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  • Ovid Technologies (Wolters Kluwer Health)  (47)
  • 1
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    Online Resource
    Icosapent Ethyl Reduces Ischemic Events in Patients With a History of Previous Coronary Artery Bypass Grafting: REDUCE-IT CABG
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Circulation Vol. 144, No. 23 ( 2021-12-07), p. 1845-1855
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 144, No. 23 ( 2021-12-07), p. 1845-1855
    Abstract: Despite advances in surgery and pharmacotherapy, there remains significant residual ischemic risk after coronary artery bypass grafting surgery. Methods: In REDUCE-IT (Reduction of Cardiovascular Events With Icosapent Ethyl–Intervention Trial), a multicenter, placebo-controlled, double-blind trial, statin-treated patients with controlled low-density lipoprotein cholesterol and mild to moderate hypertriglyceridemia were randomized to 4 g daily of icosapent ethyl or placebo. They experienced a 25% reduction in risk of a primary efficacy end point (composite of cardiovascular death, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina) and a 26% reduction in risk of a key secondary efficacy end point (composite of cardiovascular death, myocardial infarction, or stroke) when compared with placebo. The current analysis reports on the subgroup of patients from the trial with a history of coronary artery bypass grafting. Results: Of the 8179 patients randomized in REDUCE-IT, a total of 1837 (22.5%) had a history of coronary artery bypass grafting, with 897 patients randomized to icosapent ethyl and 940 to placebo. Baseline characteristics were similar between treatment groups. Randomization to icosapent ethyl was associated with a significant reduction in the primary end point (hazard ratio [HR], 0.76 [95% CI, 0.63–0.92] ; P =0.004), in the key secondary end point (HR, 0.69 [95% CI, 0.56–0.87]; P =0.001), and in total (first plus subsequent or recurrent) ischemic events (rate ratio, 0.64 [95% CI, 0.50–0.81]; P =0.0002) compared with placebo. This yielded an absolute risk reduction of 6.2% (95% CI, 2.3%–10.2%) in first events, with a number needed to treat of 16 (95% CI, 10–44) during a median follow-up time of 4.8 years. Safety findings were similar to the overall study: beyond an increased rate of atrial fibrillation/flutter requiring hospitalization for at least 24 hours (5.0% vs 3.1%; P =0.03) and a nonsignificant increase in bleeding, occurrences of adverse events were comparable between groups. Conclusions: In REDUCE-IT patients with a history of coronary artery bypass grafting, treatment with icosapent ethyl was associated with significant reductions in first and recurrent ischemic events. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01492361.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/CIRCULATIONAHA.121.056290
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 1466401-X
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  • 2
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    Reliability, Validity, and Responsiveness of the Western Ontario and McMaster Universities Osteoarthritis Index for Elderly Patients with a Femoral Neck Fracture
    Ovid Technologies (Wolters Kluwer Health) ; 2015
    In:  The Journal of Bone and Joint Surgery-American Volume Vol. 97, No. 9 ( 2015-05), p. 751-757
    Details
    In: The Journal of Bone and Joint Surgery-American Volume, Ovid Technologies (Wolters Kluwer Health), Vol. 97, No. 9 ( 2015-05), p. 751-757
    Type of Medium: Online Resource
    ISSN: 0021-9355
    URL: Article
    DOI: 10.2106/JBJS.N.00542
    RVK:
    XA 52200.A
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2015
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  • 3
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    Apolipoprotein B, Residual Cardiovascular Risk After Acute Coronary Syndrome, and Effects of Alirocumab
    Ovid Technologies (Wolters Kluwer Health) ; 2022
    In:  Circulation Vol. 146, No. 9 ( 2022-08-30), p. 657-672
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 146, No. 9 ( 2022-08-30), p. 657-672
