Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 243
Filtrar
1.
N Engl J Med ; 382(2): 120-129, 2020 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-31733180

RESUMO

BACKGROUND: Whether the direct factor Xa inhibitor rivaroxaban can prevent thromboembolic events after transcatheter aortic-valve replacement (TAVR) is unclear. METHODS: We randomly assigned 1644 patients without an established indication for oral anticoagulation after successful TAVR to receive rivaroxaban at a dose of 10 mg daily (with aspirin at a dose of 75 to 100 mg daily for the first 3 months) (rivaroxaban group) or aspirin at a dose of 75 to 100 mg daily (with clopidogrel at a dose of 75 mg daily for the first 3 months) (antiplatelet group). The primary efficacy outcome was the composite of death or thromboembolic events. The primary safety outcome was major, disabling, or life-threatening bleeding. The trial was terminated prematurely by the data and safety monitoring board because of safety concerns. RESULTS: After a median of 17 months, death or a first thromboembolic event (intention-to-treat analysis) had occurred in 105 patients in the rivaroxaban group and in 78 patients in the antiplatelet group (incidence rates, 9.8 and 7.2 per 100 person-years, respectively; hazard ratio with rivaroxaban, 1.35; 95% confidence interval [CI], 1.01 to 1.81; P = 0.04). Major, disabling, or life-threatening bleeding (intention-to-treat analysis) had occurred in 46 and 31 patients, respectively (4.3 and 2.8 per 100 person-years; hazard ratio, 1.50; 95% CI, 0.95 to 2.37; P = 0.08). A total of 64 deaths occurred in the rivaroxaban group and 38 in the antiplatelet group (5.8 and 3.4 per 100 person-years, respectively; hazard ratio, 1.69; 95% CI, 1.13 to 2.53). CONCLUSIONS: In patients without an established indication for oral anticoagulation after successful TAVR, a treatment strategy including rivaroxaban at a dose of 10 mg daily was associated with a higher risk of death or thromboembolic complications and a higher risk of bleeding than an antiplatelet-based strategy. (Funded by Bayer and Janssen Pharmaceuticals; GALILEO ClinicalTrials.gov number, NCT02556203.).


Assuntos
Aspirina/uso terapêutico , Clopidogrel/uso terapêutico , Inibidores do Fator Xa/uso terapêutico , Inibidores da Agregação de Plaquetas/uso terapêutico , Rivaroxabana/uso terapêutico , Substituição da Valva Aórtica Transcateter , Idoso , Idoso de 80 Anos ou mais , Aspirina/efeitos adversos , Fibrilação Atrial/tratamento farmacológico , Doenças Cardiovasculares/mortalidade , Clopidogrel/efeitos adversos , Quimioterapia Combinada , Inibidores do Fator Xa/efeitos adversos , Feminino , Próteses Valvulares Cardíacas , Hemorragia/induzido quimicamente , Humanos , Análise de Intenção de Tratamento , Estimativa de Kaplan-Meier , Masculino , Inibidores da Agregação de Plaquetas/efeitos adversos , Rivaroxabana/efeitos adversos , Tromboembolia/mortalidade
3.
Am Heart J ; 218: 100-109, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31715433

RESUMO

For 4 decades, antithrombotic therapy with aspirin has been a cornerstone of secondary prevention for patients with chronic atherosclerotic cardiovascular disease (ASCVD). Unfortunately, despite the use of evidence-based therapies, patients with ASCVD continue to have recurrent major adverse cardiovascular events including death, myocardial infarction, and stroke-at a rate of approximately 2%-4% per year. To combat this continuing risk, several recent trials have evaluated the efficacy and safety of more intensive antithrombotic strategies through prolonged dual antiplatelet therapy (DAPT), combining a P2Y12 receptor antagonists and low-dose aspirin, or alternatively applying a dual pathway inhibition approach, combining low-dose non-vitamin K antagonist anticoagulant and low-dose aspirin. Both combination strategies have been shown to reduce recurrent ischemic events but at the cost of increased bleeding events. The clinical application of these antithrombotic strategies requires clinicians to assess and balance the risk of recurrent ischemic and bleeding events in an individual patient. Furthermore, clinicians may also need to adapt their antithrombotic strategies to achieve best patient outcomes, as ASCVD is a progressive disease and the risks of cardiovascular ischemic and bleeding events may shift over time. This state-of-the-art article reviews evidence from the trials and provides a practical approach to the application of DAPT and dual pathway antithrombotic therapy in the long-term management of patients with chronic ASCVD.

