Utilising Health Technology Assessment to Develop Managed Access Protocols to Facilitate Drug Reimbursement in Ireland.

The Health Service Executive, responsible for operating the Irish health service, has introduced health technology management (HTM) initiatives to manage expenditure on medicines. One such approach is managed access protocols (MAPs) to support access to high-cost medicines, while providing oversight, governance and budgetary certainty to the payer. Herein we describe the development and operation of MAPs, using case studies of liraglutide (Saxenda), dupilumab (Dupixent) and calcitonin gene-related peptide monoclonal antibodies.

The ACS-NSQIP Analysis of Negative Pressure Wound Therapy Following Pancreatectomy for Pancreatic Diagnoses.

Introduction Surgical site infections (SSIs) continue to be a challenging issue among patients undergoing pancreatectomy. Anecdotally, the use of negative pressure wound therapy (NPWT) following pancreatectomy for cancer has been associated with decreased SSIs. The objective of this study was to compare the postoperative outcomes of NPWT and non-NPWT for incisional wound care following distal pancreatectomy or pancreatoduodenectomy for pancreatic diagnoses using a national surgical database.

Stratifying risk of disease in haematuria patients using machine learning techniques to improve diagnostics.

Background: Detailed and invasive clinical investigations are required to identify the causes of haematuria. Highly unbalanced patient population (predominantly male) and a wide range of potential causes make the ability to correctly classify patients and identify patient-specific biomarkers a major challenge. Studies have shown that it is possible to improve the diagnosis using multi-marker analysis, even in unbalanced datasets, by applying advanced analytical methods.

Changes in Internal Structure and Dynamics upon Binding Stabilise the Nematode Anticoagulant NAPc2.

Abnormal blood coagulation is a major health problem and natural anticoagulants from blood-feeding organisms have been investigated as novel therapeutics. NAPc2, a potent nematode-derived inhibitor of coagulation, has an unusual mode of action that requires coagulation factor Xa but does not inhibit it. Molecular dynamics simulations of NAPc2 and factor Xa were generated to better understand NAPc2.

How far We Go For Surgery: Distance to Pediatric Surgical Care in Indiana.

Introduction: Despite increasing numbers of pediatric surgery training programs, access to pediatric surgical care remains limited in non-academic and rural settings. We aimed to characterize demographic and patient factors associated with increased distance to selected pediatric surgical procedures in Indiana.

Methods: This IRB-approved retrospective review analyzed pediatric patients undergoing appendectomy, cholecystectomy, umbilical hernia repair, pyloromyotomy, and video assisted thoracic surgery (VATS) procedures from 2019 through 2021.

Outcomes of Concurrent Ventral Hernia Repair and Cholecystectomy Compared to Ventral Hernia Repair Alone.

Introduction It has been suggested that hernia repair with concomitant cholecystectomy increases the risk of postoperative complications due to potential mesh contamination. This study compares postoperative outcomes and complications between patients who underwent ventral hernia repair (VHR) with and without concomitant cholecystectomy (CCY). Methods Using the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database, from 2005 to 2019, we queried patients who underwent ventral hernia repairs using the current procedural terminology (CPT) codes 49652-49657 (laparoscopic) and 49560-49566 (open), with or without cholecystectomy.

Evolutions in Commercial Meat Poultry Breeding.

This paper provides a comprehensive overview of the history of commercial poultry breeding, from domestication to the development of science and commercial breeding structures. The development of breeding goals over time, from mainly focusing on production to broad goals, including bird welfare and health, robustness, environmental impact, biological efficiency and reproduction, is detailed. The paper outlines current breeding goals, including traits (e.

A cluster randomised controlled trial to assess the effectiveness of a multi-strategy sustainability intervention on teachers' sustained implementation of classroom physical activity breaks (energisers): study protocol.

