•Burnout persists as concerning problem for more than half of nurses.•Burnout contributes to nursing workforce turnover, however not internal transfers.•Working day (vs. night) shift and increased ...death exposure increase burnout.•Hospitals must measure burnout and wellbeing to understand and address its impact.
The National Academies of Medicine describes clinician burnout as a serious threat to organizational health, including employee turnover.
To determine the relationship between resilience, burnout, and organizational and position turnover.
We surveyed direct care nurses in three hospitals 1 year apart between 2018 and 2019; 1,688 nurses completed 3,135 surveys included in analysis.
Fifty-four percent of nurses in our sample suffer from moderate burnout, with emotional exhaustion scores increasing by 10% and cynicism scores increasing 19% after 1 year. The impact of burnout on organizational turnover was significant, with a 12% increase in a nurse leaving for each unit increase on the emotional exhaustion scale, though it was not a factor in position turnover.
These findings contribute to the growing body of evidence of nurse burnout and support policies and programs for annual measurement of burnout, increased employee wellbeing support, and improved work environments.
Osteoporosis is a prevalent but underdiagnosed condition.
To evaluate computed tomography (CT)-derived bone mineral density (BMD) assessment compared with dual-energy x-ray absorptiometry (DXA) ...measures for identifying osteoporosis by using CT scans performed for other clinical indications.
Cross-sectional study.
Single academic health center.
1867 adults undergoing CT and DXA (n = 2067 pairs) within a 6-month period over 10 years.
CT-attenuation values (in Hounsfield units HU) of trabecular bone between the T12 and L5 vertebral levels, with an emphasis on L1 measures (study test); DXA BMD measures (reference standard). Sagittal CT images assessed for moderate-to-severe vertebral fractures.
CT-attenuation values were significantly lower at all vertebral levels for patients with DXA-defined osteoporosis (P < 0.001). An L1 CT-attenuation threshold of 160 HU or less was 90% sensitive and a threshold of 110 HU was more than 90% specific for distinguishing osteoporosis from osteopenia and normal BMD. Positive predictive values for osteoporosis were 68% or greater at L1 CT-attenuation thresholds less than 100 HU; negative predictive values were 99% at thresholds greater than 200 HU. Among 119 patients with at least 1 moderate-to-severe vertebral fracture, 62 (52.1%) had nonosteoporotic T-scores (DXA false-negative results), and most (97%) had L1 or mean T12 to L5 vertebral attenuation of 145 HU or less. Similar performance was seen at all vertebral levels. Intravenous contrast did not affect CT performance.
The potential benefits and costs of using the various CT-attenuation thresholds identified were not formally assessed.
Abdominal CT images obtained for other reasons that include the lumbar spine can be used to identify patients with osteoporosis or normal BMD without additional radiation exposure or cost.
National Institutes of Health.
For societies with writing systems, hereditary leadership is documented as one of the hallmarks of early political complexity and governance. In contrast, it is unknown whether hereditary succession ...played a role in the early formation of prehistoric complex societies that lacked writing. Here we use an archaeogenomic approach to identify an elite matriline that persisted between 800 and 1130 CE in Chaco Canyon, the centre of an expansive prehistoric complex society in the Southwestern United States. We show that nine individuals buried in an elite crypt at Pueblo Bonito, the largest structure in the canyon, have identical mitochondrial genomes. Analyses of nuclear genome data from six samples with the highest DNA preservation demonstrate mother-daughter and grandmother-grandson relationships, evidence for a multigenerational matrilineal descent group. Together, these results demonstrate the persistence of an elite matriline in Chaco for ∼330 years.
Monoclonal antibodies that target amyloid-beta (Aβ) have the potential to slow cognitive and functional decline in persons with early Alzheimer's disease. Gantenerumab is a subcutaneously ...administered, fully human, anti-Aβ IgG1 monoclonal antibody with highest affinity for aggregated Aβ that has been tested for the treatment of Alzheimer's disease.