4.
Circ Cardiovasc Interv ; 12(10): e008059, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31607152

RESUMO

BACKGROUND: Recent clinical trial data support a pharmacoinvasive strategy as an alternative to primary percutaneous coronary intervention (pPCI) in ST-segment elevation myocardial infarction. We evaluated whether this is true in a real-world prehospital ST-segment elevation myocardial infarction network using ECG assessment of reperfusion coupled with clinical outcomes within 1 year. METHODS: Of the 5583 ST-segment elevation myocardial infarction patients in the Alberta Vital Heart Response Program (Cohort 1 [2006-2011]: n=3593; Cohort 2 [2013-2016]: n=1990), we studied 3287 patients who received a pharmacoinvasive strategy with tenecteplase (April 2013: half-dose tenecteplase was employed in prehospital patients ≥75 years) or pPCI. ECGs were analyzed within a core laboratory; sum ST-segment deviation resolution ≥50% was defined as successful reperfusion. The primary composite was all-cause death, congestive heart failure, cardiogenic shock, and recurrent myocardial infarction within 1 year. RESULTS: The pharmacoinvasive approach was administered in 1805 patients (54.9%), (493 [27.3%] underwent rescue/urgent percutaneous coronary intervention and 1312 [72.7%] had scheduled angiography); pPCI was performed in 1482 patients (45.1%). There was greater ST-segment resolution post-catheterization/percutaneous coronary intervention with a pharmacoinvasive strategy versus pPCI (75.8% versus 64.3%, IP-weighted odds ratio, 1.59; 95% CI, 1.33-1.90; P<0.001). The primary composite was significantly lower with a pharmacoinvasive approach (16.3% versus 23.1%, IP-weighted hazard ratio, 0.84; 95% CI, 0.72-0.99; P=0.033). Major bleeding and intracranial hemorrhage were similar between a pharmacoinvasive strategy and pPCI (7.6% versus 7.5%, P=0.867; 0.6% versus 0.6%; P=0.841, respectively). In the 82 patients ≥75 years with a prehospital pharmacoinvasive strategy, similar ST-segment resolution and rescue rates were observed with full-dose versus half-dose tenecteplase (75.8% versus 88.9%, P=0.259; 31.0% versus 29.2%, P=0.867) with no difference in the primary composite (31.0% versus 25.0%, P=0.585). CONCLUSIONS: In this large Canadian ST-segment elevation myocardial infarction registry, a pharmacoinvasive strategy was associated with improved ST-segment resolution and enhanced outcomes within 1 year compared with pPCI. Our findings support the application of a selective pharmacoinvasive reperfusion strategy when delay to pPCI exists.

5.
Psychol Med ; : 1-11, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31597581

RESUMO

BACKGROUND: Little is known about the neural substrates of suicide risk in mood disorders. Improving the identification of biomarkers of suicide risk, as indicated by a history of suicide-related behavior (SB), could lead to more targeted treatments to reduce risk. METHODS: Participants were 18 young adults with a mood disorder with a history of SB (as indicated by endorsing a past suicide attempt), 60 with a mood disorder with a history of suicidal ideation (SI) but not SB, 52 with a mood disorder with no history of SI or SB (MD), and 82 healthy comparison participants (HC). Resting-state functional connectivity within and between intrinsic neural networks, including cognitive control network (CCN), salience and emotion network (SEN), and default mode network (DMN), was compared between groups. RESULTS: Several fronto-parietal regions (k > 57, p < 0.005) were identified in which individuals with SB demonstrated distinct patterns of connectivity within (in the CCN) and across networks (CCN-SEN and CCN-DMN). Connectivity with some of these same regions also distinguished the SB group when participants were re-scanned after 1-4 months. Extracted data defined SB group membership with good accuracy, sensitivity, and specificity (79-88%). CONCLUSIONS: These results suggest that individuals with a history of SB in the context of mood disorders may show reliably distinct patterns of intrinsic network connectivity, even when compared to those with mood disorders without SB. Resting-state fMRI is a promising tool for identifying subtypes of patients with mood disorders who may be at risk for suicidal behavior.

