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1.
Diab Vasc Dis Res ; 18(2): 14791641211002475, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33752449

RESUMO

AIMS: Total and free testosterone and sex hormone-binding globulin may affect cardiovascular prognosis in women. The objective was to study the association between sex hormones and prognosis in women with dysglycemia and high cardiovascular risk. METHODS: This epidemiological report included dysglycemic women from the Outcome Reduction with an Initial Glargine Intervention trial (n = 2848) with baseline total testosterone and sex hormone-binding globulin. Free testosterone was calculated with the Vermeulen formula. Cox regression analyses adjusted for variables including age, previous diseases and pharmacological treatments were used to estimate the association between these levels and the composite cardiovascular outcome (death from cardiovascular causes, nonfatal myocardial infarction or nonfatal stroke) and all-cause mortality per one standard deviation. RESULTS: Patients (73% post-menopausal) were followed for a median of 6.1 years during which 377 cardiovascular events and 389 deaths occurred. In Cox analyses, total and free testosterone were not associated with any outcomes, but sex hormone-binding globulin was related to all-cause mortality in age adjusted (HR 1.15; 95% CI 1.06-1.24; p < 0.01) and fully adjusted analyses (HR 1.14; 95% CI 1.05-1.24; p < 0.01). CONCLUSIONS: Increasing levels of baseline sex hormone-binding globulin were associated with an increased risk of all-cause mortality in dysglycemic women at high cardiovascular risk. TRIAL REGISTRATION: ClinicalTrials.gov no. NCT00069784.

2.
J Clin Epidemiol ; 134: 95-102, 2021 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-33561528

RESUMO

OBJECTIVE: To evaluate the power of responder analyses in a randomized controlled trial. STUDY DESIGN AND SETTING: Simulations were based on the Chronic Kidney Disease Antidepressant Sertraline Trial (CAST), which compared sertraline to placebo for the treatment of depression in kidney disease. Baseline disease severity, placebo response, effect size, and the proportion of responders were varied across 72 scenarios. Power was assessed using a t-test for change scores, and the chi-square test for dichotomized outcomes of the minimal important difference (MID), improvement and remission in 10,000 datasets with a fixed sample size of 193. RESULTS: The t-test had >80% power except for scenarios with the lowest sertraline effect size. The chi-square test using the MID had <7% power in all scenarios while improvement and remission of achieved >80% power only at higher effect sizes and/or when the proportion of responders was highest at 0.5. The chi-square test for improvement had marginal power increases compared to the t-test (4/72 scenarios = 5.6%) and that for remission did not outperform the t-test in any scenario. CONCLUSIONS: The t-test outperforms the chi-square test for dichotomized outcomes regardless of baseline disease severity, placebo response, effect size and the proportion of responders to the intervention.

3.
Can J Kidney Health Dis ; 7: 2054358120968959, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33294203

RESUMO

Background: Restless legs syndrome (RLS) affects approximately 30% of patients with end-stage kidney disease and is associated with impaired sleep and health-related quality of life. Medications used to treat RLS in patients receiving dialysis may have an increased risk of adverse events with dose titration, and residual RLS symptoms are common despite the use of effective treatments. Randomized controlled trials of monotherapy and combination pharmacologic therapy for RLS in hemodialysis are needed. Objective: To perform a randomized, crossover, placebo-controlled blinded trial of pharmacologic therapy for RLS in hemodialysis. Design/setting: The DIalysis Symptom COntrol-Restless Legs Syndrome (DISCO-RLS) trial is a randomized, crossover, placebo-controlled blinded trial of fixed low-dose pharmacologic therapy in patients receiving hemodialysis in 10 centers across Canada. It uses patient partners in its design, conduct, and reporting. Participants: Adults receiving thrice-weekly hemodialysis for at least 3 months with RLS of at least mild symptoms defined International Restless Legs Syndrome Study Group Rating Scale (IRLS) of 10 or more will enter a double placebo run-in period to exclude nonadherent participants and those unable to tolerate double placebo. Seventy-two participants who completed the run-in period will be randomized to 1 of 8 treatment sequences based on modeling with 4 treatment periods. Methods: Each treatment period lasts 4 weeks and consists of ropinirole 0.5 mg daily and gabapentin 100 mg daily, both together or neither with a double dummy placebo control for each treatment. The primary outcome is the difference in change scores of the IRLS between study treatments. Secondary outcomes are the differences in change scores of the Restless Legs Syndrome-6 Scale, patient global impression, 5-level EQ-5D version, and safety outcomes. Results: This randomized, crossover, placebo-controlled blinded trial will evaluate the efficacy and safety of fixed low-dose combination of ropinirole and gabapentin in patients receiving hemodialysis with RLS. Limitations: Patients with chronic kidney disease not on dialysis, kidney transplant recipients and those receiving peritoneal dialysis or home hemodialysis are not included. The intervention's long term safety and efficacy including the risk of augmentation is not captured. Conclusion: This randomized crossover placebo controlled blinded trial will evaluate the efficacy and safety of fixed low-dose combination ropinirole and gabapentin in patients receiving hemodialysis with RLS. Trial Registration: ClinicalTrials.gov (NCT03806530).

