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1.
J Invasive Cardiol ; 32(6): E143-E150, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32479416

RESUMO

OBJECTIVES: Limited studies of percutaneous coronary intervention (PCI) of the left internal mammary artery (LIMA) graft exist. We compared outcomes of different bypass grafts to the left anterior descending (LAD) coronary artery. METHODS: Participants ≥65 years old in the CathPCI Registry who underwent PCI of a bypass graft to the LAD between 2009 and 2014 were included. Individuals were divided by graft type: LIMA; saphenous vein graft (SVG); or other. Clinical characteristics and outcomes using Medicare claims data for mortality, rehospitalization for myocardial infarction (MI), stroke, or unplanned repeat revascularization at 1 year were examined. RESULTS: There were 10,051 PCIs performed on grafts to the LAD: 6797 SVGs (67.6%), 3011 LIMA grafts (30.0%); and 243 other (2.4%). Procedural success rates (SVG 92.9%, LIMA 91.1%, other 93.4%; P=.65) and in-patient mortality rates (SVG 3.0%, LIMA 2.7%, other 2.1%; P=.61) were similar. However, dissection rates were higher in LIMA interventions (SVG 0.7%, LIMA 2.8%, other 2.5%; P<.001). At 1 year, mortality, MI, and repeat revascularization were lower in arterial grafts (mortality: SVG 16.6%, LIMA 14.8%, other 11.8% [P<.001]; MI: SVG 9.9%, LIMA, 6.6%, other 8.1% [P<.001]; revascularization: SVG 14.4%, LIMA 9.5%, other 10.4% [P<.001]). After multivariable adjustment, LIMA patients had lower rates of MI (hazard ratio, 0.71; 95% confidence interval, 0.60-0.84) and repeat revascularization (hazard ratio, 0.68; 95% confidence interval, 0.59-0.79) compared with the SVG group. Mortality was not significantly different. CONCLUSIONS: Despite similar procedural success rates compared with SVG and other graft types, LIMA interventions were independently associated with lower rates of recurrent MI and repeat revascularization at 1 year.

2.
Cancer Chemother Pharmacol ; 85(5): 959-968, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32296873

RESUMO

PURPOSE: Isocitrate dehydrogenase (IDH) mutations lead to formation of the oncometabolite 2-hydroxyglutarate (2-HG), which is elevated in several solid and liquid tumors. Ivosidenib (AG-120) is a targeted, potent, oral inhibitor of the mutant IDH1 protein. We describe detailed pharmacokinetics and pharmacodynamics of ivosidenib in patients with advanced hematologic malignancies with an IDH1 mutation treated in a phase I study (ClinicalTrials.gov NCT02074839). METHODS: Patients received single and multiple oral doses of ivosidenib from 100 mg twice daily to 1200 mg once daily (QD) in 28-day continuous cycles. Concentrations of ivosidenib and 2-HG in plasma, and 2-HG in bone marrow, were assessed at routine intervals. Plasma 4ß-hydroxycholesterol/cholesterol ratios were assessed as a marker of CYP3A activity. RESULTS: Ivosidenib was rapidly absorbed and slowly eliminated (half-life 72-138 h) after single and multiple dosing. Ivosidenib exhibited dose- and time-dependent pharmacokinetics, with exposure increasing sub-proportionally to dose, and clearance increasing with increasing dose. Plasma 2-HG concentrations were maximally and persistently inhibited in the majority of patients receiving 500-mg QD ivosidenib, to concentrations close to those observed in healthy subjects. Ivosidenib pharmacokinetics were not affected by mild or moderate renal impairment, mild hepatic impairment, age, weight, sex, race, or co-administration of weak CYP3A4 inhibitors or inducers. Moderate-to-strong CYP3A4 inhibitors decreased ivosidenib clearance. Ivosidenib also induced CYP3A enzyme activity, with increases in 4ß-hydroxycholesterol/cholesterol ratios of 119-168% at 500-mg QD ivosidenib. CONCLUSIONS: Ivosidenib 500-mg QD has favorable pharmacokinetic and pharmacodynamic profiles in patients with advanced hematologic malignancies with an IDH1 mutation. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT02074839.