We conducted two phase 3 trials (GRADUATE I and II) involving participants 50 to 90 years of age with mild cognitive impairment or mild dementia due to Alzheimer's disease and evidence of amyloid plaques on positron-emission tomography (PET) or cerebrospinal fluid (CSF) testing. Participants were randomly assigned to receive gantenerumab or placebo every 2 weeks. The primary outcome was the change from baseline in the score on the Clinical Dementia Rating scale-Sum of Boxes (CDR-SB; range, 0 to 18, with higher scores indicating greater cognitive impairment) at week 116.
A total of 985 and 980 participants were enrolled in the GRADUATE I and II trials, respectively. The baseline CDR-SB score was 3.7 in the GRADUATE I trial and 3.6 in the GRADUATE II trial. The change from baseline in the CDR-SB score at week 116 was 3.35 with gantenerumab and 3.65 with placebo in the GRADUATE I trial (difference, -0.31; 95% confidence interval CI, -0.66 to 0.05; P = 0.10) and was 2.82 with gantenerumab and 3.01 with placebo in the GRADUATE II trial (difference, -0.19; 95% CI, -0.55 to 0.17; P = 0.30). At week 116, the difference in the amyloid level on PET between the gantenerumab group and the placebo group was -66.44 and -56.46 centiloids in the GRADUATE I and II trials, respectively, and amyloid-negative status was attained in 28.0% and 26.8% of the participants receiving gantenerumab in the two trials. Across both trials, participants receiving gantenerumab had lower CSF levels of phosphorylated tau 181 and higher levels of Aβ42 than those receiving placebo; the accumulation of aggregated tau on PET was similar in the two groups. Amyloid-related imaging abnormalities with edema (ARIA-E) occurred in 24.9% of the participants receiving gantenerumab, and symptomatic ARIA-E occurred in 5.0%.
Among persons with early Alzheimer's disease, the use of gantenerumab led to a lower amyloid plaque burden than placebo at 116 weeks but was not associated with slower clinical decline. (Funded by F. Hoffmann-La Roche; GRADUATE I and II ClinicalTrials.gov numbers, NCT03444870 and NCT03443973, respectively.).
Macrocycles are of increasing interest as chemical probes and drugs for intractable targets like protein-protein interactions, but the determinants of their cell permeability and oral absorption are ...poorly understood. To enable rational design of cell-permeable macrocycles, we generated an extensive data set under consistent experimental conditions for more than 200 non-peptidic, de novo-designed macrocycles from the Broad Institute's diversity-oriented screening collection. This revealed how specific functional groups, substituents and molecular properties impact cell permeability. Analysis of energy-minimized structures for stereo- and regioisomeric sets provided fundamental insight into how dynamic, intramolecular interactions in the 3D conformations of macrocycles may be linked to physicochemical properties and permeability. Combined use of quantitative structure-permeability modeling and the procedure for conformational analysis now, for the first time, provides chemists with a rational approach to design cell-permeable non-peptidic macrocycles with potential for oral absorption.
We set out to determine which characteristics and outcomes of stroke are associated with COVID-19.
This case-control study included patients admitted with stroke to 13 hospitals in England and ...Scotland between 9 March and 5 July 2020. We collected data on 86 strokes (81 ischaemic strokes and 5 intracerebral haemorrhages) in patients with evidence of COVID-19 at the time of stroke onset (cases). They were compared with 1384 strokes (1193 ischaemic strokes and 191 intracerebral haemorrhages) in patients admitted during the same time period who never had evidence of COVID-19 (controls). In addition, the whole group of stroke admissions, including another 37 patients who appeared to have developed COVID-19 after their stroke, were included in two logistic regression analyses examining which features were independently associated with COVID-19 status and with inpatient mortality.
Cases with ischaemic stroke were more likely than ischaemic controls to occur in Asians (18.8% vs 6.7%, p<0.0002), were more likely to involve multiple large vessel occlusions (17.9% vs 8.1%, p<0.03), were more severe (median National Institutes of Health Stroke Scale score 8 vs 5, p<0.002), were associated with higher D-dimer levels (p<0.01) and were associated with more severe disability on discharge (median modified Rankin Scale score 4 vs 3, p<0.0001) and inpatient death (19.8% vs 6.9%, p<0.0001). Recurrence of stroke during the patient's admission was rare in cases and controls (2.3% vs 1.0%, NS).
