Effect of COVID-19 with or without acute kidney injury on inpatient mortality in England: a national observational study using administrative data

Objectives
To evaluate hospital outcomes and their predictors during the pandemic for patients with and without COVID-19, stratified by the presence of acute kidney injury (AKI).

Design
Retrospective observation study using the Hospital Episodes Statistics database for England.

Participants
2 385 337 unique hospital admissions of adult patients from March 2020 to March 2021 in England.

Main outcome measures
COVID-19 cases were identified by the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) code of U07.1. Patients with suspected COVID-19 (U07.2 code) and patients with end-stage kidney disease on chronic dialysis (N18.6 and Z99.2) were excluded. AKI cases were identified by the ICD10 code. Patients were categorised into four groups based on COVID-19 and AKI diagnoses: Group 1—neither; Group 2—COVID-19 only; Group 3—AKI only; Group 4—both. A multivariable logistic regression model was created with in-hospital mortality as the outcome, including diagnostic groups, demographics, admission methods, comorbidity severity, deprivation index and intensive therapy unit (ITU) admission.

Results
Among 2 385 337 admissions involving 663 628 patients, 856 544 had AKI (N17 codes) and 1 528 793 did not. Among patients without AKI, there were 1,008,774 admissions among 133,988 individuals without COVID-19 (Group 1) and 520,019 admissions among 256,037 individuals with COVID-19 (Group 2). Among patients with AKI, there were 630,342 admissions among 218,270 individuals without COVID-19 (Group 3) and 226,202 admissions among 55,333 individuals with COVID-19 (Group 4). Patients in group 4 were older (75.4 ± 13.8 years) and had greater length of stay (17.1 ± 17 days) than all other groups. They also had and had a greater proportion of males, ethnic minorities and comorbidities than other groups. Mortality was highest in Group 4 (28.7%) and lowest in Group 1 (1.1%). The increased risk of death persisted after controlling for multiple baseline factors (OR for death vs Group 1: Group 4—22.28, Group 2—9.67, Group 3—6.44). ITU admission was least required in Group 1 (1.2%) and most in Group 4 (10.9%), with mortality at 4.8% versus 47.8%, respectively.

Conclusions
Patients with COVID-19 and AKI have a high risk of mortality and should be recognised early and provided with optimal support. Planning for future pandemics should ensure adequate critical care and acute dialysis capacity.

Trial registration number
NCT04579562.

Leggi
Marzo 2025

Prioritising community-defined interventions to address the health and well-being impact of the COVID-19 pandemic on racially minoritised communities in East London: results from an adapted James Lind Alliance priority setting partnership

Objectives
Racially minoritised communities (RMCs) were disproportionately affected by COVID-19, experiencing among the highest mortality rates of the UK’s pandemic. We sought to understand the priorities for action to address the impact of the COVID-19 pandemic on the health and well-being of RMCs in the ethnically diverse and socioeconomically unequal area of East London, located in the northeastern part of London, England.

Design
Prospective surveys and a consensus meeting following the established James Lind Alliance priority setting partnership (PSP) methodology, adapted for a specific geographic location and ethnic groups.

Setting
Conducted in East London between 2021 and 2023.

Participants
Participants were individuals aged ≥18 years living and/or working in East London. Communities represented included Black African, Black Caribbean, Somali, South Asian and Bangladeshi.

Outcome measure
People were asked to submit suggestions for the priorities for action to address the impact of the COVID-19 pandemic. Return responses were reviewed and prioritised in a final workshop.

Results
816 suggestions were gathered from 187 responses to the initial survey. These were summarised into a longlist of 40 for the second survey, from which 243 respondents identified a shortlist of 26 priorities for discussion in a consensus meeting. The final top 10 priorities cover community-based support and spaces spanning education, social support, mental health and housing.

Conclusion
A systematic methodology was used to identify the priorities of RMCs in East London in the context of recovery from the COVID-19 pandemic. The breadth of the top 10 reflects how profound the effects of the pandemic have been among these communities. It also demonstrates the capacity of a PSP to articulate diverse community-driven priorities for a topic that was wider than healthcare. The findings could have applications in other disease areas that disproportionately affect RMCs.

Leggi
Marzo 2025

Access and use of general and mental health services before and during the COVID-19 pandemic: a systematic review and meta-analysis

Objectives
To quantify access to health services during the COVID-19 pandemic and measure the change in use between the prepandemic and the pandemic periods in a population with assessment of psychological distress or diagnosis of mental disorders.

Data sources
We developed and piloted a search syntax and adapted it to enter the following databases from 1 January 2020 to 31 March 2023: PubMed/MEDLINE, PsycINFO, Web of Science, Epistemonikos and the WHO International Clinical Trials Registry Platform. We reran the searches from the end of the original search to 3 December 2024.

Design
We systematically screened titles, abstracts and full texts of retrieved records.

Eligibility criteria
We included observational studies on any populations and regions, covering health services such as doctor visits, hospital admissions, diagnostic examinations, pharmaceutical therapies and mental health (MH) services. Only studies using validated scales to assess psychological distress or mental disorders as defined in the Diagnostic and Statistical Manual of Mental Disorders were included.

Data extraction and synthesis
We extracted data using a purposefully designed form and evaluated the studies’ quality with the Newcastle-Ottawa Scale. We measured the incidence rate (IR) of access to health services and the IR ratio (IRR) between the prepandemic and the pandemic periods. We calculated contacts days and catchment areas in the different periods. We used the random effects DerSimonian-Laird inverse-variance model and calculated heterogeneity with statistics I² and ². We computed pooled IR and pooled IRR and tested the hypothesis of no variation (IRR=1).

Results
We retrieved 10 014 records and examined the full text of 580 articles. We included 136 primary studies of which 44 were meta-analysed. The IR of access to services during the pandemic was 2.59 contact months per 10 000 inhabitants (IR=2.592; 95% CI: 1.301 to 5.164). We observed a reduction of 28.5% in the use of services with negligible differences by age group and type of services (IRR=0.715; 95% CI: 0.651 to 0.785). We observed significant differences in effect sizes across studies (2=5.44; p

Leggi
Marzo 2025

Lesson learnt from the COVID-19 pandemic: a qualitative inquiry into patient and family experiences in Pakistan

Objectives
This study aims to explore the perceptions of patients affected by COVID-19 and their families regarding the challenges faced, coping strategies used and lessons learnt in Pakistan.

Design
A qualitative exploratory descriptive approach was used to explore the real-time experiences of the participants.

Setting
The study was carried out in a tertiary care hospital in Karachi, Pakistan.

Participants
Purposive and snowball sampling methods were used to enrol 22 dyads of adult patients diagnosed with COVID-19 and their respective family members (FMs) (spouse, children, siblings or any other FM sharing a residence in Karachi, Pakistan, with the patient before quarantine). The 44 participants, with 23 females and 21 males, had an average age of 43.2 years.

Results
We identified five key themes: practising a healthy diet and physical activity to boost immunity; developing workplace policies for job security, safety and mental well-being; encouraging digitalisation of health through teleconsultation and virtual learning; using technology and artificial intelligence to transform healthcare delivery systems; and empowering resilience and community unity to promote mental well-being.

Conclusion
The study summarises the opinions of people directly affected by COVID-19 and the stakeholders of systemic challenges. The findings of the study can guide further strengthening of the healthcare system and improvements of organisational policies to facilitate better preparation of marginalised communities for future pandemics.

Leggi
Marzo 2025

Representative national survey on drug use during the COVID-19 stay-at-home order in the USA

Objectives
This study explores the drug use behaviour in the US general population in the early days of the COVID-19 pandemic with a focus on the relationship between sociopsychological factors, mobility restrictions from March to June 2020 and mental health conditions.

Design
A retrospective anonymous online survey representing a cross-section of the US population in 2020.

Setting
A qualified panel of 500 000 Qualtrics participants stratified by gender, race, age and geographical region to represent the US population.

Participants
3340 participants voluntarily consented to respond.

Measures
Outcome measure for illicit and non-medical use of prescription drugs based on the National Institute on Drug Abuse-Modified Alcohol, Smoking and Substance Involvement Screening Test Level-2 Substance Use for Adult Questionnaire and predictor measures include self-reports of mobility behaviours, demographics and mental states using psychometrically validated scales.

Results
2 tests showed that those who stayed home reported higher odds (p

Leggi
Marzo 2025

Theory development of under what circumstances and what works for promoting disaster preparedness among long-term care facility (LTCF) stakeholders: protocol for realist review

Introduction
The incidence of severe natural disasters has been increasing worldwide. The residents of long-term care facilities (LTCFs) are particularly vulnerable to such events. Therefore, promoting disaster preparedness among LTCF stakeholders is urgent. However, the optimal preparedness process remains unclear. To close this gap, we use a realist review (RR) to promote an understanding of under what circumstances and what works for promoting the disaster preparedness among LTCF stakeholders and develop theories for the process.

Methods and analysis
RR will be guided by the Realist and Meta-Narrative Evidence Synthesis: Evolving Standard. The following five steps will be employed: (1) literature review and search for evidence, (2) study selection, (3) data extraction, (4) data synthesis and (5) development of the initial programme theory (IPT). Evidence will be searched using MEDLINE, CINAHL, PsycINFO, Web of Science, Cochrane Library, Scopus and ICHUSHI (a Japanese database). Grey literature and citation tracking will also be used. Documents of any design or publication type will be included. The study selection, coding and synthesis will be conducted independently by two authors. An IPT will be developed in the Context–Mechanism–Outcome configuration to understand how to promote disaster preparedness among LTCF stakeholders. The developed IPT will be verified by experts or stakeholders to enhance its validity.

Ethics and dissemination
Ethical approval will not be required because this is a review of published literature. The results will be disseminated at scientific conferences and peer-reviewed journals. The developed IPT will be used in subsequent research and iteratively tested or refined to better explain under what circumstances and what works for promoting disaster preparedness among LTCF stakeholders.

Registration details
This protocol has been registered at the Open Science Framework https://doi.org/10.17605/OSF.IO/J4TU6.

Leggi
Marzo 2025

Assessing the impact of COmorbidities and Sociodemographic factors on Multiorgan Injury following COVID-19: rationale and protocol design of COSMIC, a UK multicentre observational study of COVID-negative controls

Introduction
SARS-CoV-2 disease (COVID-19) has had an enormous health and economic impact globally. Although primarily a respiratory illness, multi-organ involvement is common in COVID-19, with evidence of vascular-mediated damage in the heart, liver, kidneys and brain in a substantial proportion of patients following moderate-to-severe infection. The pathophysiology and long-term clinical implications of multi-organ injury remain to be fully elucidated. Age, gender, ethnicity, frailty and deprivation are key determinants of infection severity, and both morbidity and mortality appear higher in patients with underlying comorbidities such as ischaemic heart disease, hypertension and diabetes. Our aim is to gain mechanistic insights into the pathophysiology of multiorgan dysfunction in people with COVID-19 and maximise the impact of national COVID-19 studies with a comparison group of COVID-negative controls.

Methods and analysis
COmorbidities and Sociodemographic factors on Multiorgan Injury following COVID-19 (COSMIC) is a prospective, multicentre UK study which will recruit 200 subjects without clinical evidence of prior COVID-19 and perform extensive phenotyping with multiorgan imaging, biobank serum storage, functional assessment and patient reported outcome measures, providing a robust control population to facilitate current work and serve as an invaluable bioresource for future observational studies.

Ethics and dissemination
Approved by the National Research Ethics Service Committee East Midlands (REC reference 19/EM/0295). Results will be disseminated via peer-reviewed journals and scientific meetings.

Trial registration number
COSMIC is registered as an extension of C-MORE (Capturing Multi-ORgan Effects of COVID-19) on ClinicalTrials.gov (NCT04510025).

Leggi
Marzo 2025

Identifying colorectal cancer-specific vulnerabilities in the Wnt-driven long non-coding transcriptome

Background
Aberrant Wnt pathway activation is a key driver of colorectal cancer (CRC) and is essential to sustain tumour growth and progression. Although the downstream protein-coding target genes of the Wnt cascade are well known, the long non-coding transcriptome has not yet been fully resolved.

Objective
In this study, we aim to comprehensively reveal the Wnt-regulated long non-coding transcriptome and exploit essential molecules as novel therapeutic targets.

Design
We used global run-on sequencing to define β-catenin-regulated long non-coding RNAs (lncRNAs) in CRC. CRISPRi dropout screens were subsequently used to establish the functional relevance of a subset of these lncRNAs for long-term expansion of CRC.

Results
We uncovered that LINC02418 is essential for cancer cell clonogenic outgrowth. Mechanistically, LINC02418 regulates MYC expression levels to promote CRC stem cell functionality and prevent terminal differentiation. Furthermore, we developed effective small interfering RNA (siRNA)-based therapeutics to target LINC02418 RNA in vivo.

Conclusion
We propose that cancer-specific Wnt-regulated lncRNAs provide novel therapeutic opportunities to interfere with the Wnt pathway, which has so far defied effective pharmacological inhibition.

Leggi
Marzo 2025

Long-term safety and efficacy of anti-GM-CSF otilimab in patients with rheumatoid arthritis: long-term extension of three phase 3 randomised trials (contRAst X)

Objectives
To investigate the long-term safety and efficacy of otilimab, an antigranulocyte-macrophage colony-stimulating factor monoclonal antibody, for patients with rheumatoid arthritis (RA).

Methods
ContRAst X (NCT04333147) was a phase 3, multicentre, long-term extension trial. Patients with RA aged ≥18 years who completed a qualifying contRAst trial (contRAst 1–3) and who the investigator thought might benefit from long-term otilimab treatment were eligible to enter contRAst X. Patients who received otilimab (90 mg/150 mg) in their qualifying trial maintained the same dose; patients who received tofacitinib or sarilumab were rerandomised 1:1 to either otilimab dose. Patients could continue background conventional synthetic disease-modifying antirheumatic drugs. The primary objective was long-term safety (up to 4 years).

Results
Of the 2916 patients who entered contRAst X, 2915 received otilimab (exposure range: 7–896 days); the majority were withdrawn due to early trial termination. For otilimab 90 mg and 150 mg, the incidence of adverse events (AEs) was 62% (n=902/1456) and 64% (n=931/1459), the incidence of AEs of special interest was 8% (n=120/1456) and 7% (n=95/1459) and the incidence of serious AEs was 8% (n=123/1456) and 8% (n=114/1459), respectively. There were no instances of pulmonary alveolar proteinosis (PAP), active tuberculosis (TB), TB reactivation or serious hypersensitivity reactions. The proportions of clinical disease activity index low disease activity responders remained relatively stable throughout, with no apparent reduction following the switch from tofacitinib/sarilumab to otilimab.

Conclusion
No new safety signals or instances of PAP were associated with long-term (≤2.5 years) treatment with otilimab.

Trial registration number
ClinicalTrials.gov: NCT04333147.

Leggi
Marzo 2025

Nurse retention in peri- and post-COVID-19 work environments: a scoping review of factors, strategies and interventions

Objectives
The COVID-19 pandemic highlighted the deterioration of nurses’ working conditions and a growing global nursing shortage. Little is known about the factors, strategies and interventions that could improve nurse retention in the peri- and post-COVID-19 period. An improved understanding of strategies that support and retain nurses will provide a foundation for developing informed approaches to sustaining the nursing workforce. The aim of this scoping review is to investigate and describe the (1) factors associated with nurse retention, (2) strategies to support nurse retention and (3) interventions that have been tested to support nurse retention, during and after the COVID-19 pandemic.

Design
Scoping review.

Data sources
This scoping review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews. MEDLINE, Embase, CINAHL and Scopus databases were searched on 17 April 2024. The search was limited to a publication date of ‘2019 to present’.

Eligibility criteria
Qualitative, quantitative, mixed-methods and grey literature studies of nurses (Registered Nurse (RN), Licenced Practical Nurse (LPN), Registered Practical Nurse (RPN), Publlic Health Nurse (PHN), including factors, strategies and/or interventions to support nurse retention in the peri- and post-COVID-19 period in English (or translated into English), were included. Systematic reviews, scoping reviews and meta-syntheses were excluded, but their reference lists were hand-screened for suitable studies.

Data extraction and synthesis
The following data items were extracted: title, journal, authors, year of publication, country of publication, setting, population (n=), factors that mitigate intent to leave (or other retention measure), strategies to address nurse retention, interventions that address nurse retention, tools that measure retention/turnover intention, retention rates and/or scores. Data were evaluated for quality and synthesised qualitatively to map the current available evidence.

Results
Our search identified 130 studies for inclusion in the analysis. The majority measured some aspect of nurse retention. A number of factors were identified as impacting nurse retention including nurse demographics, safe staffing and work environments, psychological well-being and COVID-19-specific impacts. Nurse retention strategies included ensuring safe flexible staffing and quality work environments, enhancing organisational mental health and wellness supports, improved leadership and communication, more professional development and mentorship opportunities, and better compensation and incentives. Only nine interventions that address nurse retention were identified.

Conclusions
Given the importance of nurse retention for a variety of key outcomes, it is imperative that nursing leadership, healthcare organisations and governments work to develop and test interventions that address nurse retention.

Leggi
Marzo 2025

Long-Term Cognitive Decline After Subarachnoid Hemorrhage: Pathophysiology, Management, and Future Directions

Stroke, Ahead of Print. Subarachnoid hemorrhage is a critical neurological condition accounting for about 5% of all strokes, and survivors experience long-term cognitive deterioration and increased risk of dementia. The major processes involved in such decline include early brain injury, delayed cerebral ischemia, neuroinflammation, superficial siderosis, and hydrocephalus. These have emerging treatments that offer promise for the mitigation of effects such as inflammation, iron chelation, and microvascular dysfunction. Genetic predispositions have been associated with post-subarachnoid hemorrhage cognitive outcomes and emphasize a role for personalized care strategies. Management techniques reviewed include long-term cognitive health, such as endovascular coiling and surgical clipping. Other rehabilitation strategies that enhance cognitive reserve and pharmacological interventions are discussed about improving the quality of life in survivors. The review highlights the need for further research into targeted therapies, genetic markers, and innovative approaches to prevent cognitive decline, ultimately aiming to optimize long-term outcomes for individuals affected by subarachnoid hemorrhage.

Leggi
Marzo 2025