The Crossroads of Wellness and Second Victim Syndrome: Identifying Factors that Alter the Pathway of Caregiver Recovery Following an Unanticipated Adverse Patient Outcome

Introduction: Second Victim Syndrome (SVS) describes the phenomenon in which a caregiver experiences a traumatic psychological and emotional response to an adverse patient event or medical error. Using quantitative survey analysis, we aim to better understand the personal factors that affect SVS development and recovery. Methods: Caregivers at a small urban academic medical center who had experienced an adverse patient event in the past six months were invited to take part in this institution-wide, voluntary, quantitative, cross-sectional study. Three surveys were administered; the Holmes-Rahe Life Stress Inventory (HRLSI) was used as a surrogate to measure stressful life events. The Impact of Event Scale-Revised (IES-R) was used as a measure of the stress a provider senses following a traumatic event. The Second Victim Experience and Support Tool (SVEST) was used to assess the medical provider’s emotional response and level of institutional support in response to an adverse clinical event. Results: Analysis of SVEST vs. IES-R demonstrated that respondents with greater self-perception of personal distress reported increased psychological (p=0.0008) and physical (p=0.0015) distress. Respondents who reported higher HRLSI scores had a greater perception that non-work-related support (p=0.04) such as family support was inadequate; however, these respondents were less likely to perceive institutional support (p=0.04) as inadequate. The results indicate that caregivers with more perceived life stresses believe that they do not have strong non-work-related support services, which is a known protective factor; thus, they may perceive any institutional support as more adequate. Conclusion: This study suggests that personal life risk factors, institutional support, and non-work related support may play an important role in the development of SVS and the perception of stress and wellness in the setting of SVS

A comprehensive model of factors associated with subjective perceptions of living well with dementia: findings from the IDEAL study

Background: The concept of ‘living well’ is increasingly used to indicate that it is, or should be, possible for a person living with dementia to experience a subjective sense of ‘comfort, function and contentment with life.’ We used a theoretically-derived conceptual framework to investigate capability to ‘live well’ with dementia through identifying the relative contribution of domains associated with the subjective experience of living well. Methods: We analysed data from 1550 community-dwelling individuals with mild to moderate dementia participating in the baseline wave of the Improving the experience of Dementia and Enhancing Active Life (IDEAL) cohort study. Subjective perceptions of ability to live well were obtained by generating a living well latent factor from responses on the Quality of Life in Alzheimer’s disease (QoL-AD), Satisfaction with Life and WHO-5 Well-being scales. Multivariate modelling and structural equation modelling was used to investigate variables potentially associated with living well. Variables were grouped into five domains, latent variables were constructed representing Social Location, Capitals, Assets and Resources, Psychological Characteristics and Psychological Health, Physical Fitness and Health, and Managing Everyday Life with Dementia, and associations with living well were examined. All models were adjusted for age, sex and dementia sub-type. Results: Considering the domains singly, the Psychological Characteristics and Psychological Health domain was most strongly associated with living well (3.56; 95% CI: 2.25, 4.88), followed by Physical Fitness and Physical Health (1.10, 95% CI: -2.26, 4.47). Effect sizes were smaller for Capitals, Assets and Resources (0.53; 95% CI: -0.66, 1.73), Managing Everyday Life with Dementia (0.34; 95% CI: 0.20, 0.87), and Social Location (-0.12; 95% CI: -5.72, 5.47). Following adjustment for the Psychological Characteristics and Psychological Health domain, other domains did not show independent associations with living well. Conclusions: Psychological resources are central to subjective perceptions of living well and offer important targets for immediate intervention. Availability of social and environmental resources, and physical fitness, underpin these positive psychological states, and also offer potential targets for interventions and initiatives aimed at improving the experience of living with dementia

A comprehensive model of factors associated with subjective perceptions of living well with dementia: findings from the IDEAL study

Background: The concept of ‘living well’ is increasingly used to indicate that it is, or should be, possible for a person living with dementia to experience a subjective sense of ‘comfort, function and contentment with life.’ We used a theoretically-derived conceptual framework to investigate capability to ‘live well’ with dementia through identifying the relative contribution of domains associated with the subjective experience of living well. Methods: We analysed data from 1550 community-dwelling individuals with mild to moderate dementia participating in the baseline wave of the Improving the experience of Dementia and Enhancing Active Life (IDEAL) cohort study. Subjective perceptions of ability to live well were obtained by generating a living well latent factor from responses on the Quality of Life in Alzheimer’s disease (QoL-AD), Satisfaction with Life and WHO-5 Well-being scales. Multivariate modelling and structural equation modelling was used to investigate variables potentially associated with living well. Variables were grouped into five domains, latent variables were constructed representing Social Location, Capitals, Assets and Resources, Psychological Characteristics and Psychological Health, Physical Fitness and Health, and Managing Everyday Life with Dementia, and associations with living well were examined. All models were adjusted for age, sex and dementia sub-type. Results: Considering the domains singly, the Psychological Characteristics and Psychological Health domain was most strongly associated with living well (3.56; 95% CI: 2.25, 4.88), followed by Physical Fitness and Physical Health (1.10, 95% CI: -2.26, 4.47). Effect sizes were smaller for Capitals, Assets and Resources (0.53; 95% CI: -0.66, 1.73), Managing Everyday Life with Dementia (0.34; 95% CI: 0.20, 0.87), and Social Location (-0.12; 95% CI: -5.72, 5.47). Following adjustment for the Psychological Characteristics and Psychological Health domain, other domains did not show independent associations with living well. Conclusions: Psychological resources are central to subjective perceptions of living well and offer important targets for immediate intervention. Availability of social and environmental resources, and physical fitness, underpin these positive psychological states, and also offer potential targets for interventions and initiatives aimed at improving the experience of living with dementia