    Abstract: Apolipoprotein B (apoB) provides an integrated measure of atherogenic risk. Whether apoB levels and apoB lowering hold incremental predictive information on residual risk after acute coronary syndrome beyond that provided by low-density lipoprotein cholesterol is uncertain. Methods: The ODYSSEY OUTCOMES trial (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) compared the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome and elevated atherogenic lipoproteins despite optimized statin therapy. Primary outcome was major adverse cardiovascular events (MACE; coronary heart disease death, nonfatal myocardial infarction, fatal/nonfatal ischemic stroke, hospitalization for unstable angina). Associations between baseline apoB or apoB at 4 months and MACE were assessed in adjusted Cox proportional hazards and propensity score–matched models. Results: Median follow-up was 2.8 years. In proportional hazards analysis in the placebo group, MACE incidence increased across increasing baseline apoB strata (3.2 [95% CI, 2.9–3.6], 4.0 [95% CI, 3.6–4.5] , and 5.5 [95% CI, 5.0–6.1] events per 100 patient-years in strata 〈 75, 75– 〈 90, ≥90 mg/dL, respectively; P trend 〈 0.0001) and after adjustment for low-density lipoprotein cholesterol ( P trend =0.035). Higher baseline apoB stratum was associated with greater relative ( P trend 〈 0.0001) and absolute reduction in MACE with alirocumab versus placebo. In the alirocumab group, the incidence of MACE after month 4 decreased monotonically across decreasing achieved apoB strata (4.26 [95% CI, 3.78–4.79], 3.09 [95% CI, 2.69–3.54] , and 2.41 [95% CI, 2.11–2.76] events per 100 patient-years in strata ≥50, 〉 35– 〈 50, and ≤35 mg/dL, respectively). Compared with propensity score–matched patients from the placebo group, treatment hazard ratios for alirocumab also decreased monotonically across achieved apoB strata. Achieved apoB was predictive of MACE after adjustment for achieved low-density lipoprotein cholesterol or non–high-density lipoprotein cholesterol but not vice versa. Conclusions: In patients with recent acute coronary syndrome and elevated atherogenic lipoproteins, MACE increased across baseline apoB strata. Alirocumab reduced MACE across all strata of baseline apoB, with larger absolute reductions in patients with higher baseline levels. Lower achieved apoB was associated with lower risk of MACE, even after accounting for achieved low-density lipoprotein cholesterol or non–high-density lipoprotein cholesterol, indicating that apoB provides incremental information. Achievement of apoB levels as low as ≤35 mg/dL may reduce lipoprotein-attributable residual risk after acute coronary syndrome. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01663402.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/CIRCULATIONAHA.121.057807
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
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  • 4
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    Bayesian Inference Associates Rare KDR Variants With Specific Phenotypes in Pulmonary Arterial Hypertension
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Circulation: Genomic and Precision Medicine Vol. 14, No. 1 ( 2021-02)
    Details
    In: Circulation: Genomic and Precision Medicine, Ovid Technologies (Wolters Kluwer Health), Vol. 14, No. 1 ( 2021-02)
    Abstract: Approximately 25% of patients with pulmonary arterial hypertension (PAH) have been found to harbor rare mutations in disease-causing genes. To identify missing heritability in PAH, we integrated deep phenotyping with whole-genome sequencing data using Bayesian statistics. Methods: We analyzed 13 037 participants enrolled in the NBR study (NIHR BioResource—Rare Diseases), of which 1148 were recruited to the PAH domain. To test for genetic associations between genes and selected phenotypes of pulmonary hypertension, we used the Bayesian rare variant association method BeviMed. Results: Heterozygous, high impact, likely loss-of-function variants in the kinase insert domain receptor ( KDR ) gene were strongly associated with significantly reduced transfer coefficient for carbon monoxide (posterior probability=0.989) and older age at diagnosis (posterior probability=0.912). We also provide evidence for familial segregation of a rare nonsense KDR variant with these phenotypes. On computed tomographic imaging of the lungs, a range of parenchymal abnormalities were observed in the 5 patients harboring these predicted deleterious variants in KDR . Four additional PAH cases with rare likely loss-of-function variants in KDR were independently identified in the US PAH Biobank cohort with similar phenotypic characteristics. Conclusions: The Bayesian inference approach allowed us to independently validate KDR , which encodes for the VEGFR2 (vascular endothelial growth factor receptor 2), as a novel PAH candidate gene. Furthermore, this approach specifically associated high impact likely loss-of-function variants in the genetically constrained gene with distinct phenotypes. These findings provide evidence for KDR being a clinically actionable PAH gene and further support the central role of the vascular endothelium in the pathobiology of PAH.