Our data suggest that COVID-19 may be an important modifier of the onset, characteristics and outcome of acute ischaemic stroke.
Assessing the scope and severity of threats is necessary for evaluating impacts on populations to inform conservation planning. Quantitative threat assessment often requires monitoring programs that ...provide reliable data over relevant spatial and temporal scales, yet such programs can be difficult to justify until there is an apparent stressor. Leveraging efforts of wildlife management agencies to record winter counts of hibernating bats, we collated data for 5 species from over 200 sites across 27 U.S. states and 2 Canadian provinces from 1995 to 2018 to determine the impact of white‐nose syndrome (WNS), a deadly disease of hibernating bats. We estimated declines of winter counts of bat colonies at sites where the invasive fungus that causes WNS (Pseudogymnoascus destructans) had been detected to assess the threat impact of WNS. Three species undergoing species status assessment by the U.S. Fish and Wildlife Service (Myotis septentrionalis, Myotis lucifugus, and Perimyotis subflavus) declined by more than 90%, which warrants classifying the severity of the WNS threat as extreme based on criteria used by NatureServe. The scope of the WNS threat as defined by NatureServe criteria was large (36% of Myotis lucifugus range) to pervasive (79% of Myotis septentrionalis range) for these species. Declines for 2 other species (Myotis sodalis and Eptesicus fuscus) were less severe but still qualified as moderate to serious based on NatureServe criteria. Data‐sharing across jurisdictions provided a comprehensive evaluation of scope and severity of the threat of WNS and indicated regional differences that can inform response efforts at international, national, and state or provincial jurisdictions. We assessed the threat impact of an emerging infectious disease by uniting monitoring efforts across jurisdictional boundaries and demonstrated the importance of coordinated monitoring programs, such as the North American Bat Monitoring Program (NABat), for data‐driven conservation assessments and planning.
Alcance y Severidad del Síndrome de Nariz Blanca en los Murciélagos Hibernando en América del Norte
Resumen
La evaluación del alcance y la severidad de las amenazas es necesaria para los análisis de impacto sobre las poblaciones que se usan para orientar a la planeación de la conservación. La evaluación cuantitativa de amenazas con frecuencia requiere de programas de monitoreo que proporcionen datos confiables en escalas espaciales y temporales, aunque dichos programas pueden ser difíciles de justificar hasta que exista un estresante aparente. Gracias a una movilización de esfuerzos de las agencias de manejo de fauna para registrar los conteos invernales de murciélagos hibernadores, recopilamos datos para cinco especies en más de 200 sitios a lo largos de 27 estados de EUA y dos provincias canadienses entre 1995 y 2018 para determinar el impacto del síndrome de nariz blanca (SNB), una enfermedad mortal de los murciélagos hibernadores. Estimamos declinaciones en los conteos invernales de las colonias de murciélagos en sitios en donde el hongo invasivo que ocasiona el SNB (Pseudogymnoascus destructans) había sido detectado para evaluar el impacto de amenaza del SNB. Tres especies que se encuentran bajo valoración por parte del Servicio de Pesca y Vida Silvestre de los EUA (Myotis septentrionalis, Myotis lucifugus y Perimyotis subflavus) tuvieron una declinación de más del 90%, lo que justifica la clasificación de la severidad de la amenaza del SNB como extrema con base en el criterio usado por NatureServe. El alcance de la amenaza del SNB definido por el criterio de NatureServe fue desde amplio (36% de la distribución de Myotis lucifugus) hasta dominante (79% de la distribución de Myotis septentrionalis) para estas especies. Las declinaciones de otras dos especies (Myotis sodalis y Eptesicus fuscus) fueron menos severas, pero de igual manera quedaron clasificadas desde moderada hasta seria con base en los criterios de NatureServe. El intercambio de datos entre las jurisdicciones proporcionó una evaluación completa del alcance y la severidad de la amenaza del SNB e indicó las diferencias regionales que pueden guiar a los esfuerzos de respuesta realizados en las jurisdicciones internacionales, nacionales, estatales o provinciales. Evaluamos el impacto de amenaza de una enfermedad infecciosa emergente mediante la combinación de los esfuerzos de monitoreo que sobrepasan fronteras jurisdiccionales y demostramos la importancia que tienen para la planeación y la evaluación basadas en datos de la conservación los programas de monitoreo coordinados, como el Programa de Monitoreo de los Murciélagos Norteamericanos (NABat).