Functional brown adipose tissue limits cardiomyocyte injury and adverse remodeling in catecholamine-induced cardiomyopathy

Brown adipose tissue (BAT) has well recognized thermogenic properties mediated by uncoupling protein 1 (UCP1); more recently, BAT has been demonstrated to modulate cardiovascular risk factors. To investigate whether BAT also affects myocardial injury and remodeling, UCP1-deficient (UCP1−/−) mice, which have dysfunctional BAT, were subjected to catecholamine-induced cardiomyopathy. At baseline, there were no differences in echocardiographic parameters, plasma cardiac troponin I (cTnI) or myocardial fibrosis between wild-type (WT) and UCP1−/− mice. Isoproterenol infusion increased cTnI and myocardial fibrosis and induced left ventricular (LV) hypertrophy in both WT and UCP1−/− mice. UCP1−/− mice also demonstrated exaggerated myocardial injury, fibrosis, and adverse remodeling, as well as decreased survival. Transplantation of WT BAT to UCP1−/− mice prevented the isoproterenol-induced cTnI increase and improved survival, whereas UCP1−/− BAT transplanted to either UCP1−/− or WT mice had no effect on cTnI release. After 3 days of isoproterenol treatment, phosphorylated AKT and ERK were lower in the LV's of UCP1−/− mice than in those of WT mice. Activation of BAT was also noted in a model of chronic ischemic cardiomyopathy, and was correlated to LV dysfunction. Deficiency in UCP1, and accompanying BAT dysfunction, increases cardiomyocyte injury and adverse LV remodeling, and decreases survival in a mouse model of catecholamine-induced cardiomyopathy. Myocardial injury and decreased survival are rescued by transplantation of functional BAT to UCP1−/− mice, suggesting a systemic cardioprotective role of functional BAT. BAT is also activated in chronic ischemic cardiomyopathy

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Comparison of organic matter degradation in several feedstuffs in the rumen as determined with the nylon bag and gas production techniques

Organic matter (OM) degradation of 21 feedstuffs was investigated with rumen fluid using a rumen in situ technique and a gas production technique. Fitting the nylon bag data to an exponential model showed that there was a high variation in the rate of OM degradation ranging from 1.7% h-1 for protected solvent extracted soybean meal to 10.5% h-1 for potato pulp. The percentage fermentable OM (FOM), calculated from the nylon bag data, ranged from 26.9% for maize gluten meal to 76.4% for pea meal. Gas production was recorded with fully automated equipment using twice-diluted rumen fluid. The gas production profiles were fitted to a mono-phasic and a tri-phasic model. The aim of the study described is to investigate the possibilities to estimate in situ degradation characteristics using gas production characteristics and chemical composition. The in situ washout fraction (W), degradable fraction (D) and undegradable fraction (U) could be predicted from chemical composition and gas production parameters with R2 ranging from 0.50 to 0.72. There was a closer relationship between in situ degradation rate of OM (kd) and the incubation period halfway to maximum gas production (B), using the tri-phasic model (R2 = 0.58) than the mono-phasic model (R2 = 0.43). Accounting for an in situ lag-period slightly improved prediction of kd by gas production parameters (R2 = 0.47-0.62). Percentage FOM, calculated from in situ results, could be predicted from chemical composition and gas production parameters with R2 ranging from 0.50 to 0.75. Transformation of kd (determined in situ) to its half-life value of degradation ((ln 2/kd) × 100) provided a slight improvement of kd prediction by chemical composition and gas production parameters, with R2 ranging from 0.56 to 0.81. There was only a moderate relationship for OM degradation in these feedstuffs determined using an in situ and a gas production technique. © 2002 Elsevier Science B.V. All rights reserved

Unrivaled accuracy in measuring rotational transitions of greenhouse gases: THz CRDS of CF4

International audienceTetrafluoromethane CF4 is the most abundant perfluorocarbon in the atmosphere, where it is designated as PFC-14. This greenhouse gas is very stable, has an atmospheric lifetime of 50,000 years, and a high greenhouse warming potential 6500 times that of CO2. Over the last 15 years, its atmospheric concentration has increased at a rate of 0.8 ppt/year. The accurate quantification of CF4 is key to understanding the contribution of its emissions on the radiative forcing budget, the most precise spectroscopic parameters possible are hence required. In this study, a novel high finesse THz cavity, providing an interaction length in excess of 1km, has enabled highly resolved spectra, and quantification of the weak transitions of CF4 by Cavity Ring-Down Spectroscopy (CRDS). More than 50 pure rotational P6-P6: ν3-ν3 lines of CF4 have been measured, yielding both position and intensity with unequalled precision. Several tetrahedral splitting are fully resolved and measured with sub-MHz accuracy. Moreover, CRDS-THz allows determining absolute intensities and, using a global fit of the ν2 polyad series, a CF4 dipole parameter, namely µ3,3, has been fitted to 106.38(53) mD. This value is in a very good agreement with that of the ab initio-based parameter deduced from a dipole moment surface. For the first time, a set of ab initio effective dipole moment parameters is derived for the computation of the transitions of the type Pn-Pn (n=0,...,8) and the resulting line list composed of 25,863 transitions can be used to model the whole CF4 rotational spectrum. Finally, the TFMeCaSDa database is updated and is available for future spectroscopic and monitoring activities