    Type of Medium: Online Resource
    ISSN: 2574-8300
    URL: Article
    DOI: 10.1161/CIRCGEN.120.003155
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 2927603-2
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  • 5
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    Phenotypic Characterization of EIF2AK4 Mutation Carriers in a Large Cohort of Patients Diagnosed Clinically With Pulmonary Arterial Hypertension
    Ovid Technologies (Wolters Kluwer Health) ; 2017
    In:  Circulation Vol. 136, No. 21 ( 2017-11-21), p. 2022-2033
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 136, No. 21 ( 2017-11-21), p. 2022-2033
    Abstract: Pulmonary arterial hypertension (PAH) is a rare disease with an emerging genetic basis. Heterozygous mutations in the gene encoding the bone morphogenetic protein receptor type 2 ( BMPR2 ) are the commonest genetic cause of PAH, whereas biallelic mutations in the eukaryotic translation initiation factor 2 alpha kinase 4 gene ( EIF2AK4 ) are described in pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Here, we determine the frequency of these mutations and define the genotype-phenotype characteristics in a large cohort of patients diagnosed clinically with PAH. Methods: Whole-genome sequencing was performed on DNA from patients with idiopathic and heritable PAH and with pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis recruited to the National Institute of Health Research BioResource–Rare Diseases study. Heterozygous variants in BMPR2 and biallelic EIF2AK4 variants with a minor allele frequency of 〈 1:10 000 in control data sets and predicted to be deleterious (by combined annotation-dependent depletion, PolyPhen-2, and sorting intolerant from tolerant predictions) were identified as potentially causal. Phenotype data from the time of diagnosis were also captured. Results: Eight hundred sixty-four patients with idiopathic or heritable PAH and 16 with pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis were recruited. Mutations in BMPR2 were identified in 130 patients (14.8%). Biallelic mutations in EIF2AK4 were identified in 5 patients with a clinical diagnosis of pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Furthermore, 9 patients with a clinical diagnosis of PAH carried biallelic EIF2AK4 mutations. These patients had a reduced transfer coefficient for carbon monoxide (K co ; 33% [interquartile range, 30%–35%] predicted) and younger age at diagnosis (29 years; interquartile range, 23–38 years) and more interlobular septal thickening and mediastinal lymphadenopathy on computed tomography of the chest compared with patients with PAH without EIF2AK4 mutations. However, radiological assessment alone could not accurately identify biallelic EIF2AK4 mutation carriers. Patients with PAH with biallelic EIF2AK4 mutations had a shorter survival. Conclusions: Biallelic EIF2AK4 mutations are found in patients classified clinically as having idiopathic and heritable PAH. These patients cannot be identified reliably by computed tomography, but a low K co and a young age at diagnosis suggests the underlying molecular diagnosis. Genetic testing can identify these misclassified patients, allowing appropriate management and early referral for lung transplantation.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/CIRCULATIONAHA.117.028351
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2017
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  • 6
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    90th Annual Convention Poster Presentations and Abstracts
    Ovid Technologies (Wolters Kluwer Health) ; 1991
    In:  Diseases of the Colon & Rectum Vol. 34, No. 4 ( 1991-04), p. 1-40
    Details
    In: Diseases of the Colon & Rectum, Ovid Technologies (Wolters Kluwer Health), Vol. 34, No. 4 ( 1991-04), p. 1-40
    Type of Medium: Online Resource
    ISSN: 0012-3706
    URL: Article
    DOI: 10.1007/BF02050606
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 1991
    detail.hit.zdb_id: 2046914-7
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  • 7