Article impact statement: Data sharing and coordinated monitoring are needed to assess species’ response to threats to inform conservation planning at relevant scales.
The purpose of this study was to investigate the prevalence of hepatic steatosis in an asymptomatic U.S. adult population using attenuation values at unenhanced CT as the reference standard. We also ...assessed the utility of known clinical risk factors for diagnosis.
For 3,357 consecutive asymptomatic adults (1,865 women and 1,492 men; mean age, 57.0 years), hepatic and splenic CT attenuation values (Hounsfield units) were obtained by unenhanced CT using a low-dose colonography technique for colorectal cancer screening. Multiple attenuation criteria for steatosis were applied, including liver thresholds and comparison of liver and spleen attenuation. Relevant clinical risk factors were compared against a CT liver attenuation < or = 40 HU, which has been shown to exclude mild steatosis.
Mean liver attenuation was 58.8 +/- 10.8 (SD) HU. The prevalence of moderate-to-severe hepatic steatosis (defined by liver attenuation < or = 40 HU) was 6.2% (208/3,357). For CT attenuation criteria that include milder degrees of steatosis, prevalence increased to as high as 45.9% (1,542/3,357) for a liver-to-spleen attenuation ratio of < or = 1.1. Overweight status (body mass index > 25) was a sensitive indicator for moderate-to-severe steatosis (92.8%) but was highly nonspecific (37.5%). Other clinical risk factors, such as diabetes, dyslipidemia, hypertension, alcohol overuse, and hepatitis, were more specific (77.6-92.4%) but highly insensitive (1.9-37.5%). Combining clinical risk factors did not substantially increase the accuracy for screening.
Assessment of liver attenuation by use of unenhanced CT represents an objective and noninvasive means for detection of asymptomatic hepatic steatosis, whereas clinical risk factor assessment is unreliable. Further longitudinal investigation is needed to determine the most appropriate attenuation threshold and the risk for disease progression to steatohepatitis and cirrhosis.
Abstract
Given considerable variation in diagnostic and therapeutic practice, there is a need for national guidance on the use of neuroimaging, fluid biomarkers, cognitive testing, follow-up and ...diagnostic terminology in mild cognitive impairment (MCI). MCI is a heterogenous clinical syndrome reflecting a change in cognitive function and deficits on neuropsychological testing but relatively intact activities of daily living. MCI is a risk state for further cognitive and functional decline with 5–15% of people developing dementia per year. However, ~50% remain stable at 5 years and in a minority, symptoms resolve over time. There is considerable debate about whether MCI is a useful clinical diagnosis, or whether the use of the term prevents proper inquiry (by history, examination and investigations) into underlying causes of cognitive symptoms, which can include prodromal neurodegenerative disease, other physical or psychiatric illness, or combinations thereof. Cognitive testing, neuroimaging and fluid biomarkers can improve the sensitivity and specificity of aetiological diagnosis, with growing evidence that these may also help guide prognosis. Diagnostic criteria allow for a diagnosis of Alzheimer’s disease to be made where MCI is accompanied by appropriate biomarker changes, but in practice, such biomarkers are not available in routine clinical practice in the UK. This would change if disease-modifying therapies became available and required a definitive diagnosis but would present major challenges to the National Health Service and similar health systems. Significantly increased investment would be required in training, infrastructure and provision of fluid biomarkers and neuroimaging. Statistical techniques combining markers may provide greater sensitivity and specificity than any single disease marker but their practical usefulness will depend on large-scale studies to ensure ecological validity and that multiple measures, e.g. both cognitive tests and biomarkers, are widely available for clinical use. To perform such large studies, we must increase research participation amongst those with MCI.
PDF
