Preclinical trials indicate that CD34+ cells represent an effective angiogenic stem cell component. Early-phase clinical trials suggest that intramyocardial administration of autologous CD34+ cells ...may improve functional capacity and symptoms of angina. RENEW is a pivotal phase 3 trial designed to determine the efficacy of granulocyte colony-stimulating factor (G-CSF)–mobilized CD34+ stem cells for the treatment for patients with refractory angina and chronic myocardial ischemia. Patients (n = 444) receiving maximally tolerated antianginal therapies and lacking conventional revascularization options with Canadian Cardiovascular Society class III or IV angina and ischemia on stress testing will be randomized 2:1:1 to cell therapy (G-CSF–mediated stem cell mobilization, apheresis, and intramyocardial injection of 1 × 105 autologous CD34+ cells/kg), active control (G-CSF–mediated stem cell mobilization, apheresis, and intramyocardial placebo injection), or open-label standard of care. The primary efficacy end point is change in exercise treadmill time in the treated vs active control patients, with 90% power to detect a 60-second difference in exercise time between cell-treated (n = 200) and active control (n = 100) patients. Key secondary end points include total number of anginal episodes per week and the incidence of independently adjudicated major adverse cardiac events and serious adverse events. RENEW will be the first adequately powered study aimed at definitively determining the efficacy of a cell therapy (intramyocardially delivered autologous CD34+ cells) for improvement of functional capacity in patients with refractory angina.
Background Obesity and allergic diseases have increased dramatically in recent decades. Although adiposity has been associated with asthma, associations with allergic sensitization have been ...inconsistent. Objective To examine the association of adiposity and lipid profiles with allergic sensitization. Methods This study included 1187 rural Chinese twins (653 men) age 18 to 39 years, with skin prick tests, anthropometric and dual-energy x-ray absorptiometry–assessed adiposity measures, and lipid assessments. Allergic sensitization was defined as positive SPT to ≥1 allergen (9 foods and 5 aeroallergens tested). We applied sex-stratified generalized estimating equations to assess the association of adiposity and serum lipids with allergic sensitization, and structural equation models to estimate the genetic/environmental influences on any observed associations. Results Men had lower percent body fat (% BF) (13.9% vs. 28.8%) but higher rates of allergic sensitization (56.2% vs 36.7%) than women. Men in the highest %BF quartile were 2.1 times more likely to be sensitized than the lowest quartile (95% CI, 1.3-3.5; P trend = .003). In men, the risk of allergic sensitization increased with high-density lipoprotein (HDL) <40 mg/dL (odds ratio = 4.0; 95% CI, 1.8-9.2) and higher low-density lipoprotein quartiles ( P trend = .007). This appeared to be partially explained by shared genetic factors between serum lipid levels and allergic sensitization. In females, lower HDL was associated with increased risk of allergic sensitization. Conclusion In this relatively lean Chinese population, higher %BF, lower HDL and higher LDL were associated with greater risk of allergic sensitization, most notable in men. The observed associations among adiposity, serum lipids, and allergic sensitization in men appear to be partially explained by common genetic influences on these traits.
In the cores of some clusters of galaxies the hot intracluster plasma is dense enough that it should cool radiatively in the cluster's lifetime, leading to continuous 'cooling flows' of gas sinking ...towards the cluster centre, yet no such cooling flow has been observed. The low observed star-formation rates and cool gas masses for these 'cool-core' clusters suggest that much of the cooling must be offset by feedback to prevent the formation of a runaway cooling flow. Here we report X-ray, optical and infrared observations of the galaxy cluster SPT-CLJ2344-4243 (ref. 11) at redshift z = 0.596. These observations reveal an exceptionally luminous (8.2 × 10(45) erg s(-1)) galaxy cluster that hosts an extremely strong cooling flow (around 3,820 solar masses a year). Further, the central galaxy in this cluster appears to be experiencing a massive starburst (formation of around 740 solar masses a year), which suggests that the feedback source responsible for preventing runaway cooling in nearby cool-core clusters may not yet be fully established in SPT-CLJ2344-4243. This large star-formation rate implies that a significant fraction of the stars in the central galaxy of this cluster may form through accretion of the intracluster medium, rather than (as is currently thought) assembling entirely via mergers.
