Direct and indirect effects of the COVID-19 pandemic on mortality: an individual-level population-scale analysis using linked electronic health records, Wales, United Kingdom, 2016 to 2022.

BackgroundThe COVID-19 pandemic resulted in increased mortality directly and indirectly associated with COVID-19.AimTo assess the impact of the COVID-19 pandemic on all-cause and disease-specific mortality and explore potential health inequalities associated with area-level deprivation in Wales.MethodsTwo population-based cohort studies were derived from multi-sourced, linked demographic, administrative and electronic health record data from 2016 to 2019 (n = 3,113,319) and 2020 to 2022 (n = 3,571,471).

Efficacy of 3D-TSE Sequence-based Radiosurgery in Prolonging Time to Distant Intracranial Failure: A Session-wise Analysis in a Histology-Diverse Patient Cohort.

Background: Stereotactic radiosurgery (SRS) for patients with brain metastases (BM) is associated with a risk of distant intracranial failure (DIF). This study evaluates the impact of integrating dedicated 3D-TSE sequences to MPRAGE in BM detection and DIF prolongation in a histology-agnostic patient cohort.

Methods: The study population included adults treated with SRS from February 2019 to January 2024 who underwent MPRAGE alone or dual-sequence with the addition of 3D-TSE starting from February 2020.

Biochemical challenges for testing novel anti-panic drugs in humans.

Current medications for panic disorder each carry significant limitations that indicate the need for novel anxiolytics. The high costs and low success rates of drug development demand that testing trials be efficient. Lab panicogenic challenges in humans allow for the rapid biochemical induction of panic symptoms and hence an efficient means of testing potential anti-panic drugs.

Virtual Reality-Based Simulated Hallucinations to Enhance Empathy Toward Individuals With Schizophrenia.

Individuals affected by schizophrenia often relay frustration that persons in their life are unable to understand their symptoms. We sought to examine whether a brief virtual reality (VR) experience for students in an undergraduate psychopathology course entailing simulated hallucinations could increase empathy, decrease negative affect, and positively affect attitudes toward persons with schizophrenia. After the unit on schizophrenia, 41 participants engaged in a VR experience with simulated auditory and visual hallucinations.

Factors Associated With Early Motor Function Trajectories in DMD After Glucocorticoid Initiation: Post Hoc Analysis of the FOR-DMD Trial.

Background And Objectives: Clinical trials in Duchenne muscular dystrophy (DMD) require 3-6 months of stable glucocorticoids, and the primary outcome is explored at 48-52 weeks. The factors that influence the clinical outcome assessment (COA) trajectories soon after glucocorticoid initiation are relevant for the design and analysis of clinical trials of novel drugs. We describe early COA trajectories, associated factors, and the time from glucocorticoid initiation to COA peak.

Breathing on the job: investigating predictors of air quality protective actions and information seeking among outdoor workers.

Background: Air quality issues, exacerbated by wildfire smoke and excessive ozone that is worsened by climate change, pose significant health risks to outdoor workers, who are often overlooked in regulatory protection and communication efforts. This study examined how outdoor worker demographics, risk perceptions, and efficacy beliefs predict air quality protective actions and information seeking. Additionally, it investigates the sources of information that this population relies on for understanding air quality.

The systematics of the pseudoscorpion genus Indohya (Pseudoscorpiones: Hyidae) in Australia.

The pseudoscorpion genus Indohya Beier, 1974 is known to occur in three Gondwanan fragments around the Indian Oceansouthern India, Madagascar and north-western Australiasuggesting that the genus had evolved prior to the breakup of Gondwana and was present on each landmass as they rifted apart during the Mesozoic. The Australian fauna is the most diverse, with nine species previously described from Cape Range and the Kimberley region of north-western Australia. The present study documents the genus Indohya in Australia using a combination of morphology and DNA sequence data.

Revealing The Morphology of Ink and Aerosol Jet Printed Palladium-Silver Alloys Fabricated from Metal Organic Decomposition Inks.

Palladium films hold signicance due to their remarkable affinity for hydrogen diffusion, rendering them valauble for the seperation and purification of hydrogen in membrane reactors. However, palladium is expensive, and its films can become brittle after only a few cycles of hydrogen separation. Alloying with silver has been shown to overcome the problem of palladium embrittlement.

Normal behavioral discrimination of envelope statistics in budgerigars with kainate-induced cochlear synaptopathy.

Cochlear synaptopathy is a common pathology in humans associated with aging and potentially sound overexposure. Synaptopathy is widely expected to cause "hidden hearing loss," including difficulty perceiving speech in noise, but support for this hypothesis is controversial. Here in budgerigars (Melopsittacus undulatus), we evaluated the impact of long-term cochlear synaptopathy on behavioral discrimination of Gaussian noise (GN) and low-noise noise (LNN) signals processed to have a flatter envelope.

Clustering long-term health conditions among 67728 people with multimorbidity using electronic health records in Scotland.

There is still limited understanding of how chronic conditions co-occur in patients with multimorbidity and what are the consequences for patients and the health care system. Most reported clusters of conditions have not considered the demographic characteristics of these patients during the clustering process. The study used data for all registered patients that were resident in Fife or Tayside, Scotland and aged 25 years or more on 1st January 2000 and who were followed up until 31st December 2018.