4.
ESC Heart Fail ; 2020 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-33269549

RESUMO

AIMS: The LE index (Length of hospitalization plus number of Emergent visits ≤6 months) predicts 30 day all-cause readmission or death following hospitalization for heart failure (HF). We combined N-terminal pro-B type natriuretic peptide (NT-proBNP) levels with the LE index to derive and validate the LENT index for risk prediction at the point of care on the day of hospital discharge. METHODS AND RESULTS: In this prospective cohort sub-study of the Patient-centred Care Transitions in HF clinical trial, we used log-binomial regression models with LE index and either admission or discharge NT-proBNP as the predictors and 30 day composite all-cause readmission or death as the primary outcome. No other variables were added to the model. We used regression coefficients to derive the LENT index and bootstrapping analysis for internal validation. There were 772 patients (mean [SD] age 77.0 [12.4] years, 49.9% female). Each increment in the LE index was associated with a 25% increased risk of the primary outcome (RR 1.25, 95% CI 1.16-1.35; C-statistic 0.63). Adjusted for the LE index, every 10-fold increase in admission and discharge NT-proBNP was associated with a 48% (RR 1.48; 95% CI 1.10, 1.99; C-statistic 0.64; net reclassification index [NRI] 0.19) and 56% (RR 1.56; 95% CI 1.08, 2.25; C-statistic 0.64; NRI 0.21) increased risk of the primary outcome, respectively. The predicted probability of the primary outcome increased to a similar extent with incremental LENT, regardless of whether admission or discharge NT-proBNP level was used. CONCLUSIONS: The point-of-care LENT index predicts 30 day composite all-cause readmission or death among patients hospitalized with HF, with improved risk reclassification compared with the LE index. The performance of this simple, 3-variable index - without adjustment for comorbidities - is comparable to complex risk prediction models in HF.

5.
Ther Innov Regul Sci ; 54(6): 1477-1488, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32514736

RESUMO

In late 2018, the Food and Drug Administration (FDA) outlined a framework for evaluating the possible use of real-world evidence (RWE) to support regulatory decision-making. This framework was created to facilitate studies that would generate high-quality RWE, including pragmatic clinical trials (PCTs), which are randomized trials designed to inform clinical or policy decisions by assessing the real-world effectiveness of an intervention. There is general agreement among experts that the use of existing healthcare and patient-generated data holds promise for making randomized trials more efficient, less costly, and more generalizable. Yet the benefits of relying on real-world data sources must be weighed against difficulties with ensuring data integrity and completeness. Additionally, appropriately monitoring patient safety in randomized trials of new drugs using healthcare system data that might not be available in real time can be quite difficult. Recognizing that these and other concerns are critical to the development and acceptability of PCTs, a group of stakeholders from academia, industry, professional organizations, regulatory bodies, government agencies, and patient advocates discussed a path forward for PCT growth and sustainability at a think tank meeting entitled "Monitoring and Analyzing Data from Pragmatic Streamlined Randomized Clinical Trials," which took place in January 2019 (Washington, DC). The goals of this meeting were to: (1) evaluate study design and methodological options specific to PCTs that have the potential to yield high-quality evidence; (2) discuss best practices to ensure data quality in PCTs; and (3) identify appropriate methods for study monitoring. Proceedings from the think tank meeting are summarized in this manuscript.

