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Reexamination of the Embolic Stroke of Undetermined Source Concept.
Albers, GW, Bernstein, R, Brachmann, J, Camm, AJ, Fromm, P, Goto, S, Granger, CB, Hohnloser, SH, Hylek, E, Krieger, D, et al
Stroke. 2021;(8):2715-2722
Abstract
Occult atrial fibrillation (AF) is a leading cause of stroke of unclear cause. The optimal approach to secondary stroke prevention for these patients remains elusive. The term embolic stroke of undetermined source (ESUS) was coined to describe ischemic strokes in which the radiographic features demonstrate territorial infarcts resembling those seen in patients with confirmed sources of embolism but without a clear source of embolism detected. It was assumed that patients with ESUS had a high rate of occult AF and would benefit from treatment with direct oral anticoagulants, which are at least as effective as vitamin K antagonists for secondary stroke prevention in patients with AF, but with a much lower risk of intracerebral hemorrhage. Two recent large randomized trials failed to show superiority of direct oral anticoagulants over aspirin in ESUS patients. These findings prompt a reexamination of the ESUS concept, with the goal of improving specificity for detecting patients with a cardioembolic cause. Based on the negative trial results, there is renewed interest in the role of long-term cardiac monitoring for AF in patients who fit the current ESUS definition, as well as the clinical implication of detecting AF. Ongoing trials are exploring these questions. Current ESUS definitions do not accurately detect the patients who should be prescribed direct oral anticoagulants, potentially because occult AF is less common than expected in these patients and/or anticoagulants may be less beneficial in patients with ESUS but no AF than they are for patients with stroke with established AF. More specific criteria to identify patients who may be at higher risk for occult AF and reduce their risk of subsequent stroke have been developed and are being tested in ongoing clinical trials.
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New Avenues for Optimal Treatment of Atrial Fibrillation and Stroke Prevention.
De Marchis, GM, Sposato, LA, Kühne, M, Dittrich, TD, Bonati, LH, Fischer, U, Chaturvedi, S
Stroke. 2021;(4):1490-1499
Abstract
One in 3 individuals free of atrial fibrillation (AF) at index age 55 years is estimated to develop AF later in life. AF increases not only the risk of ischemic stroke but also of dementia, even in stroke-free patients. In this review, we address recent advances in the heart-brain interaction with focus on AF. Issues discussed are (1) the timing of direct oral anticoagulants start following an ischemic stroke; (2) the comparison of direct oral anticoagulants versus vitamin K antagonists in early secondary stroke prevention; (3) harms of bridging with heparin before direct oral anticoagulants; (4) importance of appropriate direct oral anticoagulants dosing; (5) screening for AF in high-risk populations, including the role of wearables; (6) left atrial appendage occlusion as an alternative to oral anticoagulation; (7) the role of early rhythm-control therapy; (8) effect of lifestyle interventions on AF; (9) AF as a risk factor for dementia. An interdisciplinary approach seems appropriate to address the complex challenges posed by AF.
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Department of Veterans Affairs (VA) and U.S. Department of Defense (DoD) guidelines for management of dyslipidemia and cardiovascular disease risk reduction: Putting evidence in context.
Al Rifai, M, Blumenthal, RS, Stone, NJ, Schofield, RS, Orringer, CE, Michos, ED, Heidenreich, PA, Braun, L, Birtcher, KK, Smith, SC, et al
Progress in cardiovascular diseases. 2021;:2-6
Abstract
Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of morbidity and mortality in the United States (U.S.) and incurs significant cost to the healthcare system. Management of cholesterol remains central for ASCVD prevention and has been the focus of multiple national guidelines. In this review, we compare the American Heart Association (AHA)/American College of Cardiology (ACC) and the U.S. Department of Veterans Affairs (VA) and U.S. Department of Defense (DoD) Cholesterol guidelines. We review the evidence base that was used to generate recommendations focusing on 4 distinct themes: 1) the threshold of absolute 10-year ASCVD risk to start a clinician-patient discussion for the initiation of statin therapy in primary prevention patients; 2) the utility of coronary artery calcium score to guide clinician-patient risk discussion pertaining to the initiation of statin therapy for primary ASCVD prevention; 3) the use of moderate versus high-intensity statin therapy in patients with established ASCVD; and 4) the utility of ordering lipid panels after initiation or intensification of lipid lowering therapy to document efficacy and monitor adherence to lipid lowering therapy. We discuss why the VA/DoD and AHA/ACC may have reached different conclusions on these key issues.
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Effect of Monthly Vitamin D Supplementation on Preventing Exacerbations of Asthma or Chronic Obstructive Pulmonary Disease in Older Adults: Post Hoc Analysis of a Randomized Controlled Trial.
