Cognitive Status, Initiation of Lifestyle Changes and Medication Adherence after Acute Coronary Syndrome: TRACE-CORE (Transitions, Risks, and Actions in Coronary Events- Center for Outcomes Research and Education)

Background: Lifestyle changes and medication adherence are often recommended to patients after acute coronary syndrome (ACS) as secondary prevention strategies. However, the impact of cognitive impairment (CI) on these secondary prevention strategies following ACS has not been examined. Methods: Cognitive status of 1374 patients with ACS from six hospitals in Massachusetts and Georgia enrolled in the ongoing TRACE-CORE (Transitions, Risks, and Actions in Coronary Events- Center for Outcomes Research and Education) study was assessed during hospitalization using the 41-point Telephone Interview for Cognitive Status (TICS). Information on recommendation and initiation of changes to diet, exercise, tobacco and alcohol use, stress, and cardiac rehabilitation attendance was collected through self-report one month after discharge. Medication adherence was assessed using the 8-item Morisky Scale. Among patients who reported receiving a recommendation for a lifestyle change, we modeled associations between CI and initiation of lifestyle changes and medication adherence, adjusting for demographics via logistic regression. Results: Mean age of participants was 63.0±11.1 years, 67% were male and 79% white; 526 (38.3%) screened positive for CI (TICS score ≤30) during hospitalization. Screening positive for CI was associated with being older, male, non-white, and less educated. Patients with CI more frequently received a recommendation to reduce alcohol use (25% vs. 16% of drinkers, p=.003) but were referred less often to a cardiac rehabilitation program (45% vs. 61%, p=.01). Among patients referred to cardiac rehabilitation (n=743), those with CI at baseline were less likely to report rehabilitation attendance at 1-month (OR= 0.70, 95%CI 0.50-0.97) compared to patients with normal cognitive function. Initiation of other lifestyle changes and medication adherence did not differ by cognitive status. Conclusions: CI is common among patients hospitalized for ACS and is associated with recommendation and initiation of certain lifestyle changes, making it an important factor to consider during the peri-discharge period

Increase in the proportion of patients hospitalized with acute myocardial infarction with do-not-resuscitate orders already in place between 2001 and 2007: a nonconcurrent prospective study

BACKGROUND AND OBJECTIVE: Shared decision making and advance planning in end-of-life decisions have become increasingly important aspects of the management of seriously ill patients. Here, we describe the use and timing of do-not-resuscitate (DNR) orders in patients hospitalized with acute myocardial infarction (AMI). STUDY DESIGN AND SETTING: The nonconcurrent prospective study population consisted of 4182 patients hospitalized with AMI in central Massachusetts in four annual periods between 2001 and 2007. RESULTS: One-quarter (25%) of patients had a DNR order written either prior to or during hospitalization. The frequency of DNR orders remained constant (24% in 2001; 26% in 2007). Among patients with DNR orders, there was a significant increase in orders written prior to hospitalization (2001: 9%; 2007: 55%). Older patients and those with a medical history of heart failure or myocardial infarction were more likely to have prior DNR orders than respective comparison groups. Patients with prior DNR orders were less likely to die 1 month after hospitalization than patients whose DNRs were written during hospitalization. CONCLUSION: Although the use of DNR orders in patients hospitalized with AMI was stable during the period under study, in more recent years, patients are increasingly being hospitalized with DNR orders already in place

The impact of cardiac and noncardiac comorbidities on the short-term outcomes of patients hospitalized with acute myocardial infarction: a population-based perspective

OBJECTIVES: The objectives of our large observational study were to describe the prevalence of cardiac and noncardiac comorbidities in a community-based population of patients hospitalized with acute myocardial infarction (AMI) at all medical centers in central Massachusetts, and to examine whether multiple comorbidities were associated with in-hospital death rates and hospital length of stay. METHODS: The study sample consisted of 2,972 patients hospitalized with AMI at all eleven greater Worcester medical centers in central Massachusetts during the three study years of 2003, 2005, and 2007. RESULTS: The average age of this hospitalized population was 71 years, 55% were men, 93% were Caucasian, and approximately one third had developed an ST segment elevation AMI during the years under study. Hypertension (75%) was the most common cardiac condition identified in patients hospitalized with AMI whereas renal disease (22%) was the most common noncardiac comorbidity diagnosed in this study population. Approximately one in every four hospitalized patients had any four or more of the seven cardiac conditions examined, while one in 13 had any three or more of the five noncardiac conditions studied. Patients with four or more cardiac comorbidities were more than twice as likely to have died during hospitalization and have a prolonged hospital length of stay, compared to those without any cardiac comorbidities. Patients with three or more noncardiac comorbidities had markedly increased odds of dying during hospitalization and having a prolonged hospital stay compared to those with no noncardiac comorbidities previously diagnosed. CONCLUSION: Our findings highlight the need for additional contemporary data to improve the short-term outcomes of patients hospitalized with AMI and multiple concurrent medical illnesses

Associations with photoreceptor thickness measures in the UK Biobank.

