Background The impact of COVID-19 on physical and mental health and employment after hospitalisation with acute disease is not well understood. The aim of this study was to determine the effects of COVID-19-related hospitalisation on health and employment, to identify factors associated with recovery, and to describe recovery phenotypes. MethodsThe Post-hospitalisation COVID-19 study (PHOSP-COVID) is a multicentre, long-term follow-up study of adults (aged ≥18 years) discharged from hospital in the UK with a clinical diagnosis of COVID-19, involving an assessment between 2 and 7 months after discharge, including detailed recording of symptoms, and physiological and biochemical testing. Multivariable logistic regression was done for the primary outcome of patient-perceived recovery, with age, sex, ethnicity, body-mass index, comorbidities, and severity of acute illness as covariates. A posthoc cluster analysis of outcomes for breathlessness, fatigue, mental health, cognitive impairment, and physical performance was done using the clustering large applications k-medoids approach. The study is registered on the ISRCTN Registry (ISRCTN10980107). Findings We report findings for 1077 patients discharged from hospital between March 5 and Nov 30, 2020, who underwent assessment at a median of 5•9 months (IQR 4•9-6•5) after discharge. Participants had a mean age of 58 years (SD 13); 384 (36%) were female, 710 (69%) were of white ethnicity, 288 (27%) had received mechanical ventilation, and 540 (50%) had at least two comorbidities. At follow-up, only 239 (29%) of 830 participants felt fully recovered, 158 (20%) of 806 had a new disability (assessed by the Washington Group Short Set on Functioning), and 124 (19%) of 641 experienced a health-related change in occupation. Factors associated with not recovering were female sex, middle age (40-59 years), two or more comorbidities, and more severe acute illness. The magnitude of the persistent health burden was substantial but only weakly associated with the severity of acute illness. Four clusters were identified with different severities of mental and physical health impairment (n=767): very severe (131 patients, 17%), severe (159, 21%), moderate along with cognitive impairment (127, 17%), and mild (350, 46%). Of the outcomes used in the cluster analysis, all were closely related except for cognitive impairment. Three (3%) of 113 patients in the very severe cluster, nine (7%) of 129 in the severe cluster, 36 (36%) of 99 in the moderate cluster, and 114 (43%) of 267 in the mild cluster reported feeling fully recovered. Persistently elevated serum C-reactive protein was positively associated with cluster severity.Interpretation We identified factors related to not recovering after hospital admission with COVID-19 at 6 months after discharge (eg, female sex, middle age, two or more comorbidities, and more acute severe illness), and four different recovery phenotypes. The severity of physical and mental health impairments were closely related, whereas cognitive health impairments w...
IntroductionThe impact of the SARS-CoV-2 pandemic, and lockdown measures, on acute exacerbations of COPD (AECOPD) is unknown. We aimed to evaluate the change in AECOPD treatment frequency during the first 6 weeks of lockdown in the UK compared with 2019 and assess changes in self-reported behaviour and well-being.MethodsIn this observational study in Leicestershire, UK, patients with COPD under a secondary care clinic were recruited. Exacerbation frequency in the first 6 weeks of COVID lockdown was compared with the same period in 2019 using electronic health records. A telephone survey was used to assess changes in anxiety, inhaler adherence, physical activity, and behaviour during the pre-lockdown and lockdown periods compared to normal.Results160 participants were recruited (mean [sd] age 67.3 [8.1] years, 88 [55%] male, FEV1 34.3 [13] % predicted). 140 [88%] reported at least one AECOPD in the previous year. Significantly more community treated exacerbations were observed in 2020 compared with 2019 (126 versus 99, p=0.026). The increase was a result of multiple courses of treatment, with a similar proportion of patients receiving at least one course (34.4% versus 33.8%).During “lockdown” participants reported significantly increased anxiety, adherence to their preventative inhalers, and good adherence to shielding advice (all p<0.001). A significant reduction in self-reported physical activity and visitors was reported (both p<0.001).DiscussionTreatment for AECOPD events increased during the first 6 weeks of the SARS-CoV-2 pandemic in the UK compared to 2019. This was associated with increased symptoms of anxiety and significant behavioural change.
Karyopherin beta 1 (Kpnb1) is a nuclear transport receptor that imports cargoes into the nucleus. Recently, elevated Kpnb1 expression was found in certain cancers and Kpnb1 silencing with siRNA was shown to induce cancer cell death. This study aimed to identify novel small molecule inhibitors of Kpnb1, and determine their anticancer activity. An in silico screen identified molecules that potentially bind Kpnb1 and Inhibitor of Nuclear Import-43, INI-43
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