Camargo, CA, Toop, L, Sluyter, J, Lawes, CMM, Waayer, D, Khaw, KT, Martineau, AR, Scragg, R
Nutrients. 2021;(2)
Abstract
Randomized controlled trials have suggested that vitamin D supplementation can prevent asthma and chronic obstructive pulmonary disease (COPD) exacerbations. For COPD, the benefit appears to be limited to individuals with baseline 25-hydroxyvitamin D (25OHD) levels <25 nmol/L. We performed a post hoc analysis of data from a randomized, double-blinded, placebo-controlled trial to investigate the effect that monthly, high-dose vitamin D supplementation (versus placebo) had on older adults with asthma and/or COPD. Specifically, we investigated whether vitamin D supplementation prevented exacerbations of these conditions. Participants were randomly assigned either to an initial oral dose of 200,000 IU vitamin D3 followed by 100,000 IU monthly or to placebo, with an average follow-up period of 3.3 years. Among the 5110 participants, 775 had asthma or COPD at the beginning of the study, and were eligible for inclusion in this analysis. Exacerbations were defined by the prescription of a short-burst of oral corticosteroids. The mean age of the participants was 67 years old, and 56% were male. The mean baseline blood 25OHD level was 63 nmol/L; 2.3% were <25 nmol/L. Overall, we found that vitamin D supplementation did not affect the exacerbation risk (hazard ratio 1.08; 95%CI 0.84-1.39). Among those with baseline 25OHD <25 nmol/L, however, the hazard ratio was 0.11 (95%CI 0.02-0.51); p for interaction = 0.001. Although monthly vitamin D supplementation had no overall impact on risk of exacerbations of asthma or COPD, we found evidence of a probable benefit among those with severe vitamin D deficiency.
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Ranolazine in the prevention and treatment of atrial fibrillation: A protocol for meta-analysis.
Yuan, C, Luo, W, Ren, X, Ya, M, Yan, W, Hui, Q
Medicine. 2021;(16):e25437
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Abstract
BACKGROUND Atrial fibrillation (AF) is the most common clinical arrhythmia and a major cause of morbidity and mortality in clinical practice. This study aims to determine the ranolazine for prevention and treatment of atrial fibrillation. METHOD This study adheres to the Preferred Reporting Items for Systematic Reviews and Meta-analysis for Protocols. Chinese electronic Database (CBM, Wanfang, and CNKI) and international electronic databases (PubMed, Embase, Cochrane Library, and Web of Science) will be searched for all relevant published articles. We will apply no language or the year of publication restrictions. Study selection, data collection, and assessment of study bias will be conducted independently by a pair of independent reviewers. The Cochrane risk of bias (ROB) tool will be used for the risk of bias assessment. The quality of evidence will be evaluated by Grading of Recommendations Assessment Development and Evaluation (GRADE) system. The statistical analysis of this meta-analysis will be calculated by Review manager version 5.3. RESULTS The results of this study will be published in a peer-reviewed journal. CONCLUSION This review will evaluate the value of ranolazine interventions for patients with AF, and provide meaningful conclusions or high-level evidence for clinical practice and further research. TRIAL REGISTRATION This study protocol was registered in open Science framework (OSF), (Registration DOI: 10.17605/OSF.IO/T6W9Q).
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Twice-weekly topical calcipotriene/betamethasone dipropionate foam as proactive management of plaque psoriasis increases time in remission and is well tolerated over 52 weeks (PSO-LONG trial).
Lebwohl, M, Kircik, L, Lacour, JP, Liljedahl, M, Lynde, C, Mørch, MH, Papp, KA, Perrot, JL, Gold, LS, Takhar, A, et al
Journal of the American Academy of Dermatology. 2021;(5):1269-1277
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Abstract
BACKGROUND Topical psoriasis treatment relies on a reactive rather than a long-term proactive approach to disease relapse. OBJECTIVE Assess long-term efficacy and safety of proactive psoriasis management with twice-weekly calcipotriene 0.005%/betamethasone dipropionate 0.064% (Cal/BD) foam. METHODS Phase III trial (NCT02899962) included a 4-week open-label lead-in phase (Cal/BD foam once daily) and a 52-week, randomized, double-blind, maintenance phase. A total of 545 patients achieved treatment success (physician's global assessment "clear"/"almost clear," ≥2-grade improvement from baseline) and were randomized to proactive management (Cal/BD foam; n = 272) or reactive management (vehicle foam; n = 273) twice-weekly, with rescue treatment of Cal/BD foam once daily for 4 weeks upon relapse. Primary endpoint was time to first relapse (physician's global assessment "mild" or higher). RESULTS A total of 251 randomized patients (46.1%) completed the trial. Median time to first relapse was 56 days (proactive) and 30 days (reactive). Patients in the proactive group had an additional 41 days in remission compared with the reactive group over 1 year (P < .001). Number of relapses per year of exposure was 3.1 (proactive) and 4.8 (reactive). Cal/BD foam was well tolerated. LIMITATIONS Maintenance phase dropout rate (53.9%) was within the expected range but provides challenges in statistical analysis. CONCLUSION Long-term proactive management with Cal/BD foam demonstrated superior efficacy vs reactive management.
