.19, 95% CI 0.05 to 0.67, p=0.01). No death occurred during follow-up and no bleeding recurrence needed surgery.Four adverse events (one major with systemic emboli) occurred during hospitalisation, all in the BAE strategy (11.8% vs 0%; difference 11.8%, 95% CI 0.9 to 22.6, p=0.045); all eventually resolved. CONCLUSION: In non-severe haemoptysis of mild abundance, BAE associated with medical therapy had a superior efficacy for preventing bleeding recurrences at 30 and 90 days, as compared with medical therapy alone. However, it was associated with a higher rate of adverse events. TRIAL REGISTRATION NUMBER: NCT01278199.

14.
N Engl J Med ; 385(4): 297-308, 2021 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-33999545

RESUMO

BACKGROUND: In patients with ST-elevation myocardial infarction (STEMI) who have multivessel disease, percutaneous coronary intervention (PCI) for nonculprit lesions (complete revascularization) is superior to treatment of the culprit lesion alone. However, whether complete revascularization that is guided by fractional flow reserve (FFR) is superior to an angiography-guided procedure is unclear. METHODS: In this multicenter trial, we randomly assigned patients with STEMI and multivessel disease who had undergone successful PCI of the infarct-related artery to receive complete revascularization guided by either FFR or angiography. The primary outcome was a composite of death from any cause, nonfatal myocardial infarction, or unplanned hospitalization leading to urgent revascularization at 1 year. RESULTS: The mean (±SD) number of stents that were placed per patient for nonculprit lesions was 1.01±0.99 in the FFR-guided group and 1.50±0.86 in the angiography-guided group. During follow-up, a primary outcome event occurred in 32 of 586 patients (5.5%) in the FFR-guided group and in 24 of 577 patients (4.2%) in the angiography-guided group (hazard ratio, 1.32; 95% confidence interval, 0.78 to 2.23; P = 0.31). Death occurred in 9 patients (1.5%) in the FFR-guided group and in 10 (1.7%) in the angiography-guided group; nonfatal myocardial infarction in 18 (3.1%) and 10 (1.7%), respectively; and unplanned hospitalization leading to urgent revascularization in 15 (2.6%) and 11 (1.9%), respectively. CONCLUSIONS: In patients with STEMI undergoing complete revascularization, an FFR-guided strategy did not have a significant benefit over an angiography-guided strategy with respect to the risk of death, myocardial infarction, or urgent revascularization at 1 year. However, given the wide confidence intervals for the estimate of effect, the findings do not allow for a conclusive interpretation. (Funded by the French Ministry of Health and Abbott; FLOWER-MI ClinicalTrials.gov number, NCT02943954.).


Assuntos
Angiografia Coronária , Reserva Fracionada de Fluxo Miocárdico , Intervenção Coronária Percutânea/métodos , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Idoso , Intervalos de Confiança , Estenose Coronária/cirurgia , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Revascularização Miocárdica/métodos , Modelos de Riscos Proporcionais , Infarto do Miocárdio com Supradesnível do Segmento ST/mortalidade , Infarto do Miocárdio com Supradesnível do Segmento ST/fisiopatologia , Método Simples-Cego , Stents
15.
J Am Coll Cardiol ; 77(19): 2366-2377, 2021 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-33985681