6.
Circulation ; 140(23): 1921-1932, 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31557056

RESUMO

BACKGROUND: The safety and efficacy of antithrombotic regimens may differ between patients with atrial fibrillation who have acute coronary syndromes (ACS), treated medically or with percutaneous coronary intervention (PCI), and those undergoing elective PCI. METHODS: Using a 2×2 factorial design, we compared apixaban with vitamin K antagonists and aspirin with placebo in patients with atrial fibrillation who had ACS or were undergoing PCI and were receiving a P2Y12 inhibitor. We explored bleeding, death and hospitalization, as well as death and ischemic events, by antithrombotic strategy in 3 prespecified subgroups: patients with ACS treated medically, patients with ACS treated with PCI, and those undergoing elective PCI. RESULTS: Of 4614 patients enrolled, 1097 (23.9%) had ACS treated medically, 1714 (37.3%) had ACS treated with PCI, and 1784 (38.8%) had elective PCI. Apixaban compared with vitamin K antagonist reduced International Society on Thrombosis and Haemostasis major or clinically relevant nonmajor bleeding in patients with ACS treated medically (hazard ratio [HR], 0.44 [95% CI, 0.28-0.68]), patients with ACS treated with PCI (HR, 0.68 [95% CI, 0.52-0.89]), and patients undergoing elective PCI (HR, 0.82 [95% CI, 0.64-1.04]; Pinteraction=0.052) and reduced death or hospitalization in the ACS treated medically (HR, 0.71 [95% CI, 0.54-0.92]), ACS treated with PCI (HR, 0.88 [95% CI, 0.74-1.06]), and elective PCI (HR, 0.87 [95% CI, 0.72-1.04]; Pinteraction=0.345) groups. Compared with vitamin K antagonists, apixaban resulted in a similar effect on death and ischemic events in the ACS treated medically, ACS treated with PCI, and elective PCI groups (Pinteraction=0.356). Aspirin had a higher rate of bleeding than did placebo in patients with ACS treated medically (HR, 1.49 [95% CI, 0.98-2.26]), those with ACS treated with PCI (HR, 2.02 [95% CI, 1.53-2.67]), and those undergoing elective PCI (HR, 1.91 [95% CI, 1.48-2.47]; Pinteraction=0.479). For the same comparison, there was no difference in outcomes among the 3 groups for the composite of death or hospitalization (Pinteraction=0.787) and death and ischemic events (Pinteraction=0.710). CONCLUSIONS: An antithrombotic regimen consisting of apixaban and a P2Y12 inhibitor without aspirin provides superior safety and similar efficacy in patients with atrial fibrillation who have ACS, whether managed medically or with PCI, and those undergoing elective PCI compared with regimens that include vitamin K antagonists, aspirin, or both. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02415400.

7.
Atherosclerosis ; 289: 118-125, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31494384

RESUMO

This review aims to provide insights into contemporary therapeutic options for the treatment of patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) and compares current international guidelines. AF is a common cardiac arrhythmia and a major risk factor for stroke. The risk of stroke can be reduced with the use of oral anticoagulant (OAC) therapy. However, for patients with AF, PCI necessitates the use of combined antithrombotic therapies (OAC and antiplatelet therapies) to reduce thrombotic coronary complications. Optimal combinations and durations of OAC and/or antiplatelet therapy remains an area of clinical debate. Nuances exist within the current guidelines regarding duration and combination of antithrombotic therapy for AF patients requiring PCI. However, consensus was found across the following key points: (i) recent evidence supports a preferred role for a dual antithrombotic approach (OAC plus 1 antiplatelet); (ii) limited use of triple antithrombotic therapy is recommended across all guidelines for patients where the ischemic risk outweighs the risk of bleeding, with the duration to be kept as short as possible; and (iii) lifelong management using monotherapy with an OAC from 12 months post PCI is recommended for stable patients across all guidelines.