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Mediterranean Diet Reduces Atherosclerosis Progression in Coronary Heart Disease: An Analysis of the CORDIOPREV Randomized Controlled Trial.
Jimenez-Torres, J, Alcalá-Diaz, JF, Torres-Peña, JD, Gutierrez-Mariscal, FM, Leon-Acuña, A, Gómez-Luna, P, Fernández-Gandara, C, Quintana-Navarro, GM, Fernandez-Garcia, JC, Perez-Martinez, P, et al
Stroke. 2021;(11):3440-3449
Abstract
BACKGROUND AND PURPOSE Lifestyle and diet affect cardiovascular risk, although there is currently no consensus about the best dietary model for the secondary prevention of cardiovascular disease. The CORDIOPREV study (Coronary Diet Intervention With Olive Oil and Cardiovascular Prevention) is an ongoing prospective, randomized, single-blind, controlled trial in 1002 coronary heart disease patients, whose primary objective is to compare the effect of 2 healthy dietary patterns (low-fat rich in complex carbohydrates versus Mediterranean diet rich in extra virgin olive oil) on the incidence of cardiovascular events. Here, we report the results of one secondary outcome of the CORDIOPREV study. Thus, to evaluate the efficacy of these diets in reducing cardiovascular disease risk. Intima-media thickness of both common carotid arteries (IMT-CC) was ultrasonically assessed bilaterally. IMT-CC is a validated surrogate for the status and future cardiovascular disease risk. METHODS From the total participants, 939 completed IMT-CC evaluation at baseline and were randomized to follow a Mediterranean diet (35% fat, 22% monounsaturated fatty acids, <50% carbohydrates) or a low-fat diet (28% fat, 12% monounsaturated fatty acids, >55% carbohydrates) with IMT-CC measurements at 5 and 7 years. We also analyzed the carotid plaque number and height. RESULTS The Mediterranean diet decreased IMT-CC at 5 years (−0.027±0.008 mm; P<0.001), maintained at 7 years (−0.031±0.008 mm; P<0.001), compared to baseline. The low-fat diet did not modify IMT-CC. IMT-CC and carotid plaquemax height were higher decreased after the Mediterranean diet, compared to the low-fat diet, throughout follow-up. Baseline IMT-CC had the strongest association with the changes in IMT-CC after the dietary intervention. CONCLUSIONS Long-term consumption of a Mediterranean diet rich in extravirgin olive oil, if compared to a low-fat diet, was associated with decreased atherosclerosis progression, as shown by reduced IMT-CC and carotid plaque height. These findings reinforce the clinical benefits of the Mediterranean diet in the context of secondary cardiovascular prevention. REGISTRATION URL: https://www.clinicaltrials.gov; Unique identifier: NCT00924937.
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Ustekinumab is more effective than azathioprine to prevent endoscopic postoperative recurrence in Crohn's disease.
Buisson, A, Nancey, S, Manlay, L, Rubin, DT, Hebuterne, X, Pariente, B, Fumery, M, Laharie, D, Roblin, X, Bommelaer, G, et al
United European gastroenterology journal. 2021;(5):552-560
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Abstract
BACKGROUND Preventing postoperative recurrence (POR) is a major concern in Crohn's disease (CD). While azathioprine is an option, no data is available on ustekinumab efficacy in this situation. AIMS We compared the effectiveness of ustekinumab versus azathioprine in preventing endoscopic POR in CD. METHODS We retrospectively collected data from all consecutive CD patients treated with ustekinumab after intestinal resection in 9 centers. The control group (azathioprine alone) was composed of patients who participated in a randomized controlled trial conducted in the same centers comparing azathioprine alone or in combination with curcumin. Propensity score analyses (inversed probability of treatment weighting = IPTW) were applied to compare the two groups. The primary endpoint was endoscopic POR (Rutgeerts' index ≥ i2) at 6 months. RESULTS Overall, 32 patients were included in the ustekinumab group and 31 in the azathioprine group. The propensity score analysis was adjusted on the main risk factors (smoking, fistulizing phenotype, prior bowel resection, resection length >30 cm and ≥2 biologics before surgery) and thiopurines or ustekinumab exposure prior to surgery making the two arms comparable (∣d∣ < 0.2). After IPTW, the rate of endoscopic POR at 6 months was lower in patients treated with ustekinumab compared to azathioprine (28.0% vs. 54.5%, p = 0.029). After IPTW, the rates of i2b-endoscopic POR (Rutgeerts' index ≥ i2b) and severe endoscopic POR (Rutgeerts' index ≥ i3) were 20.8% versus 42.5% (p = 0.066) and 16.9% versus 27.9% (p = 0.24), in the ustekinumab and azathioprine groups, respectively. CONCLUSION Ustekinumab seemed to be more effective than azathioprine in preventing POR in this cohort of CD patients.
