Pulmonary endothelial permeability and tissue fluid balance depend on the viscosity of the perfusion solution

Fluid filtration in the pulmonary microcirculation depends on the hydrostatic and oncotic pressure gradients across the endothelium and the selective permeability of the endothelial barrier. Maintaining normal fluid balance depends both on specific properties of the endothelium and of the perfusing blood. Although some of the essential properties of blood needed to prevent excessive fluid leak have been identified and characterized, our understanding of these remains incomplete. The role of perfusate viscosity in maintaining normal fluid exchange has not previously been examined. We prepared a high-viscosity perfusion solution (HVS) with a relative viscosity of 2.5, i.e., within the range displayed by blood flowing in vessels of different diameters in vivo (1.5–4.0). Perfusion of isolated murine lungs with HVS significantly reduced the rate of edema formation compared with perfusion with a standard solution (SS), which had a lower viscosity similar to plasma (relative viscosity 1.5). HVS did not alter capillary filtration pressure. Increased endothelial shear stress produced by increasing flow rates of SS, to mimic the increased shear stress produced by HVS, did not reduce edema formation. HVS significantly reduced extravasation of Evans bluelabeled albumin compared with SS, indicating that it attenuated endothelial leak. These findings demonstrate for the first time that the viscosity of the solution perfusing the pulmonary microcirculation is an important physiological property contributing to the maintenance of normal fluid exchange. This has significant implications for our understanding of fluid homeostasis in the healthy lung, edema formation in disease, and reconditioning of donor organs for transplantation

Anxiety and depression following critical illness: A comparison of the recovery trajectories of patients and caregivers

Background: Following critical illness, family members are often required to adopt caregiving responsibilities. Anxiety and depression are common long term problems for both patients and caregivers. However, at present, it is not known how the trajectories of these symptoms compare between patients and caregivers. Objectives: The aim of this study was to investigate and compare the trajectories of anxiety and depression in patients and caregivers in the first year following critical illness. Methods: This study analyses data from a prospective multicentre cohort study of patients and caregivers who underwent a complex recovery intervention following critical illness. Paired patients and caregivers were recruited. The Hospital Anxiety and Depression Scale was used to evaluate symptoms of anxiety and depression at three timepoints: baseline; 3 months; and 12 months in both patient and caregivers. A linear mixed-effects regression model was used to evaluate the trajectories of these symptoms over the first year following critical illness. Results: 115 paired patients and caregivers, who received the complex recovery intervention, were recruited. There was no significant difference in the relative trajectory of depressive symptoms between patients and caregivers in the first 12 months following critical illness (p = 0.08). There was, however, a significant difference in the trajectory of anxiety symptoms between patients and caregivers during this time period (p = 0.04), with caregivers seeing reduced resolution of symptoms in comparison to patients. Conclusions: Following critical illness, symptoms of anxiety and depression are common in both patients and caregivers. The trajectory of symptoms of depression was similar between caregivers and patients; however, there was a significantly different recovery trajectory in symptoms of anxiety. Further research is required to understand the recovery pathway of caregivers in order to design effective interventions

A multicentre evaluation exploring the impact of an integrated health and social care intervention for the caregivers of ICU survivors

Background: Caregivers and family members of Intensive Care Unit (ICU) survivors can face emotional problems following patient discharge from hospital. We aimed to evaluate the impact of a multi-centre integrated health and social care intervention, on caregiver and family member outcomes. Methods: This study evaluated the impact of the Intensive Care Syndrome: Promoting Independence and Return to Employment (InS:PIRE) programme across 9 sites in Scotland. InS:PIRE is an integrated health and social care intervention. We compared caregivers who attended this programme with a contemporary control group of ICU caregivers (usual care cohort), who did not attend. Results: The primary outcome was anxiety measured via the Hospital Anxiety and Depression Scale at 12 months post-hospital discharge. Secondary outcome measures included depression, carer strain and clinical insomnia. A total of 170 caregivers had data available at 12 months for inclusion in this study; 81 caregivers attended the InS:PIRE intervention and completed outcome measures at 12 months post-hospital discharge. In the usual care cohort of caregivers, 89 completed measures. The two cohorts had similar baseline demographics. After adjustment, those caregivers who attended InS:PIRE demonstrated a significant improvement in symptoms of anxiety (OR: 0.42, 95% CI: 0.20–0.89, p = 0.02), carer strain (OR: 0.39; 95% CI: 0.16–0.98 p = 0.04) and clinical insomnia (OR: 0.40; 95% CI: 0.17–0.77 p < 0.001). There was no significant difference in symptoms of depression at 12 months. Conclusions: This multicentre evaluation has shown that caregivers who attended an integrated health and social care intervention reported improved emotional health and less symptoms of insomnia, 12 months after the delivery of the intervention

Medication related problems in ICU survivors: learning from a multi-centre programme

No abstract available

Slow Solar Wind Connection Science during Solar Orbiter’s First Close Perihelion Passage

The Slow Solar Wind Connection Solar Orbiter Observing Plan (Slow Wind SOOP) was developed to utilize the extensive suite of remote-sensing and in situ instruments on board the ESA/NASA Solar Orbiter mission to answer significant outstanding questions regarding the origin and formation of the slow solar wind. The Slow Wind SOOP was designed to link remote-sensing and in situ measurements of slow wind originating at open–closed magnetic field boundaries. The SOOP ran just prior to Solar Orbiter’s first close perihelion passage during two remote-sensing windows (RSW1 and RSW2) between 2022 March 3–6 and 2022 March 17–22, while Solar Orbiter was at respective heliocentric distances of 0.55–0.51 and 0.38–0.34 au from the Sun. Coordinated observation campaigns were also conducted by Hinode and IRIS. The magnetic connectivity tool was used, along with low-latency in situ data and full-disk remote-sensing observations, to guide the target pointing of Solar Orbiter. Solar Orbiter targeted an active region complex during RSW1, the boundary of a coronal hole, and the periphery of a decayed active region during RSW2. Postobservation analysis using the magnetic connectivity tool, along with in situ measurements from MAG and SWA/PAS, showed that slow solar wind originating from two out of three of the target regions arrived at the spacecraft with velocities between ∼210 and 600 km s−1. The Slow Wind SOOP, despite presenting many challenges, was very successful, providing a blueprint for planning future observation campaigns that rely on the magnetic connectivity of Solar Orbiter

