Calibrating Observational Health Record Data Against a Randomized Trial.

Importance: The conditions required for health record data sources to accurately assess treatment effectiveness remain unclear. Emulation of randomized clinical trials (RCTs) with health record data and subsequent calibration of the results can help elucidate this.

Objective: To pilot an emulation of the KEYNOTE-189 RCT using a commercially available electronic health record (EHR) data source.

Effect of volatile anaesthetic agents on intracranial pressure, cerebrovascular flow and autoregulation: a protocol for a systematic review and meta-analysis.

Introduction: The use of volatile anaesthetic agents for the sedation of patients requiring critical care treatment offers several theoretical advantages over intravenous sedation, which may be of benefit in neurocritical care. However, there are concerns that they may increase intracranial pressure. The objective of this systematic review is to assess whether, and if so, to what extent volatile anaesthetic agents affect intracranial pressure, cerebral blood flow (CBF), cerebral oximetry and cerebrovascular autoregulation.

Histone deacetylase-3 regulates the expression of the amyloid precursor protein and its inhibition promotes neuroregenerative pathways in Alzheimer's disease models.

HDAC3 inhibition has been shown to improve memory and reduce amyloid-β (Aβ) in Alzheimer's disease (AD) models, but the underlying mechanisms are unclear. We investigated the molecular effects of HDAC3 inhibition on AD pathology, using in vitro and ex vivo models of AD, based on our finding that HDAC3 expression is increased in AD brains. For this purpose, N2a mouse neuroblastoma cells as well as organotypic brain cultures (OBCSs) of 5XFAD and wild-type mice were incubated with various concentrations of the HDAC3 selective inhibitor RGFP966 (0.

Capturing Data on Antimicrobial Resistance Patterns and Trends in Use in Regions of Asia (CAPTURA).

Background: In 2015, the UK government established the Fleming Fund with the aim to address critical gaps in surveillance of antimicrobial resistance (AMR) in low- and middle-income countries in Asia and Africa. Among a large portfolio of grants, the Capturing Data on Antimicrobial Resistance Patterns and Trends in Use in Regions of Asia (CAPTURA) project was awarded with the specific objective of expanding the volume of historical data on AMR, consumption (AMC), and use (AMU) in the human healthcare sector across 12 countries in South and Southeast Asia.

Methods: Starting in early 2019, the CAPTURA consortium began working with local governments and >100 relevant data-holding facilities across the region to identify, assess for quality, prioritize, and subsequently retrieve data on AMR, AMC, and AMU.

Methodological Approach to Identify and Expand the Volume of Antimicrobial Resistance (AMR) Data in the Human Health Sector in Low- and Middle-Income Countries in Asia: Implications for Local and Regional AMR Surveillance Systems Strengthening.

Antimicrobial resistance (AMR) is a multifaceted global health problem disproportionately affecting low- and middle-income countries (LMICs). The Capturing data on Antimicrobial resistance Patterns and Trends in Use in Regions of Asia (CAPTURA) project was tasked to expand the volume of AMR and antimicrobial use data in Asia. The CAPTURA project used 2 data-collection streams: facility data and project metadata.

Point-of-care ultrasonography-An essential skill for medical graduates?

The recent proliferation of point-of-care ultrasonography (POCUS) in the clinical practice of many medical specialties has exposed persistent barriers to education, training and standardisation. Specialist training curriculums are already overwhelming, having grossly insufficient time available for the specialist trainees and for the small number of available trainers alike to incorporate POCUS into postgraduate education. The logical solution to overcome these barriers could be to incorporate basic POCUS education and training into the undergraduate university curriculums, introducing longitudinal integration with other relevant medical sciences.

Pilot study of lung cancer screening for survivors of Hodgkin lymphoma.

Hodgkin lymphoma (HL) treatment increases the risk of lung cancer. Most HL survivors are not eligible for lung cancer screening (LCS) programs developed for the general population, and the utility of these programs has not been tested in HL survivors. We ran a LCS pilot in HL survivors to describe screening uptake, participant characteristics, impact of a decision aid and screen findings.

Optical control of ultrafast structural dynamics in a fluorescent protein.