3.
J Cataract Refract Surg ; 46(2): 276-286, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32126042

RESUMO

PURPOSE: To compare accelerated corneal crosslinking (CXL) alone, CXL with simultaneous intrastromal corneal ring segments (CXL-ICRS), and CXL with simultaneous topography-guided photorefractive keratectomy (CXL-TG-PRK) in progressive keratoconus, pellucid marginal degeneration (PMD), or laser in situ keratomileusis (LASIK)-induced ectasia. SETTING: The Kensington Eye Institute and Bochner Eye Institute, Toronto, Canada. DESIGN: Prospective nonrandomized interventional study. METHODS: Visual and topographical outcomes using a comparative analysis adjusting for preoperative maximum keratometry (Kmax) were evaluated 1 year postoperatively. RESULTS: Four hundred fifty-two eyes from 375 patients with progressive keratoconus, PMD, or LASIK-induced ectasia that underwent accelerated (9 mW/cm, 10 minutes) CXL alone (n = 204), CXL-ICRS (n = 126), or CXL-TG-PRK (n = 122) were included. Change in logarithm of the minimum angle of resolution uncorrected distance visual acuity was significant with CXL-ICRS (-0.31; 95% CI, -0.38 to -0.24) and CXL-TG-PRK (-0.16; 95% CI, -0.24 to -0.09), but not with CXL alone. No significant differences in change were found between the 3 groups. Change in corrected distance visual acuity (CDVA) was significant in all 3 groups: -0.12 (95% CI, -0.15 to -0.10) with CXL alone, -0.23 (95% CI, -0.27 to -0.20) with CXL-ICRS, and -0.17 (95% CI, -0.21 to -0.13) with CXL-TG-PRK. Improvement in CDVA was greater with CXL-ICRS than with CXL alone (-0.08 ± 0.02; P < .0001) and CXL-TG-PRK (-0.05 ± 0.02; P = .005). Change in Kmax was significant with CXL-ICRS [-3.21 diopters (D); 95% CI, -3.98 to -2.45] and CXL-TG-PRK (-3.69 D; 95% CI, -4.49 to -2.90), but not with CXL alone (-0.05 D; 95% CI, -0.66 to 0.55). CONCLUSIONS: CXL alone might be best for keratoconic patients who meet the inclusion criteria. CXL-ICRS might be more effective for eyes with more irregular astigmatism and worse CDVA and CXL-TG-PRK for eyes requiring improvements in irregular astigmatism but still have good CDVA.

4.
Circulation ; 141(13): 1071-1079, 2020 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-32098500

RESUMO

BACKGROUND: Patients with bicuspid aortic valve (AV) stenosis were excluded from the pivotal evaluations of transcatheter AV replacement (TAVR) devices. We sought to evaluate the outcomes of TAVR in patients with bicuspid AV stenosis in comparison with those with tricuspid AV stenosis. METHODS: We used data from the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry (November 2011 through November 2018) to determine device success, procedural outcomes, post-TAVR valve performance, and in-hospital clinical outcomes (mortality, stroke, and major bleeding) according to valve morphology (bicuspid versus tricuspid). Results were stratified by older and current (Sapien 3 and Evolut R) generation valve prostheses. Medicare administrative claims were used to evaluate mortality and stroke to 1 year among eligible individuals (≥65 years). RESULTS: After exclusions, there were 170 959 eligible procedures at 593 sites during the specified interval. Of these, 5412 TAVR procedures (3.2%) were performed in patients with bicuspid AV, including 3705 with current-generation devices. In comparison with patients with tricuspid valves, patients with bicuspid AV were younger and had a lower Society of Thoracic Surgeons Predicted Risk of Operative Mortality score. When current-generation devices were used to treat patients with bicuspid AV, device success increased (93.5 versus 96.3; P=0.001) and the incidence of 2+ aortic insufficiency declined (14.0% versus 2.7%; P<0.001) in comparison with older-generation devices. With current-generation devices, device success was slightly lower in the bicuspid (versus tricuspid) AV group (96.3% in bicuspid versus 97.4% in tricuspid, P=0.07), with a slightly higher incidence of residual moderate or severe aortic insufficiency among patients with bicuspid AV (2.7% versus 2.1%; P<0.001). A lower 1-year adjusted risk of mortality (hazard ratio, 0.88 [95% CI, 0.78-0.99]) was observed for patients with bicuspid AV versus patients with tricuspid AV in the Medicare-linked cohort, whereas no difference was observed in the 1-year adjusted risk of stroke (hazard ratio, 1.14 [95% CI, 0.94-1.39]). CONCLUSIONS: Using current-generation devices, procedural, postprocedural, and 1-year outcomes were comparable following TAVR for bicuspid AV versus tricuspid AV disease. With newer-generation devices, TAVR is a viable treatment option for patients with bicuspid AV disease.

5.
Mult Scler Relat Disord ; 40: 101950, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31982662

RESUMO

BACKGROUND: Recent international studies suggest that ethnicity may predict relapse types and outcomes in NMOSD. Our aim was to evaluate ethnicity as a predictor of diagnostic phenotype and prognosis in a multi-ethnic NMOSD cohort from a single geographic region. METHODS: This was a multi-centre retrospective cohort study of NMOSD subjects in Toronto, Canada. Ethnicity was classified as Asian, black, Caucasian, and other. Regression models were used to assess the relationship between ethnicity and each of diagnostic phenotype (2006 vs. only 2015 diagnostic criteria), annualized relapse rate, and EDSS at last follow-up. RESULTS: Out of 81 patients with NMOSD, 87.7% were female, 70.4% positive for aquaporin-4 (AQP4) IgG, with mean age of onset 38.9 (17) years and median disease duration [IQR] of 9.8 [4.50, 16.59] years. Blacks compared to Asians were less likely to exhibit classic NMO as per 2006 diagnostic criteria (p = 0.006). Caucasians, compared to Asians, had lower EDSS scores at last follow-up (p = 0.008) despite a trend towards higher annualized relapse rates. Older age of onset was significantly associated with greater disability as measured by the EDSS (p = 0.003). CONCLUSIONS: In this multi-ethnic cohort from Toronto, Canada, blacks with NMOSD were less likely than Asians to demonstrate classic NMO by 2006 diagnostic criteria. Caucasians had better long-term disability outcomes compared to Asians as measured by the EDSS.