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    Whole Genome Sequence Analysis of the Plasma Proteome in Black Adults Provides Novel Insights Into Cardiovascular Disease
    Ovid Technologies (Wolters Kluwer Health) ; 2022
    In:  Circulation Vol. 145, No. 5 ( 2022-02), p. 357-370
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 145, No. 5 ( 2022-02), p. 357-370
    Abstract: Plasma proteins are critical mediators of cardiovascular processes and are the targets of many drugs. Previous efforts to characterize the genetic architecture of the plasma proteome have been limited by a focus on individuals of European descent and leveraged genotyping arrays and imputation. Here we describe whole genome sequence analysis of the plasma proteome in individuals with greater African ancestry, increasing our power to identify novel genetic determinants. Methods: Proteomic profiling of 1301 proteins was performed in 1852 Black adults from the Jackson Heart Study using aptamer-based proteomics (SomaScan). Whole genome sequencing association analysis was ascertained for all variants with minor allele count ≥5. Results were validated using an alternative, antibody-based, proteomic platform (Olink) as well as replicated in the Multi-Ethnic Study of Atherosclerosis and the HERITAGE Family Study (Health, Risk Factors, Exercise Training and Genetics). Results: We identify 569 genetic associations between 479 proteins and 438 unique genetic regions at a Bonferroni-adjusted significance level of 3.8×10 -11 . These associations include 114 novel locus-protein relationships and an additional 217 novel sentinel variant-protein relationships. Novel cardiovascular findings include new protein associations at the APOE gene locus including ZAP70 (sentinel single nucleotide polymorphism [SNP] rs7412-T, β=0.61±0.05, P =3.27×10 -30 ) and MMP-3 (β=-0.60±0.05, P =1.67×10 -32 ), as well as a completely novel pleiotropic locus at the HPX gene, associated with 9 proteins. Further, the associations suggest new mechanisms of genetically mediated cardiovascular disease linked to African ancestry; we identify a novel association between variants linked to APOL1-associated chronic kidney and heart disease and the protein CKAP2 (rs73885319-G, β=0.34±0.04, P =1.34×10 -17 ) as well as an association between ATTR amyloidosis and RBP4 levels in community-dwelling individuals without heart failure. Conclusions: Taken together, these results provide evidence for the functional importance of variants in non-European populations, and suggest new biological mechanisms for ancestry-specific determinants of lipids, coagulation, and myocardial function.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/CIRCULATIONAHA.121.055117
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
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  • 8
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    Primary Results of the Multicenter ARISE II Study (Analysis of Revascularization in Ischemic Stroke With EmboTrap)
    Ovid Technologies (Wolters Kluwer Health) ; 2018
    In:  Stroke Vol. 49, No. 5 ( 2018-05), p. 1107-1115
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 49, No. 5 ( 2018-05), p. 1107-1115
    Abstract: EmboTrap is a novel stent retriever designed to achieve rapid and substantial flow restoration in acute ischemic stroke secondary to large-vessel occlusions. Here, we evaluated EmboTrap’s safety and efficacy compared with established stent retrievers. Methods— ARISE II (Analysis of Revascularization in Ischemic Stroke With EmboTrap) was a single-arm, prospective, multicenter study, comparing the EmboTrap device to a composite performance goal criterion derived using a Bayesian meta-analysis from the pivotal SWIFT (Solitaire device) and TREVO 2 (Trevo device) trials. Patients at 11 US and 8 European sites were eligible for inclusion if they had large-vessel occlusions and moderate-to-severe neurological deficits within 8 hours of symptom onset. The primary efficacy end point was achievement of modified Thrombolysis in Cerebral Ischemia (mTICI) reperfusion scores of ≥2b within 3 EmboTrap passes as adjudicated by the core laboratory. The primary safety end point was a composite of symptomatic intracerebral