Background Prematurity (<37 weeks) has been inconsistently associated with asthma and wheezing. Chorioamnionitis may promote both prematurity and inflammatory pathways in infants' airways. Objective ...To investigate the relationship of prematurity and chorioamnionitis with the development of early childhood recurrent wheezing. Methods The Boston Birth Cohort (n = 1096) were followed prospectively from birth to a mean age of 2.2 ± 2 years. Perinatal and postnatal clinical data and placental pathology were collected. The primary outcome was recurrent wheezing (≥2 physician documented episodes). Secondary outcomes included physician-diagnosed asthma, food allergy, and eczema. Preterm children were grouped by gestational age into moderately (33-36.9 weeks) and very preterm (<33 weeks) with and without chorioamnionitis, and compared with term children without chorioamnionitis (reference group). Chorioamnionitis was diagnosed either by intrapartum fever or by placental histology findings. Logistic regression models were performed to investigate the independent and joint associations of degree of prematurity and chorioamnionitis. Results Prematurity was associated with recurrent wheezing (odds ratio OR, 1.7; 95% CI, 1.2-2.6). However, when subjects were grouped by degree of prematurity with or without chorioamnionitis, the highest risk of wheezing (OR, 4.0; 95% CI, 2.0-8.0) and physician-diagnosed asthma (OR, 4.4; 95% CI, 2.2-8.7) was present in the very preterm children with chorioamnionitis. The effect on both wheezing (OR, 5.4; 95% CI, 2.4-12.0) and asthma (OR, 5.2; 95% CI, 2.3-11.9) was greater in African Americans. Neither prematurity nor chorioamnionitis was associated with food allergy or eczema. Conclusion We found a strong joint effect of prematurity and chorioamnionitis on early childhood wheezing. This effect was stronger in African American subjects.
Abstract Background: Medication errors contribute to significant morbidity, mortality, and costs to the health system. Little is known about the characteristics of Emergency Department (ED) ...medication errors. Study Objective: To examine the frequency, types, causes, and consequences of voluntarily reported ED medication errors in the United States. Methods: A cross-sectional study of all ED errors reported to the MEDMARX system between 2000 and 2004. MEDMARX is an anonymous, confidential, de-identified, Internet-accessible medication error-reporting program designed to allow hospitals to report, track, and share error data in a standardized format. Results: There were 13,932 medication errors from 496 EDs analyzed. The error rate was 78 reports per 100,000 visits. Physicians were responsible for 24% of errors, nurses for 54%. Errors most commonly occurred in the administration phase (36%). The most common type of error was improper dose/quantity (18%). Leading causes were not following procedure/protocol (17%), and poor communication (11%), whereas contributing factors were distractions (7.5%), emergency situations (4.1%), and workload increase (3.4%). Computerized provider order entry caused 2.5% of errors. Harm resulted in 3% of errors. Actions taken as a result of the error included informing the staff member who committed the error (26%), enhancing communication (26%), and providing additional training (12%). Patients or family members were notified about medication errors 2.7% of the time. Conclusion: ED medication errors may be a result of the acute, crowded, and fast-paced nature of care. Further research is needed to identify interventions to reduce these risks and evaluate the effectiveness of these interventions.
The South Pole Telescope (SPT) is currently surveying 2500 deg2 of the southern sky to detect massive galaxy clusters out to the epoch of their formation using the Sunyaev-Zel'dovich (SZ) effect. ...This paper presents a catalog of the 26 most significant SZ cluster detections in the full survey region. The catalog includes 14 clusters which have been previously identified and 12 that are new discoveries. These clusters were identified in fields observed to two differing noise depths: 1500 deg2 at the final SPT survey depth of 18 Delta *mK arcmin at 150 GHz and 1000 deg2 at a depth of 54 Delta *mK arcmin. Clusters were selected on the basis of their SZ signal-to-noise ratio (S/N) in SPT maps, a quantity which has been demonstrated to correlate tightly with cluster mass. The S/N thresholds were chosen to achieve a comparable mass selection across survey fields of both depths. Cluster redshifts were obtained with optical and infrared imaging and spectroscopy from a variety of ground- and space-based facilities. The redshifts range from 0.098 <= z <= 1.132 with a median of z med = 0.40. The measured SZ S/N and redshifts lead to unbiased mass estimates ranging from 9.8 X 1014 M h --1 70 <= M 200( Delta *rmean) <= 3.1 X 1015 M h --1 70. Based on the SZ mass estimates, we find that none of the clusters are individually in significant tension with the Delta *LCDM cosmological model. We also test for evidence of non-Gaussianity based on the cluster sample and find the data show no preference for non-Gaussian perturbations.
