87 research outputs found
Hepatitis B assessment without hepatitis B virus DNA quantification: a prospective cohort study in Uganda
BACKGROUND: Chronic hepatitis B infection affects 240 million people, with the highest prevalence in Africa and Asia, and results in 700 000 deaths annually. Access to diagnostics, particularly for hepatitis B virus viral load quantification (HBV DNA), is a major barrier to treatment. We aimed to test World Health Organization guidelines for hepatitis B management in resource-limited settings. METHODS: We compared treatment allocation with and without the use of HBV DNA in a cohort in Uganda. Hepatitis B surface antigen test-positive, human immunodeficiency virus-negative, treatment-naïve adults were recruited prospectively. Following liver ultrasound and routine haematological and biochemical tests, preliminary allocations into treatment and observation groups were made. HBV DNA was performed for each participant and final treatment decisions were made and compared with preliminary allocations. RESULTS: Full assessment was completed for 100 participants; treatment was indicated in 20. Assessment without HBV DNA identified patients for treatment with a positive predictive value of 88.2% and a negative predictive value of 94% compared with assessment using HBV DNA. CONCLSUIONS: Where HBV DNA is unavailable, patients with hepatitis B can be assessed by liver ultrasound and routine laboratory tests. These findings will enable physicians in resource-limited settings to initiate treatment more readily and inform policy with regards to viral hepatitis elimination
Gpr40 Is Expressed in Enteroendocrine Cells and Mediates Free Fatty Acid Stimulation of Incretin Secretion
OBJECTIVE—The G-protein–coupled receptor Gpr40 is expressed in β-cells where it contributes to free fatty acid (FFA) enhancement of glucose-stimulated insulin secretion (1–4). However, other sites of Gpr40 expression, including the intestine, have been suggested. The transcription factor IPF1/PDX1 was recently shown to bind to an enhancer element within the 5′-flanking region of Gpr40 (5), implying that IPF1/PDX1 might regulate Gpr40 expression. Here, we addressed whether 1) Gpr40 is expressed in the intestine and 2) Ipf1/Pdx1 function is required for Gpr40 expression
Demographics and outcomes of initial phase of COVID-19 medicines delivery units across 4 UK centers during peak B1.1.529 Omicron epidemic: a service evaluation
Background
COVID-19 medicines delivery units (CMDU) were established in late December 2021 to deliver early antiviral therapy to patients classified as at risk with the aim of preventing hospitalization.
Methods
We performed a service evaluation at 4 CMDUs in England. We assessed demographics and triage outcomes of CMDU referral, uptake of antiviral therapy, and the rate of subsequent hospitalizations within 2 weeks of CMDU referral.
Results
Over a 3-week period, 4788 patients were referred and 3989 were ultimately assessed by a CMDU. Overall, 832 of the patients referred (17%) were judged eligible for treatment and 628 (13%) were ultimately prescribed an antiviral agent. The overall rate of admission within 14 days was 1%. Patients who were admitted were significantly older than those who did not require hospitalization. Of patients prescribed molnupiravir and sotrovimab, 1.8% and 3.2%, respectively, were admitted.
Conclusions
There was a high volume of referrals to CMDU service during the initial surge of the Omicron wave in the United Kingdom. A minority of patients were judged to be eligible for therapy. In a highly vaccinated population, the overall hospitalization rate was low
Physical, cognitive, and mental health impacts of COVID-19 after hospitalisation (PHOSP-COVID): a UK multicentre, prospective cohort study
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. // Methods: The 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 post-hoc 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 were independent. In clinical care, a proactive approach is needed across the acute severity spectrum, with interdisciplinary working, wide access to COVID-19 holistic clinical services, and the potential to stratify care
Molnupiravir or nirmatrelvir-ritonavir versus usual care in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial
Background: Molnupiravir and nirmatrelvir-ritonavir (Paxlovid) are oral antivirals that have been proposed as treatments for patients admitted to hospital with COVID-19.
Methods: In this randomised, controlled, open-label, adaptive platform trial, several potential treatments for patients hospitalised with COVID-19 pneumonia were evaluated. Molnupiravir and nirmatrelvir-ritonavir were assessed in separate comparisons in RECOVERY, both of which are reported here. Eligible and consenting adults could join the molnupiravir comparison, the nirmatrelvir-ritonavir comparison, or both. For each comparison, participants were randomly allocated in a 1:1 ratio to the relevant antiviral (five days of molnupiravir 800mg twice daily or nirmatrelvir-ritonavir 300mg/100mg twice daily) or to usual care without the relevant antiviral drug, using web-based unstratified randomisation with allocation concealment. The primary outcome was 28-day mortality, and secondary outcomes were time to discharge alive from hospital, and among those not on invasive ventilation at baseline, progression to invasive ventilation or death. Analysis was by intention-to-treat. Both comparisons were stopped by the investigators because of low recruitment. ISRCTN (50189673) and clinicaltrials.gov (NCT04381936).
