Cognitive and psychiatric symptom trajectories 2–3 years after hospital admission for COVID-19: a longitudinal, prospective cohort study in the UK

Background COVID-19 is known to be associated with increased risks of cognitive and psychiatric outcomes after the acute phase of disease. We aimed to assess whether these symptoms can emerge or persist more than 1 year after hospitalisation for COVID-19, to identify which early aspects of COVID-19 illness predict longer-term symptoms, and to establish how these symptoms relate to occupational functioning. Methods The Post-hospitalisation COVID-19 study (PHOSP-COVID) is a prospective, longitudinal cohort study of adults (aged ≥18 years) who were hospitalised with a clinical diagnosis of COVID-19 at participating National Health Service hospitals across the UK. In the C-Fog study, a subset of PHOSP-COVID participants who consented to be recontacted for other research were invited to complete a computerised cognitive assessment and clinical scales between 2 years and 3 years after hospital admission. Participants completed eight cognitive tasks, covering eight cognitive domains, from the Cognitron battery, in addition to the 9-item Patient Health Questionnaire for depression, the Generalised Anxiety Disorder 7-item scale, the Functional Assessment of Chronic Illness Therapy Fatigue Scale, and the 20-item Cognitive Change Index (CCI-20) questionnaire to assess subjective cognitive decline. We evaluated how the absolute risks of symptoms evolved between follow-ups at 6 months, 12 months, and 2–3 years, and whether symptoms at 2–3 years were predicted by earlier aspects of COVID-19 illness. Participants completed an occupation change questionnaire to establish whether their occupation or working status had changed and, if so, why. We assessed which symptoms at 2–3 years were associated with occupation change. People with lived experience were involved in the study. Findings 2469 PHOSP-COVID participants were invited to participate in the C-Fog study, and 475 participants (191 [40·2%] females and 284 [59·8%] males; mean age 58·26 [SD 11·13] years) who were discharged from one of 83 hospitals provided data at the 2–3-year follow-up. Participants had worse cognitive scores than would be expected on the basis of their sociodemographic characteristics across all cognitive domains tested (average score 0·71 SD below the mean [IQR 0·16–1·04]; p<0·0001). Most participants reported at least mild depression (263 [74·5%] of 353), anxiety (189 [53·5%] of 353), fatigue (220 [62·3%] of 353), or subjective cognitive decline (184 [52·1%] of 353), and more than a fifth reported severe depression (79 [22·4%] of 353), fatigue (87 [24·6%] of 353), or subjective cognitive decline (88 [24·9%] of 353). Depression, anxiety, and fatigue were worse at 2–3 years than at 6 months or 12 months, with evidence of both worsening of existing symptoms and emergence of new symptoms. Symptoms at 2–3 years were not predicted by the severity of acute COVID-19 illness, but were strongly predicted by the degree of recovery at 6 months (explaining 35·0–48·8% of the variance in anxiety, depression, fatigue, and subjective cognitive decline); by a biocognitive profile linking acutely raised D-dimer relative to C-reactive protein with subjective cognitive deficits at 6 months (explaining 7·0–17·2% of the variance in anxiety, depression, fatigue, and subjective cognitive decline); and by anxiety, depression, fatigue, and subjective cognitive deficit at 6 months. Objective cognitive deficits at 2–3 years were not predicted by any of the factors tested, except for cognitive deficits at 6 months, explaining 10·6% of their variance. 95 of 353 participants (26·9% [95% CI 22·6–31·8]) reported occupational change, with poor health being the most common reason for this change. Occupation change was strongly and specifically associated with objective cognitive deficits (odds ratio [OR] 1·51 [95% CI 1·04–2·22] for every SD decrease in overall cognitive score) and subjective cognitive decline (OR 1·54 [1·21–1·98] for every point increase in CCI-20). Interpretation Psychiatric and cognitive symptoms appear to increase over the first 2–3 years post-hospitalisation due to both worsening of symptoms already present at 6 months and emergence of new symptoms. New symptoms occur mostly in people with other symptoms already present at 6 months. Early identification and management of symptoms might therefore be an effective strategy to prevent later onset of a complex syndrome. Occupation change is common and associated mainly with objective and subjective cognitive deficits. Interventions to promote cognitive recovery or to prevent cognitive decline are therefore needed to limit the functional and economic impacts of COVID-19. Funding National Institute for Health and Care Research Oxford Health Biomedical Research Centre, Wolfson Foundation, MQ Mental Health Research, MRC-UK Research and Innovation, and National Institute for Health and Care Research