6.
Invest New Drugs ; 38(2): 433-444, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31028664

RESUMO

Background Mutant isocitrate dehydrogenase 1 and 2 (IDH1/IDH2) enzymes produce the oncometabolite D-2-hydroxyglutarate (2-HG). Ivosidenib (AG-120) is a targeted mutant IDH1 inhibitor under evaluation in a phase 1 dose escalation and expansion study of IDH1-mutant advanced solid tumors including cholangiocarcinoma, chondrosarcoma, and glioma. We explored the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of ivosidenib in these populations. Methods Ivosidenib was administered orally once (QD) or twice (BID) daily in continuous 28-day cycles; 168 patients received ≥1 dose within the range 100 mg BID to 1200 mg QD. PK and PD were assessed using validated liquid chromatography-tandem mass spectrometry assays. Results Ivosidenib demonstrated good oral exposure after single and multiple doses, was rapidly absorbed, and had a long terminal half-life (mean 40-102 h after single dose). Exposure increased less than dose proportionally. Steady state was reached by day 15, with moderate accumulation across all tumors (1.5- to 1.7-fold for area-under-the-curve at 500 mg QD). None of the intrinsic and extrinsic factors assessed affected ivosidenib exposure, including patient/disease characteristics and concomitant administration of weak CYP3A4 inhibitors/inducers. After multiple doses in patients with cholangiocarcinoma or chondrosarcoma, plasma 2-HG was reduced by up to 98%, to levels seen in healthy subjects. Exposure-response relationships for safety and efficacy outcomes were flat across the doses tested. Conclusions Ivosidenib demonstrated good oral exposure and a long half-life. Robust, persistent plasma 2-HG inhibition was observed in IDH1-mutant cholangiocarcinoma and chondrosarcoma. Ivosidenib 500 mg QD is an appropriate dose irrespective of various intrinsic and extrinsic factors. Trial RegistrationClinicalTrials.gov (NCT02073994).

7.
Br J Dev Psychol ; 38(1): 90-107, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31556971

RESUMO

The present study aimed to examine the reciprocal relationship between parental psychological control and students' academic functioning in urban China. Participants were 731 Chinese high school students in grade 10 (356 boys; Mage  = 15.64 years, SD = 0.68). Two waves of 1-year longitudinal data were collected using student reports of parental psychological control and academic-related beliefs, strategies, and behaviours. Results showed that parental psychological control at Time 1 significantly triggered an increase in students' maladaptive academic functioning at Time 2; and students' adaptive academic functioning at Time 1 significantly predicted parental psychological control at Time 2. Limitations of the present study and implications for practice are discussed. Statement of contribution What is already known on this subject? According to self-determination theory, parental psychological control has been found to be harmful on students' academic learning in Western societies. We know little about the relation between parental psychological control and academic functioning (adaptive vs. maladaptive) in Eastern societies such as China. What does this study add? Parental psychological control increased maladaptive academic functioning, and adaptive academic functioning decreased parental psychological control, suggesting a more fluid, dynamic parenting-child interaction over time. The predicted relations between parental psychological control and academic functioning of high school students hold across gender. More urbanized adolescents had a high tendency to perceive their parents as psychological controlling, suggesting a change in culture regarding the importance of personal autonomy for more urbanized adolescents.

8.
J Allergy Clin Immunol Pract ; 8(1): 166-175.e10, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31678300

RESUMO

BACKGROUND: Early dietary introduction of highly allergenic foods has been associated with decreased risk of food allergy in high-risk infants. OBJECTIVE: Early introduction of highly allergenic foods for lower risk infants was examined using Canadian Healthy Infant Longitudinal Development (CHILD) Study data. METHODS: CHILD participants were recruited from the general population before birth. Every 6 months, caregivers reported food introduction and allergic reactions. At ages 1 and 3 years, sensitization to peanut, egg, and cow's milk was measured by skin prick testing (SPT) and atopic dermatitis diagnosed at clinical visits. Multivariable logistic regression was used to examine associations between timing of introduction to peanut, egg, and cow's milk and the presence at 3 years of sensitization (positive SPT) and probable clinical IgE-mediated allergy (sensitization with no current consumption and convincing history of allergic reaction to the specific food). RESULTS: Among 2669 CHILD participants at age 3 years, 101 (3.80%) showed sensitization to peanut, 59 (2.21%) to egg, and 30 (1.12%) to cow's milk; 46 (1.78%) showed probable clinical IgE-mediated allergy to peanut, 4 (0.16%) to egg, and 2 (0.08%) to cow's milk. Infants introduced to peanut after 12 months had increased odds of sensitization (odds ratio [OR]: 2.38, 95% confidence interval [CI]: 1.39-4.07) and probable clinical allergy (OR: 4.04, 95% CI: 1.66-9.85) to peanut at 3 years. Associations persisted after exclusion of high-risk infants with moderate-to-severe atopic dermatitis in the first year/egg sensitization at 1 year. CONCLUSIONS: General-population infants introduced to peanut after age 12 months were more likely to have sensitization and probable clinical allergy to peanut at 3 years.