8.
Can J Cardiol ; 35(10): 1377-1385, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31492492

RESUMO

BACKGROUND: Robust comparisons between oral P2Y12 inhibitors (clopidogrel, prasugrel, ticagrelor) in ST-elevation myocardial infarction (STEMI) patients who undergo primary percutaneous coronary intervention are lacking. We sought to evaluate outcomes on the basis of P2Y12 inhibitor therapy in patients from the Thrombectomy With PCI Versus PCI Alone in Patients With STEMI Undergoing Primary PCI (TOTAL) trial. METHODS: We grouped 9932 patients according to P2Y12 inhibitor at hospital discharge: clopidogrel (n = 6500; 65.5%), prasugrel (n = 1244; 12.5%), or ticagrelor (n = 2188; 22.0%). The primary composite end point of cardiovascular death, recurrent myocardial infarction, cardiogenic shock, or New York Heart Association class IV heart failure was examined at 1 year. Secondary efficacy and safety end points were also assessed. Cox proportional hazard ratios were determined and adjusted for confounders via propensity scoring. RESULTS: Baseline characteristics differing between the 3 groups were mainly age 75 years or older, diabetes, and previous stroke. After adjustment, ticagrelor use was associated with a lower rate of the primary composite outcome compared with clopidogrel (adjusted hazard ratio [aHR], 0.72; 95% confidence interval [CI], 0.57-0.91; P < 0.02) and prasugrel (aHR, 0.65; 95% CI, 0.48-0.89; P = 0.02). Prasugrel use was not associated with a lower rate of the primary outcome compared with clopidogrel (aHR, 1.09; 95% CI, 0.86-1.39; P > 0.99). Neither prasugrel nor ticagrelor were associated with increased risk of stroke compared with clopidogrel. Compared with clopidogrel, ticagrelor was associated with significantly lower rates of major bleeding. CONCLUSIONS: In this observational analysis of STEMI patients who underwent primary percutaneous coronary intervention, ticagrelor was associated with improved outcomes compared with clopidogrel and prasugrel. An appropriately powered randomized trial is needed to confirm these findings.

9.
JAMA Cardiol ; 4(7): 680-684, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31141104

RESUMO

Importance: Physician behavior in response to knowledge of a patient's CYP2C19 clopidogrel metabolizer status is unknown. Objective: To investigate the association of mandatory reporting of CYP2C19 pharmacogenomic testing, provided to investigators with no direct recommendations on how to use these results, with changes in P2Y12 inhibitor use, particularly clopidogrel, in the Randomized Trial to Compare the Safety of Rivaroxaban vs Aspirin in Addition to Either Clopidogrel or Ticagrelor in Acute Coronary Syndrome (GEMINI-ACS-1) clinical trial. Design, Setting, and Participants: The GEMINI-ACS-1 trial compared rivaroxaban, 2.5 mg twice daily, with aspirin, 100 mg daily, plus open-label clopidogrel or ticagrelor (provided), in patients with recent acute coronary syndromes (ACS). The trial included 371 clinical centers in 21 countries and 3037 patients with ACS. Data were analyzed between May 2017 and February 2019. Interventions: Investigators were required to prestipulate their planned response to CYP2C19 metabolizer status. In response to a regulatory mandate, results for all patients were reported to investigators approximately 1 week after randomization. Main Outcomes and Measures: Reasons for switching P2Y12 inhibitors and occurrence of bleeding and ischemic events were collected. Results: Of 3037 patients enrolled (mean [SD] age, 62.8 [9.0] years; 2275 men [74.9%], and 2824 white race/ethnicity [93.0%]), investigators initially treated 1704 (56.1%) with ticagrelor and 1333 (43.9%) with clopidogrel. Investigators prestipulated that they would use CYP2C19 metabolizer status to change P2Y12 inhibitor in 48.5% of genotyped clopidogrel-treated patients (n = 642 of 1324) and 5.5% of genotyped ticagrelor-treated patients (n = 93 of 1692). P2Y12 inhibitor switching for any reason occurred in 197 patients and was more common in patients treated with ticagrelor (146 of 1704 [8.6%]) compared with clopidogrel (51 of 1333 [3.8%]). Of patients initially treated with ticagrelor, only 1 (0.1% overall; 0.7% of all who switched) was switched based on CYP2C19 status. Of patients initially treated with clopidogrel, 23 (1.7% overall,;45.1% of all who switched) were switched owing to metabolizer status. Of 48 patients (3.6%) with reduced metabolizer status treated initially with clopidogrel, 15 (31.3%) were switched based on metabolizer status, including 48.1% (13 of 27) in which switching was prestipulated. Conclusions and Relevance: Physicians were evenly split on how to respond to knowledge of CYP2C19 metabolizer status in clopidogrel-treated patients. Mandatory provision of this information rarely prompted P2Y12 inhibitor switching overall, including a minority of patients with reduced metabolizer status. These findings highlight the clinical equipoise among physicians regarding use of this information and the reluctance to use information from routine genotyping in the absence of definitive clinical trial data demonstrating the efficacy of this approach. Clinical Trial Registration: ClinicalTrials.gov identifier: NCT02293395.

