Effectiveness and Toxicity in Older Patients Receiving Anticancer Agents: A Retrospective Analysis of Australian Patients.

The number of older adults being treated for cancer is increasing. Despite this, older patients are under-represented in clinical trials. Those who are included are unlikely to be an accurate reflection of real-world patients as many are excluded based on performance status and comorbidities.

Implementing DPYD genotyping to predict chemotherapy toxicity in Australia: a feasibility study.

Background: Implementing pharmacogenomic-guided management in cancer patients equitably and effectively in a large population presents challenges. DPYD genotyping determines clinically significant variants of patients at increased risk of developing grade3-5 fluoropyrimidine (FP) toxicity. FP chemotherapies are prescribed for ~16,000 Australians with a 10%-40% grade3-4 toxicity incidence and 1% mortality.

Massively parallel in vivo Perturb-seq screening.

Advances in genomics have identified thousands of risk genes impacting human health and diseases, but the functions of these genes and their mechanistic contribution to disease are often unclear. Moving beyond identification to actionable biological pathways requires dissecting risk gene function and cell type-specific action in intact tissues. This gap can in part be addressed by in vivo Perturb-seq, a method that combines state-of-the-art gene editing tools for programmable perturbation of genes with high-content, high-resolution single-cell genomic assays as phenotypic readouts.

DPYD genotype-guided dose personalisation for fluoropyrimidine-based chemotherapy prescribing in solid organ cancer patients in Australia: GeneScreen 5-FU study protocol.

Background: Fluoropyrimidine (FP) chemotherapies are commonly prescribed for upper and lower gastrointestinal, breast and head and neck malignancies. Over 16,000 people with cancer require FP chemotherapies per annum in Australia. Between 10 and 40% patients experience grade 3-4 (≥ G3) toxicities that require hospital-based management ± intensive care admission.

Evaluation of early fluoropyrimidine toxicity in solid organ cancer patients: a retrospective observational study in Australia.

Background: Despite common global usage, fluoropyrimidine (FP; 5-flurouracil and capecitabine)-related chemotherapy toxicity is poorly reported in the literature, with serious toxicity ranging from 10% to 40% and early toxicity (within 60 days of exposure) quoted at 14%. Data reflecting the incidence of Grades 3-5 FP-related toxicity in Australian cancer patients is scant, despite the significant impact of toxicity on patients (hospitalisations, intensive care unit (ICU) admissions and even death).

Aims: This retrospective audit evaluated Grades 3-5 toxicities in a contemporaneous cohort of 500 patients receiving FP chemotherapies within the Hunter-New England Local Health District from June 2020 to June 2022.

Intersections of climate change, migration, and health: experiences of first-generation migrants from Latin America to the Atlanta-metropolitan area.

Climate change is an important driver of migration, but little research exists on whether migrant communities in the U.S. identify climate change-related factors as reasons for migrating.

Exposure of iPSC-derived human microglia to brain substrates enables the generation and manipulation of diverse transcriptional states in vitro.

Microglia, the macrophages of the brain parenchyma, are key players in neurodegenerative diseases such as Alzheimer's disease. These cells adopt distinct transcriptional subtypes known as states. Understanding state function, especially in human microglia, has been elusive owing to a lack of tools to model and manipulate these cells.

Compensation for Board of Pharmacy members in the United States.

Background: No published data exist regarding per diem pay differences between the 50 United States Boards of Pharmacy.

Objectives: The purpose of this study was to quantify and compare the per diem pay rate of Board of Pharmacy members for each state in the U.S.

Burnout reduction in acute care surgeons: Impact of faculty schedule change at a level 1 trauma and tertiary care center.

Background: Acute care surgeons are prone to burnout because of heavy workload, concurrent clinical responsibilities, and busy in-house call. Modifiable burnout factors have been identified, but few studies have looked for longitudinal effects after change is implemented. We hypothesized that optimizing faculty workflow could decrease burnout without compromising productivity.

Dihydropyrimidine Dehydrogenase Deficiency and Implementation of Upfront DPYD Genotyping.

Fluoropyrimidines (FP; 5-fluorouracil, capecitabine, and tegafur) are a commonly prescribed class of antimetabolite chemotherapies, used for various solid organ malignancies in over 2 million patients globally per annum. Dihydropyrimidine dehydrogenase (DPD), encoded by the DPYD gene, is the critical enzyme implicated in FP metabolism. DPYD variant genotypes can result in decreased DPD production, leading to the development of severe toxicities resulting in hospitalization, intensive care admission, and even death.