The photoisomerization reaction of a fluorescent protein chromophore occurs on the ultrafast timescale. The structural dynamics that result from femtosecond optical excitation have contributions from vibrational and electronic processes and from reaction dynamics that involve the crossing through a conical intersection. The creation and progression of the ultrafast structural dynamics strongly depends on optical and molecular parameters.

Renal safety of critical care sedation with sevoflurane: a systematic review and meta-analysis.

Volatile anesthetic agents are increasingly widely used for critical care sedation. There are concerns that sevoflurane presents a risk of renal injury when used in this role. RCTs comparing the use of critical care sevoflurane sedation with any control in humans were systematically identified using MEDLINE, Cochrane CENTRAL, web of Science, and CINAHL (until May 2022), if they presented comparative data on renal function or serum inorganic fluoride levels.

Cardiovascular Burden of Narcolepsy Disease (CV-BOND): a real-world evidence study.

Study Objectives: Narcolepsy is associated with cardiovascular risk factors; however, the risk of new-onset cardiovascular events in this population is unknown. This real-world study evaluated the excess risk of new-onset cardiovascular events in U.S.

Rapid Genomic Characterization and Global Surveillance of Klebsiella Using Pathogenwatch.

Background: Klebsiella species, including the notable pathogen K. pneumoniae, are increasingly associated with antimicrobial resistance (AMR). Genome-based surveillance can inform interventions aimed at controlling AMR.

Assignment of epidemiological lineages in an emerging pandemic using the pangolin tool.

The response of the global virus genomics community to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been unprecedented, with significant advances made towards the 'real-time' generation and sharing of SARS-CoV-2 genomic data. The rapid growth in virus genome data production has necessitated the development of new analytical methods that can deal with orders of magnitude of more genomes than previously available. Here, we present and describe Phylogenetic Assignment of Named Global Outbreak Lineages (pangolin), a computational tool that has been developed to assign the most likely lineage to a given SARS-CoV-2 genome sequence according to the Pango dynamic lineage nomenclature scheme.

CLIMB-COVID: continuous integration supporting decentralised sequencing for SARS-CoV-2 genomic surveillance.

In response to the ongoing SARS-CoV-2 pandemic in the UK, the COVID-19 Genomics UK (COG-UK) consortium was formed to rapidly sequence SARS-CoV-2 genomes as part of a national-scale genomic surveillance strategy. The network consists of universities, academic institutes, regional sequencing centres and the four UK Public Health Agencies. We describe the development and deployment of CLIMB-COVID, an encompassing digital infrastructure to address the challenge of collecting and integrating both genomic sequencing data and sample-associated metadata produced across the COG-UK network.

A Proposal for Decentralized, Global, Verifiable Health Care Credential Standards Grounded in Pharmaceutical Authorized Trading Partners.

The twin forces of privacy law and data breaches have fundamentally challenged how we collect, store, and share sensitive information. Within this landscape, healthcare information is sacrosanct - and intimately tied to identity and data ownership. Building on prior work with UCLA Health, Genentech (a member of the Roche Group), Sanofi, Amgen, Biogen, and others, we offer this opinion piece to promote the development of a standard for decentralized Verifiable Credentials (VCs).

Ecosystem type drives tea litter decomposition and associated prokaryotic microbiome communities in freshwater and coastal wetlands at a continental scale.

Wetland ecosystems are critical to the regulation of the global carbon cycle, and there is a high demand for data to improve carbon sequestration and emission models and predictions. Decomposition of plant litter is an important component of ecosystem carbon cycling, yet a lack of knowledge on decay rates in wetlands is an impediment to predicting carbon preservation. Here, we aim to fill this knowledge gap by quantifying the decomposition of standardised green and rooibos tea litter over one year within freshwater and coastal wetland soils across four climates in Australia.

In-vitro 3D Analysis of Sacroiliac Joint Kinematics: Primary and Coupled Motions.

Study Design: An in-vitro biomechanical study of human cadaver sacroiliac joints.

Objective: Our study aimed to develop a more comprehensive understanding of the native motion of the SIJ within the context of spinal kinematics and spinal implant evaluation.

Summary Of Background Data: Increasing attention has been given to the sacroiliac joint (SIJ) as a source of low back pain, despite its limited range of motion.