10.
Psychoneuroendocrinology ; 104: 219-227, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30889471

RESUMO

BACKGROUND: We have previously demonstrated that pre-scan salivary cortisol is associated with attentuated frontal-subcortical brain activation during emotion processesing and semantic list-learning paradigms in depressed subjects. Additionally, altered functional connectivity is observed after remission of acute depression symptoms (rMDD). It is unknown whether cortisol also predicts altered functional connectivity during remission. METHODS: Participants were 47 healthy controls (HC) and 73 rMDD, 18-30 years old who provided salivary cortisol samples before and after undergoing resting-state fMRI. We tested whether salivary cortisol by diagnosis interactions were associated with seed-based resting connectivity of the default mode (DMN) and salience and emotion (SN) networks using whole-brain, cluster-level corrected (p < .01) regression in SPM8. RESULTS: Pre-scan cortisol predicted decreased (HC) and increased (rMDD) cross-network connectivity to the dorsal anterior cingulate, dorso-medial and lateral- prefrontal cortex, brain stem and cerebellum (all seeds) and precuneus (DMN seeds). By and large, pre/post-scan cortisol change predicted the same pattern of findings. In network analyses, cortisol predominantly predicted enhanced cross-network connectivity to cognitive control network regions in rMDD. CONCLUSIONS: The association of cortisol with connections of default and salience networks to executive brain networks differs between individuals with and without a history of depression. Further investigation is needed to better understand the role of cortisol and related stress hormones as a potential primary and interactive driver of network coherence in depression.

11.
Neuroimage ; 191: 278-291, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30790672

RESUMO

The amygdala is critically involved in processing emotion. Through bidirectional connections, the prefrontal cortex (PFC) is hypothesized to influence amygdala reactivity. However, research that elucidates the nature of amygdala-PFC interactions - through mapping amygdala-prefrontal tracts, quantifying variability among tracts, and linking this variability to amygdala activation - is lacking. Using probabilistic tractography to map amygdala-prefrontal white matter connectivity in 142 adolescents, the present study found that white matter connectivity was greater between the amygdala and the subgenual cingulate, orbitofrontal (OFC), and dorsomedial (dmPFC) prefrontal regions than with the dorsal cingulate and dorsolateral regions. Then, using a machine-learning regression, we found that greater amygdala-PFC white matter connectivity was related to attenuated amygdala reactivity. This effect was driven by amygdala white matter connectivity with the dmPFC and OFC, supporting implicit emotion processing theories which highlight the critical role of these regions in amygdala regulation. This study is among the first to map and compare specific amygdala-prefrontal white matter tracts and to relate variability in connectivity to amygdala activation, particularly among a large sample of adolescents from a well-sampled study. By examining the association between specific amygdala-PFC tracts and amygdala activation, the present study provides novel insight into the nature of this emotion-based circuit.


Assuntos
Tonsila do Cerebelo , Emoções/fisiologia , Vias Neurais , Córtex Pré-Frontal , Substância Branca , Adolescente , Tonsila do Cerebelo/anatomia & histologia , Tonsila do Cerebelo/fisiologia , Mapeamento Encefálico/métodos , Imagem de Tensor de Difusão/métodos , Feminino , Humanos , Masculino , Vias Neurais/anatomia & histologia , Vias Neurais/fisiologia , Córtex Pré-Frontal/anatomia & histologia , Córtex Pré-Frontal/fisiologia , Substância Branca/anatomia & histologia , Substância Branca/fisiologia
12.
Eur Heart J ; 40(15): 1188-1197, 2019 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-30698711

RESUMO

AIMS: Spontaneous coronary artery dissection (SCAD) was underdiagnosed and poorly understood for decades. It is increasingly recognized as an important cause of myocardial infarction (MI) in women. We aimed to assess the natural history of SCAD, which has not been adequately explored. METHODS AND RESULTS: We performed a multicentre, prospective, observational study of patients with non-atherosclerotic SCAD presenting acutely from 22 centres in North America. Institutional ethics approval and patient consents were obtained. We recorded baseline demographics, in-hospital characteristics, precipitating/predisposing conditions, angiographic features (assessed by core laboratory), in-hospital major adverse events (MAE), and 30-day major adverse cardiovascular events (MACE). We prospectively enrolled 750 SCAD patients from June 2014 to June 2018. Mean age was 51.8 ± 10.2 years, 88.5% were women (55.0% postmenopausal), 87.7% were Caucasian, and 33.9% had no cardiac risk factors. Emotional stress was reported in 50.3%, and physical stress in 28.9% (9.8% lifting >50 pounds). Predisposing conditions included fibromuscular dysplasia 31.1% (45.2% had no/incomplete screening), systemic inflammatory diseases 4.7%, peripartum 4.5%, and connective tissue disorders 3.6%. Most were treated conservatively (84.3%), but 14.1% underwent percutaneous coronary intervention and 0.7% coronary artery bypass surgery. In-hospital composite MAE was 8.8%; peripartum SCAD patients had higher in-hospital MAE (20.6% vs. 8.2%, P = 0.023). Overall 30-day MACE was 8.8%. Peripartum SCAD and connective tissue disease were independent predictors of 30-day MACE. CONCLUSION: Spontaneous coronary artery dissection predominantly affects women and presents with MI. Despite majority of patients being treated conservatively, survival was good. However, significant cardiovascular complications occurred within 30 days. Long-term follow-up and further investigations on management are warranted.