6.
Europace ; 22(6): 870-877, June., 2020. tab., ilus.
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: biblio-1123436

RESUMO

ABSTRACT: Aims Data on patient characteristics, prevalence, and outcomes of atrial fibrillation (AF) patients without traditional risk factors, often labelled 'lone AF', are sparse. METHODS AND RESULTS: The RE-LY AF registry included 15 400 individuals who presented to emergency departments with AF in 47 countries. This analysis focused on patients without traditional risk factors, including age ≥60 years, hypertension, coronary artery disease, heart failure, left ventricular hypertrophy, congenital heart disease, pulmonary disease, valve heart disease, hyperthyroidism, and prior cardiac surgery. Patients without traditional risk factors were compared with age- and region-matched controls with traditional risk factors (1:3 fashion). In 796 (5%) patients, no traditional risk factors were present. However, 98% (779/796) had less-established or borderline risk factors, including borderline hypertension (130-140/80-90 mmHg; 47%), chronic kidney disease (eGFR < 60 mL/min; 57%), obesity (body mass index > 30; 19%), diabetes (5%), excessive alcohol intake (>14 units/week; 4%), and smoking (25%). Compared with patients with traditional risk factors (n = 2388), patients without traditional risk factors were more often men (74% vs. 59%, P < 0.001) had paroxysmal AF (55% vs. 37%, P < 0.001) and less AF persistence after 1 year (21% vs. 49%, P < 0.001). Furthermore, 1-year stroke occurrence rate (0.6% vs. 2.0%, P = 0.013) and heart failure hospitalizations (0.9% vs. 12.5%, P < 0.001) were lower. However, risk of AF-related re-hospitalization was similar (18% vs. 21%, P = 0.09). CONCLUSION: Almost all patients without traditionally defined AF risk factors have less-established or borderline risk factors. These patients have a favourable 1-year prognosis, but risk of AF-related re-hospitalization remains high. Greater emphasis should be placed on recognition and management of less-established or borderline risk factors.


Assuntos
Fibrilação Atrial , Transtorno da Personalidade Borderline , Fatores de Risco
8.
Br J Anaesth ; 125(1): 38-46, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32416996

RESUMO

BACKGROUND: Delirium is common after cardiac surgery and is associated with adverse outcomes. Perioperative benzodiazepine use is associated with delirium and is common during cardiac surgery, which may increase the risk of postoperative delirium. We undertook a pilot study to inform the feasibility of a large randomised cluster crossover trial examining whether an institutional policy of restricted benzodiazepine administration during cardiac surgery (compared with liberal administration) would reduce delirium. METHODS: We conducted a two-centre, pilot, randomised cluster crossover trial with four 4 week crossover periods. Each centre was randomised to a policy of restricted or liberal use, and then alternated between the two policies during the remaining three periods. Our feasibility outcomes were adherence to each policy (goal ≥80%) and outcome assessment (one delirium assessment per day in the ICU in ≥90% of participants). We also evaluated the incidence of intraoperative awareness in one site using serial Brice questionnaires. RESULTS: Of 800 patients undergoing cardiac surgery during the trial period, 127/800 (15.9%) had delirium. Of these, 355/389 (91.3%) received benzodiazepines during the liberal benzodiazepine periods and 363/411 (88.3%) did not receive benzodiazepines during the restricted benzodiazepine periods. Amongst the 800 patients, 740 (92.5%) had ≥1 postoperative delirium assessment per day in the ICU. Of 521 patients screened for intraoperative awareness, one patient (0.2%), managed during the restricted benzodiazepine period (but who received benzodiazepine), experienced intraoperative awareness. CONCLUSIONS: This pilot study demonstrates the feasibility of a large, multicentre, randomised, cluster crossover trial examining whether an institutional policy of restricted vs liberal benzodiazepine use during cardiac surgery will reduce postoperative delirium. CLINICAL TRIAL REGISTRATION: NCT03053869.


Assuntos
Anestesia em Procedimentos Cardíacos/métodos , Benzodiazepinas/administração & dosagem , Delírio/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle , Idoso , Canadá , Análise por Conglomerados , Estudos Cross-Over , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Projetos Piloto
9.
Cardiovasc Res ; 2020 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-32142099

