328 research outputs found

    Influence of coronary artery disease on morbidity and mortality after abdominal aortic aneurysmectomy: A population-based study, 1971–1987

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    AbstractThe prognostic importance of coronary artery disease at the time of elective abdominal aortic aneurysmectomy was evaluated among 131 residents of Olmsted County, Minnesota who underwent elective aneurysmectomy from 1971 to 1987 and were followed up to 1988 for death and cardiac events (cardiac death, myocardial infarction, coronary bypass surgery and angioplasty). Before aneurysmectomy, 75 patients (Group 1) had no clinically recognized coronary disease, 47 patients (Group 2) had suspected or overt uncorrected coronary artery disease (history of prior myocardial infarction, angina or a positive stress test) and 9 patients (Group 3) had undergone coronary artery bypass grafting or coronary angioplasty.The 30 day operative mortality rate was 3% (2 of 75) in Group 1 and 9% (4 of 47) in Group 2 (p = 0.15). According to Kaplan-Meier analysis, estimated survival 8 years after aneurysmectomy was 59% (expected rate 68%, p = 0.29) in Group 1 versus 34% (expected rate 61%, p = 0.01) in Group 2. The cumulative incidence rate of cardiac events at 8 years was 15% and 61%, respectively, for patients without and with suspected/overt coronary artery disease (p < 0.01). Using multivariable proportional hazards analysis, uncorrected coronary artery disease was associated with a nearly twofold increased risk of death (hazard ratio 1.79, 95% confidence interval 1.06 to 3.00) and a fourfold increased risk of cardiac events (hazard ratio 3.71, 95% confidence interval 1.79 to 7.69).These population-based data support an aggressive lifelong approach to the management of coronary artery disease in patients undergoing abdominal aortic aneurysmectomy

    Prevalent inhibitors in haemophilia B subjects enrolled in the Universal Data Collection database

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    Several risk factors for inhibitors have recently been described for hemophilia A. It has been assumed that similar risk factors are also relevant for hemophilia B, but there is limited data to confirm this notion

    Effects of chronic exercise on feelings of energy and fatigue: A quantitative synthesis

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    The authors investigated the effect of chronic exercise on feelings of energy and fatigue using metaanalytic techniques. Chronic exercise increased feelings of energy and lessened feelings of fatigue compared with control conditions by a mean effect delta of 0.37. The effect varied according to the presence or absence of a placebo control or whether chronic exercise was completed alone or in combination with an additional therapy. Investigations that used a placebo control and examined chronic exercise alone found no effect of chronic exercise on feelings of energy and fatigue. Certain placebo controls may increase feelings of energy and lessen feelings of fatigue when used with older adults or people with psychological distress. The results highlight the need for research identifying the most useful control conditions for accurately interpreting mental health outcome data obtained in chronic exercise investigations

    Extent of hypoattenuation on CT angiography source images in Basilar Artery occlusion: prognostic value in the Basilar Artery International Cooperation Study

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    &lt;p&gt;&lt;b&gt;Background and Purpose:&lt;/b&gt; The posterior circulation Acute Stroke Prognosis Early CT Score (pc-ASPECTS) quantifies the extent of early ischemic changes in the posterior circulation with a 10-point grading system. We hypothesized that pc-ASPECTS applied to CT angiography source images predicts functional outcome of patients in the Basilar Artery International Cooperation Study (BASICS).&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methods:&lt;/b&gt; BASICS was a prospective, observational registry of consecutive patients with acute symptomatic basilar artery occlusion. Functional outcome was assessed at 1 month. We applied pc-ASPECTS to CT angiography source images of patients with CT angiography for confirmation of basilar artery occlusion. We calculated unadjusted and adjusted risk ratios (RRs) of pc-ASPECTS dichotomized at &#8805;8 versus &#60;8. Primary outcome measure was favorable outcome (modified Rankin Scale scores 0–3). Secondary outcome measures were mortality and functional independence (modified Rankin Scale scores 0–2).&lt;/p&gt; &lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; Of 158 patients included, 78 patients had a CT angiography source images pc-ASPECTS ≥8. Patients with a pc-ASPECTS ≥8 more often had a favorable outcome than patients with a pc-ASPECTS &#60;8 (crude RR, 1.7; 95% CI, 0.98–3.0). After adjustment for age, baseline National Institutes of Health Stroke Scale score, and thrombolysis, pc-ASPECTS &#8805;8 was not related to favorable outcome (RR, 1.3; 95% CI, 0.8–2.2), but it was related to reduced mortality (RR, 0.7; 95% CI, 0.5–0.98) and functional independence (RR, 2.0; 95% CI, 1.1–3.8). In post hoc analysis, pc-ASPECTS dichotomized at &#8805;6 versus &#60;6 predicted a favorable outcome (adjusted RR, 3.1; 95% CI, 1.2–7.5).&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; pc-ASPECTS on CT angiography source images independently predicted death and functional independence at 1 month in the CT angiography subgroup of patients in the BASICS registry.&lt;/p&gt

