Assessment of Discordance Between Physicians and Family Members Regarding Prognosis in Patients With Severe Acute Brain Injury.

Shared decision-making requires key stakeholders to align in perceptions of prognosis and likely treatment outcomes. For patients with severe acute brain injury, the objective of this study was to better understand prognosis discordance between physicians and families by determining prevalence and associated factors. This mixed-methods cross-sectional study analyzed a cohort collected from January 4, 2018, to July 22, 2020. This study was conducted in the medical and cardiac intensive care units of a single neuroscience center. Participants included families, physicians, and nurses of patients admitted with severe acute brain injury. Severe acute brain injury was defined as stroke, traumatic brain injury, or hypoxic ischemic encephalopathy with a Glasgow Coma Scale score less than or equal to 12 points after hospital day 2. Prognosis discordance was defined as a 20% or greater difference between family and physician prognosis predictions; misunderstanding was defined as a 20% or greater difference between physician prediction and the family's estimate of physician prediction; and optimistic belief difference was defined as any difference (>0%) between family prediction and their estimate of physician prediction. Logistic regression was used to identify associations with discordance. Optimistic belief differences were analyzed as a subgroup of prognosis discordance. Among 222 enrolled patients, prognostic predictions were available for 193 patients (mean [SD] age, 57 [19] years; 106 men [55%]). Prognosis discordance occurred for 118 patients (61%) and was significantly more common among families who identified with minoritized racial groups compared with White families (odds ratio [OR], 3.14; CI, 1.40-7.07, P = .006); among siblings (OR, 4.93; 95% CI, 1.35-17.93, P = .02) and adult children (OR, 2.43; 95% CI, 1.10-5.37; P = .03) compared with spouses; and when nurses perceived family understanding as poor compared with good (OR, 3.73; 95% CI, 1.88-7.40; P < .001). Misunderstanding was present for 80 of 173 patients (46%) evaluated for this type of prognosis discordance, and optimistic belief difference was present for 94 of 173 patients (54%). In qualitative analysis, faith and uncertainty emerged as themes underlying belief differences. Nurse perception of poor family understanding was significantly associated with misunderstanding (OR, 2.06; 95% CI, 1.07-3.94; P = .03), and physician perception with optimistic belief differences (OR, 2.32; 95% CI, 1.10-4.88; P = .03). Results of this cross-sectional study suggest that for patients with severe acute brain injury, prognosis discordance between physicians and families was common. Efforts to improve communication and decision-making should aim to reduce this discordance and find ways to target both misunderstanding and optimistic belief differences

On the influence of the cosmological constant on gravitational lensing in small systems

The cosmological constant Lambda affects gravitational lensing phenomena. The contribution of Lambda to the observable angular positions of multiple images and to their amplification and time delay is here computed through a study in the weak deflection limit of the equations of motion in the Schwarzschild-de Sitter metric. Due to Lambda the unresolved images are slightly demagnified, the radius of the Einstein ring decreases and the time delay increases. The effect is however negligible for near lenses. In the case of null cosmological constant, we provide some updated results on lensing by a Schwarzschild black hole.Comment: 8 pages, 1 figure; v2: extended discussion on the lens equation, references added, results unchanged, in press on PR

Search for long-lived doubly charged Higgs bosons in p(p)over-bar collisions at root s=1.96 TeV

We present a search for long-lived doubly charged Higgs bosons (H+/-+/-), with signatures of high ionization energy loss and muonlike penetration. We use 292 pb(-1) of data collected in p (p) over bar collisions at root s=1.96 TeV by the CDF II detector at the Fermilab Tevatron. Observing no evidence of long-lived doubly charged particle production, we exclude H-L(+/-+/-) and H-R(+/-+/-) bosons with masses below 133 GeV/c(2) and 109 GeV/c(2), respectively. In the degenerate case we exclude H+/-+/- mass below 146 GeV/c(2). All limits are quoted at the 95% confidence level

Search for chargino-neutralino production in ppbar collisions at sqrt(s) = 1.96 TeV