RESUMO

AIM: To examine the rates of VTE in high-income, upper middle-income and lower middle/low-income countries (World Bank Classification). METHODS AND RESULTS: We examined the rates of VTE in high-income, upper middle-income and lower middle/low-income countries (World Bank Classification) in a cohort derived from four prospective international studies (PURE, HOPE-3, ORIGIN, COMPASS). The primary outcome was a composite of pulmonary embolism, deep vein thrombosis and thrombophlebitis. We calculated age- and sex- standardized incidence rates (per 1000 person-years) and used a Cox frailty model adjusted for covariates to examine associations between the incidence of VTE and country income level. A total of 215,307 individuals (1·5 million person-years of follow-up) from high-income (n = 60,403), upper middle-income (n = 42,066) and lower middle/low-income (n = 112,838) countries were included. The age- and sex-standardized incidence rates of VTE per 1000 person-years in high-, upper middle- and lower middle/low-income countries were 0·87, 0·25 and 0·06, respectively. After adjusting for age, body mass index, smoking, antiplatelet therapy, anticoagulant therapy, education level, ethnicity, and incident cancer diagnosis or hospitalization, individuals from high-income and upper middle-income countries had a significantly higher risk of VTE than those from lower middle/low-income countries (hazard ratio [HR] 3·57, 95% confidence interval [CI] 2·40-5·30 and HR 2·27, 95%CI 1·59-3·23, respectively). The effect of country income level on VTE risk was markedly stronger in people with a lower BMI, hypertension, diabetes, non-white ethnicity and higher education. CONCLUSION: The rates of VTE are substantially higher in high-income than low-income countries. The factors underlying the increased VTE risk in higher income countries remain unknown. TRANSLATIONAL PERSPECTIVE: We investigated the burden of VTE by country income by combining information from 4 large prospective studies (215,307 individuals from 53 countries). This is the largest study on the global incidence of VTE published to date. We observed a higher incidence of VTE in richer compared to poorer countries. We also demonstrated that differences in rates of VTE are not explained by risk factors commonly associated with VTE. Further study is needed to understand whether these findings can be explained by differences in genetic or other markers, or whether they are due to differences in access to health care.

10.
Europace ; 22(6): 870-877, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32215649

RESUMO

AIMS: Data on patient characteristics, prevalence, and outcomes of atrial fibrillation (AF) patients without traditional risk factors, often labelled 'lone AF', are sparse. METHODS AND RESULTS: The RE-LY AF registry included 15 400 individuals who presented to emergency departments with AF in 47 countries. This analysis focused on patients without traditional risk factors, including age ≥60 years, hypertension, coronary artery disease, heart failure, left ventricular hypertrophy, congenital heart disease, pulmonary disease, valve heart disease, hyperthyroidism, and prior cardiac surgery. Patients without traditional risk factors were compared with age- and region-matched controls with traditional risk factors (1:3 fashion). In 796 (5%) patients, no traditional risk factors were present. However, 98% (779/796) had less-established or borderline risk factors, including borderline hypertension (130-140/80-90 mmHg; 47%), chronic kidney disease (eGFR < 60 mL/min; 57%), obesity (body mass index > 30; 19%), diabetes (5%), excessive alcohol intake (>14 units/week; 4%), and smoking (25%). Compared with patients with traditional risk factors (n = 2388), patients without traditional risk factors were more often men (74% vs. 59%, P < 0.001) had paroxysmal AF (55% vs. 37%, P < 0.001) and less AF persistence after 1 year (21% vs. 49%, P < 0.001). Furthermore, 1-year stroke occurrence rate (0.6% vs. 2.0%, P = 0.013) and heart failure hospitalizations (0.9% vs. 12.5%, P < 0.001) were lower. However, risk of AF-related re-hospitalization was similar (18% vs. 21%, P = 0.09). CONCLUSION: Almost all patients without traditionally defined AF risk factors have less-established or borderline risk factors. These patients have a favourable 1-year prognosis, but risk of AF-related re-hospitalization remains high. Greater emphasis should be placed on recognition and management of less-established or borderline risk factors.

11.
Am Heart J ; 220: 116-126, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31805422

RESUMO

The stepped-wedge (SW) cluster randomized controlled trial, in which clusters cross over in a randomized sequence from control to intervention, is ideal for the implementation and testing of complex health service interventions. In certain cases however, implementation of the intervention may pose logistical challenges, and variations in SW design may be required. We examine the logistical and statistical implications of variations in SW design using the optimization of the Patient-Centered Care Transitions in Heart Failure trial for illustration. We review the following complete SW design variations: a typical SW design; an SW design with multiple clusters crossing over per period to achieve balanced cluster sizes at each step; hierarchical randomization to account for higher-level clustering effects; nested substudies to measure outcomes requiring a smaller sample size than the primary outcomes; and hybrid SW design, which combines parallel cluster with SW design to improve efficiency. We also reviewed 3 incomplete SW design variations in which data are collected in some but not all steps to ease measurement burden. These include designs with a learning period that improve fidelity to the intervention, designs with reduced measurements to minimize collection burden, and designs with early and late blocks to accommodate cluster readiness. Variations in SW design offer pragmatic solutions to logistical challenges but have implications to statistical power. Advantages and disadvantages of each variation should be considered before finalizing the design of an SW randomized controlled trial.