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; p5mg/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. Funding: UK Research and Innovation and National Institute for Health Research

Large-scale phenotyping of patients with long COVID post-hospitalization reveals mechanistic subtypes of disease

One in ten severe acute respiratory syndrome coronavirus 2 infections result in prolonged symptoms termed long coronavirus disease (COVID), yet disease phenotypes and mechanisms are poorly understood1. Here we profiled 368 plasma proteins in 657 participants ≥3 months following hospitalization. Of these, 426 had at least one long COVID symptom and 233 had fully recovered. Elevated markers of myeloid inflammation and complement activation were associated with long COVID. IL-1R2, MATN2 and COLEC12 were associated with cardiorespiratory symptoms, fatigue and anxiety/depression; MATN2, CSF3 and C1QA were elevated in gastrointestinal symptoms and C1QA was elevated in cognitive impairment. Additional markers of alterations in nerve tissue repair (SPON-1 and NFASC) were elevated in those with cognitive impairment and SCG3, suggestive of brain–gut axis disturbance, was elevated in gastrointestinal symptoms. Severe acute respiratory syndrome coronavirus 2-specific immunoglobulin G (IgG) was persistently elevated in some individuals with long COVID, but virus was not detected in sputum. Analysis of inflammatory markers in nasal fluids showed no association with symptoms. Our study aimed to understand inflammatory processes that underlie long COVID and was not designed for biomarker discovery. Our findings suggest that specific inflammatory pathways related to tissue damage are implicated in subtypes of long COVID, which might be targeted in future therapeutic trials

The transition from freight consolidation to logistics: The case of Hong Kong

This paper examines the challenges and opportunities confronting the traditional container consolidation industry in Hong Kong as it strives to modernise by adopting logistics functions. The study is based upon a series of detailed surveys of the industry undertaken during a period of adjustment. Improving value-added services is seen as the key to the survival of Hong Kong as a major transportation centre; this study indicates that making the improvements represents unique challenges to the firms actually involved. The barriers and potentials for these firms to transform themselves to third-party logistics service providers are analysed. © 2003 Elsevier Ltd. All rights reserved

Native oxide and hydroxides and their implications for bulk AlN crystal growth

Oxygen degrades the properties of AlN, thus producing bulk single crystals with low oxygen concentrations is an important goal. Most of the oxygen in bulk AlN single crystals grown by the sublimation-recondensation method originates from the hydroxides and oxides that spontaneously form on the surfaces of the AlN source powder. For a typical AlN powder with an average particle size of 1-2 microns, a 1-3 nm thick oxide and/or hydroxide can account for most of its oxygen (generally on the order of 1.0 wt%) and hydrogen (200-300 ppm). Heating the AlN powder source at 1950 °C for 10 h in a nitrogen atmosphere reduced its surface area by a factor of 160 (due to sintering), the oxygen concentration by 16, and the hydrogen concentration by 67. The difference in these reduction factors suggests some of the oxygen is dissolved into the bulk AlN with this heat treatment. By first annealing the AlN powder at a low temperature (950-1000 °C) for several hours before sintering at 1950 °C, the oxygen and hydrogen concentrations were reduced to lower levels. The low temperature treatment is effective eliminating oxygen and hydrogen from the surface of the powder, while high temperature sintering reduces the specific surface area of the source. The combination of heat treatments produced a source with oxygen and hydrogen concentrations as low as 0.015 wt% O (1.9 x 10[superscript]19 atoms O cm[superscript]-3) and 1.7 ppm H (3.4 x 10[superscript]18 atoms H cm[superscript]-3). Annealing becomes less effective at removing oxygen and hydrogen with longer heat treatments, suggesting there is a minimum oxygen concentration that can be produced with this method

Identifying Student Research Project Impact Using the Buxton and Hanney Payback Framework