RESUMO

BACKGROUND: THEMIS (The Effect of Ticagrelor on Health Outcomes in Diabetes Mellitus Patients Intervention Study) (n = 19,220) and its pre-specified THEMIS-PCI (The Effect of Ticagrelor on Health Outcomes in Diabetes Mellitus Patients Intervention Study-Percutaneous Coronary Intervention) (n = 11,154) subanalysis showed, in individuals with type 2 diabetes mellitus (median duration 10.0 years; HbA1c 7.1%) and stable coronary artery disease without prior myocardial infarction (MI) or stroke, that ticagrelor plus aspirin (compared with placebo plus aspirin) produced a favorable net clinical benefit (composite of all-cause mortality, MI, stroke, fatal bleeding, and intracranial bleeding) if the patients had a previous percutaneous coronary intervention. OBJECTIVES: In these post hoc analyses, the authors examined whether the primary efficacy outcome (cardiovascular death, MI, stroke: 3-point major adverse cardiovascular events [MACE]), primary safety outcome (Thrombolysis In Myocardial Infarction-defined major bleeding) and net clinical benefit varied with diabetes-related factors. METHODS: Outcomes were analyzed across baseline diabetes duration, HbA1c, and antihyperglycemic medications. RESULTS: In THEMIS, the incidence of 3-point MACE increased with diabetes duration (6.7% for ≤5 years, 11.1% for >20 years) and HbA1c (6.4% for ≤6.0%, 11.8% for >10.0%). The relative benefits of ticagrelor plus aspirin on 3-point MACE reduction (hazard ratio [HR]: 0.90; p = 0.04) were generally consistent across subgroups. Major bleeding event rate (overall: 1.6%) did not vary by diabetes duration or HbA1c and was increased similarly by ticagrelor across all subgroups (HR: 2.32; p < 0.001). These findings were mirrored in THEMIS-PCI. The efficacy and safety of ticagrelor plus aspirin did not differ by baseline antihyperglycemic therapy. In THEMIS-PCI, but not THEMIS, ticagrelor generally produced favorable net clinical benefit across diabetes duration, HbA1c, and antihyperglycemic medications. CONCLUSION: Ticagrelor plus aspirin yielded generally consistent and favorable net clinical benefit across the diabetes-related factors in THEMIS-PCI but not in the overall THEMIS population.

16.
Joint Bone Spine ; 88(4): 105171, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33689840

RESUMO

OBJECTIVE: Despite its prevalence, there are few worldwide hand osteoarthritis (HOA) cohorts. The main objective of DIGItal COhort Design (DIGICOD) cohort is to investigate prognostic clinical, biological, genetic and imaging factors of clinical worsening after 6years follow-up. METHODS: DIGICOD is a hospital-based prospective cohort including patients>35years-old with symptomatic HOA fulfilling: (i) ACR criteria for HOA with≥2 symptomatic joints among proximal/distal interphalangeal joints or 1st interphalangeal joint with Kellgren-Lawrence (KL)≥2; or (ii) symptomatic thumb base OA with KL≥2. Main exclusion criteria were inflammatory arthritis and crystal arthropathies. Annual clinical evaluations were scheduled with imaging (X-rays of the hands and of other OA symptomatic joints) and biological sampling every 3years. Hand radiographs are scored using KL and anatomical Verbruggen-Veys scores. Follow-up visits are ongoing. Cohort methodology and baseline characteristics are presented. RESULTS: Between April 2013 and June 2017, from the 436 HOA included patients, 426 have been analysed of whom 357 (84%) are women. Mean age±standard deviation was 66.7±7.3years and mean disease duration was 12.6±9.6years. Metabolic syndrome affected 151 (36.5%) patients. Mean Visual Analog Scale (VAS) hand pain (0-100mm) was 44.4±26.7mm at activity. Mean FIHOA (0-100) was 19.9±18.6. Elevated serum CRP level (≥5mg/L) involved 10% patients. Mean KL score (0-128) was 46.7±18 and the mean number of joint with KL≥2 was 15.1±6.3. Erosive HOA (defined as≥1 Erosive or Remodeling phase joint according to Verbruggen-Veys score) involved 195/426 (45.8%) patients and the median number (interquartile range) of erosive joints in erosive patients was 3.0 (1.0-5.0). CONCLUSION: DIGICOD is a unique prospective HOA cohort with a long-term 6years standardized assessment and has included severe radiologically HOA patients with a high prevalence of erosive disease.