Assuntos
Insuficiência Cardíaca/terapia , Assistência Centrada no Paciente , Projetos de Pesquisa , Cuidado Transicional , Estudos Cross-Over , Estudos Transversais , Humanos , Avaliação de Resultados em Cuidados de Saúde , Medidas de Resultados Relatados pelo Paciente , Tamanho da Amostra
12.
Diabetes Care ; 43(2): 433-439, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31727687

RESUMO

OBJECTIVE: Diabetes is a major risk factor for renal function decline and failure. The availability of multiplex panels of biochemical markers provides the opportunity to identify novel biomarkers that can better predict changes in renal function than routinely available clinical markers. RESEARCH DESIGN AND METHODS: The concentration of 239 biochemical markers was measured in stored serum from participants in the biomarker substudy of Outcome Reduction With Initial Glargine Intervention (ORIGIN) trial. Repeated-measures mixed-effects models were used to compute the annual change in eGFR (measured as mL/min/1.73 m2/year) for the 7,482 participants with a recorded baseline and follow-up eGFR. Linear regression models using forward selection were used to identify the independent biomarker determinants of the annual change in eGFR after accounting for baseline HbA1c, baseline eGFR, and routinely measured clinical risk factors. The incidence of the composite renal outcome (i.e., renal replacement therapy, renal death, renal failure, albuminuria progression, doubling of serum creatinine) and death within each fourth of change in eGFR predicted from these models was also estimated. RESULTS: During 6.2 years of median follow-up, the median annual change in eGFR was -0.18 mL/min/1.73 m2/year. Fifteen biomarkers independently predicted eGFR decline after accounting for cardiovascular risk factors, as did 12 of these plus 1 additional biomarker after accounting for renal risk factors. Every 0.1 mL/min/1.73 m2 predicted annual fall in eGFR predicted a 13% (95% CI 12, 14%) higher mortality. CONCLUSIONS: Adding up to 16 biomarkers to routinely measured clinical risk factors improves the prediction of annual change in eGFR in people with dysglycemia.


Assuntos
Biomarcadores/análise , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/fisiopatologia , Insulina Glargina/uso terapêutico , Testes de Função Renal/métodos , Rim/fisiopatologia , Idoso , Albuminúria/sangue , Biomarcadores/sangue , Biomarcadores/urina , Creatinina/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Progressão da Doença , Feminino , Taxa de Filtração Glomerular/fisiologia , Humanos , Hiperglicemia/complicações , Hiperglicemia/diagnóstico , Hiperglicemia/tratamento farmacológico , Hiperglicemia/fisiopatologia , Rim/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
13.
Trials ; 20(1): 595, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31619260

RESUMO

Following publication of the original article [1], we have been notified of a few mistakes in the "Sample size calculations" section, second paragraph.

14.
Neurology ; 92(13): e1435-e1446, 2019 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-30814321

RESUMO

OBJECTIVE: To assess whether long-term treatment with candesartan/hydrochlorothiazide, rosuvastatin, or their combination can slow cognitive decline in older people at intermediate cardiovascular risk. METHODS: The Heart Outcomes Prevention Evaluation-3 (HOPE-3) study was a double-blind, randomized, placebo-controlled clinical trial using a 2 × 2 factorial design. Participants without known cardiovascular disease or need for treatment were randomized to candesartan (16 mg) plus hydrochlorothiazide (12.5 mg) or placebo and to rosuvastatin (10 mg) or placebo. Participants who were ≥70 years of age completed the Digit Symbol Substitution Test (DSST), the modified Montreal Cognitive Assessment, and the Trail Making Test Part B at baseline and study end. RESULTS: Cognitive assessments were completed by 2,361 participants from 228 centers in 21 countries. Compared with placebo, candesartan/hydrochlorothiazide reduced systolic blood pressure by 6.0 mm Hg, and rosuvastatin reduced low-density lipoprotein cholesterol by 24.8 mg/dL. Participants were followed up for 5.7 years (median), and 1,626 completed both baseline and study-end assessments. Mean participant age was 74 years (SD ±3.5 years); 59% were women; 45% had hypertension; and 24% had ≥12 years of education. The mean difference in change in DSST scores was -0.91 (95% confidence interval [CI] -2.25 to 0.42) for candesartan/hydrochlorothiazide compared with placebo, -0.54 (95% CI -1.88 to 0.80) for rosuvastatin compared with placebo, and -1.43 (95% CI -3.37 to 0.50) for combination therapy vs double placebo. No significant differences were found for other measures. CONCLUSIONS: Long-term blood pressure lowering with candesartan plus hydrochlorothiazide, rosuvastatin, or their combination did not significantly affect cognitive decline in older people. CLINICALTRIALSGOV IDENTIFIER: NCT00468923. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for older people, candesartan plus hydrochlorothiazide, rosuvastatin, or their combination does not significantly affect cognitive decline.