9.
Blood ; 135(7): 463-471, 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-31841594

RESUMO

Ivosidenib (AG-120) is an oral, targeted agent that suppresses production of the oncometabolite 2-hydroxyglutarate via inhibition of the mutant isocitrate dehydrogenase 1 (IDH1; mIDH1) enzyme. From a phase 1 study of 258 patients with IDH1-mutant hematologic malignancies, we report results for 34 patients with newly diagnosed acute myeloid leukemia (AML) ineligible for standard therapy who received 500 mg ivosidenib daily. Median age was 76.5 years, 26 patients (76%) had secondary AML, and 16 (47%) had received ≥1 hypomethylating agent for an antecedent hematologic disorder. The most common all-grade adverse events were diarrhea (n = 18; 53%), fatigue (n = 16; 47%), nausea (n = 13; 38%), and decreased appetite (n = 12; 35%). Differentiation syndrome was reported in 6 patients (18%) (grade ≥3 in 3 [9%]) and did not require treatment discontinuation. Complete remission (CR) plus CR with partial hematologic recovery (CRh) rate was 42.4% (95% confidence interval [CI], 25.5% to 60.8%); CR 30.3% (95% CI, 15.6% to 48.7%). Median durations of CR+CRh and CR were not reached, with 95% CI lower bounds of 4.6 and 4.2 months, respectively; 61.5% and 77.8% of patients remained in remission at 1 year. With median follow-up of 23.5 months (range, 0.6-40.9 months), median overall survival was 12.6 months (95% CI, 4.5-25.7). Of 21 transfusion-dependent patients (63.6%) at baseline, 9 (42.9%) became transfusion independent. IDH1 mutation clearance was seen in 9/14 patients achieving CR+CRh (5/10 CR; 4/4 CRh). Ivosidenib monotherapy was well-tolerated and induced durable remissions and transfusion independence in patients with newly diagnosed AML. This trial was registered at www.clinicaltrials.gov as #NCT02074839.

10.
J Vis Exp ; (152)2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31710042

RESUMO

Cell-free protein synthesis (CFPS) is an emerging technology in systems and synthetic biology for the in vitro production of proteins. However, if CFPS is going to move beyond the laboratory and become a widespread and standard just in time manufacturing technology, we must understand the performance limits of these systems. Toward this question, we developed a robust protocol to quantify 40 compounds involved in glycolysis, the pentose phosphate pathway, the tricarboxylic acid cycle, energy metabolism and cofactor regeneration in CFPS reactions. The method uses internal standards tagged with 13C-aniline, while compounds in the sample are derivatized with 12C-aniline. The internal standards and sample were mixed and analyzed by reversed-phase liquid chromatography-mass spectrometry (LC/MS). The co-elution of compounds eliminated ion suppression, allowing the accurate quantification of metabolite concentrations over 2-3 orders of magnitude where the average correlation coefficient was 0.988. Five of the forty compounds were untagged with aniline, however, they were still detected in the CFPS sample and quantified with a standard curve method. The chromatographic run takes approximately 10 min to complete. Taken together, we developed a fast, robust method to separate and accurately quantify 40 compounds involved in CFPS in a single LC/MS run. The method is a comprehensive and accurate approach to characterize cell-free metabolism, so that ultimately, we can understand and improve the yield, productivity and energy efficiency of cell-free systems.

11.
Artigo em Inglês | MEDLINE | ID: mdl-31674728

RESUMO

Talent development constitutes an important phenomenon of human development; yet it is rarely considered a mainstream topic in the field of child and adolescent development. Conversely, in the field of gifted and talented studies, various talent development (TD) models developed in the past have had minimal interaction with the literature on child and adolescent development, despite the urgent need for TD models and theories that focus on developmental processes rather than individual traits. In this article, I first identify reasons why talent development has been overlooked, and why existing TD models were not able to pick up the slack. I then introduce developmental systems approaches as a new trend in research, and explain how it reinstates the topic of talent development in developmental research, and by so doing enriches our understanding of human development. I then explore the viability of talent development research and theoretical development being guided by the developmental systems framework. Finally, I identify potential contributions of talent development research to the field of child and adolescent development. My overarching argument is that a relational developmental systems approach to talent development provides a new window for the field to explore the nature and development of human potential.