13.
Depress Anxiety ; 36(2): 141-152, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30516853

RESUMO

BACKGROUND: Three well-established intrinsic connectivity networks (ICNs) involved in cognitive-affective processing include the cognitive control network (CCN), default mode network (DMN), and salience and emotional network (SEN). Despite recent advances in understanding developmental changes in these ICNs, the majority of research has focused on single seeds or networks in isolation with limited age ranges. Additionally, although internalizing psychopathologies (IPs), such as anxiety and depression, are often characterized by maladaptive cognitive-affective processing styles, it is not clear how IP history influences age-related changes in brain networks. METHOD: The current study aimed to characterize the normative development of the CCN, DMN, and SEN across a large age-span (7-29 year olds) of typically developing (TD) individuals (n = 97). We also explore how age may impact differences in network connectivity between TD individuals and patients with IPs (n = 136). RESULTS: Among TD individuals, DMN and CCN connectivity strengthened with age, whereas connectivity between the SEN and ventromedial prefrontal cortex weakened across development. When exploring group (IP vs. TD) differences, the IP group was characterized by greater connectivity between the CCN and cerebellum and between the SEN and caudate from childhood to early adulthood, relative to TD individuals. In addition, patients with IPs, versus TD individuals, exhibited reduced connectivity between the SEN and medial frontal gyrus from adolescence to adulthood. CONCLUSIONS: The current findings shed light on differential age-related changes in brain network patterns among psychiatrically free, TD individuals and those with internalizing disorders, and may provide plausible targets for novel mechanism-based treatments that differ based on developmental stage.


Assuntos
Ansiedade/fisiopatologia , Encéfalo/crescimento & desenvolvimento , Encéfalo/fisiopatologia , Depressão/fisiopatologia , Vias Neurais/fisiologia , Vias Neurais/fisiopatologia , Descanso/psicologia , Adolescente , Adulto , Afeto , Ansiedade/patologia , Encéfalo/patologia , Encéfalo/fisiologia , Estudos de Casos e Controles , Cerebelo/patologia , Cerebelo/fisiopatologia , Criança , Cognição , Depressão/patologia , Emoções , Feminino , Humanos , Masculino , Vias Neurais/crescimento & desenvolvimento , Vias Neurais/patologia , Córtex Pré-Frontal/patologia , Córtex Pré-Frontal/fisiopatologia , Adulto Jovem
14.
Neuropsychopharmacology ; 44(3): 495-502, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30337638

RESUMO

Neuropeptide Y (NPY) produces anxiolytic effects in rodent models, and naturally occurring low NPY expression in humans has been associated with negative emotional phenotypes. Studies in rodent models have also demonstrated that NPY elicits reward behaviors through its action in the nucleus accumbens (NAc), but the impact of NPY on the human NAc is largely unexplored. We recruited 222 healthy young adults of either sex and genetically selected 53 of these subjects at the extremes of NPY expression (Low-NPY and High-NPY) to participate in functional magnetic resonance imaging. Responses of the NAc and surrounding ventral striatum were quantified during a monetary incentive delay task in which stimuli varied by salience (high versus low) and valence (win versus loss). We found that bilateral NAc responses to high-salience versus low-salience stimuli were greater for Low-NPY subjects relative to High-NPY subjects, regardless of stimulus valence. To our knowledge, these results provide the first evidence in humans linking NPY with salience sensitivity of the NAc, raising the possibility that individual differences in NPY expression moderate the risk for disorders of mesoaccumbal function such as addictions and mood disorders. Additionally, we found that head motion was greater among High-NPY subjects, consistent with previous reports linking NPY with hyperactivity. Future studies in animal models are warranted to elucidate the neural mechanisms through which NPY influences NAc function and related behaviors.