Background: Governments internationally have invested hugely in the implementation and scale-up of school-based physical activity interventions, but have little evidence of how to best sustain these interventions once active implementation support ceases. This study will assess the effectiveness of a multi-strategy sustainability intervention on classroom teachers' sustainment of energisers (short 3-5 min physical activity breaks during class-time) scheduled across the school day from baseline to 12 and 24-month follow-up.

Methods: A cluster randomised controlled trial will be conducted in 50 primary schools within the Hunter New England, Illawarra Shoalhaven, Murrumbidgee and Northern New South Wales (NSW) Local Health Districts of NSW Australia.

Establishing national diagnostic reference levels in radiography, mammography, and dual-energy x-ray absorptiometry services in Ireland and comparing these with European diagnostic reference levels.

Objectives: The aim of this work was to establish national diagnostic reference levels (DRLs) in Ireland and compare these to existing European DRLs where available. This work surveyed all radiological facilities providing radiography, mammography, and dual-energy x-ray absorptiometry (DXA) services in Ireland.

Methods: A list of common procedures and clinical tasks was established.

Nanoscaled Discovery of a Shunt Rifamycin from Using a Three-Color GFP-Tagged Macrophage Infection Assay.

Antimicrobial resistance has emerged as a global public health threat, and development of novel therapeutics for treating infections caused by multi-drug resistant bacteria is urgent. is a major human and animal pathogen, responsible for high levels of morbidity and mortality worldwide. The intracellular survival of in macrophages contributes to immune evasion, dissemination, and resilience to antibiotic treatment.

A Survey of Didemnin Depsipeptide Production in .

As one of the first families of marine natural products to undergo clinical trials, the didemnin depsipeptides have played a significant role in inspiring the discovery of marine drugs. Originally developed as anticancer therapeutics, the recent re-evaluation of these compounds including synthetically derived dehydrodidemnin B or Aplidine, has led to their advancement towards antiviral applications. While conventionally associated with production in colonial tunicates of the family , recent studies have identified their biosynthetic gene clusters from the marine-derived bacteria .

A Longitudinal Examination of Young People's Gambling Behaviours and Participation in Team Sports.

This paper develops and expands upon social identity theory as an explanation for gambling among youth engaged in team sport. Analysing longitudinal data for over 4500 20-year-olds from the Growing Up in Ireland study, reveals that online gambling increased from 2.6 to 9.

Kinase inhibitors for cancer alter metabolism, blood glucose, and insulin.

Small molecule kinase inhibitors (SMKIs) are a class of therapeutic drugs that target protein kinases in diseases such as cancer. SMKIs are often designed to inhibit kinases involved in cell proliferation, but these drugs alter cell metabolism and the endocrine control of organismal metabolism. SMKI treatment in diabetic cancer patients reveals that certain SMKIs improve blood glucose levels and can mitigate insulin dependence or diabetic medication requirements in both type 1 diabetes (T1D) and type 2 diabetes (T2D).

Biomarkers to assess the risk of bladder cancer in patients presenting with haematuria are gender-specific.

Introduction: Haematuria is a common red flag symptom of urinary tract cancer. Bladder cancer (BC) is the most common cancer to present with haematuria. Women presenting with haematuria are often underdiagnosed.

Cluster randomised controlled trial to determine the impact of an activity enabling uniform on primary school student's fitness and physical activity: study protocol for the Active WeAR Everyday (AWARE) study.

Unlabelled: IntroductionMulticomponent school-based physical activity (PA) interventions can improve students' cardiorespiratory fitness (CRF) and PA. Due to the complex nature of such interventions when delivered at scale their effect sizes markedly reduce. Modifying student school uniforms, so that they are more PA enabling, may be a simple intervention that could enhance student health.

Postbiotics engage IRF4 in adipocytes to promote sex-dependent changes in blood glucose during obesity.

Postbiotics are microbial-derived components or metabolites that can influence host immunity and metabolism. Some postbiotics can improve blood glucose control and lower inflammation during bacterial or nutritional stress. Bacterial cell wall-derived muramyl dipeptide (MDP) is a potent insulin-sensitizing postbiotic that engages NOD2, RIPK2, and requires interferon regulatory factor 4 (IRF4) to lower inflammation and improve blood glucose.