12.
JAMA Cardiol ; 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31746963

RESUMO

Importance: Pulmonary hypertension (pHTN) is associated with increased risk of mortality after mitral valve surgery for mitral regurgitation. However, its association with clinical outcomes in patients undergoing transcatheter mitral valve repair (TMVr) with a commercially available system (MitraClip) is unknown. Objective: To assess the association of pHTN with readmissions for heart failure and 1-year all-cause mortality after TMVr. Design, Setting, and Participants: This retrospective cohort study analyzed 4071 patients who underwent TMVr with the MitraClip system from November 4, 2013, through March 31, 2017, across 232 US sites in the Society of Thoracic Surgery/American College of Cardiology Transcatheter Valve Therapy registry. Patients were stratified into the following 4 groups based on invasive mean pulmonary arterial pressure (mPAP): 1103 with no pHTN (mPAP, <25 mm Hg [group 1]); 1399 with mild pHTN (mPAP, 25-34 mm Hg [group 2]); 1011 with moderate pHTN (mPAP, 35-44 mm Hg [group 3]); and 558 with severe pHTN (mPAP, ≥45 mm Hg [group 4]). Data were analyzed from November 4, 2013, through March 31, 2017. Interventions: Patients were stratified into groups before TMVr, and clinical outcomes were assessed at 1 year after intervention. Main Outcomes and Measures: Primary end point was a composite of 1-year mortality and readmissions for heart failure. Secondary end points were 30-day and 1-year mortality and readmissions for heart failure. Linkage to Centers for Medicare & Medicaid Services administrative claims was performed to assess 1-year outcomes in 2381 patients. Results: Among the 4071 patients included in the analysis, the median age was 81 years (interquartile range, 73-86 years); 1885 (46.3%) were women and 2186 (53.7%) were men. The composite rate of 1-year mortality and readmissions for heart failure was 33.6% (95% CI, 31.6%-35.7%), which was higher in those with pHTN (27.8% [95% CI, 24.2%-31.5%] in group 1, 32.4% [95% CI, 29.0%-35.8%] in group 2, 36.0% [95% CI, 31.8%-40.2%] in group 3, and 45.2% [95% CI, 39.1%-51.0%] in group 4; P < .001). Similarly, 1-year mortality (16.3% [95% CI, 13.4%-19.5%] in group 1, 19.8% [95% CI, 17.0%-22.8%] in group 2, 22.4% [95% CI, 18.8%-26.1%] in group 3, and 27.8% [95% CI, 22.6%-33.3%] in group 4; P < .001) increased across pHTN groups. The association of pHTN with mortality persisted despite multivariable adjustment (hazard ratio per 5-mm Hg mPAP increase, 1.05; 95% CI, 1.01-1.09; P = .02). Conclusions and Relevance: These findings suggest that pHTN is associated with increased mortality and readmission for heart failure in patients undergoing TMVr using the MitraClip system for severe mitral regurgitation. Further efforts are needed to determine whether earlier intervention before pHTN develops will improve clinical outcomes.

13.
Am Heart J ; 216: 53-61, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31401443

RESUMO

Percutaneous coronary intervention (PCI) may be performed in the same procedure as diagnostic coronary angiography (ad hoc PCI). This study aimed to evaluate current rates of ad hoc PCI use and associated risks of adverse outcomes in patients with stable coronary artery disease (CAD). METHODS: We identified 550,742 patients with stable CAD who underwent PCI in the National Cardiovascular Data Registry CathPCI Registry from 2009 to 2017. We compared in-hospital bleeding, acute kidney injury (AKI), and mortality between patients receiving ad hoc versus non-ad hoc PCI using logistic regression with inverse probability weighted propensity adjustment. RESULTS: Between 2009 and 2017, 82.9% of patients underwent ad hoc PCI. Patients who did not undergo ad hoc PCI had higher prevalence of peripheral vascular disease, heart failure, chronic kidney disease, and coronary artery bypass graft. Ad hoc PCI was associated with lower bleeding risk (adjusted odds ratio [aOR] 0.83, 95% CI 0.79-0.87) but no differences in risks of AKI (aOR 0.95, 95% CI 0.90-1.00) or mortality (aOR 1.09, 95% CI 0.97-1.23) compared with non-ad hoc PCI. Ad hoc PCI was associated with AKI risk in patients with glomerular filtration rate <30 mL/min (interaction P < .001), mortality risk in multivessel PCI (interaction P = .031), and risks of AKI and mortality in PCI of chronic total occlusions (interaction P = .045 and .002, respectively). CONCLUSIONS: Ad hoc PCI is extremely common among US patients with stable CAD and is associated with lower bleeding risk but no differences in risks of AKI or mortality compared with non-ad hoc PCI.


Assuntos
Angiografia Coronária , Doença da Artéria Coronariana/cirurgia , Intervenção Coronária Percutânea/estatística & dados numéricos , Sistema de Registros/estatística & dados numéricos , Lesão Renal Aguda/epidemiologia , Idoso , Ponte de Artéria Coronária/mortalidade , Ponte de Artéria Coronária/estatística & dados numéricos , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/mortalidade , Feminino , Insuficiência Cardíaca/epidemiologia , Humanos , Modelos Logísticos , Masculino , Razão de Chances , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/mortalidade , Doenças Vasculares Periféricas/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Hemorragia Pós-Operatória/epidemiologia , Insuficiência Renal Crônica/epidemiologia , Resultado do Tratamento
14.
J Pediatr ; 211: 105-111.e2, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31104850