Assuntos
Anti-Hipertensivos/uso terapêutico , Benzimidazóis/uso terapêutico , Disfunção Cognitiva/epidemiologia , Hidroclorotiazida/uso terapêutico , Hipolipemiantes/uso terapêutico , Rosuvastatina Cálcica/uso terapêutico , Tetrazóis/uso terapêutico , Idoso , Cognição , Combinação de Medicamentos , Feminino , Humanos , Masculino
15.
Neurology ; 92(13): 1435-1446, Mar. 2019. tabela, gráfico, ilustração
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: biblio-1024632

RESUMO

OBJECTIVE: To assess whether long-term treatment with candesartan/hydrochlorothiazide, rosuvastatin, or their combination can slow cognitive decline in older people at intermediate cardiovascular risk. METHODS: The Heart Outcomes Prevention Evaluation-3 (HOPE-3) study was a double-blind, randomized, placebo-controlled clinical trial using a 2 × 2 factorial design. Participants without known cardiovascular disease or need for treatment were randomized to candesartan (16 mg) plus hydrochlorothiazide (12.5 mg) or placebo and to rosuvastatin (10 mg) or placebo. Participants who were ≥70 years of age completed the Digit Symbol Substitution Test (DSST), the modified Montreal Cognitive Assessment, and the Trail Making Test Part B at baseline and study end. RESULTS: Cognitive assessments were completed by 2,361 participants from 228 centers in 21 countries. Compared with placebo, candesartan/hydrochlorothiazide reduced systolic blood pressure by 6.0 mm Hg, and rosuvastatin reduced low-density lipoprotein cholesterol by 24.8 mg/dL. Participants were followed up for 5.7 years (median), and 1,626 completed both baseline and study-end assessments. Mean participant age was 74 years (SD ±3.5 years); 59% were women; 45% had hypertension; and 24% had ≥12 years of education. The mean difference in change in DSST scores was -0.91 (95% confidence interval [CI] -2.25 to 0.42) for candesartan/hydrochlorothiazide compared with placebo, -0.54 (95% CI -1.88 to 0.80) for rosuvastatin compared with placebo, and -1.43 (95% CI -3.37 to 0.50) for combination therapy vs double placebo. No significant differences were found for other measures. CONCLUSIONS: Long-term blood pressure lowering with candesartan plus hydrochlorothiazide, rosuvastatin, or their combination did not significantly affect cognitive decline in older people.(AU)


Assuntos
Cognição , Hipertensão/complicações
16.
JAMA ; 321(8): 753-761, 2019 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-30806695

RESUMO

Importance: Health care services that support the hospital-to-home transition can improve outcomes in patients with heart failure (HF). Objective: To test the effectiveness of the Patient-Centered Care Transitions in HF transitional care model in patients hospitalized for HF. Design, Setting, and Participants: Stepped-wedge cluster randomized trial of 2494 adults hospitalized for HF across 10 hospitals in Ontario, Canada, from February 2015 to March 2016, with follow-up until November 2016. Interventions: Hospitals were randomized to receive the intervention (n = 1104 patients), in which nurse-led self-care education, a structured hospital discharge summary, a family physician follow-up appointment less than 1 week after discharge, and, for high-risk patients, structured nurse homevisits and heart function clinic care were provided to patients, or usual care (n = 1390 patients), in which transitional care was left to the discretion of clinicians. Main Outcomes and Measures: Primary outcomes were hierarchically ordered as composite all-cause readmission, emergency department (ED) visit, or death at 3 months; and composite all-cause readmission or ED visit at 30 days. Secondary outcomes were B-PREPARED score for discharge preparedness (range: 0 [most prepared] to 22 [least prepared]); the 3-Item Care Transitions Measure (CTM-3) for quality of transition (range: 0 [worst transition] to 100 [best transition]); the 5-level EQ-5D version (EQ-5D-5L) for quality of life (range: 0 [dead] to 1 [full health]); and quality-adjusted life-years (QALY; range: 0 [dead] to 0.5 [full health at 6 months]). Results: Among eligible patients, all 2494 (mean age, 77.7 years; 1258 [50.4%] women) completed the trial. There was no significant difference between the intervention and usual care groups in the first primary composite outcome (545 [49.4%] vs 698 [50.2%] events, respectively; hazard ratio [HR], 0.99 [95% CI, 0.83-1.19]) or in the second primary composite outcome (304 [27.5%] vs 408 [29.3%] events, respectively; HR, 0.93 [95% CI, 0.73-1.18]). There were significant differences between the intervention and usual care groups in the secondary outcomes of mean B-PREPARED score at 6 weeks (16.6 vs 13.9; difference, 2.65 [95% CI, 1.37-3.92]; P < .001); mean CTM-3 score at 6 weeks (76.5 vs 70.3; difference, 6.16 [95% CI, 0.90-11.43]; P = .02); and mean EQ-5D-5L score at 6 weeks (0.7 vs 0.7; difference, 0.06 [95% CI, 0.01 to 0.11]; P = .02) and 6 months (0.7 vs 0.6; difference, 0.06 [95% CI, 0.01-0.12]; P = .02). There was no significant difference in mean QALY between groups at 6 months (0.3 vs 0.3; difference, 0.00 [95% CI, -0.02 to 0.02]; P = .98). Conclusions and Relevance: Among patients with HF in Ontario, Canada, implementation of a patient-centered transitional care model compared with usual care did not improve a composite of clinical outcomes. Whether this type of intervention could be effective in other health care systems or locations would require further research. Trial Registration: ClinicalTrials.gov Identifier: NCT02112227.