hemorrhage and serious adverse device effects. Secondary end points included functional independence (modified Rankin Scale, 0–2) and all-cause mortality at 90 days. Results— Between October 2015 and February 2017, 227 patients were enrolled and treated with the EmboTrap device. The primary efficacy end point (mTICI ≥2b within 3 passes) was achieved in 80.2% (95% confidence interval, 74%–85% versus 56% performance goal criterion; P value, 〈 0.0001), and mTICI 2c/3 was 65%. After all interventions, mTICI 2c/3 was achieved in 76%, and mTICI ≥2b was 92.5%. The rate of first pass (mTICI ≥2b following a single pass) was 51.5%. The primary safety end point composite rate of symptomatic intracerebral hemorrhage or serious adverse device effects was 5.3%. Functional independence and all-cause mortality at 90 days were 67% and 9%, respectively. Conclusions— The EmboTrap stent-retriever mechanical thrombectomy device demonstrated high rates of substantial reperfusion and functional independence in patients with acute ischemic stroke secondary to large-vessel occlusions. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT02488915.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/STROKEAHA.117.020125
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2018
    detail.hit.zdb_id: 1467823-8
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  • 9
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    Randomized controlled trial of deutetrabenazine for tardive dyskinesia : The ARM-TD study
    Ovid Technologies (Wolters Kluwer Health) ; 2017
    In:  Neurology Vol. 88, No. 21 ( 2017-05-23), p. 2003-2010
    Details
    In: Neurology, Ovid Technologies (Wolters Kluwer Health), Vol. 88, No. 21 ( 2017-05-23), p. 2003-2010
    Abstract: To determine the efficacy and safety of deutetrabenazine as a treatment for tardive dyskinesia (TD). Methods: One hundred seventeen patients with moderate to severe TD received deutetrabenazine or placebo in this randomized, double-blind, multicenter trial. Eligibility criteria included an Abnormal Involuntary Movement Scale (AIMS) score of ≥6 assessed by blinded central video rating, stable psychiatric illness, and stable psychoactive medication treatment. Primary endpoint was the change in AIMS score from baseline to week 12. Secondary endpoints included treatment success at week 12 on the Clinical Global Impression of Change (CGIC) and Patient Global Impression of Change. Results: For the primary endpoint, deutetrabenazine significantly reduced AIMS scores from baseline to week 12 vs placebo (least-squares mean [standard error] −3.0 [0.45] vs −1.6 [0.46], p = 0.019). Treatment success on CGIC (48.2% vs 40.4%) favored deutetrabenazine but was not significant. Deutetrabenazine and placebo groups showed low rates of psychiatric adverse events: anxiety (3.4% vs 6.8%), depressed mood/depression (1.7% vs 1.7%), and suicidal ideation (0% vs 1.7%, respectively). In addition, no worsening in parkinsonism, as measured by the Unified Parkinson's Disease Rating Scale motor subscale, was noted from baseline to week 12 in either group. Conclusions: In patients with TD, deutetrabenazine was well tolerated and significantly reduced abnormal movements. Classification of evidence: This study provides Class I evidence that in patients with TD, deutetrabenazine reduces AIMS scores.
    Type of Medium: Online Resource
    ISSN: 0028-3878 , 1526-632X
    URL: Article
    DOI: 10.1212/WNL.0000000000003960
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2017
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  • 10
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    Lasmiditan is an effective acute treatment for migraine : A phase 3 randomized study
    Ovid Technologies (Wolters Kluwer Health) ; 2018
    In:  Neurology Vol. 91, No. 24 ( 2018-12-11)
    Details
    In: Neurology, Ovid Technologies (Wolters Kluwer Health), Vol. 91, No. 24 ( 2018-12-11)
    Type of Medium: Online Resource
    ISSN: 0028-3878 , 1526-632X
    URL: Article
    DOI: 10.1212/WNL.0000000000006641
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2018
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