Assuntos
Articulação da Mão , Osteoartrite , Idoso , Estudos de Coortes , Feminino , Articulação da Mão/diagnóstico por imagem , Hospitais , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite/diagnóstico por imagem , Osteoartrite/epidemiologia , Estudos Prospectivos
17.
Nat Commun ; 12(1): 1483, 2021 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-33674611

RESUMO

Acute myocardial infarction is a common condition responsible for heart failure and sudden death. Here, we show that following acute myocardial infarction in mice, CD8+ T lymphocytes are recruited and activated in the ischemic heart tissue and release Granzyme B, leading to cardiomyocyte apoptosis, adverse ventricular remodeling and deterioration of myocardial function. Depletion of CD8+ T lymphocytes decreases apoptosis within the ischemic myocardium, hampers inflammatory response, limits myocardial injury and improves heart function. These effects are recapitulated in mice with Granzyme B-deficient CD8+ T cells. The protective effect of CD8 depletion on heart function is confirmed by using a model of ischemia/reperfusion in pigs. Finally, we reveal that elevated circulating levels of GRANZYME B in patients with acute myocardial infarction predict increased risk of death at 1-year follow-up. Our work unravels a deleterious role of CD8+ T lymphocytes following acute ischemia, and suggests potential therapeutic strategies targeting pathogenic CD8+ T lymphocytes in the setting of acute myocardial infarction.


Assuntos
Linfócitos T CD8-Positivos/metabolismo , Granzimas/genética , Granzimas/metabolismo , Coração/fisiopatologia , Remodelação Ventricular/fisiologia , Animais , Apoptose , Linfócitos T CD8-Positivos/patologia , Modelos Animais de Doenças , Feminino , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/patologia , Proteínas de Homeodomínio/genética , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Infarto do Miocárdio/metabolismo , Miocárdio/patologia , Suínos , Transcriptoma
18.
Eur Heart J Acute Cardiovasc Care ; 10(2): 207-215, 2021 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-33675658

RESUMO

AIMS: We estimated the 2020 European Society of Cardiology-Acute Cardio Vascular Care (ESC-ACVC) quality indicators (QI) for the management of acute myocardial infarction, from three existing registries to determine the feasibility of assessment, room for improvement, association with outcomes, and suitability for centre benchmarking. METHODS AND RESULTS: Data were extracted from three French nationwide registries, namely FAST-MI 2005, 2010, and 2015. Feasibility of assessment and room for improvement were estimated by the denominator (patients in whom QI could be measured) and numerator (patients who satisfied the QI, among those eligible). Associations between composite QIs (CQIs) and mortality were assessed by multivariate analysis. Centre benchmarking was based on the centres mean CQI, vs. the national mean. The 2020 QIs were measured in 12 660/13 130 patients from FAST-MI. Measurement feasibility ranged from 15% to 100% with greater potential for implementation with the 2020 QI set. The mean (±SD) value of the opportunity-based CQI was 0.72 ± 0.01 and attainment of the all-or-none CQI 8.5%. Both CQIs were associated with adjusted 1-year mortality. Centre categorization into low, intermediate, and high quality was feasible, and distinguished centres with differing mortality. CONCLUSION: Most of the 2020 QI can be measured from existing registries in all domains but not in the patient's satisfaction domain. This assessment shows potential for implementation. Both CQIs were inversely associated with one-year mortality and centre benchmarking was feasible.

19.
Open Heart ; 8(1)2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33563776

RESUMO

OBJECTIVE: To assess associations of health-related quality of life (HRQoL) with patient profile, resource use, cardiovascular (CV) events and mortality in stable patients post-myocardial infarction (MI). METHODS: The global, prospective, observational TIGRIS Study enrolled 9126 patients 1-3 years post-MI. HRQoL was assessed at enrolment and 6-month intervals using the patient-reported EuroQol-5 dimension (EQ-5D) questionnaire, with scores anchored at 0 (worst possible) and 1 (perfect health). Resource use, CV events and mortality were recorded during 2-years' follow-up. Regression models estimated the associations of index score at enrolment with patient characteristics, resource use, CV events and mortality over 2-years' follow-up. RESULTS: Among 8978 patients who completed the EQ-5D questionnaire, 52% reported 'some' or 'severe' problems on one or more health dimensions. Factors associated with a lower index score were: female sex, older age, obesity, smoking, higher heart rate, less formal education, presence of comorbidity (eg, angina, stroke), emergency room visit in the previous 6 months and non-ST-elevation MI as the index event. Compared with an index score of 1 at enrolment, a lower index score was associated with higher risk of all-cause death, with an adjusted rate ratio of 3.09 (95% CI 2.20 to 4.31), and of a CV event, with a rate ratio of 2.31 (95% CI 1.76 to 3.03). Patients with lower index score at enrolment had almost two times as many hospitalisations over 2-years' follow-up. CONCLUSIONS: Clinicians managing patients post-acute coronary syndrome should recognise that a poorer HRQoL is clearly linked to risk of hospitalisations, major CV events and death. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT01866904) (https://clinicaltrials.gov).