Objectives. To determine whether evidence of the impact of student quality improvement projects and research projects on practice sites and the community can be identified using the Buxton and Hanney Payback Framework (BHPF). Methods. The BHPF was used to identify the broader impact of quality improvement projects and research projects conducted by the Doctor of Pharmacy (PharmD) class of 2020. The BHPF includes five domains of community impact: knowledge production, benefits to health or the health sector, benefits to future research, economic benefits, and policy and product development. Data were collected by having project preceptors complete a questionnaire and by reviewing student project posters. Data were analyzed by calculating frequencies and percentages for each domain. Results. Projects (N=73) were completed by 107 pharmacy students at health-system sites, community sites, academic sites, and other sites, and most often involved clinical care and pharmacy services (49%). Thirty-three preceptors (55%) responded to the questionnaire, and 73 project posters were reviewed. The most frequently identified impact types were knowledge production (n=43 for questionnaire, n=24 for posters) and health/health sector benefits (n=46 for questionnaire, n=8 for posters). Less frequently identified were economic benefits (total n=19), benefits to future research (total n=13), and policy and product development (total n=10). Conclusions. This study provides evidence that the impact of PharmD student quality improvement and research projects on practice sites and communities can be identified using the BHPF framework, and this impact extends beyond the usual academic outcomes of poster presentations and publications to include benefits related to improving quality of services, improving workflow, and providing opportunity for personal development. © 2023 America nAssociation of Colleges of Pharmacy.Immediate accessThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Assessment of Interprofessional Collaborative Practices and Outcomes in Adults With Diabetes and Hypertension in Primary Care: A Systematic Review and Meta-analysis

Importance: Interprofessional collaborative practice (ICP), the collaboration of health workers from different professional backgrounds with patients, families, caregivers, and communities, is central to optimal primary care. However, limited evidence exists regarding its association with patient outcomes. Objective: To examine the association of ICP with hemoglobin A1C (HbA1c), systolic blood pressure (SBP), and diastolic blood pressure (DBP) levels among adults receiving primary care. Data Sources: A literature search of English language journals (January 2013-2018; updated through March 2020) was conducted using MEDLINE; Embase; Ovid IPA; Cochrane Central Register of Controlled Trials: Issue 2 of 12, February 2018; NHS Economic Evaluation Database: Issue 2 of 4, April 2015; Clarivate Analytics WOS Science Citation Index Expanded (1990-2018); EBSCOhost CINAHL Plus With Full Text (1937-2018); Elsevier Scopus; FirstSearch OAIster; AHRQ PCMH Citations Collection; ClinicalTrials.gov; and HSRProj. Study Selection: Studies needed to evaluate the association of ICP (≥3 professions) with HbA1c, SBP, or DBP levels in adults with diabetes and/or hypertension receiving primary care. A dual review was performed for screening and selection. Data Extraction and Synthesis: This systematic review and meta-analysis followed the PRISMA guideline for data abstractions and Cochrane Collaboration recommendations for bias assessment. Two dual review teams conducted independent data extraction with consensus. Data were pooled using a random-effects model for meta-analyses and forest plots constructed to report standardized mean differences (SMDs). For high heterogeneity (I2), data were stratified by baseline level and by study design. Main Outcomes and Measures: The primary outcomes included HbA1c, SBP, and DBP levels as determined before data collection. Results: A total of 3543 titles or abstracts were screened; 170 abstracts or full texts were reviewed. Of 50 articles in the systematic review, 39 (15 randomized clinical trials [RCTs], 24 non-RCTs) were included in the meta-analyses of HbA1c (n = 34), SBP (n = 25), and DBP (n = 24). The sample size ranged from 40 to 20 524, and mean age ranged from 51 to 70 years, with 0% to 100% participants being male. Varied ICP features were reported. The SMD varied by baseline HbA1c, although all SMDs significantly favored ICP (HbA1c <8, SMD = -0.13; P < .001; HbA1c ≥8 to < 9, SMD = -0.24; P = .007; and HbA1c ≥9, SMD = -0.60; P < .001). The SMD for SBP and DBP were -0.31 (95% CI, -0.46 to -0.17); P < .001 and -0.28 (95% CI, -0.42 to -0.14); P < .001, respectively, with effect sizes not associated with baseline levels. Overall I2 was greater than 80% for all outcomes. Conclusions and Relevance: This systematic review and meta-analysis found that ICP was associated with reductions in HbA1c regardless of baseline levels as well as with reduced SBP and DBP. However, the greatest reductions were found with HbA1c levels of 9 or higher. The implementation of ICP in primary care may be associated with improvements in patient outcomes in diabetes and hypertension.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]