Relationship between exertional symptoms and functional capacity in patients with heart failure

AbstractOBJECTIVESThe present study was undertaken to investigate the relationship over time between exertional symptoms in heart failure and functional capacity.BACKGROUNDMost clinicians rely on exertional symptoms rather than on exercise testing to assess functional capacity in heart failure. However, it remains uncertain whether the subjective symptoms reported by patients provide a reliable index of functional capacity.METHODSFifty patients with heart failure underwent serial cardiopulmonary exercise testing and evaluation of exertional fatigue and dyspnea over a period of one to four years. Exercise testing was performed using the Naughton treadmill protocol and a MedGraphics metabolic cart. Fatigue and dyspnea were each scored from 0 to 3 (p = none, 1 = mild, 2 = moderate, 3 = severe). A composite symptom score was determined by adding together the fatigue and dyspnea scores.RESULTSPatients underwent a total of 185 tests at an average interval of 4.3 months (average tests/patient = 3.7). Composite symptom scores noted at the time of exercise testing correlated significantly with peak exercise minute oxygen consumption (VO2) (r = 0.47, p < 0.01). In addition, the change in symptoms scores and change in peak VO2noted between the baseline and final exercise test correlated significantly (r = 0.50, p < 0.01). However, patients reported few or no symptoms (symptom score ≤2) 45% of the time when peak VO2was <14 ml/min/kg, consistent with a severe functional disability, and 72% of the time when peak VO2was 14 to 18 ml/min/kg, consistent with moderate functional disability.CONCLUSIONSExertional symptoms reported by patients with heart failure generally correlate with maximal exercise capacity. However, exertional symptoms frequently underestimate the severity of functional disability. Cardiopulmonary exercise testing rather than symptoms should be used to assess functional capacity in heart failure

Quality Delivered: How a Pandemic Fostered Innovation and Creative Solutions in Clinical Education

Background: Clinical education placements for students enrolled in healthcare programs were abruptly upended in March 2020 due to COVID-19. Programs were faced with decisions of how to mitigate substantive challenges due to an unforeseen pandemic within timeframes that would align with curricular sequences and graduation dates. Schools quickly modified curriculum formats, implemented alternative teaching and learning instruction and developed safety protocols to protect students, clinical faculty, and patients. Purpose: The aim of this study explored the strategies employed by one physical therapy school’s clinical education team, which resulted in successful completion of clinical course requirements and on-time graduation. Method: Data was collected on a single cohort of eighty (n=80) students who experienced changes in the timing, location, and/or progression of their clinical experiences due to COVID-19 related complications. The use of innovative clinically-oriented teaching strategies including web-based patient case simulation, virtual grand rounds, and other creative learning activities effectively supported student engagement both in and outside of clinical settings. Alternative learning strategies provided students the opportunity to progress through the clinical education curriculum, meet educational objectives, and satisfy the standard requirements by the Commission on Accreditation in Physical Therapy Education (CAPTE). Performance on the Clinical Performance Instrument (CPI) for the cohort of students affected by COVID-19 was compared to a cohort from 2019 who were not affected by COVID-19 related issues. Results: Analysis using Mann Whitney U statistics showed there were no significant differences in performance on the CPI between the groups (p=0.874). Conclusion: Looking forward, there is an opportunity for schools to build on what was learned during the pandemic and apply those strategies to other non-pandemic related situations with successful outcomes. Innovative teaching and learning strategies can help to bridge the gap of time out of clinic for any student who may experience an interruption in clinical education due to injury, illness, or other situation, and can provide a way for students to progress successfully through their physical therapy education

Selection of patients for heart transplantationin the current era of heart failure therapy

AbstractObjectivesWe sought to assess the relationship between survival, peak exercise oxygen consumption (Vo2), and heart failure survival score (HFSS) in the current era of heart failure (HF) therapy.BackgroundBased on predicted survival, HF patients with peak Vo2<14 ml/min/kg or medium- to high-risk HFSS are currently considered eligible for heart transplantation. However, these criteria were developed before the widespread use of beta-blockers, spironolactone, and defibrillators—interventions known to improve the survival of HF patients.MethodsPeak Vo2and HFSS were assessed in 320 patients followed from 1994 to 1997 (past era) and in 187 patients followed from 1999 to 2001 (current era). Outcomes were compared between these two groups of patients and those who underwent heart transplantation from 1993 to 2000.ResultsSurvival in the past era was 78% at one year and 67% at two years, as compared with 88% and 79%, respectively, in the current era (both p < 0.01). One-year event-free survival (without urgent transplantation or left ventricular assist device) was improved in the current era, regardless of initial peak Vo2: 64% vs. 48% for peak Vo2<10 ml/min/kg (p = 0.09), 81% vs. 70% for 10 to 14 ml/min/kg (p = 0.05), and 93% vs. 82% for >14 ml/min/kg (p = 0.04). Of the patients with peak Vo2of 10 to 14 ml/min/kg, 55% had low-risk HFSS and exhibited 88% one-year event-free survival. One-year survival after transplantation was 88%, which is similar to the 85% rate reported by the United Network for Organ Sharing for 1999 to 2000.ConclusionsSurvival for HF patients in the current era has improved significantly, necessitating re-evaluation of the listing criteria for heart transplantation

Fermi/LAT Observations of Swift/BAT Seyferts: on the Contribution of Radio-quiet AGN to the Extragalactic Gamma-ray Background