Assuntos
Serviço Hospitalar de Emergência/estatística & dados numéricos , Insuficiência Cardíaca/terapia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Readmissão do Paciente/estatística & dados numéricos , Assistência Centrada no Paciente , Cuidado Transicional , Idoso , Feminino , Insuficiência Cardíaca/mortalidade , Hospitalização , Humanos , Masculino , Ontário , Anos de Vida Ajustados por Qualidade de Vida , Resultado do Tratamento
17.
J Am Coll Cardiol ; 73(2): 121-130, 2019 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-30654882

RESUMO

BACKGROUND: Patients with recent coronary artery bypass graft (CABG) surgery are at risk for early graft failure, which is associated with a risk of myocardial infarction and death. In the COMPASS (Cardiovascular OutcoMes for People Using Anticoagulation StrategieS) trial, rivaroxaban 2.5 mg twice daily plus aspirin 100 mg once daily compared with aspirin 100 mg once daily reduced the primary major adverse cardiovascular events (MACE) outcome of cardiovascular death, stroke, or myocardial infarction. Rivaroxaban 5 mg twice daily alone did not significantly reduce MACE. OBJECTIVES: This pre-planned substudy sought to determine whether the COMPASS treatments are more effective than aspirin alone for preventing graft failure and MACE after CABG surgery. METHODS: The substudy randomized 1,448 COMPASS trial patients 4 to 14 days after CABG surgery to receive the combination of rivaroxaban plus aspirin, rivaroxaban alone, or aspirin alone. The primary outcome was graft failure, diagnosed by computed tomography angiogram 1 year after surgery. RESULTS: The combination of rivaroxaban and aspirin and the regimen of rivaroxaban alone did not reduce the graft failure rates compared with aspirin alone (combination vs. aspirin: 113 [9.1%] vs. 91 [8.0%] failed grafts; odds ratio [OR]: 1.13; 95% confidence interval [CI]: 0.82 to 1.57; p = 0.45; rivaroxaban alone vs. aspirin: 92 [7.8%] vs. 92 [8.0%] failed grafts; OR: 0.95; 95% CI: 0.67 to 1.33; p = 0.75). Compared with aspirin, the combination was associated with fewer MACE (12 [2.4%] vs. 16 [3.5%]; hazard ratio [HR]: 0.69; 95% CI: 0.33 to 1.47; p = 0.34), whereas rivaroxaban alone was not (16 [3.3%] vs. 16 [3.5%]; HR: 0.99, CI: 0.50 to 1.99; p = 0.98). There was no fatal bleeding or tamponade within 30 days of randomization. CONCLUSIONS: The combination of rivaroxaban 2.5 mg twice daily plus aspirin or rivaroxaban 5 mg twice daily alone compared with aspirin alone did not reduce graft failure in patients with recent CABG surgery, but the combination of rivaroxaban 2.5 mg twice daily plus aspirin was associated with similar reductions in MACE, as observed in the larger COMPASS trial. (Cardiovascular OutcoMes for People Using Anticoagulation StrategieS [COMPASS]; NCT01776424).