Spectral-domain OCT (SD-OCT) provides high resolution images enabling identification of individual retinal layers. We included 32,923 participants aged 40-69 years old from UK Biobank. Questionnaires, physical examination, and eye examination including SD-OCT imaging were performed. SD OCT measured photoreceptor layer thickness includes photoreceptor layer thickness: inner nuclear layer-retinal pigment epithelium (INL-RPE) and the specific sublayers of the photoreceptor: inner nuclear layer-external limiting membrane (INL-ELM); external limiting membrane-inner segment outer segment (ELM-ISOS); and inner segment outer segment-retinal pigment epithelium (ISOS-RPE). In multivariate regression models, the total average INL-RPE was observed to be thinner in older aged, females, Black ethnicity, smokers, participants with higher systolic blood pressure, more negative refractive error, lower IOPcc and lower corneal hysteresis. The overall INL-ELM, ELM-ISOS and ISOS-RPE thickness was significantly associated with sex and race. Total average of INL-ELM thickness was additionally associated with age and refractive error, while ELM-ISOS was additionally associated with age, smoking status, SBP and refractive error; and ISOS-RPE was additionally associated with smoking status, IOPcc and corneal hysteresis. Hence, we found novel associations of ethnicity, smoking, systolic blood pressure, refraction, IOPcc and corneal hysteresis with photoreceptor thickness

Investigation of associations between retinal microvascular parameters and albuminuria in UK Biobank: a cross-sectional case-control study.

BACKGROUND: Associations between microvascular variation and chronic kidney disease (CKD) have been reported previously. Non-invasive retinal fundus imaging enables evaluation of the microvascular network and may offer insight to systemic risk associated with CKD. METHODS: Retinal microvascular parameters (fractal dimension [FD] - a measure of the complexity of the vascular network, tortuosity, and retinal arteriolar and venular calibre) were quantified from macula-centred fundus images using the Vessel Assessment and Measurement Platform for Images of the REtina (VAMPIRE) version 3.1 (VAMPIRE group, Universities of Dundee and Edinburgh, Scotland) and assessed for associations with renal damage in a case-control study nested within the multi-centre UK Biobank cohort study. Participants were designated cases or controls based on urinary albumin to creatinine ratio (ACR) thresholds. Participants with ACR ≥ 3 mg/mmol (ACR stages A2-A3) were characterised as cases, and those with an ACR < 3 mg/mmol (ACR stage A1) were categorised as controls. Participants were matched on age, sex and ethnic background. RESULTS: Lower FD (less extensive microvascular branching) was associated with a small increase in odds of albuminuria independent of blood pressure, diabetes and other potential confounding variables (odds ratio [OR] 1.18, 95% confidence interval [CI] 1.03-1.34 for arterioles and OR 1.24, CI 1.05-1.47 for venules). Measures of tortuosity or retinal arteriolar and venular calibre were not significantly associated with ACR. CONCLUSIONS: This study supports previously reported associations between retinal microvascular FD and other metabolic disturbances affecting the systemic vasculature. The association between retinal microvascular FD and albuminuria, independent of diabetes and blood pressure, may represent a useful indicator of systemic vascular damage associated with albuminuria

Haploidentical vs. sibling, unrelated, or cord blood hematopoietic cell transplantation for acute lymphoblastic leukemia

The role of haploidentical hematopoietic cell transplantation (HCT) using posttransplant cyclophosphamide (PTCy) for acute lymphoblastic leukemia (ALL) is being defined. We performed a retrospective, multivariable analysis comparing outcomes of HCT approaches by donor for adults with ALL in remission. The primary objective was to compare overall survival (OS) among haploidentical HCTs using PTCy and HLA-matched sibling donor (MSD), 8/8 HLAmatched unrelated donor (MUD), 7 /8 HLA-MUD, or umbilical cord blood (UCB) HCT. Comparing haploidentical HCT to MSD HCT, we found that OS, leukemia-free survival (LFS), nonrelapse mortality (NRM), relapse, and acute graft-versus-host disease (aGVHD) were not different but chronic GVHD (cGVHD) was higher in MSD HCT. Compared with MUD HCT, OS, LFS, and relapse were not different, but MUD HCT had increased NRM (hazard ratio [HR], 1.42; P = .02), grade 3 to 4 aGVHD (HR, 1.59; P = .005), and cGVHD. Compared with 7/8 UD HCT, LFS and relapse were not different, but 7/8 UD HCT had worse OS (HR, 1.38; P = .01) and increased NRM (HR, 2.13; P <_ .001), grade 3 to 4 aGVHD (HR, 1.86; P = .003), and cGVHD (HR, 1.72; P <_ .001). Compared with UCB HCT, late OS, late LFS, relapse, and cGVHD were not different but UCB HCT had worse early OS (<_18 months; HR, 1.93; P < .001), worse early LFS (HR, 1.40; P = .007) and increased incidences of NRM (HR, 2.08; P < .001) and grade 3 to 4 aGVHD (HR, 1.97; P < .001). Haploidentical HCT using PTCy showed no difference in survival but less GVHD compared with traditional MSD and MUD HCT and is the preferred alternative donor HCT option for adults with ALL in complete remission