RESUMO

OBJECTIVES: To determine the association between cow's milk-fat and non-high-density lipoprotein (non-HDL) cholesterol, a marker of cardiovascular disease (CVD) risk in young children, and whether this association is mediated by the typical volume of cow's milk consumed. STUDY DESIGN: A longitudinal study in 2- to 8-year-old children (n = 2890) was conducted through The Applied Research Group for Kids (TARGet Kids!), a practice-based research network in Toronto, Canada. Generalized estimating equations were used to examine the relationship between parent-reported cow's milk-fat percentage intake and serum non-HDL cholesterol concentrations as well as having high non-HDL cholesterol (≥3.75 mmol/L [145 mg/dL]), adjusting for covariates including age, sex, body mass index z score, breastfeeding duration, mother's ethnicity, and parental history of CVD. Bootstrap resampling (10 000 repetitions) was used to assess whether typical volume consumed mediated the association between cow's milk-fat percentage and non-HDL cholesterol. RESULTS: In total, 156 (5.4%) had high non-HDL cholesterol. Each percent increase in cow's milk-fat was associated with a 0.035 mmol/L (1.35 mg/dL) (P < .001) and 0.024 mmol/L (0.92 mg/dL) (P = .01) increase in non-HDL cholesterol, unadjusted and adjusted for covariates respectively. Cow's milk-fat percentage was not associated with greater odds of having high non-HDL cholesterol. Volume of cow's milk partially mediated the association between cow's milk-fat percentage and non-HDL cholesterol, accounting for 28% of the relationship (P < .001). CONCLUSIONS: Consumption of higher-fat cow's milk was associated with a small increase in non-HDL cholesterol but not greater odds of having high non-HDL cholesterol. Further research is needed to assess this relationship with other CVD risk factors in young children. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01869530.


Assuntos
Doenças Cardiovasculares/sangue , Colesterol/sangue , Gorduras na Dieta/administração & dosagem , Lipoproteínas/sangue , Leite/efeitos adversos , Animais , Índice de Massa Corporal , Aleitamento Materno , Canadá/epidemiologia , Doenças Cardiovasculares/epidemiologia , Sistema Cardiovascular , Bovinos , Criança , Pré-Escolar , Coleta de Dados , Gorduras na Dieta/efeitos adversos , Feminino , Humanos , Estudos Longitudinais , Masculino , Leite/química , Atenção Primária à Saúde , Fatores de Risco , Resultado do Tratamento
15.
Neurorehabil Neural Repair ; 33(6): 432-441, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31072222

RESUMO

Background. Understanding the relationship between movement quality (impairment) and performance (activity) in poststroke patients is important for rehabilitation intervention studies. This has led to an interest in kinematic characterization of upper limb motor impairment. Since instrumented motion analysis is not readily clinically available, observational kinematics may be a viable alternative. Objective. To determine if upper limb movement quality during a reach-to-grasp task identified by observation could be used to describe the relationship between motor impairments and the time to perform functional tasks. Methods. Cross-sectional, secondary analysis of baseline data from 141 participants with stroke, age 18 to 85 years, who participated in a multicenter randomized controlled trial. Clinical assessment of movement quality using the Reaching Performance Scale for Stroke (RPSS-Close and Far targets) and of performance (activity) from the Wolf Motor Function Test (WMFT-7 items) was assessed. The degree to which RPSS component scores explained scores on WMFT items was determined by multivariable regression. Results. Clinically significant decreases (>2 seconds) in performance time for some of the more complex WMFT tasks involving prehension were predicted from RPSS-Close and Far target components. Trunk compensatory movements did not predict either increases or decreases in performance time for the WMFT tasks evaluated. Overall, the strength of the regression models was low. Conclusions. In lieu of kinematic analysis, observational clinical movement analysis may be a valid and accessible method to determine relationships between motor impairment, compensations and upper limb function in poststroke patients. Specific relationships are unlikely to generalize to all tasks due to kinematic redundancy and task specificity.


Assuntos
Atividades Cotidianas , Exercício Físico/fisiologia , Observação , Desempenho Psicomotor/fisiologia , Índice de Gravidade de Doença , Acidente Vascular Cerebral/fisiopatologia , Extremidade Superior/fisiopatologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/fisiopatologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
16.
Front Psychol ; 10: 833, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31068851

RESUMO

The nature of creative thinking is complex and multifaceted, often involving cognitive processes and dispositions modulated by implicit cultural belief systems and ways of thinking. In this article, we build on existing research on the relations of creative thinking and culture, and explore how specific cultural resources can be harnessed to foster creative problem-solving in education. We first review the recent changes in our understanding of creative thinking, from an exclusive focus on cognitive processes to a more inclusive view of creative problem-solving as socially negotiated and culturally modulated, carrying important cultural functions. We then introduce a pedagogical model, QEOSA, to illustrate how cultural resources, particularly culture-specific ways of thinking about the world, can be harnessed to foster creative thinking in education, and what developmental and pedagogical considerations are involved to make it effective. We finally conclude this article by indicating the value of this line of work that integrates psychological, cultural, developmental, and educational principles in fostering the development of a creative mind-set with relevant knowledge, skills, dispositions, and values.