We present the results of a search for associated production of the chargino and neutralino supersymmetric particles using up to 1.1 fb-1 of integrated luminosity collected by the CDF II experiment at the Tevatron ppbar collider at a center-of-mass energy of 1.96 TeV. The search is conducted by analyzing events with a large transverse momentum imbalance and either three charged leptons or two charged leptons of the same electric charge. The numbers of observed events are found to be consistent with standard model expectations. Upper limits on the production cross section are derived in different theoretical models. In one of these models a lower limit on the mass of the chargino is set at 129 GeV/c^2 at the 95% confidence level.Comment: To be submitted to Phys.Rev.Let

Measurement of the W+W- Production Cross Section in ppbar Collisions at sqrt(s)=1.96 TeV using Dilepton Events

We present a measurement of the W+W- production cross section using 184/pb of ppbar collisions at a center-of-mass energy of 1.96 TeV collected with the Collider Detector at Fermilab. Using the dilepton decay channel W+W- -> l+l-vvbar, where the charged leptons can be either electrons or muons, we find 17 candidate events compared to an expected background of 5.0+2.2-0.8 events. The resulting W+W- production cross section measurement of sigma(ppbar -> W+W-) = 14.6 +5.8 -5.1 (stat) +1.8 -3.0 (syst) +-0.9 (lum) pb agrees well with the Standard Model expectation.Comment: 8 pages, 2 figures, 2 tables. To be submitted to Physical Review Letter

Measurement of the ttbar Production Cross Section in ppbar collisions at sqrt s = 1.96 TeV in the All Hadronic Decay Mode

We report a measurement of the ttbar production cross section using the CDF-II detector at the Fermilab Tevatron. The analysis is performed using 311 pb-1 of ppbar collisions at sqrt(s)=1.96 TeV. The data consist of events selected with six or more hadronic jets with additional kinematic requirements. At least one of these jets must be identified as a b-quark jet by the reconstruction of a secondary vertex. The cross section is measured to be sigma(tbart)=7.5+-2.1(stat.)+3.3-2.2(syst.)+0.5-0.4(lumi.) pb, which is consistent with the standard model prediction.Comment: By CDF collaboratio

Post-acute COVID-19 neuropsychiatric symptoms are not associated with ongoing nervous system injury

A proportion of patients infected with severe acute respiratory syndrome coronavirus 2 experience a range of neuropsychiatric symptoms months after infection, including cognitive deficits, depression and anxiety. The mechanisms underpinning such symptoms remain elusive. Recent research has demonstrated that nervous system injury can occur during COVID-19. Whether ongoing neural injury in the months after COVID-19 accounts for the ongoing or emergent neuropsychiatric symptoms is unclear. Within a large prospective cohort study of adult survivors who were hospitalized for severe acute respiratory syndrome coronavirus 2 infection, we analysed plasma markers of nervous system injury and astrocytic activation, measured 6 months post-infection: neurofilament light, glial fibrillary acidic protein and total tau protein. We assessed whether these markers were associated with the severity of the acute COVID-19 illness and with post-acute neuropsychiatric symptoms (as measured by the Patient Health Questionnaire for depression, the General Anxiety Disorder assessment for anxiety, the Montreal Cognitive Assessment for objective cognitive deficit and the cognitive items of the Patient Symptom Questionnaire for subjective cognitive deficit) at 6 months and 1 year post-hospital discharge from COVID-19. No robust associations were found between markers of nervous system injury and severity of acute COVID-19 (except for an association of small effect size between duration of admission and neurofilament light) nor with post-acute neuropsychiatric symptoms. These results suggest that ongoing neuropsychiatric symptoms are not due to ongoing neural injury

SARS-CoV-2-specific nasal IgA wanes 9 months after hospitalisation with COVID-19 and is not induced by subsequent vaccination