    Using polymorphisms in FKBP5 to define biologically distinct subtypes of posttraumatic stress disorder: Evidence from endocrine and gene expression studies

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    Context: Polymorphisms in the gene encoding the glucocorticoid receptor (GR) regulating co-chaperone FKBP5 have been shown to alter GR sensitivity and are associated with an increased risk to develop posttraumatic stress disorder (PTSD). Objective: To investigate interactions of the FKBP5 single-nucleotide polymorphism rs9296158 and PTSD symptoms on baseline cortisol level, low-dose dexamethasone suppression, and whole-blood gene expression. Design: Association of FKBP5 genotypes and PTSD symptoms with endocrine measures and genome-wide expression profiles. Setting: Waiting rooms of general medical and gynecological clinics of an urban hospital at Emory University. Participants: The 211 participants were primarily African American (90.05%) and of low socioeconomic status and had high rates of trauma and PTSD. Main Outcome Measures: Baseline and post-dexamethasone suppression cortisol measures and gene expression levels. Results: In our endocrine study, we found that only risk allele A carriers of rs9296158 showed GR supersensitivity with PTSD; in contrast, baseline cortisol levels were decreased in PTSD only in patients with the GG genotype. Expression of 183 transcripts was significantly correlated with PTSD symptoms after multiple testing corrections. When adding FKBP5 genotype and its interaction with PTSD symptoms, expression levels of an additional 32 genes were significantly regulated by the interaction term. Within these 32 genes, previously reported PTSD candidates were identified, including FKBP5 and the IL18 and STAT pathways. Significant overrepresentation of steroid hormone transcription factor binding sites within these 32 transcripts was observed, highlighting the fact that the earlier-described genotype and PTSDdependent differences in GR sensitivity could drive the observed gene expression pattern. Results were validated by reverse transcriptase-polymerase chain reaction and replicated in an independent sample (N=98). Conclusions: These data suggest that the inheritance of GR sensitivity-moderating FKBP5 polymorphisms can determine specific types of hypothalamic-pituitaryadrenal axis dysfunction within PTSD, which are also reflected in gene-expression changes of a subset of GRresponsive genes. Thus, these findings indicate that functional variants in FKBP5 are associated with biologically distinct subtypes of PTSD

    Early Intubation in Endovascular Therapy for Basilar Artery Occlusion:A Post Hoc Analysis of the BASICS Trial

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    BACKGROUND: The optimal anesthetic management for endovascular therapy (EVT) in patients with posterior circulation stroke remains unclear. Our objective was to investigate the impact of early intubation in patients enrolled in the BASICS trial (Basilar Artery International Cooperation Study). METHODS: BASICS was a multicenter, randomized, controlled trial that compared the efficacy of EVT compared with the best medical care alone in patients with basilar artery occlusion. In this post hoc analysis, early intubation within the first 24 hours of the estimated time of basilar artery occlusion was examined as an additional covariate using regression modeling. We estimated the adjusted relative risks (RRs) for favorable outcomes, defined as modified Rankin Scale scores of 0 to 3 at 90 days. An adjusted common odds ratio was estimated for a shift in the distribution of modified Rankin Scale scores at 90 days. RESULTS: Of 300 patients in BASICS, 289 patients were eligible for analysis (151 in the EVT group and 138 in the best medical care group). compared with medical care alone, EVT was related to a higher risk of early intubation (RR, 1.29 [95% CI, 1.09–1.53]; P&lt;0.01), and early intubation was negatively associated with favorable outcome (RR, 0.61 [95% CI, 0.45–0.84]; P=0.002). Whereas there was no overall treatment effect of EVT on favorable outcome (RR, 1.22 [95% CI, 0.95–1.55]; P=0.121), EVT was associated with favorable outcome (RR, 1.34 [95% CI, 1.05–1.71]; P=0.018) and a shift toward lower modified Rankin Scale scores (adjusted common odds ratio, 1.63 [95% CI, 1.04–2.57]; P=0.033) if adjusted for early intubation. CONCLUSIONS: In this post hoc analysis of the neutral BASICS trial, early intubation was linked to unfavorable outcomes, which might mitigate a potential benefit from EVT by indirect effects due to an increased risk of early intubation. This relationship may be considered when assessing the efficacy of EVT in patients with basilar artery occlusion in future trials.</p