Developing a Natural History Model for Duchenne Muscular Dystrophy.

Background: The aim of this study was to pool multiple data sets to build a patient-centric, data-informed, natural history model (NHM) for Duchenne muscular dystrophy (DMD) to estimate disease trajectory across patient lifetime under current standard of care in future economic evaluations. The study was conducted as part of Project HERCULES, a multi-stakeholder collaboration to develop tools to support health technology assessments of new treatments for DMD.

Methods: Health states were informed by a review of NHMs for DMD and input from clinicians, patients and caregivers, and defined using common outcomes in clinical trials and real-world practice.

Natural history of Duchenne muscular dystrophy in the United Kingdom: A descriptive study using the Clinical Practice Research Datalink.

Background: Duchenne muscular dystrophy (DMD) is a rare, muscle-degenerative disease predominantly affecting males. Natural history models capture the full disease pathway under current care and combine with estimates of new interventions' effects to assess cost-effectiveness by health technology decision-makers. These models require mortality estimates throughout a patient's lifetime, but rare disease datasets typically contain relatively few patients with short follow-ups.

Modeling the multi-state natural history of rare diseases with heterogeneous individual patient data: A simulation study.

Multi-state survival models are used to represent the natural history of a disease, forming the basis of a health technology assessment comparing a novel treatment to current practice. Constructing such models for rare diseases is problematic, since evidence sources are typically much sparser and more heterogeneous. This simulation study investigated different one-stage and two-stage approaches to meta-analyzing individual patient data (IPD) in a multi-state survival setting when the number and size of studies being meta-analyzed are small.

Individual participant data from digital sources informed and improved precision in the evaluation of predictive biomarkers in Bayesian network meta-analysis.

Objectives: We aimed to develop a network meta-analytic model for the evaluation of treatment effectiveness within predictive biomarker subgroups, by combining evidence from individual participant data (IPD) from digital sources (in the absence of randomized controlled trials) and aggregate data (AD).

Study Design And Setting: A Bayesian framework was developed for modeling time-to-event data to evaluate predictive biomarkers. IPD were sourced from electronic health records, using a target trial emulation approach, or digitized Kaplan-Meier curves.

Transporting Comparative Effectiveness Evidence Between Countries: Considerations for Health Technology Assessments.

Internal validity is often the primary concern for health technology assessment agencies when assessing comparative effectiveness evidence. However, the increasing use of real-world data from countries other than a health technology assessment agency's target population in effectiveness research has increased concerns over the external validity, or "transportability", of this evidence, and has led to a preference for local data. Methods have been developed to enable a lack of transportability to be addressed, for example by accounting for cross-country differences in disease characteristics, but their consideration in health technology assessments is limited.

Histological Correlates of Auditory Nerve Injury from Kainic Acid in the Budgerigar (Melopsittacus undulatus).

Purpose: Loss of auditory nerve afferent synapses with cochlear hair cells, called cochlear synaptopathy, is a common pathology in humans caused by aging and noise overexposure. The perceptual consequences of synaptopathy in isolation from other cochlear pathologies are still unclear. Animal models provide an effective approach to resolve uncertainty regarding the physiological and perceptual consequences of auditory nerve loss, because neural lesions can be induced and readily quantified.

Meningeal origins and dynamics of perivascular fibroblast development on the mouse cerebral vasculature.

Perivascular fibroblasts (PVFs) are a fibroblast-like cell type that reside on large-diameter blood vessels in the adult meninges and central nervous system (CNS). PVFs contribute to fibrosis following injury but their homeostatic functions are not defined. PVFs were previously shown to be absent from most brain regions at birth and are only detected postnatally within the cerebral cortex.

Trajectories in chronic disease accrual and mortality across the lifespan in Wales, UK (2005-2019), by area deprivation profile: linked electronic health records cohort study on 965,905 individuals.

Background: Understanding and quantifying the differences in disease development in different socioeconomic groups of people across the lifespan is important for planning healthcare and preventive services. The study aimed to measure chronic disease accrual, and examine the differences in time to individual morbidities, multimorbidity, and mortality between socioeconomic groups in Wales, UK.

Methods: Population-wide electronic linked cohort study, following Welsh residents for up to 20 years (2000-2019).

Olfaction evaluation in dogs with sudden acquired retinal degeneration syndrome.

Purpose: To evaluate olfaction in dogs with sudden acquired retinal degeneration syndrome (SARDS) compared with sighted dogs and blind dogs without SARDS as control groups.

Animals Studied: Forty client-owned dogs.

Procedure: Olfactory threshold testing was performed on three groups: SARDS, sighted, and blind/non-SARDS using eugenol as the test odorant.

Prognostic Value of Neurotrophic Tyrosine Receptor Kinase Gene Fusions in Solid Tumors for Overall Survival: A Systematic Review and Meta-Analysis.

Purpose: Evidence suggests that neurotrophic tyrosine receptor kinase () gene fusions in solid tumors are predictive biomarkers for targeted inhibition across a number of adult and pediatric tumor types. However, despite robust clinical response to tyrosine receptor kinase (TRK) inhibitors, the natural history and prognostic implications of fusions in solid tumors are poorly understood. It is important to evaluate their prognostic significance on survival to provide some context to the clinical effectiveness observed in clinical trials of TRK-targeted therapies.