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Lifestyle and Treatment Adherence Intervention after a Coronary Event Based on an Interactive Web Application (EVITE): Randomized Controlled Clinical Trial Protocol.
Bernal-Jiménez, MÁ, Calle-Pérez, G, Gutiérrez-Barrios, A, Gheorghe, L, Solano-Mulero, AM, Rodríguez-Martín, A, Tur, JA, Vázquez-García, R, Santi-Cano, MJ
Nutrients. 2021;(6)
Abstract
Coronary heart disease is one of the main causes of morbimortality around the world. Patients that survive a coronary event suffer a high risk of readmission, relapse and mortality, attributed to the sub-optimal control of cardiovascular risk factors (CVRF), which highlights the need to improve secondary prevention strategies aimed at improving their lifestyle and adherence to treatment. Through a randomized controlled clinical trial, this study aims to evaluate the effect of an intervention involving an online health application supported by a mobile telephone or tablet (mHealth) on lifestyle (diet, physical activity, and tobacco consumption) and treatment adherence among people with coronary heart disease after percutaneous coronary intervention. The sample will comprise 240 subjects (120 in each arm: intervention and usual care). They are assessed immediately and nine months after their hospital discharge about sociodemographic, clinical, CVRF, lifestyle, and treatment adherence characteristics. The educative intervention, involving a follow-up and self-monitoring, will be performed using an online mHealth tool consisting of an application for mobile phones and tablets. The quantitative primary outcomes from the two groups will be compared using an analysis of covariance (ANCOVA) adjusted for age and gender. A multivariate analysis will be performed to examine the association of the intervention with lifestyle habits, the control of CVRFs, and outcomes after discharge in terms of the use of health services, emergency visits, cardiovascular events and readmissions.
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Brief formula low-energy-diet for relapse management during weight loss maintenance in the Diabetes Remission Clinical Trial (DiRECT).
Brosnahan, N, Leslie, W, McCombie, L, Barnes, A, Thom, G, McConnachie, A, Messow, CM, Sattar, N, Taylor, R, Lean, MEJ
Journal of human nutrition and dietetics : the official journal of the British Dietetic Association. 2021;(3):472-479
Abstract
BACKGROUND Weight loss maintenance (WLM) is critical for sustaining type 2 diabetes (T2D) remission, but poorly evidenced. We evaluated brief return to formula low-energy-diet (LED) as relapse treatments (RTs) during the WLM phase of the Diabetes Remission Clinical Trial (DiRECT). METHODS This post-hoc evaluation included all participants commencing the WLM phase of DiRECT. The protocol offered RT when regain of >2 kg occurred. RESULTS In total, 123/149 (83%) DiRECT intervention participants commenced the WLM phase after 26 (17%) had withdrawn prior to the WLM phase. Most participants [99/123 (80%)] regained >2 kg during the WLM phase, among whom 60/99 (61%) were recorded as using RT and 39/99 (39%) not using any RT. At baseline, RT users had a higher mean (SD) body mass index [35.8 (4.9) kg m-2 vs. 33.8 (3.9) kg m-2 , p = 0.0231] and had greater social deprivation (P = 0.0003) than non-users, although otherwise the groups were similar. Weight loss ≥ 2k g was achieved in 30/93 (32%) of RT attempts. At 2 years, those regaining >2 kg and using RT (n = 60) had mean (SD) weight losses of 7.4 (6.1) kg, with 25 (42%) remissions and 7 (12%) programme withdrawals. Those regaining >2 kg but not using RT (n = 39) had weight losses of 8.8 (6.0) kg, with 21 (54%) remissions and 4 (10%) programme withdrawals (all not significant). Twelve participants were never recorded as having regained >2 kg or using RTs and, at 2 years, their weight losses were 12.9 (9.2) kg, with 4 (33%) remissions and 8 (67%) programme withdrawals. CONCLUSIONS Most people with T2D experience weight regain >2 kg during the 2 years after substantial weight loss with a LED. Only one-third of RTs corrected their 2-kg regain, resulting in similar weight losses, remissions and programme withdrawals at 2 years compared to those not using RTs; however, both groups had weight losses below those not recorded as regaining >2 kg during WLM.