    Predicting outcomes after acute reperfusion therapy for basilar artery occlusion

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    Background and purpose Basilar artery occlusion (BAO) leads to high rates of morbidity and mortality, despite successful recanalization. The discordance between flow restoration and long-term functional status clouds clinical decision-making regarding further aggressive care. We sought to develop and validate a practical, prognostic tool for the prediction of 3-month favorable outcome after acute reperfusion therapy for BAO. Methods This retrospective, multicenter, observational study was conducted at four high-volume stroke centers in the USA and Europe. Multivariate regression analysis was performed to identify predictors of favorable outcome (90-day modified Rankin scale scores 0-2) and derive a clinically applicable prognostic model (the Pittsburgh Outcomes after Stroke Thrombectomy-Vertebrobasilar (POST-VB) score). The POST-VB score was evaluated and internally validated with regard to calibration and discriminatory ability. External validity was assessed in patient cohorts at three separate centers. Results In the derivation cohort of 59 patients, independent predictors of favorable outcome included smaller brainstem infarct volume on post-procedure magnetic resonance imaging (P = 125. Conclusions The POST-VB score effectively predicts 3-month functional outcome following acute reperfusion therapy for BAO and may aid in guiding post-procedural care.Peer reviewe

    Genome-wide mapping of genetic determinants influencing DNA methylation and gene expression in human hippocampus

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    Emerging evidence emphasizes the strong impact of regulatory genomic elements in neurodevelopmental processes and the complex pathways of brain disorders. The present genome-wide quantitative trait loci analyses explore the cis-regulatory effects of single-nucleotide polymorphisms (SNPs) on DNA methylation (meQTL) and gene expression (eQTL) in 110 human hippocampal biopsies. We identify cis-meQTLs at 14,118 CpG methylation sites and cis-eQTLs for 302 3'-mRNA transcripts of 288 genes. Hippocampal cis-meQTL-CpGs are enriched in flanking regions of active promoters, CpG island shores, binding sites of the transcription factor CTCF and brain eQTLs. Cis-acting SNPs of hippocampal meQTLs and eQTLs significantly overlap schizophrenia-associated SNPs. Correlations of CpG methylation and RNA expression are found for 34 genes. Our comprehensive maps of cis-acting hippocampal meQTLs and eQTLs provide a link between disease-associated SNPs and the regulatory genome that will improve the functional interpretation of non-coding genetic variants in the molecular genetic dissection of brain disorders

    Development and Validity of the Rating-of-Fatigue Scale

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    Objective: The purpose of these experiments was to develop a rating-of-fatigue (ROF) scale capable of tracking the intensity of perceived fatigue in a variety of contexts. Methods: Four experiments were carried out. The first provided the evidential basis for the construction of the ROF scale. The second tested the face validity of the ROF, and the third tested the convergent and divergent validity of the ROF scale during ramped cycling to exhaustion and 30 min of resting recovery. The final experiment tested the convergent validity of the ROF scale with time of day and physical activity (accelerometer counts) across a whole week. Results: Modal selections of descriptions and diagrams at different levels of exertion and recovery were found during Experiment 1 upon which the ROF scale was constructed and finalised. In Experiment 2, a high level of face validity was indicated, in that ROF was reported to represent fatigue rather than exertion. Descriptor and diagrammatic elements of ROF reportedly added to the coherence and ease of use of the scale. In Experiment 3, high convergence between ROF and various physiological measures were found during exercise and recovery (heart rate, blood lactate concentration, oxygen uptake, carbon dioxide production, respiratory exchange ratio and ventilation rate were all P < 0.001). During ramped cycling to exhaustion ROF and RPE did correspond (P < 0.0001) but not during recovery, demonstrating discriminant validity. Experiment 4 found ROF to correspond with waking time during each day (Mon–Sun all P < 0.0001) and with physical activity (accelerometer count) (Mon–Sun all P < 0.001). Conclusions: The ROF scale has good face validity and high levels of convergent validity during ramped cycling to exhaustion, resting recovery and daily living activities. The ROF scale has both theoretical and applied potential in understanding changes in fatigue in a variety of contexts
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