Assuntos
Eletrocardiografia , Nível de Saúde , Infarto do Miocárdio/psicologia , Qualidade de Vida , Sistema de Registros , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico , Prognóstico , Estudos Prospectivos , Inquéritos e Questionários , Fatores de Tempo
20.
JAMA ; 325(6): 552-560, 2021 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-33560322

RESUMO

Importance: The optimal transfusion strategy in patients with acute myocardial infarction and anemia is unclear. Objective: To determine whether a restrictive transfusion strategy would be clinically noninferior to a liberal strategy. Design, Setting, and Participants: Open-label, noninferiority, randomized trial conducted in 35 hospitals in France and Spain including 668 patients with myocardial infarction and hemoglobin level between 7 and 10 g/dL. Enrollment could be considered at any time during the index admission for myocardial infarction. The first participant was enrolled in March 2016 and the last was enrolled in September 2019. The final 30-day follow-up was accrued in November 2019. Interventions: Patients were randomly assigned to undergo a restrictive (transfusion triggered by hemoglobin ≤8; n = 342) or a liberal (transfusion triggered by hemoglobin ≤10 g/dL; n = 324) transfusion strategy. Main Outcomes and Measures: The primary clinical outcome was major adverse cardiovascular events (MACE; composite of all-cause death, stroke, recurrent myocardial infarction, or emergency revascularization prompted by ischemia) at 30 days. Noninferiority required that the upper bound of the 1-sided 97.5% CI for the relative risk of the primary outcome be less than 1.25. The secondary outcomes included the individual components of the primary outcome. Results: Among 668 patients who were randomized, 666 patients (median [interquartile range] age, 77 [69-84] years; 281 [42.2%] women) completed the 30-day follow-up, including 342 in the restrictive transfusion group (122 [35.7%] received transfusion; 342 total units of packed red blood cells transfused) and 324 in the liberal transfusion group (323 [99.7%] received transfusion; 758 total units transfused). At 30 days, MACE occurred in 36 patients (11.0% [95% CI, 7.5%-14.6%]) in the restrictive group and in 45 patients (14.0% [95% CI, 10.0%-17.9%]) in the liberal group (difference, -3.0% [95% CI, -8.4% to 2.4%]). The relative risk of the primary outcome was 0.79 (1-sided 97.5% CI, 0.00-1.19), meeting the prespecified noninferiority criterion. In the restrictive vs liberal group, all-cause death occurred in 5.6% vs 7.7% of patients, recurrent myocardial infarction occurred in 2.1% vs 3.1%, emergency revascularization prompted by ischemia occurred in 1.5% vs 1.9%, and nonfatal ischemic stroke occurred in 0.6% of patients in both groups. Conclusions and Relevance: Among patients with acute myocardial infarction and anemia, a restrictive compared with a liberal transfusion strategy resulted in a noninferior rate of MACE after 30 days. However, the CI included what may be a clinically important harm. Trial Registration: ClinicalTrials.gov Identifier: NCT02648113.


Assuntos
Anemia/terapia , Transfusão de Sangue , Infarto do Miocárdio/terapia , Idoso , Idoso de 80 Anos ou mais , Anemia/complicações , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Feminino , Hemoglobinas/análise , Humanos , Masculino , Infarto do Miocárdio/sangue , Infarto do Miocárdio/complicações
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...