We present the analysis of 2.1 years of Fermi/LAT data on 491 Seyfert galaxies detected by the Swift/BAT survey. Only the two nearest objects, NGC 1068 and NGC 4945, which were identified in the Fermi First-year Catalog, are detected. Using the Swift/BAT and radio 20 cm fluxes, we define a new radio-loudness parameter $R_{X, BAT}$ where radio loud objects have $\log R_{X, BAT} > - 4.7$. Based on this parameter, only radio loud sources are detected by Fermi/LAT. An upper limit to the flux of the undetected sources is derived to be $\sim 2 \times 10^{-11}$ photons cm$^{-2}$ s$^{-1}$, approximately seven times lower than the observed flux of NGC 1068. Assuming a median redshift of 0.031, this implies an upper limit to the $\gamma$-ray (1--100 GeV) luminosity of $\lesssim 3 \times 10^{41}$ erg s$^{-1}$. In addition, we identified 120 new Fermi/LAT sources near the Swift/BAT Seyferts with significant Fermi/LAT detections. A majority of these objects do not have \bat counterparts, but their possible optical counterparts include blazars, FSRQs, and quasars.Comment: 19 pages preprint style, including 2 tables and 4 figures. Accepted for publication by the Astrophysical Journa

The First Stars

The first stars to form in the Universe -- the so-called Population III stars -- bring an end to the cosmological Dark Ages, and exert an important influence on the formation of subsequent generations of stars and on the assembly of the first galaxies. Developing an understanding of how and when the first Population III stars formed and what their properties were is an important goal of modern astrophysical research. In this review, I discuss our current understanding of the physical processes involved in the formation of Population III stars. I show how we can identify the mass scale of the first dark matter halos to host Population III star formation, and discuss how gas undergoes gravitational collapse within these halos, eventually reaching protostellar densities. I highlight some of the most important physical processes occurring during this collapse, and indicate the areas where our current understanding remains incomplete. Finally, I discuss in some detail the behaviour of the gas after the formation of the first Population III protostar. I discuss both the conventional picture, where the gas does not undergo further fragmentation and the final stellar mass is set by the interplay between protostellar accretion and protostellar feedback, and also the recently advanced picture in which the gas does fragment and where dynamical interactions between fragments have an important influence on the final distribution of stellar masses.Comment: 72 pages, 4 figures. Book chapter to appear in "The First Galaxies - Theoretical Predictions and Observational Clues", 2012 by Springer, eds. V. Bromm, B. Mobasher, T. Wiklin

Correction to: First results on survival from a large Phase 3 clinical trial of an autologous dendritic cell vaccine in newly diagnosed glioblastoma

Following publication of the original article [1], the authors reported an error in the spelling of one of the author names. In this Correction the incorrect and correct author names are indicated and the author name has been updated in the original publication. The authors also reported an error in the Methods section of the original article. In this Correction the incorrect and correct versions of the affected sentence are indicated. The original article has not been updated with regards to the error in the Methods section.https://deepblue.lib.umich.edu/bitstream/2027.42/144529/1/12967_2018_Article_1552.pd

Clinical Sequencing Exploratory Research Consortium: Accelerating Evidence-Based Practice of Genomic Medicine

Despite rapid technical progress and demonstrable effectiveness for some types of diagnosis and therapy, much remains to be learned about clinical genome and exome sequencing (CGES) and its role within the practice of medicine. The Clinical Sequencing Exploratory Research (CSER) consortium includes 18 extramural research projects, one National Human Genome Research Institute (NHGRI) intramural project, and a coordinating center funded by the NHGRI and National Cancer Institute. The consortium is exploring analytic and clinical validity and utility, as well as the ethical, legal, and social implications of sequencing via multidisciplinary approaches; it has thus far recruited 5,577 participants across a spectrum of symptomatic and healthy children and adults by utilizing both germline and cancer sequencing. The CSER consortium is analyzing data and creating publically available procedures and tools related to participant preferences and consent, variant classification, disclosure and management of primary and secondary findings, health outcomes, and integration with electronic health records. Future research directions will refine measures of clinical utility of CGES in both germline and somatic testing, evaluate the use of CGES for screening in healthy individuals, explore the penetrance of pathogenic variants through extensive phenotyping, reduce discordances in public databases of genes and variants, examine social and ethnic disparities in the provision of genomics services, explore regulatory issues, and estimate the value and downstream costs of sequencing. The CSER consortium has established a shared community of research sites by using diverse approaches to pursue the evidence-based development of best practices in genomic medicine

Age at first birth in women is genetically associated with increased risk of schizophrenia

Prof. Paunio on PGC:n jäsenPrevious studies have shown an increased risk for mental health problems in children born to both younger and older parents compared to children of average-aged parents. We previously used a novel design to reveal a latent mechanism of genetic association between schizophrenia and age at first birth in women (AFB). Here, we use independent data from the UK Biobank (N = 38,892) to replicate the finding of an association between predicted genetic risk of schizophrenia and AFB in women, and to estimate the genetic correlation between schizophrenia and AFB in women stratified into younger and older groups. We find evidence for an association between predicted genetic risk of schizophrenia and AFB in women (P-value = 1.12E-05), and we show genetic heterogeneity between younger and older AFB groups (P-value = 3.45E-03). The genetic correlation between schizophrenia and AFB in the younger AFB group is -0.16 (SE = 0.04) while that between schizophrenia and AFB in the older AFB group is 0.14 (SE = 0.08). Our results suggest that early, and perhaps also late, age at first birth in women is associated with increased genetic risk for schizophrenia in the UK Biobank sample. These findings contribute new insights into factors contributing to the complex bio-social risk architecture underpinning the association between parental age and offspring mental health.Peer reviewe