Background The relationship between the prenatal environment, maternal-fetal interaction, and allergic disease in the offspring remains understudied. Objective We sought to determine whether ...gestational diabetes (GDM) modifies the risk of early childhood atopic manifestations, including atopic dermatitis and allergen sensitization. Methods This study includes 680 children from the Boston Birth Cohort. Mother-child dyads were recruited at birth and followed prospectively to a mean age of 3.2 ± 2.3 years, with study visits aligned with the pediatric primary care schedule. The primary outcomes were physician-diagnosed atopic dermatitis on standardized medical record abstraction and allergen sensitization based on ImmunoCAP to 7 common foods and 5 common aeroallergens (specific IgE, ≥0.10 kUA/L; Phadia, Uppsala, Sweden). GDM was determined by means of standardized medical record review. Logistic regression analysis, stratified by term/preterm status, evaluated the association of GDM with atopic dermatitis and allergen sensitization, respectively, controlling for maternal prepregnancy body mass index, fetal growth, and pertinent covariates. Results Of the 680 children, 488 were term, and 192 were preterm (<37 weeks' gestation). Overall, 4.9% of the mothers had GDM. Among the 680 children, 34.4% had atopic dermatitis, and 51% had allergen sensitization. In term births GDM was significantly associated with atopic dermatitis (odds ratio OR, 7.2; 95% CI, 1.5-34.5) and allergen sensitization (OR, 5.7; 95% CI, 1.2-28.0). Adjusting for fetal growth had little effect. The association with sensitization was driven primarily by food sensitization (OR, 8.3; 95% CI, 1.6-43.3). The above associations were not observed in preterm births. Conclusions In term births GDM increased the risk of atopic dermatitis and early childhood allergen sensitization independently of maternal prepregnancy body mass index and fetal growth.
The adiabatic evolution of the temperature of the cosmic microwave background (CMB) is a key prediction of standard cosmology. We study deviations from the expected adiabatic evolution of the CMB ...temperature of the form T(z) = T0(1 + z)1 - ... using measurements of the spectrum of the Sunyaev-Zel'dovich effect with the South Pole Telescope (SPT). We present a method for using the ratio of the Sunyaev-Zel'dovich signal measured at 95 and 150 GHz in the SPT data to constrain the temperature of the CMB. We demonstrate that this approach provides unbiased results using mock observations of clusters from a new set of hydrodynamical simulations. We apply this method to a sample of 158 SPT-selected clusters, spanning the redshift range 0.05 < z < 1.35, and measure α=0.017..., consistent with the standard model prediction of α = 0. In combination with other published results, we find α = 0.005 ± 0.012, an improvement of ~10 per cent over published constraints. This measurement also provides a strong constraint on the effective equation of state in models of decaying dark energy w... = -0.994 ± 0.010. (ProQuest: ... denotes formulae/symbols omitted.)
OBJECTIVES: Overutilization of laboratory services is now recognized as harmful to patients and wasteful. In fact, the American Board of Internal Medicine’s Choosing Wisely campaign recommends ...against ordering routine testing that does not answer a clinical question. Per peer benchmarking, our institution as a whole occupied an extreme outlier position at the 100th percentile for laboratory utilization. We sought to address this problem starting in our medical ICUs with a quality improvement project. DESIGN: Quality improvement project using the design, measure, analyze, improve, and control process. The primary endpoint was a sustained reduction in laboratory utilization. Counterbalance metrics were also followed, and these included mortality, renal replacement therapy initiation rates, stat laboratory orders, and central catheter–associated blood stream infections. SETTING: The medical ICU at the Ohio State University Medical Center. PATIENTS: All patients admitted to the medical ICU from March 2019 to March 2020. INTERVENTIONS: Root causes were identified and addressed with the implementation of a wide range of interventions involving a multidisciplinary team led by trainee physicians. MEASUREMENTS AND MAIN RESULTS: There was a sustained 20% reduction in the number of tests performed per patient day, with no change in the counterbalance metrics. CONCLUSIONS: Trainees can affect positive change in the culture and processes at their institutions to safely reduce laboratory utilization.
PDF