Chimpanzee Extraversion scores vary with epigenetic modification of dopamine receptor gene D2 () and early rearing conditions.

Chimpanzees have consistent individual differences in behaviour, also referred to as personality. Similar to human personality structure, five dimensions are commonly found in chimpanzee studies that show evidence for convergent and predictive validity (Dominance, Openness, Extraversion, Agreeableness, and Reactivity/Undependability). These dimensions are to some extent heritable, indicating a genetic component that explains part of the variation in personality scores, but are also influenced by environmental factors, such as the early social rearing background of the individuals.

Examination of Intersectionality and the Pipeline for Black Academic Surgeons.

Importance: The lack of underrepresented in medicine physicians within US academic surgery continues, with Black surgeons representing a disproportionately low number.

Objective: To evaluate the trend of general surgery residency application, matriculation, and graduation rates for Black trainees compared with their racial and ethnic counterparts over time.

Design, Setting, And Participants: In this nationwide multicenter study, data from the Electronic Residency Application Service (ERAS) for the general surgery residency match and Graduate Medical Education (GME) surveys of graduating general surgery residents were retrospectively reviewed and stratified by race, ethnicity, and sex.

Mobile Health Technologies Are Essential for Reimagining the Future of Water, Sanitation, and Hygiene.

The new Lancet Commission on water, sanitation, and hygiene (WASH) hopes to reimagine and guide global WASH efforts. This comes at a time when unequal living conditions and global disparities in response and recovery have been highlighted by the COVID-19 pandemic and recent large impact trials have delivered mostly disappointing results suggesting the need for radically more effective interventions to improve global public health. We find ourselves at an inflection point in global WASH with an opportunity to build new approaches with potentially more equitable, cost-effective, and scalable solutions.

Ethnic Diversity of DPD Activity and the Gene: Review of the Literature.

Pharmacogenomic screening can identify patients with gene variants that predispose them to the development of severe toxicity from fluoropyrimidine (FP) chemotherapy. Deficiency of the critical metabolic enzyme dihydropyrimidine dehydrogenase (DPD) leads to excessive toxicity on exposure to fluoropyrimidine chemotherapy. This can result in hospitalisation, intensive care admissions and even death.

Effective use of weight-based enoxaparin for deep vein thrombosis chemoprophylaxis in patients with traumatic brain injury.

Background: Enoxaparin is the recommended agent for deep vein thrombosis (DVT) chemoprophylaxis in trauma patients. Current literature suggests weight-based dosing is superior to standard dosing for adequate chemoprophylaxis. Literature regarding the use of weight-based enoxaparin in the setting of traumatic brain injury (TBI) however is limited.

Achievement of goal anti-Xa activity with weight-based enoxaparin dosing for venous thromboembolism prophylaxis in trauma patients.

Study Objective: The purpose of this study was to evaluate the utility of routine anti-Xa peak monitoring for trauma patients initiated on weight-based enoxaparin for venous thromboembolism (VTE) prophylaxis and identify patient populations where monitoring is necessary.

Design: Retrospective study.

Setting: Augusta University (AU) Medical Center in Augusta, Georgia, a level 1 trauma center.

VIP interneurons in mouse primary visual cortex selectively enhance responses to weak but specific stimuli.

Vasoactive intestinal peptide-expressing (VIP) interneurons in the cortex regulate feedback inhibition of pyramidal neurons through suppression of somatostatin-expressing (SST) interneurons and, reciprocally, SST neurons inhibit VIP neurons. Although VIP neuron activity in the primary visual cortex (V1) of mouse is highly correlated with locomotion, the relevance of locomotion-related VIP neuron activity to visual coding is not known. Here we show that VIP neurons in mouse V1 respond strongly to low contrast front-to-back motion that is congruent with self-motion during locomotion but are suppressed by other directions and contrasts.

Age-associated epigenetic change in chimpanzees and humans.

Methylation levels have been shown to change with age at sites across the human genome. Change at some of these sites is so consistent across individuals that it can be used as an 'epigenetic clock' to predict an individual's chronological age to within a few years. Here, we examined how the pattern of epigenetic ageing in chimpanzees compares with humans.

'Zero Leprosy' and other endgame strategies: Rhetoric vs. realism in public health campaigns.

For over half a century, many public health campaigns related to infectious disease have focused on disease 'eradication,' rather than 'control' or 'management.' In this article, I will focus on the example of a recent global leprosy (Hansen's Disease) control campaign, Triple Zero. Drawing on examples from other public health initiatives, this article explores how the language of 'zero disease' or 'endgame strategies' is appealing to certain audiences but how it can also be misleading and have unexpected and unintended consequences.