Findings: From 24 January 2022 to 24 May 2023, 923 patients were recruited to the molnupiravir comparison (445 allocated molnupiravir and 478 allocated usual care), and from 31 March 2022 to 24 May 2023, 137 patients were recruited to the nirmatrelvir-ritonavir comparison (68 allocated nirmatrelvir-ritonavir and 69 allocated usual care). More than three-quarters of the patients in both comparisons were vaccinated and had anti-spike antibodies at randomisation, and more than two-thirds were receiving other SARS-CoV-2 antivirals (including remdesivir or sotrovimab). In the molnupiravir comparison, 74 (17%) patients allocated to molnupiravir and 79 (17%) patients allocated usual care died within 28 days (hazard ratio [HR] 0.93; 95% confidence interval [CI] 0.68-1.28; p=0.66). In the nirmatrelvir-ritonavir comparison, 13 (19%) patients allocated nirmatrelvir-ritonavir and 13 (19%) patients allocated usual care died within 28 days (HR 1.02; 95% CI 0.47-2.23; p=0.96). In neither comparison was there evidence of a significant difference in the duration of hospitalisation or the proportion of patients progressing to invasive ventilation or death.
Interpretation: In adults hospitalised with COVID-19, neither molnupiravir nor nirmatrelvir-ritonavir were associated with reductions in 28-day mortality, duration of hospital stay, or risk of progressing to invasive mechanical ventilation or death although these comparisons had limited statistical power due to low recruitment.
Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health and Care Research (Grant ref: MC_PC_19056), and Wellcome Trust (Grant Ref: 222406/Z/20/Z).
Trial registration: ClinicalTrials.gov NCT04381936 https://clinicaltrials.gov/ct2/show/NCT0438193
Physical, cognitive, and mental health impacts of COVID-19 after hospitalisation (PHOSP-COVID): a UK multicentre, prospective cohort study
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. Methods: The 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 post-hoc 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 were independent. In clinical care, a proactive approach is needed across the acute severity spectrum, with interdisciplinary working, wide access to COVID-19 holistic clinical services, and the potential to stratify care. Funding: UK Research and Innovation and National Institute for Health Research.UK Research and Innovation and National Institute for Health Research
Clinical characteristics with inflammation profiling of long COVID and association with 1-year recovery following hospitalisation in the UK: a prospective observational study
Copyright © 2022 The Author(s). Background: No effective pharmacological or non-pharmacological interventions exist for patients with long COVID. We aimed to describe recovery 1 year after hospital discharge for COVID-19, identify factors associated with patient-perceived recovery, and identify potential therapeutic targets by describing the underlying inflammatory profiles of the previously described recovery clusters at 5 months after hospital discharge. Methods: The Post-hospitalisation COVID-19 study (PHOSP-COVID) is a prospective, longitudinal cohort study recruiting adults (aged ≥18 years) discharged from hospital with COVID-19 across the UK. Recovery was assessed using patient-reported outcome measures, physical performance, and organ function at 5 months and 1 year after hospital discharge, and stratified by both patient-perceived recovery and recovery cluster. Hierarchical logistic regression modelling was performed for patient-perceived recovery at 1 year. Cluster analysis was done using the clustering large applications k-medoids approach using clinical outcomes at 5 months. Inflammatory protein profiling was analysed from plasma at the 5-month visit. This study is registered on the ISRCTN Registry, ISRCTN10980107, and recruitment is ongoing. Findings: 2320 participants discharged from hospital between March 7, 2020, and April 18, 2021, were assessed at 5 months after discharge and 807 (32·7%) participants completed both the 5-month and 1-year visits. 279 (35·6%) of these 807 patients were women and 505 (64·4%) were men, with a mean age of 58·7 (SD 12·5) years, and 224 (27·8%) had received invasive mechanical ventilation (WHO class 7–9). The proportion of patients reporting full recovery was unchanged between 5 months (501 [25·5%] of 1965) and 1 year (232 [28·9%] of 804). Factors associated with being less likely to report full recovery at 1 year were female sex (odds ratio 0·68 [95% CI 0·46–0·99]), obesity (0·50 [0·34–0·74]) and invasive mechanical ventilation (0·42 [0·23–0·76]). Cluster analysis (n=1636) corroborated the previously reported four clusters: very severe, severe, moderate with cognitive impairment, and mild, relating to the severity of physical health, mental health, and cognitive impairment at 5 months. We found increased inflammatory mediators of tissue damage and repair in both the very severe and the moderate with cognitive impairment clusters compared with the mild cluster, including IL-6 concentration, which was increased in both comparisons (n=626 participants). We found a substantial deficit in median EQ-5D-5L utility index from before COVID-19 (retrospective assessment; 0·88 [IQR 0·74–1·00]), at 5 months (0·74 [0·64–0·88]) to 1 year (0·75 [0·62–0·88]), with minimal improvements across all outcome measures at 1 year after discharge in the whole cohort and within each of the four clusters. Interpretation: The sequelae of a hospital admission with COVID-19 were substantial 1 year after discharge across a range of health domains, with the minority in our cohort feeling fully recovered. Patient-perceived health-related quality of life was reduced at 1 year compared with before hospital admission. Systematic inflammation and obesity are potential treatable traits that warrant further investigation in clinical trials. Funding: UK Research and Innovation and National Institute for Health Research.UK Research and Innovation and National Institute for Health Researc
- …