17.
N Engl J Med ; 380(26): 2541-2550, 2019 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-30946551

RESUMO

BACKGROUND: During the introduction of transcatheter aortic-valve replacement (TAVR) in the United States, requirements regarding procedural volume were mandated by the Centers for Medicare and Medicaid Services as a condition of reimbursement. A better understanding of the relationship between hospital volume of TAVR procedures and patient outcomes could inform policy decisions. METHODS: We analyzed data from the Transcatheter Valve Therapy Registry regarding procedural volumes and outcomes from 2015 through 2017. The primary analyses examined the association between hospital procedural volume as a continuous variable and risk-adjusted mortality at 30 days after transfemoral TAVR. Secondary analysis included risk-adjusted mortality according to quartile of hospital procedural volume. A sensitivity analysis was performed after exclusion of the first 12 months of transfemoral TAVR procedures at each hospital. RESULTS: Of 113,662 TAVR procedures performed at 555 hospitals by 2960 operators, 96,256 (84.7%) involved a transfemoral approach. There was a significant inverse association between annualized volume of transfemoral TAVR procedures and mortality. Adjusted 30-day mortality was higher and more variable at hospitals in the lowest-volume quartile (3.19%; 95% confidence interval [CI], 2.78 to 3.67) than at hospitals in the highest-volume quartile (2.66%; 95% CI, 2.48 to 2.85) (odds ratio, 1.21; P = 0.02). The difference in adjusted mortality between a mean annualized volume of 27 procedures in the lowest-volume quartile and 143 procedures in the highest-volume quartile was a relative reduction of 19.45% (95% CI, 8.63 to 30.26). After the exclusion of the first 12 months of TAVR procedures at each hospital, 30-day mortality remained higher in the lowest-volume quartile than in the highest-volume quartile (3.10% vs. 2.61%; odds ratio, 1.19; 95% CI, 1.01 to 1.40). CONCLUSIONS: An inverse volume-mortality association was observed for transfemoral TAVR procedures from 2015 through 2017. Mortality at 30 days was higher and more variable at hospitals with a low procedural volume than at hospitals with a high procedural volume. (Funded by the American College of Cardiology Foundation National Cardiovascular Data Registry and the Society of Thoracic Surgeons.).


Assuntos
Estenose da Valva Aórtica/cirurgia , Hospitais com Alto Volume de Atendimentos/estatística & dados numéricos , Hospitais com Baixo Volume de Atendimentos/estatística & dados numéricos , Substituição da Valva Aórtica Transcateter/mortalidade , Idoso , Idoso de 80 Anos ou mais , Valva Aórtica/cirurgia , Centers for Medicare and Medicaid Services, U.S. , Feminino , Mortalidade Hospitalar , Humanos , Reembolso de Seguro de Saúde/normas , Masculino , Estudos Retrospectivos , Substituição da Valva Aórtica Transcateter/métodos , Substituição da Valva Aórtica Transcateter/estatística & dados numéricos , Resultado do Tratamento , Estados Unidos/epidemiologia
18.
Int J Obes (Lond) ; 43(7): 1354-1362, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30940913

RESUMO

BACKGROUND/OBJECTIVES: We examined the association for rates of age- and sex-standardized body mass index (zBMI) gain between 0-3, 3-18, and 18-36 months with BP in children at 36-72 months of age. METHODS: We collected repeated measures of zBMI and BP in 2502 children. zBMI was calculated using the World Health Organization standards. Each child's zBMI at birth and rates of zBMI gain in each period from birth to 36 months were estimated using linear spline multilevel models. Generalized estimating equations were used to determine whether zBMI at birth and zBMI gain between 0-3, 3-18, and 18-36 months were each associated with repeated measures of BP at 36-72 months of age. We sequentially conditioned on zBMI at birth and zBMI gain in each period prior to each period tested, as covariates, and adjusted for important socio-demographic, familial, and study design covariates. We examined whether these associations were modified by birthweight or maternal obesity, by including interaction terms. RESULTS: After adjusting for all covariates and conditioning on prior zBMI gains, a 1 standard deviation unit faster rate of zBMI gain during 0-3 months, (ß = 0.59 mmHg; 95% CI 0.31, 0.86) and 3-18 months (ß = 0.74 mmHg; 95% CI 0.46, 1.03) were each associated with higher systolic BP at 36-72 months. No significant associations were observed, however, for zBMI at birth or zBMI gain in the 18-36 month growth period. zBMI gains from 0-3 and 3-18 months were also associated with diastolic BP. Birthweight significantly modified the relationship during the 3-18 month period (p = 0.02), with the low birthweight group exhibiting the strongest association for faster rate of zBMI gain with higher systolic BP (ß = 1.31 mmHg; 95% CI 0.14, 2.48). CONCLUSIONS: Given that long-term exposure to small elevations in BP are associated with subclinical cardiovascular disease, promoting interventions targeting healthy growth in infancy may be important.