BACKGROUND: Most studies of immunity to SARS-CoV-2 focus on circulating antibody, giving limited insights into mucosal defences that prevent viral replication and onward transmission. We studied nasal and plasma antibody responses one year after hospitalisation for COVID-19, including a period when SARS-CoV-2 vaccination was introduced. METHODS: In this follow up study, plasma and nasosorption samples were prospectively collected from 446 adults hospitalised for COVID-19 between February 2020 and March 2021 via the ISARIC4C and PHOSP-COVID consortia. IgA and IgG responses to NP and S of ancestral SARS-CoV-2, Delta and Omicron (BA.1) variants were measured by electrochemiluminescence and compared with plasma neutralisation data. FINDINGS: Strong and consistent nasal anti-NP and anti-S IgA responses were demonstrated, which remained elevated for nine months (p < 0.0001). Nasal and plasma anti-S IgG remained elevated for at least 12 months (p < 0.0001) with plasma neutralising titres that were raised against all variants compared to controls (p < 0.0001). Of 323 with complete data, 307 were vaccinated between 6 and 12 months; coinciding with rises in nasal and plasma IgA and IgG anti-S titres for all SARS-CoV-2 variants, although the change in nasal IgA was minimal (1.46-fold change after 10 months, p = 0.011) and the median remained below the positive threshold determined by pre-pandemic controls. Samples 12 months after admission showed no association between nasal IgA and plasma IgG anti-S responses (R = 0.05, p = 0.18), indicating that nasal IgA responses are distinct from those in plasma and minimally boosted by vaccination. INTERPRETATION: The decline in nasal IgA responses 9 months after infection and minimal impact of subsequent vaccination may explain the lack of long-lasting nasal defence against reinfection and the limited effects of vaccination on transmission. These findings highlight the need to develop vaccines that enhance nasal immunity. FUNDING: This study has been supported by ISARIC4C and PHOSP-COVID consortia. ISARIC4C is supported by grants from the National Institute for Health and Care Research and the Medical Research Council. Liverpool Experimental Cancer Medicine Centre provided infrastructure support for this research. The PHOSP-COVD study is jointly funded by UK Research and Innovation and National Institute of Health and Care Research. The funders were not involved in the study design, interpretation of data or the writing of this manuscript

Effects of sleep disturbance on dyspnoea and impaired lung function following hospital admission due to COVID-19 in the UK: a prospective multicentre cohort study

Background: Sleep disturbance is common following hospital admission both for COVID-19 and other causes. The clinical associations of this for recovery after hospital admission are poorly understood despite sleep disturbance contributing to morbidity in other scenarios. We aimed to investigate the prevalence and nature of sleep disturbance after discharge following hospital admission for COVID-19 and to assess whether this was associated with dyspnoea. Methods: CircCOVID was a prospective multicentre cohort substudy designed to investigate the effects of circadian disruption and sleep disturbance on recovery after COVID-19 in a cohort of participants aged 18 years or older, admitted to hospital for COVID-19 in the UK, and discharged between March, 2020, and October, 2021. Participants were recruited from the Post-hospitalisation COVID-19 study (PHOSP-COVID). Follow-up data were collected at two timepoints: an early time point 2–7 months after hospital discharge and a later time point 10–14 months after hospital discharge. Sleep quality was assessed subjectively using the Pittsburgh Sleep Quality Index questionnaire and a numerical rating scale. Sleep quality was also assessed with an accelerometer worn on the wrist (actigraphy) for 14 days. Participants were also clinically phenotyped, including assessment of symptoms (ie, anxiety [Generalised Anxiety Disorder 7-item scale questionnaire], muscle function [SARC-F questionnaire], dyspnoea [Dyspnoea-12 questionnaire] and measurement of lung function), at the early timepoint after discharge. Actigraphy results were also compared to a matched UK Biobank cohort (non-hospitalised individuals and recently hospitalised individuals). Multivariable linear regression was used to define associations of sleep disturbance with the primary outcome of breathlessness and the other clinical symptoms. PHOSP-COVID is registered on the ISRCTN Registry (ISRCTN10980107). Findings: 2320 of 2468 participants in the PHOSP-COVID study attended an early timepoint research visit a median of 5 months (IQR 4–6) following discharge from 83 hospitals in the UK. Data for sleep quality were assessed by subjective measures (the Pittsburgh Sleep Quality Index questionnaire and the numerical rating scale) for 638 participants at the early time point. Sleep quality was also assessed using device-based measures (actigraphy) a median of 7 months (IQR 5–8 months) after discharge from hospital for 729 participants. After discharge from hospital, the majority (396 [62%] of 638) of participants who had been admitted to hospital for COVID-19 reported poor sleep quality in response to the Pittsburgh Sleep Quality Index questionnaire. A comparable proportion (338 [53%] of 638) of participants felt their sleep quality had deteriorated following discharge after COVID-19 admission, as assessed by the numerical rating scale. Device-based measurements were compared to an age-matched, sex-matched, BMI-matched, and time from discharge-matched UK Biobank cohort who had recently been admitted to hospital. Compared to the recently hospitalised matched UK Biobank cohort, participants in our study slept on average 65 min (95% CI 59 to 71) longer, had a lower sleep regularity index (–19%; 95% CI –20 to –16), and a lower sleep efficiency (3·83 percentage points; 95% CI 3·40 to 4·26). Similar results were obtained when comparisons were made with the non-hospitalised UK Biobank cohort. Overall sleep quality (unadjusted effect estimate 3·94; 95% CI 2·78 to 5·10), deterioration in sleep quality following hospital admission (3·00; 1·82 to 4·28), and sleep regularity (4·38; 2·10 to 6·65) were associated with higher dyspnoea scores. Poor sleep quality, deterioration in sleep quality, and sleep regularity were also associated with impaired lung function, as assessed by forced vital capacity. Depending on the sleep metric, anxiety mediated 18–39% of the effect of sleep disturbance on dyspnoea, while muscle weakness mediated 27–41% of this effect. Interpretation: Sleep disturbance following hospital admission for COVID-19 is associated with dyspnoea, anxiety, and muscle weakness. Due to the association with multiple symptoms, targeting sleep disturbance might be beneficial in treating the post-COVID-19 condition. Funding: UK Research and Innovation, National Institute for Health Research, and Engineering and Physical Sciences Research Council