A new integrated and homogenized global monthly land surface air temperature dataset for the period since 1900

A new dataset of integrated and homogenized monthly surface air temperature over global land for the period since 1900 [China Meteorological Administration global Land Surface Air Temperature (CMA-LSAT)] is developed. In total, 14 sources have been collected and integrated into the newly developed dataset, including three global (CRUTEM4, GHCN, and BEST), three regional and eight national sources. Duplicate stations are identified, and those with the higher priority are chosen or spliced. Then, a consistency test and a climate outlier test are conducted to ensure that each station series is quality controlled. Next, two steps are adopted to assure the homogeneity of the station series: (1) homogenized station series in existing national datasets (by National Meteorological Services) are directly integrated into the dataset without any changes (50% of all stations), and (2) the inhomogeneities are detected and adjusted for in the remaining data series using a penalized maximal t test (50% of all stations). Based on the dataset, we re-assess the temperature changes in global and regional areas compared with GHCN-V3 and CRUTEM4, as well as the temperature changes during the three periods of 1900–2014, 1979–2014 and 1998–2014. The best estimates of warming trends and there 95% confidence ranges for 1900–2014 are approximately 0.102 ± 0.006 °C/decade for the whole year, and 0.104 ± 0.009, 0.112 ± 0.007, 0.090 ± 0.006, and 0.092 ± 0.007 °C/decade for the DJF (December, January, February), MAM, JJA, and SON seasons, respectively. MAM saw the most significant warming trend in both 1900–2014 and 1979–2014. For an even shorter and more recent period (1998–2014), MAM, JJA and SON show similar warming trends, while DJF shows opposite trends. The results show that the ability of CMA-LAST for describing the global temperature changes is similar with other existing products, while there are some differences when describing regional temperature changes

Proceedings of the 3rd Biennial Conference of the Society for Implementation Research Collaboration (SIRC) 2015: advancing efficient methodologies through community partnerships and team science

It is well documented that the majority of adults, children and families in need of evidence-based behavioral health interventionsi do not receive them [1, 2] and that few robust empirically supported methods for implementing evidence-based practices (EBPs) exist. The Society for Implementation Research Collaboration (SIRC) represents a burgeoning effort to advance the innovation and rigor of implementation research and is uniquely focused on bringing together researchers and stakeholders committed to evaluating the implementation of complex evidence-based behavioral health interventions. Through its diverse activities and membership, SIRC aims to foster the promise of implementation research to better serve the behavioral health needs of the population by identifying rigorous, relevant, and efficient strategies that successfully transfer scientific evidence to clinical knowledge for use in real world settings [3]. SIRC began as a National Institute of Mental Health (NIMH)-funded conference series in 2010 (previously titled the “Seattle Implementation Research Conference”; $150,000 USD for 3 conferences in 2011, 2013, and 2015) with the recognition that there were multiple researchers and stakeholdersi working in parallel on innovative implementation science projects in behavioral health, but that formal channels for communicating and collaborating with one another were relatively unavailable. There was a significant need for a forum within which implementation researchers and stakeholders could learn from one another, refine approaches to science and practice, and develop an implementation research agenda using common measures, methods, and research principles to improve both the frequency and quality with which behavioral health treatment implementation is evaluated. SIRC’s membership growth is a testament to this identified need with more than 1000 members from 2011 to the present.ii SIRC’s primary objectives are to: (1) foster communication and collaboration across diverse groups, including implementation researchers, intermediariesi, as well as community stakeholders (SIRC uses the term “EBP champions” for these groups) – and to do so across multiple career levels (e.g., students, early career faculty, established investigators); and (2) enhance and disseminate rigorous measures and methodologies for implementing EBPs and evaluating EBP implementation efforts. These objectives are well aligned with Glasgow and colleagues’ [4] five core tenets deemed critical for advancing implementation science: collaboration, efficiency and speed, rigor and relevance, improved capacity, and cumulative knowledge. SIRC advances these objectives and tenets through in-person conferences, which bring together multidisciplinary implementation researchers and those implementing evidence-based behavioral health interventions in the community to share their work and create professional connections and collaborations

Genomic epidemiology of SARS-CoV-2 in a UK university identifies dynamics of transmission

AbstractUnderstanding SARS-CoV-2 transmission in higher education settings is important to limit spread between students, and into at-risk populations. In this study, we sequenced 482 SARS-CoV-2 isolates from the University of Cambridge from 5 October to 6 December 2020. We perform a detailed phylogenetic comparison with 972 isolates from the surrounding community, complemented with epidemiological and contact tracing data, to determine transmission dynamics. We observe limited viral introductions into the university; the majority of student cases were linked to a single genetic cluster, likely following social gatherings at a venue outside the university. We identify considerable onward transmission associated with student accommodation and courses; this was effectively contained using local infection control measures and following a national lockdown. Transmission clusters were largely segregated within the university or the community. Our study highlights key determinants of SARS-CoV-2 transmission and effective interventions in a higher education setting that will inform public health policy during pandemics.</jats:p

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p&lt;0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p&lt;0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p&lt;0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP &gt;5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

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