19.
Eur J Clin Pharmacol ; 75(8): 1099-1108, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31011758

RESUMO

PURPOSE: To assess the effect of ethnicity, food, and itraconazole (strong CYP3A4 inhibitor) on the pharmacokinetics of ivosidenib after single oral doses in healthy subjects. METHODS: Three phase 1 open-label studies were performed. Study 1: Japanese and Caucasian subjects received single doses of 250, 500, or 1000 mg ivosidenib (NCT03071770). Part 1 of study 2 (a two-period crossover study): subjects received 500 mg ivosidenib after either an overnight fast or a high-fat meal. Subjects received 1000 mg ivosidenib after an overnight fast in the single period of part 2 (NCT02579707). Study 3: in period 1, subjects received 250 mg ivosidenib; then, in period 2, subjects received oral itraconazole (200 mg once daily) on days 1-18, plus 250 mg ivosidenib on day 5 (NCT02831972). RESULTS: Ivosidenib was well tolerated in all three studies. Study 1: pharmacokinetic profiles were generally comparable, although AUC and Cmax were slightly lower in Japanese subjects than in Caucasian subjects, by ~ 30 and 17%, respectively. Study 2: AUC increased by ~ 25% and Cmax by ~ 98%, when ivosidenib was administered with a high-fat meal compared with a fasted state. Study 3: co-administration of itraconazole increased ivosidenib AUC by 169% (90% CI 145-195) but had no effect on ivosidenib Cmax. CONCLUSIONS: No ivosidenib dose adjustment is deemed necessary for Japanese subjects. High-fat meals should be avoided when ivosidenib is taken with food. When co-administered with strong CYP3A4 inhibitors, monitoring for QT interval prolongation (a previously defined adverse event of interest) is recommended and an ivosidenib dose interruption or reduction may be considered. CLINICALTRIALS.GOV : NCT03071770, NCT02579707, and NCT02831972.


Assuntos
Antineoplásicos/farmacocinética , Inibidores do Citocromo P-450 CYP3A/farmacologia , Glicina/análogos & derivados , Itraconazol/farmacologia , Síndrome do QT Longo/epidemiologia , Piridinas/farmacocinética , Administração Oral , Adulto , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Área Sob a Curva , Grupo com Ancestrais do Continente Asiático , Estudos Cross-Over , Relação Dose-Resposta a Droga , Interações Medicamentosas/etnologia , Feminino , Interações Alimento-Droga/etnologia , Glicina/administração & dosagem , Glicina/efeitos adversos , Glicina/farmacocinética , Voluntários Saudáveis , Humanos , Itraconazol/administração & dosagem , Leucemia Mieloide Aguda/tratamento farmacológico , Síndrome do QT Longo/diagnóstico , Síndrome do QT Longo/etiologia , Masculino , Pessoa de Meia-Idade , Piridinas/administração & dosagem , Piridinas/efeitos adversos
20.
J Am Coll Cardiol ; 73(10): 1135-1146, 2019 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-30871697

RESUMO

BACKGROUND: Patients with severe aortic stenosis (AS) have repeat hospitalizations for multiple conditions. OBJECTIVES: The purpose of this study was to assess the effect of transcatheter aortic valve replacement (TAVR) on hospitalizations in severe AS. METHODS: Using data from the Society of Thoracic Surgeons/American College of Cardiology TVT (Transcatheter Valve Therapy) registry with linkage to Medicare claims, the authors examined rates of all-cause, cardiovascular, and noncardiovascular hospitalizations and hospital days, as well as inpatient costs in the year pre-TAVR and post-TAVR. Multivariable modeling was used to determine rate ratios of post-TAVR versus pre-TAVR hospitalizations and costs. RESULTS: Among 15,324 patients at 328 sites with Medicare linkage undergoing TAVR, the median age was 84 years, the median Society of Thoracic Surgeons Predicted Risk of Mortality score was 7.0, and 61.1% patients underwent TAVR via transfemoral access. Post-TAVR, heart failure hospitalization rates and hospitalized days were reduced compared with pre-TAVR (rate ratio: 0.87 and 0.95 respectively; p < 0.01 for all). However, all-cause, noncardiovascular, and bleeding hospitalization rates and hospitalized days were increased (p < 0.01 for all). Post-TAVR hospitalizations were reduced the most among those with left ventricular ejection fraction <30%. Mean post-TAVR costs were reduced among all TAVR patients and among 1-year survivors (rate ratio: 0.95, p < 0.01; and 0.90; p < 0.01, respectively). CONCLUSIONS: Patients had lower costs and fewer heart failure hospitalizations but more all-cause, noncardiovascular, and bleeding hospitalizations post-TAVR. Reduction in hospitalizations varied by specific patient subgroups, and thus, payors and providers seeking to reduce resource use may consider strategies designed to improve processes of care among patients with increased resource utilization post-TAVR as compared with pre-TAVR.


Assuntos
Estenose da Valva Aórtica , Hospitalização , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Complicações Pós-Operatórias , Substituição da Valva Aórtica Transcateter , Idoso , Idoso de 80 Anos ou mais , Estenose da Valva Aórtica/economia , Estenose da Valva Aórtica/mortalidade , Estenose da Valva Aórtica/cirurgia , Feminino , Mortalidade Hospitalar , Hospitalização/economia , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Medicare/estatística & dados numéricos , Mortalidade , Avaliação de Processos e Resultados em Cuidados de Saúde , Complicações Pós-Operatórias/classificação , Complicações Pós-Operatórias/economia , Fatores de Risco , Índice de Gravidade de Doença , Fatores de Tempo , Substituição da Valva Aórtica Transcateter/economia , Substituição da Valva Aórtica Transcateter/estatística & dados numéricos , Estados Unidos/epidemiologia
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