Case studies of health economic analyses informing pharmaceutical health technology assessments for essential medicine selection and public-sector guidelines in South Africa.

Background: Constrained resources under universal health coverage (UHC) necessitate a balance between medication costs and essential health system requirements. Policymakers practice priority-setting, as either implicit or explicit rationing, embedded in evidence-informed decision-making processes to guide funding decisions. Health technology assessment (HTA) is a method that may assist explicit evidence-informed priority setting.

Alternative Anticoagulant Strategy to Improve the Test Sensitivity of ASTM F2888-19 Standard for Platelet and Leukocyte Count Assay.

The ASTM F2888-19 standard for platelet and leukocyte count assay is the only standardized test method for assessing platelet and leukocyte interactions with blood-contacting device materials. This study aimed to address two limitations of the ASTM F2888-19 standard: low test sensitivity for leukocyte count and high test sample surface area to blood ratio (12 cm/mL). Human blood from healthy adult donors was drawn into polypropylene tubes with either 3.

A comparative analysis of robotic versus laparoscopic total pancreatectomy: insights from the National Cancer Database.

Total pancreatectomy is a complex procedure used in the management of pancreatic cancer. While minimally invasive techniques have been increasingly adopted, limited data exist comparing robotic total pancreatectomy (RTP) and laparoscopic total pancreatectomy (LTP). This study evaluates the utilization, short- and long-term outcomes of RTP and LTP using the National Cancer Database.

Longitudinal Impacts of High Versus Low Greenness on Cardiovascular Disease Conditions.

Background: Greenness-or vegetative presence-has been identified as a factor in chronic disease. The present study examines the longitudinal relationship between objective measures of greenness at the residential block level and incidence of 6 cardiovascular disease conditions.

Methods And Results: Analyses examined the impact of consistently high versus consistently low "precision" greenness at the Census block level on the 5-year incidence of cardiovascular disease conditions, including acute myocardial infarction, atrial fibrillation, heart failure, ischemic heart disease, stroke/transient ischemic attack, and hypertension, among 229 034 US Medicare beneficiaries in Miami-Dade County, Florida, USA.

Molecular Biomarkers for In Vitro Thrombogenicity Assessment of Medical Device Materials.

To develop standardized in vitro thrombogenicity test methods for evaluating medical device materials, three platelet activation biomarkers, beta-thromboglobulin (β-TG), platelet factor 4 (PF4), soluble p-selectin (CD62P), and a plasma coagulation marker, thrombin-antithrombin complex (TAT), were investigated. Whole blood, drawn from six healthy human volunteers into Anticoagulant Citrate Dextrose Solution A was recalcified and heparinized over a concentration range of 0.5-1.

Rare disease genomic testing in the UK and Ireland: promoting timely and equitable access.

Purpose And Scope: The aim of this position statement is to provide recommendations regarding the delivery of genomic testing to patients with rare disease in the UK and Ireland. The statement has been developed to facilitate timely and equitable access to genomic testing with reporting of results within commissioned turnaround times.

Methods Of Statement Development: A 1-day workshop was convened by the UK Association for Clinical Genomic Science and attended by key stakeholders within the NHS Genomic Medicine Service, including clinical scientists, clinical geneticists and patient support group representatives.

A toolbox for surfacing health equity harms and biases in large language models.

Large language models (LLMs) hold promise to serve complex health information needs but also have the potential to introduce harm and exacerbate health disparities. Reliably evaluating equity-related model failures is a critical step toward developing systems that promote health equity. We present resources and methodologies for surfacing biases with potential to precipitate equity-related harms in long-form, LLM-generated answers to medical questions and conduct a large-scale empirical case study with the Med-PaLM 2 LLM.

Dietary fibers boost gut microbiota-produced B vitamin pool and alter host immune landscape.

Background: Dietary fibers can alter microbial metabolic output in support of healthy immune function; however, the impact of distinct fiber sources and immunomodulatory effects beyond short-chain fatty acid production are underexplored. In an effort to discern the effects of diverse fibers on host immunity, we employed five distinct rodent diets with varying fiber content and source in specific-pathogen-free, gnotobiotic (containing a 14-member synthetic human gut microbiota), and germ-free mice.

Results: Broad-scale metabolomics analysis of cecal contents revealed that fiber deprivation consistently reduced the concentrations of microbiota-produced B vitamins.

Development of a large diameter in vitro flow loop thrombogenicity test system.

Background: To accommodate a wider range of medical device sizes, a larger in vitro flow loop thrombogenicity test system using 9.5 -mm inner diameter (ID) tubing was developed and evaluated based on our previously established 6.4 -mm ID tubing system.

TRKing down drug resistance in NTRK fusion-positive cancers.