Assuntos
Desvalorização pelo Atraso/fisiologia , Movimentos da Cabeça/fisiologia , Neuropeptídeo Y/fisiologia , Núcleo Accumbens/fisiologia , Recompensa , Adolescente , Adulto , Feminino , Neuroimagem Funcional , Expressão Gênica/genética , Humanos , Imagem por Ressonância Magnética , Masculino , Neuropeptídeo Y/genética , Núcleo Accumbens/diagnóstico por imagem , Adulto Jovem
16.
Eur Heart J Acute Cardiovasc Care ; : 2048872618812135, 2018 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-30421616

RESUMO

AIMS:: The purpose of this study was to compare outcomes associated with medical management of ST-elevation myocardial infarction and non-ST-elevation myocardial infarction patients presenting to hospitals with and without onsite catheterization facilities. METHODS: All patients ( n=25,921) with ST-elevation myocardial infarction ( n=10,563) or non-ST-elevation myocardial infarction ( n=15,358) in Alberta, Canada between April 2010-March 2016 were categorized according to availability of catheterization facilities at the hospital they presented to and their management strategy (medically managed without coronary angiography or medically managed after coronary angiography). RESULTS:: Overall, 51% presented to hospitals without catheterization facilities; and 34% were managed medically (18% without coronary angiography, and 16% after coronary angiography). Rates of medical management were higher at hospitals without versus those with catheterization facilities (43% vs. 24%, p<0.01). However, both the rate of presentation to hospitals without catheterization facilities (70% non-ST-elevation myocardial infarction, 24% ST-elevation myocardial infarction, p<0.01) and medical management (45% non-ST-elevation myocardial infarction, 18% ST-elevation myocardial infarction, p<0.01) differed by myocardial infarction type. The lack of catheterization facilities at the presenting hospital had no association with in-hospital mortality in patients medically managed without coronary angiography, but was associated with a lower risk of mortality among patients medically managed after coronary angiography. However, the latter benefit was restricted to non-ST-elevation myocardial infarction patients only (adjusted hazard ratio 0.43, 95% confidence interval: 0.25-0.76). CONCLUSION:: The availability of catheterization facilities at the hospital at which non-ST-elevation myocardial infarction and ST-elevation myocardial infarction patients presented influenced their likelihood of being medically managed, but was not associated with adverse short- or long-term mortality outcomes.

17.
Soc Cogn Affect Neurosci ; 13(10): 1081-1090, 2018 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-30285231

RESUMO

Individuals in a major depressive episode often display impairment in cognitive control, and this impairment exists outside of the acute phase of illness. Impairment in cognitive control also has been associated with exposure to childhood adversity (CA). The current study examined whether exposure to CA can explain variance in a component of cognitive control-inhibitory control-independent of diagnostic status in young adults with and without a history of depression. Healthy control individuals (n = 40) and individuals with remitted major depressive disorder (n = 53) completed a task measuring inhibitory control, reported level of CA and completed a scanning session to assess gray matter volume and resting state connectivity in regions associated with cognitive control. The results demonstrate that higher levels of CA were associated with poorer inhibitory control, reduced right middle frontal gyrus gray matter, decreased connectivity of salience and emotion networks and increased connectivity in cognitive control networks, even after controlling for diagnostic status, residual depression symptoms and current stressors. Together, the results suggest that inhibitory control impairment and intrinsic connectivity changes may be characterized as developmental sequelae of early stress exposure.


Assuntos
Encéfalo/diagnóstico por imagem , Cognição/fisiologia , Transtorno Depressivo Maior/diagnóstico por imagem , Função Executiva/fisiologia , Substância Cinzenta/diagnóstico por imagem , Adolescente , Transtorno Depressivo Maior/psicologia , Emoções , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Testes Neuropsicológicos , Adulto Jovem
18.
Neuroimage ; 183: 617-626, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30172004

RESUMO

Despite prior extensive investigations of the interactions between the amygdala and prefrontal cortex, few studies have simultaneously considered activation and structural connectivity in this circuit, particularly as it pertains to adolescent socioemotional development. The current multi-modal study delineated the correspondence between uncinate fasciculus (UF) connectivity and amygdala habituation in a large adolescent sample that was drawn from a population-based sample. We then examined the influence of demographic variables (age, gender, and pubertal status) on the relation between UF connectivity and amygdala habituation. 106 participants (15-17 years) completed DTI and an fMRI emotional face processing task. Left UF fractional anisotropy was associated with left amygdala habituation to fearful faces, suggesting that increased structural connectivity of the UF may facilitate amygdala regulation. Pubertal status moderated this structure-function relation, such that the association was stronger in those who were less mature. Therefore, UF connectivity may be particularly important for emotion regulation during early puberty. This study is the first to link structural and functional limbic circuitry in a large adolescent sample with substantial representation of ethnic minority participants, providing a more comprehensive understanding of socioemotional development in an understudied population.