Accelarated immune ageing is associated with COVID-19 disease severity

Background The striking increase in COVID-19 severity in older adults provides a clear example of immunesenescence, the age-related remodelling of the immune system. To better characterise the association between convalescent immunesenescence and acute disease severity, we determined the immune phenotype of COVID-19 survivors and non-infected controls. Results We performed detailed immune phenotyping of peripheral blood mononuclear cells isolated from 103 COVID-19 survivors 3–5 months post recovery who were classified as having had severe (n = 56; age 53.12 ± 11.30 years), moderate (n = 32; age 52.28 ± 11.43 years) or mild (n = 15; age 49.67 ± 7.30 years) disease and compared with age and sex-matched healthy adults (n = 59; age 50.49 ± 10.68 years). We assessed a broad range of immune cell phenotypes to generate a composite score, IMM-AGE, to determine the degree of immune senescence. We found increased immunesenescence features in severe COVID-19 survivors compared to controls including: a reduced frequency and number of naïve CD4 and CD8 T cells (p < 0.0001); increased frequency of EMRA CD4 (p < 0.003) and CD8 T cells (p < 0.001); a higher frequency (p < 0.0001) and absolute numbers (p < 0.001) of CD28−ve CD57+ve senescent CD4 and CD8 T cells; higher frequency (p < 0.003) and absolute numbers (p < 0.02) of PD-1 expressing exhausted CD8 T cells; a two-fold increase in Th17 polarisation (p < 0.0001); higher frequency of memory B cells (p < 0.001) and increased frequency (p < 0.0001) and numbers (p < 0.001) of CD57+ve senescent NK cells. As a result, the IMM-AGE score was significantly higher in severe COVID-19 survivors than in controls (p < 0.001). Few differences were seen for those with moderate disease and none for mild disease. Regression analysis revealed the only pre-existing variable influencing the IMM-AGE score was South Asian ethnicity ( = 0.174, p = 0.043), with a major influence being disease severity ( = 0.188, p = 0.01). Conclusions Our analyses reveal a state of enhanced immune ageing in survivors of severe COVID-19 and suggest this could be related to SARS-Cov-2 infection. Our data support the rationale for trials of anti-immune ageing interventions for improving clinical outcomes in these patients with severe disease