In a recent issue of The Journal of Pathology, Chen and colleagues established novel patient-derived ex vivo models of NTRK fusion-positive soft tissue sarcoma to characterize resistance mechanisms against targeted therapy with tyrosine kinase inhibitors. Prolonged exposure to escalating concentrations of the tyrosine kinase inhibitor, entrectinib, ultimately led to the occurrence of resistant clones that harbored an inactivating mutation in the NF2 gene, not previously described in this context, accompanied by increased PI3K/AKT/mTOR and Ras/Raf/MEK/ERK signaling. Finally, an inhibitor screen identified, among others, MEK and mTOR inhibitors as potential combination agents.

Implementation of a Multimodal Enhanced Recovery Protocol in Ambulatory Anorectal Surgery: A Randomized Trial.

Background: Few studies report outcomes for enhanced recovery pathways in ambulatory anorectal surgery. We hypothesize that an ambulatory anorectal enhanced recovery pathway with multimodal analgesia can reduce postoperative opioid use.

Objective: To compare postoperative opioid use in patients undergoing ambulatory anorectal surgery who receive multimodal analgesia versus standard of care without multimodal analgesia.

Lead Decreases Bone Morphogenetic Protein-7 (BMP-7) Expression and Increases Renal Cell Carcinoma Growth in a Sex-Divergent Manner.

Both tissue and blood lead levels are elevated in renal cell carcinoma (RCC) patients. These studies assessed the impact of the subchronic lead challenge on the progression of RCC in vitro and in vivo. Lead challenge of Renca cells with 0.

Aggressive high-grade NF2 mutant meningiomas downregulate oncogenic YAP signaling via the upregulation of VGLL4 and FAT3/4.

Meningiomas are the most common primary brain tumors in adults. Although generally benign, a subset of meningiomas is of higher grade, shows aggressive growth behavior and recurs even after multiple surgeries. Around half of all meningiomas harbor inactivating mutations in NF2.

Institutionalizing Health Technology Assessment in South Africa-An Opportunity in National Health Insurance.

While South Africa has some experience in various forms of health technology assessment (HTA), it is currently fragmented across numerous players. Additionally, there is a lack of systematic and consistently applied HTA processes that inform priority-setting and budget allocations. To address this, the country is journeying toward more institutionalized use of HTA.

Longitudinal Impacts of Precision Greenness on Alzheimer's Disease.

Background: The potential for greenness as a novel protective factor for Alzheimer's disease (AD) requires further exploration.

Objectives: This study assesses prospectively and longitudinally the association between precision greenness - greenness measured at the micro-environmental level, defined as the Census block - and AD incidence.

Design: Older adults living in consistently high greenness Census blocks across 2011 and 2016 were compared to those living in consistently low greenness blocks on AD incidence during 2012-2016.

ERK signaling promotes resistance to TRK kinase inhibition in NTRK fusion-driven glioma mouse models.

Pediatric-type high-grade gliomas frequently harbor gene fusions involving receptor tyrosine kinase genes, including neurotrophic tyrosine kinase receptor (NTRK) fusions. Clinically, these tumors show high initial response rates to tyrosine kinase inhibition but ultimately recur due to the accumulation of additional resistance-conferring mutations. Here, we developed a series of genetically engineered mouse models of treatment-naïve and -experienced NTRK1/2/3 fusion-driven gliomas.

Enabling High-throughput Transgene Expression Studies Using Automated Liquid Handling for Etiolated Maize Leaf Protoplasts.

The field of plant biotechnology has witnessed remarkable advancements in recent years, revolutionizing the ability to manipulate and engineer plants for various purposes. However, as research in this field increases in diversity and becomes increasingly sophisticated, the need for early, efficient, dependable, and high-throughput transient screening solutions to narrow down strategies proceeding to stable transformation is more apparent. One method that has re-emerged in recent years is the utilization of plant protoplast, for which methods of isolation and transfection are available in numerous species, tissues, and developmental stages.

Effectiveness of the BNT162b2 vaccine in preventing morbidity and mortality associated with COVID-19 in children aged 5 to 11 years: A systematic review and meta-analysis.

A rapid systematic review, based on Cochrane rapid review methodology was conducted to assess the effectiveness of two 10μg doses of BNT162b2 vaccine in preventing morbidity and mortality associated with COVID-19 in children aged 5 to 11 years. We searched the Cochrane Library COVID-19 study register, the COVID-NMA living review database and the McMaster University Living Evidence Synthesis for pre-appraised trials and observational studies up to 7 December 2022. Records were screened independently in duplicate.

The effect of experiential learning interventions on physical activity outcomes in children: A systematic review.

Background: This systematic review examined the effectiveness of experiential learning interventions for improving children's physical activity knowledge, attitudes, and behaviours. It also aimed to identify intervention characteristics that resulted in the greatest impact.

Methods: Four databases: Education Research Complete, Scopus, Web of Science and PsychINFO were searched from database inception to January 2023.