Assuntos
Desenvolvimento do Adolescente/fisiologia , Tonsila do Cerebelo , Imagem de Tensor de Difusão/métodos , Emoções/fisiologia , Neuroimagem Funcional/métodos , Habituação Psicofisiológica/fisiologia , Córtex Pré-Frontal , Puberdade/fisiologia , Substância Branca , Adolescente , Tonsila do Cerebelo/anatomia & histologia , Tonsila do Cerebelo/diagnóstico por imagem , Tonsila do Cerebelo/fisiologia , Expressão Facial , Feminino , Humanos , Masculino , Vias Neurais/anatomia & histologia , Vias Neurais/diagnóstico por imagem , Vias Neurais/fisiologia , Córtex Pré-Frontal/anatomia & histologia , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/fisiologia , Substância Branca/anatomia & histologia , Substância Branca/diagnóstico por imagem , Substância Branca/fisiologia
19.
Can J Cardiol ; 34(9): 1200-1209, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30170675

RESUMO

Chronic mitral regurgitation (MR) remains a common cardiovascular condition resulting in significant morbidity and mortality. With an aging population, increasing trends for both primary (degenerative) and secondary (functional) MR have become apparent. Although the gold standard remains surgical intervention with mitral valve repair/replacement, comorbid conditions have steered the development of less invasive technologies to mitigate perioperative surgical risk. Transcatheter mitral valve repair using a percutaneous edge-to-edge technique is the most widely available choice at present. However, other transcatheter mitral valve repair techniques such as annuloplasty and chordal implantation are notable alternatives. Moreover, emerging technologies in transcatheter mitral valve replacement are rapidly establishing their roles in the field of chronic severe MR therapy. Hence, it is imperative to understand the indications and limitations of these various transcatheter mitral valve interventions to provide the best and most up-to-date clinical care for patients. This review will outline current evidence and patient selection criteria for such device-based therapies.


Assuntos
Tecnologia Biomédica/métodos , Anuloplastia da Valva Mitral , Insuficiência da Valva Mitral/cirurgia , Idoso , Humanos , Anuloplastia da Valva Mitral/métodos , Anuloplastia da Valva Mitral/tendências , Seleção de Pacientes , Risco Ajustado
20.
Can J Cardiol ; 34(10): 1298-1306, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30170782

RESUMO

BACKGROUND: Little is known about the resource use and cost burden of acute myocardial infarction (AMI) beyond the index event. We examined resource use and care costs during the first and each subsequent year, among patients with incident AMI. METHODS: Patients aged ≥18 years who were admitted with incident AMI at emergency departments or hospitals in Alberta, Canada, between April 2004 and March 2014 were included. Incident cases were defined as those without an AMI hospitalization in the previous 10 years. Inpatient, outpatient, practitioner claims, drug claims, and vital statistics were linked and follow-up data were available until March 2016. Resource use and care costs per patient for each year after the AMI were calculated. RESULTS: The analysis included 41,210 patients with incident AMI (non-ST-segment elevation myocardial infarction [NSTEMI] = 50.8%, ST-segment elevation myocardial infarction = 36.8%, and undefined myocardial infarction [MI] = 12.5%). Resource use and care costs were highest during the first year. Compared with other MI groups, patients with ST-segment elevation myocardial infarction had more frequent outpatient visits (mean 1.64 vs 0.99 [NSTEMI] and 0.87 [undefined MI] visits) but spent fewer days in hospital (mean 7.72 vs 9.23 [NSTEMI] and 8.5 [undefined MI] days) during the first year. AMI costs were $19,842 during the first year and $845 per year for the next 5 years. Hospitalization costs accounted for the majority of costs during the first year (81.1%), whereas drug costs did for the next 5 years (62.1%). CONCLUSIONS: The long-term annual cost burden of AMI is modest compared with care costs during the first year. Although hospitalization dominates first year costs, pharmaceuticals do so in the long term.


Assuntos
Recursos em Saúde/estatística & dados numéricos , Custos Hospitalares , Hospitalização/economia , Assistência de Longa Duração/economia , Infarto do Miocárdio/economia , Pacientes Ambulatoriais , Médicos/economia , Idoso , Idoso de 80 Anos ou mais , Alberta/epidemiologia , Feminino , Seguimentos , Mortalidade Hospitalar/tendências , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA