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Early sepsis care with the National Early Warning Score 2-guided Sepsis Hour-1 Bundle in the emergency department: hybrid type 1 effectiveness-implementation pilot stepped wedge randomised controlled trial (NEWS-1 TRIPS) protocol

Por: Lam · R. P. K. · Hung · K. K. C. · Lui · C. T. · Kwok · W. S. · Lam · W. W. T. · Lau · E. H. Y. · Sridhar · S. · Ng · P. Y. T. · Cheng · C. H. · Tsang · T. C. · Tsui · M. S. H. · Graham · C. A. · Rainer · T. H.
Introduction

Early sepsis treatment in the emergency department (ED) is crucial to improve patient survival. Despite international promulgation, the uptake of the Surviving Sepsis Campaign (SSC) Hour-1 Bundle (lactate measurement, blood culture, broad-spectrum antibiotics, 30 mL/kg crystalloid for hypotension/lactate ≥4 mmol/L and vasopressors for hypotension during/after fluid resuscitation within 1 hour of sepsis recognition) is low across healthcare settings. Delays in sepsis recognition and a lack of high-quality evidence hinder its implementation. We propose a novel sepsis care model (National Early Warning Score, NEWS-1 care), in which the SSC Hour-1 Bundle is triggered objectively by a high NEWS-2 (≥5). This study aims to determine the feasibility of a full-scale type 1 hybrid effectiveness-implementation trial on the NEWS-1 care in multiple EDs.

Methods and analysis

We will conduct a pilot type 1 hybrid trial and prospectively recruit 200 patients from 4 public EDs in Hong Kong cluster randomised in a stepped wedge design over 10 months. All study sites will start with an initial period of standard care and switch in random order at 2-month intervals to the NEWS-1 care unidirectionally. The implementation evaluation will employ mixed methods guided by the Reach, Effectiveness, Adoption, Implementation and Maintenance framework, which includes qualitative and quantitative data from focus group interviews, staff survey and clinical record reviews. We will analyse the 14 feasibility outcomes as progression criteria to a full-scale trial, including trial acceptability to patients and staff, patient and staff recruitment rates, accuracy of sepsis screening, protocol adherence, accessibility to follow-up data, safety and preliminary clinical impacts of the NEWS1 care, using descriptive statistics.

Ethics and dissemination

The institutional review boards of all study sites approved this study. This study will establish the feasibility of a full-scale hybrid trial. We will disseminate the findings through peer-reviewed publications, conference presentations and educational activities.

Trial registration number

NCT05731349.

Comparison of healthcare quality for uninsured and underinsured children through community health centres in Canada and the USA: a scoping review protocol

Por: Suleman · S. · Calleja · S. · Parmar · P. K. · Cohen · E.
Introduction

Children and youth who are uninsured or underinsured in Canada and the USA have limited options where they can receive healthcare. In both countries, community health centres (CHCs) have been established as a solution to provide quality care to children without adequate insurance, including those who are newcomers or refugees. However, little is known about how well these models deliver paediatric care. Cross-country analysis provides an important viewpoint to identify areas of success and growth. The purpose of this scoping review is to compare quality of care for uninsured and underinsured children through CHCs in the USA and Canada.

Methods

This scoping review follows the methodological guidelines from the Joanna Briggs Institute Evidence synthesis. The protocol has been registered with the Open Science Framework Registries and can be accessed online. A search will be conducted in electronic databases of peer-reviewed literature (Ovid MEDLINE ALL, CINAHL Complete via EbscoHost, Scopus; Health Business Elite via EbscoHost and Sociological Abstracts via ProQuest) as well as the grey literature. Two reviewers will review all titles and abstracts for inclusion in full-text review. Studies that meet inclusion criteria will be included in full-text review. Data will be extracted into Covidence, using the Donabedian model as a conceptual framework. Findings will be synthesised in a narrative format.

Ethics and dissemination

As this study only uses publicly available data, ethics approval is not required. Findings will be shared at national and international conferences and published in a peer-reviewed journal. In addition, findings will be prepared into a policy brief or white paper to be shared with relevant policy stakeholders to advocate for a better model of care for marginalised children and youth.

Gene expression signatures of stepwise progression of Hepatocellular Carcinoma

by Manisri Porukala, P. K. Vinod

The molecular pathogenesis of Hepatocellular Carcinoma (HCC) is a complex process progressing from premalignant stages to cancer in a stepwise manner. Mostly, HCC is detected at advanced stages, leading to high mortality rates. Hence, characterising the molecular underpinnings of HCC from normal to cancer state through precancerous state may help in early detection and improve its prognosis and treatment. In this work, we analysed the transcriptomic profile of tumour and premalignant samples from HCC or chronic liver disease patients, who had undergone either total or partial hepatectomy. The normal samples from patients with metastatic cancer/polycystic liver disease/ cholangiocarcinoma were also included. A gene co-expression network approach was applied to identify hierarchical changes: modules, pathways, and genes related to different trajectories of HCC and patient survival. Our analysis shows that the progression from premalignant conditions to tumour is accompanied by differences in the downregulation of genes associated with HNF4A activity and the immune system and upregulation of cell cycle genes, bringing about variability in patient outcomes. However, an increase in immune and cell cycle activity is observed in premalignant samples. Interestingly, co-expression modules and genes from premalignant stages are associated with survival. THBD, a classical marker for dendritic cells, is a predictor of survival at the premalignant stage. Further, genes linked to microtubules, kinetochores, and centromere are altered in both premalignant and tumour conditions and are associated with survival. Our analysis revealed a three-way molecular axis of liver function, immune pathways, and cell cycle driving HCC pathogenesis.

Trends in age of tobacco use initiation over time in Bangladesh, India and Pakistan: analysis of cross-sectional nationally representative surveys

Por: Singh · L. · Jain · P. · Kumar · C. · Singh · A. · Lal · P. · Yadav · A. · Singh · P. K. · Singh · S.
Objective

Tobacco use begins at an early age and typically leads to a long-term addiction. The age of initiation for tobacco use is not well studied in South Asia, where 22% of tobacco smokers and 81% of smokeless tobacco (SLT) users reside.

Methods

Data from the nationally representative Global Adult Tobacco Surveys in India, Bangladesh and Pakistan were analysed to examine patterns of initiation among smokers and smokeless tobacco users.

Results

Data on 94 651 individuals were analysed, of which 13 396 reported were ever daily smokers and 17 684 were ever SLT users. The proportion of individuals initiating tobacco use before the age of 15 years has increased over time. The rates of SLT initiation among those aged 15–24 years increased markedly in Bangladesh (by 7.8%) and Pakistan (by 37.7%) between 1983 and 1999–2000. Among males, the increase in SLT initiation was higher in individuals aged below 15 years compared with other age groups in India and Bangladesh. Smoking initiation among females aged below 15 years has also significantly increased in India over time. Compared with the initiation of tobacco smoking before the age of 15 years, a greater increase in the proportion of SLT users was observed in urban areas.

Conclusion

Our findings indicate that the proportion of youth initiating tobacco (both smoking and smokeless) before the age of 15 years has increased over time in all three countries. Moreover, variations in age at initiation for different types of tobacco products across countries, and by rurality, were noticeable. Younger youths (aged up to 15 years) should therefore be a priority population for tobacco control interventions. Strategies such as raising the legal age of tobacco sale and use to 21 years, and, other measures under WHO Framework Convention on Tobacco Control (FCTC), may prevent underage use and avert lifelong addiction to tobacco products.

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