Evaluation of Decentralized Verifiable Credentials to Authenticate Authorized Trading Partners and Verify Drug Provenance.

Summary: In 2013, the Drug Supply Chain Security Act (DSCSA) was signed into law to address the growing threat of counterfeit drugs and to ensure prescription drugs remain safe and effective for patients. As part of this law, US pharmaceutical supply chain stakeholders are required to confirm the authorized status of trading partners for transactions and information disclosures, even when there is no prior business relationship. While larger Authorized Trading Partners (ATPs) have connectivity solutions in place, newer and smaller ATPs have not traditionally participated, including tens of thousands of dispensers.

Globetrotting strangles: the unbridled national and international transmission of between horses.

The equine disease strangles, which is characterized by the formation of abscesses in the lymph nodes of the head and neck, is one of the most frequently diagnosed infectious diseases of horses around the world. The causal agent, subspecies , establishes a persistent infection in approximately 10 % of animals that recover from the acute disease. Such 'carrier' animals appear healthy and are rarely identified during routine veterinary examinations pre-purchase or transit, but can transmit to naïve animals initiating new episodes of disease.

Analysis of lung cancer risk model (PLCO and LLP) performance in a community-based lung cancer screening programme.

Introduction: Low-dose CT (LDCT) screening of high-risk smokers reduces lung cancer (LC) specific mortality. Determining screening eligibility using individualised risk may improve screening effectiveness and reduce harm. Here, we compare the performance of two risk prediction models (PLCO and Liverpool Lung Project model (LLP)) and National Lung Screening Trial (NLST) eligibility criteria in a community-based screening programme.

Spirometry performed as part of the Manchester community-based lung cancer screening programme detects a high prevalence of airflow obstruction in individuals without a prior diagnosis of COPD.

Background: COPD is a major cause of morbidity and mortality in populations eligible for lung cancer screening. We investigated the role of spirometry in a community-based lung cancer screening programme.

Methods: Ever smokers, age 55-74, resident in three deprived areas of Manchester were invited to a 'Lung Health Check' (LHC) based in convenient community locations.

Visualizing variation within Global Pneumococcal Sequence Clusters (GPSCs) and country population snapshots to contextualize pneumococcal isolates.

Knowledge of pneumococcal lineages, their geographic distribution and antibiotic resistance patterns, can give insights into global pneumococcal disease. We provide interactive bioinformatic outputs to explore such topics, aiming to increase dissemination of genomic insights to the wider community, without the need for specialist training. We prepared 12 country-specific phylogenetic snapshots, and international phylogenetic snapshots of 73 common Global Pneumococcal Sequence Clusters (GPSCs) previously defined using PopPUNK, and present them in Microreact.

Relative efficacy and safety of inhaled corticosteroids in patients with asthma: Systematic review and network meta-analysis.

Background: Inhaled corticosteroids (ICSs) are recommended as first-line controller medications for persistent asthma. However, guidelines on the initial ICS doses, step-up and step-down algorithms, and when to switch to combination therapy vary.

Objective: To understand the ideal starting doses of ICS therapy based on current evidence and to systematically compare low, moderate, and high starting doses of ICSs as monotherapy and in combination with long-acting β-agonists with respect to efficacy and safety.

The Last Mile: DSCSA Solution Through Blockchain Technology: Drug Tracking, Tracing, and Verification at the Last Mile of the Pharmaceutical Supply Chain with BRUINchain.

Purpose: As part of the FDA's DSCSA Pilot Project Program, UCLA and its solution partner, LedgerDomain (collectively referred to as the team hereafter), focused on building a complete, working blockchain-based system, BRUINchain, which would meet all the key objectives of the Drug Supply Chain Security Act (DSCSA) for a dispenser operating solely on commercial off-the-shelf (COTS) technology.

Methods: The BRUINchain system requirements include scanning the drug package for a correctly formatted 2D barcode, flagging expired products, verifying the product with the manufacturer, and quarantining suspect and illegitimate products at the last mile: pharmacist to patient, the most complex area of the drug supply chain.The authors demonstrate a successful implementation where product-tracing notifications are sent automatically to key stakeholders, resulting in enhanced timeliness and reduction in paperwork burden.