Assuntos
Aspirina/uso terapêutico , Ponte de Artéria Coronária , Inibidores do Fator Xa/uso terapêutico , Fibrinolíticos/uso terapêutico , Oclusão de Enxerto Vascular/prevenção & controle , Rivaroxabana/uso terapêutico , Idoso , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
18.
Diabetes Obes Metab ; 21(2): 429-433, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30203580

RESUMO

We compared cardiovascular and other outcomes in patients with dysglycaemia with or without anti-glutamic acid dehydrogenase (GAD) antibodies participating in the Outcome Reduction with Initial Glargine Intervention (ORIGIN) trial. Of the 12 537 participants, 8162 had anti-GAD measured at baseline and 267 were anti-GAD positive. The effects of insulin glargine versus standard care and of n-3 fatty acids supplements versus placebo were compared by testing the interaction of the treatment effects and anti-GAD status. The effect of glargine on development of new diabetes was assessed in participants without previous diabetes at baseline. The overall incidence of outcomes did not differ between anti-GAD positive and anti-GAD negative subjects. The incidence of the composite of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke did not differ between anti-GAD positive participants randomized to insulin glargine or to standard care, with a hazard ratio (HR) (95% confidence interval [CI]) of 0.80 (0.44-1.44) or in anti-GAD negative participants with a HR of 1.07 (0.96-1.20) (P for interaction = 0.20).


Assuntos
Autoanticorpos/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glutamato Descarboxilase/imunologia , Insulina Glargina/uso terapêutico , Insulina/uso terapêutico , Padrão de Cuidado , Idoso , Glicemia/análise , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/mortalidade , Feminino , Hemoglobina A Glicada/análise , Hemoglobina A Glicada/metabolismo , Humanos , Insulina/normas , Masculino , Pessoa de Meia-Idade , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Estudos Retrospectivos , Padrão de Cuidado/estatística & dados numéricos , Resultado do Tratamento
20.
Trials ; 19(1): 688, 2018 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-30558680

RESUMO

BACKGROUND: A wide range of prophylactic antibiotic regimens are used for patients undergoing open-heart cardiac surgery. This reflects clinical equipoise in choice and duration of antibiotic agents. Although individual-level randomized control trials (RCT) are considered the gold standard when evaluating the efficacy of an intervention, this approach is highly resource intensive and a cluster RCT can be more appropriate for testing clinical effectiveness in a real-world setting. METHODS/DESIGN: We are conducting a factorial cluster-randomized crossover pilot trial in cardiac surgery patients to evaluate the feasibility of this design for a definite trial to evaluate the optimal duration and choice of perioperative antibiotic prophylaxis. Specifically, we will evaluate: (a) the non-inferiority of a single preoperative dose compared to prolonged prophylaxis and (b) the potential superiority of adding vancomycin to routine cefazolin in terms of preventing deep and organ/space sternal surgical site infections (s-SSIs). There are four strategies: (i) short-term cefazolin, (ii) long-term cefazolin, (iii) short-term cefazolin + vancomycin, and (iv) long-term cefazolin + vancomycin. These strategies are delivered in a different order in each health-care center participating in the trial. The centers are randomized to an order, and the current strategy becomes the standard operating procedure in that center during the study. The three feasibility outcomes include: (1) the proportion of patients receiving preoperative, intra-operative, and postoperative antibiotics according to the study protocol, (2) the proportion of completed follow-up assessments, and (3) a full and final assessment of the incidence of s-SSIs by the outcome adjudication committee. DISCUSSION: We believe that a cluster-randomized factorial crossover trial is an effective and feasible design for these research questions, allowing an evaluation of the clinical effectiveness in a real-world setting. A waiver of individual informed consent was considered appropriate by the research ethics boards in each participating site in Canada as long as an information letter with an opt-out option was provided. However, a waiver of consent was not approved at two sites in Germany and Switzerland, respectively. TRIAL REGISTRATION: Clinicaltrials.gov, NCT02285140 . Registered on 15 October 2015.


Assuntos
Antibacterianos/administração & dosagem , Antibioticoprofilaxia/métodos , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Cefazolina/administração & dosagem , Infecção da Ferida Cirúrgica/prevenção & controle , Vancomicina/administração & dosagem , Antibacterianos/efeitos adversos , Antibioticoprofilaxia/efeitos adversos , Canadá , Cefazolina/efeitos adversos , Estudos Cross-Over , Esquema de Medicação , Quimioterapia Combinada , Europa (Continente) , Estudos de Viabilidade , Humanos , Estudos Multicêntricos como Assunto , Projetos Piloto , Ensaios Clínicos Pragmáticos como Assunto , Infecção da Ferida Cirúrgica/diagnóstico , Infecção da Ferida Cirúrgica/microbiologia , Fatores de Tempo , Resultado do Tratamento , Vancomicina/efeitos adversos
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