The Relationship Between Ambient Atmospheric Fine Particulate Matter (PM2.5) and Glaucoma in a Large Community Cohort.

Purpose: Glaucoma is more common in urban populations than in others. Ninety percent of the world's population are exposed to air pollution above World Health Organization (WHO) recommended limits. Few studies have examined the association between air pollution and glaucoma. Methods: Questionnaire data, ophthalmic measures, and ambient residential area air quality data for 111,370 UK Biobank participants were analyzed. Particulate matter with an aerodynamic diameter < 2.5 μm (PM2.5) was selected as the air quality exposure of interest. Eye measures included self-reported glaucoma, intraocular pressure (IOP), and average thickness of macular ganglion cell-inner plexiform layer (GCIPL) across nine Early Treatment Diabetic Retinopathy Study (ETDRS) retinal subfields as obtained from spectral-domain optical coherence tomography. We examined the associations of PM2.5 concentration with self-reported glaucoma, IOP, and GCIPL. Results: Participants resident in areas with higher PM2.5 concentration were more likely to report a diagnosis of glaucoma (odds ratio = 1.06, 95% confidence interval [CI] = 1.01-1.12, per interquartile range [IQR] increase P = 0.02). Higher PM2.5 concentration was also associated with thinner GCIPL (β = -0.56 μm, 95% CI = -0.63 to -0.49, per IQR increase, P = 1.2 × 10-53). A dose-response relationship was observed between higher levels of PM2.5 and thinner GCIPL (P < 0.001). There was no clinically relevant relationship between PM2.5 concentration and IOP. Conclusions: Greater exposure to PM2.5 is associated with both self-reported glaucoma and adverse structural characteristics of the disease. The absence of an association between PM2.5 and IOP suggests the relationship may occur through a non-pressure-dependent mechanism, possibly neurotoxic and/or vascular effects

Beyond outputs: pathways to symmetrical evaluations of university sustainable development partnerships

As the United Nations Decade of Education for Sustainable Development (2005–2014) draws to a close, it is timely to review ways in which the sustainable development initiatives of higher education institutions have been, and can be, evaluated. In their efforts to document and assess collaborative sustainable development program outcomes and impacts, universities in the North and South are challenged by similar conundrums that confront development agencies. This article explores pathways to symmetrical evaluations of transnationally partnered research, curricula, and public-outreach initiatives specifically devoted to sustainable development. Drawing on extensive literature and informed by international development experience, the authors present a novel framework for evaluating transnational higher education partnerships devoted to sustainable development that addresses design, management, capacity building, and institutional outreach. The framework is applied by assessing several full-term African higher education evaluation case studies with a view toward identifying key limitations and suggesting useful future symmetrical evaluation pathways. University participants in transnational sustainable development initiatives, and their supporting donors, would be well-served by utilizing an inclusive evaluation framework that is infused with principles of symmetry

Fc-Optimized Anti-CD25 Depletes Tumor-Infiltrating Regulatory T Cells and Synergizes with PD-1 Blockade to Eradicate Established Tumors

CD25 is expressed at high levels on regulatory T (Treg) cells and was initially proposed as a target for cancer immunotherapy. However, anti-CD25 antibodies have displayed limited activity against established tumors. We demonstrated that CD25 expression is largely restricted to tumor-infiltrating Treg cells in mice and humans. While existing anti-CD25 antibodies were observed to deplete Treg cells in the periphery, upregulation of the inhibitory Fc gamma receptor (FcγR) IIb at the tumor site prevented intra-tumoral Treg cell depletion, which may underlie the lack of anti-tumor activity previously observed in pre-clinical models. Use of an anti-CD25 antibody with enhanced binding to activating FcγRs led to effective depletion of tumor-infiltrating Treg cells, increased effector to Treg cell ratios, and improved control of established tumors. Combination with anti-programmed cell death protein-1 antibodies promoted complete tumor rejection, demonstrating the relevance of CD25 as a therapeutic target and promising substrate for future combination approaches in immune-oncology