Clinical features and predictive biomarkers for bladder cancer in patients with type 2 diabetes presenting with haematuria.

Aims: To identify clinical features and protein biomarkers associated with bladder cancer (BC) in individuals with type 2 diabetes mellitus presenting with haematuria.

Materials And Methods: Data collected from the Haematuria Biomarker (HaBio) study was used in this analysis. A matched sub-cohort of patients with type 2 diabetes and patients without diabetes was created based on age, sex, and BC diagnosis, using approximately a 1:2 fixed ratio.

Erodible thermogelling hydrogels for localized mitochondrial transplantation to the spinal cord.

We developed a thermal-gelling, erodible hydrogel system for localized delivery of viable mitochondria in vivo, as well as labeled transplanted mitochondria with specific dyes and/or genetically modified mitochondria tagged with red fluorescence protein (RFP). We also employed cell lines to optimize a hydrogel composed of methylcellulose and hyaluronic acid designed to preserve bioenergetics while facilitating mitochondrial release. We further investigated how transplantation of allogeneic or xenogeneic mitochondria into respective cell lines affects host cellular metabolism, as measured by MTS assay.

SPCS: a spatial and pattern combined smoothing method for spatial transcriptomic expression.

High-dimensional, localized ribonucleic acid (RNA) sequencing is now possible owing to recent developments in spatial transcriptomics (ST). ST is based on highly multiplexed sequence analysis and uses barcodes to match the sequenced reads to their respective tissue locations. ST expression data suffer from high noise and dropout events; however, smoothing techniques have the promise to improve the data interpretability prior to performing downstream analyses.

Cannabinol inhibits oxytosis/ferroptosis by directly targeting mitochondria independently of cannabinoid receptors.

The oxytosis/ferroptosis regulated cell death pathway recapitulates many features of mitochondrial dysfunction associated with the aging brain and has emerged as a potential key mediator of neurodegeneration. It has thus been proposed that the oxytosis/ferroptosis pathway can be used to identify novel drug candidates for the treatment of age-associated neurodegenerative diseases that act by preserving mitochondrial function. Previously, we identified cannabinol (CBN) as a potent neuroprotector.

Gut microbiota-based vaccination engages innate immunity to improve blood glucose control in obese mice.

Objective: Obesity and diabetes increase circulating levels of microbial components derived from the gut microbiota. Individual bacterial factors (i.e.

DAPT: A package enabling distributed automated parameter testing.

Modern agent-based models (ABM) and other simulation models require evaluation and testing of many different parameters. Managing that testing for large scale parameter sweeps (grid searches), as well as storing simulation data, requires multiple, potentially customizable steps that may vary across simulations. Furthermore, parameter testing, processing, and analysis are slowed if simulation and processing jobs cannot be shared across teammates or computational resources.

Multi-strategy intervention increases school implementation and maintenance of a mandatory physical activity policy: outcomes of a cluster randomised controlled trial.

Objectives: To assess if a multi-strategy intervention effectively increased weekly minutes of structured physical activity (PA) implemented by classroom teachers at 12 months and 18 months.

Methods: A cluster randomised controlled trial with 61 primary schools in New South Wales Australia. The 12-month multi-strategy intervention included; centralised technical assistance, ongoing consultation, principal's mandated change, identifying and preparing school champions, development of implementation plans, educational outreach visits and provision of educational materials.

Inflammation promotes adipocyte lipolysis via IRE1 kinase.

Obesity associates with inflammation, insulin resistance, and higher blood lipids. It is unclear if immune responses facilitate lipid breakdown and release from adipocytes via lipolysis in a separate way from hormones or adrenergic signals. We found that an ancient component of ER stress, inositol-requiring protein 1 (IRE1), discriminates inflammation-induced adipocyte lipolysis versus lipolysis from adrenergic or hormonal stimuli.