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Paul A Brown,1 Morgan Slater,2 Aisha Lofters2,3 1Department of Community Health and Psychiatry, University of the West Indies, Kingston, Jamaica; 2Department of Family and Community Medicine, St. Michael’s Hospital, Toronto, ON, Canada; 3Department of Family & Community Medicine, University of Toronto, Toronto, ON, Canada Purpose: Burnout is a syndrome comprised of three major dimensions, namely, emotional exhaustion, depersonalization, and reduced personal accomplishment. Its etiology appears to be multifactorial, involving work-related and personal factors including personality traits. Personality has been associated with burnout among various physician groups; however, this has not been studied well amongst primary care physicians. This study therefore aimed to investigate the association between personality type and burnout in primary care physicians in Canada and Jamaica. Methods: This cross-sectional study involved primary care physicians in Canada and Jamaica. Participants completed a questionnaire that included the Maslach Burnout Inventory Human Services Survey and The Big Five Inventory. Responses were analyzed to determine relationships between burnout, personality type, and various demographic factors. Results: Seventy-seven physicians participated in the study. Approximately 38% of participants reported low levels of accomplishment, 34% reported high levels of emotional exhaustion, and 20% reported high levels of depersonalization, all equating to high levels of burnout. Neuroticism was negatively correlated with personal accomplishment (P

Depression and anxiety are potential psychological problems that a heart transplant patient may face both before and after transplant. In addition, there is the potential for difficulty in adjusting to life after transplantation. Anxiety and depression and their effects, both pretransplant and posttransplant, are explored. A case study is used to illustrate the psychological effects of trans plantation. [ABSTRACT FROM AUTHOR]

The optimal use of immunosuppressant drugs requires an understanding of their mechanism of action as well as a basic understanding of the biology of transplant rejection and tolerance. The ability to tailor a drug regimen that strikes a fine balance between allograft maintenance and patient well-being demands a sensitivity to the patient's needs and expectations as well. The object of this article is to cover the basic biological principles involved in selecting an immunosuppressant protocol while sharing our experiences with these various regimen. [ABSTRACT FROM AUTHOR]

Nutrition plays a significant role in the course, treatment, and effects of cancer. By using numerous strategies to improve the nutritional state of cancer patients, outcomes and quality of life can be enhanced. [ABSTRACT FROM AUTHOR]

In July 1992, the British government published its White Paper 'The Health of the Nation, a Strategy for Health in England' (HON). The authors contend that this initiative has largely been accepted by the nursing profession with critical response to the HON being minimal. The authors argue that the medicalized negative interpretation of health and the narrow individualistic lifestyle-orientated definition of health promotion contained within the strategy ought to be rejected by nurses in favour of both a positive, holistic conception of health and a more humanistic health promotion methodology acknowledging the impact of structural-material factors influencing individual health related behaviour. [ABSTRACT FROM AUTHOR]

Abstract Background In New Zealand, around 45,000 people live with stroke and many studies have reported that benefits gained during initial rehabilitation are not sustained. Evidence indicates that participation in physical interventions can prevent the functional decline that frequently occurs after discharge from acute care facilities. However, on-going stroke services provision following discharge from acute care is often related to non-medical factors such as availability of resources and geographical location. Currently most people receive no treatment beyond three months post stroke. The study aims to determine if the Augmented Community Telerehabilitation Intervention (ACTIV) results in better physical function for people with stroke than usual care, as measured by the Stroke Impact Scale, physical subcomponent. Methods/design This study will use a multi-site, two-arm, assessor blinded, parallel randomised controlled trial design. People will be eligible if they have had their first ever stroke, are over 20 and have some physical impairment in either arm or leg, or both. Following discharge from formal physiotherapy services (inpatient, outpatient or community), participants will be randomised into ACTIV or usual care. ACTIV uses readily available technology, telephone and mobile phones, combined with face-to-face visits from a physiotherapist over a six-month period, to help people with stroke resume activities they enjoyed before the stroke. The impact of stroke on physical function and quality of life will be assessed, measures of cost will be collected and a discrete choice survey will be used to measure preferences for rehabilitation options. These outcomes will be collected at baseline, six months and 12 months. In-depth interviews will be used to explore the experiences of people participating in the intervention arm of the study. Discussion The lack of on-going rehabilitation for people with stroke diminishes the chance of their best possible outcome and may contribute to a functional decline following discharge from formal rehabilitation. Best practice guidelines recommend a prolonged period of rehabilitation, however this is expensive and therefore not undertaken in most publicly funded centres. An effective, cost-effective, and preference-sensitive therapy using basic technology to assist programme delivery may improve patient autonomy as they leave formal rehabilitation and return home. Trial registration ACTRN12612000464864

Abstract Background Many smoking-cessation programs and pharmaceutical aids demonstrate substantial health gains for a relatively low allocation of resources. Genetic information represents a type of individualized or personal feedback regarding the risk of developing lung cancer, and hence the potential benefits from stopping smoking, may motivate the person to remain smoke-free. The purpose of this study was to explore what the impact of a genetic test needs to have within a typical smoking-cessation program aimed at heavy smokers in order to be cost-effective. Methods Two strategies were modelled for a hypothetical cohort of heavy smokers aged 50 years; individuals either received or did not receive a genetic test within the course of a usual smoking-cessation intervention comprising nicotine replacement therapy (NRT) and counselling. A Markov model was constructed using evidence from published randomized controlled trials and meta-analyses for estimates on 12-month quit rates and long-term relapse rates. Epidemiological data were used for estimates on lung cancer risk stratified by time since quitting and smoking patterns. Extensive sensitivity analyses were used to explore parameter uncertainty. Results The discounted incremental cost per QALY was AU$34,687 (95% CI $12,483, $87,734) over 35 years. At a willingness-to-pay of AU$20,000 per QALY gained, the genetic testing strategy needs to produce a 12-month quit rate of at least 12.4% or a relapse rate 12% lower than NRT and counselling alone for it to be equally cost-effective. The likelihood that adding a genetic test to the usual smoking-cessation intervention is cost-effective was 20.6% however cost-effectiveness ratios were favourable in certain situations (e.g., applied to men only, a 60 year old cohort). Conclusions The findings were sensitive to small changes in critical variables such as the 12-month quit rates and relapse rates. As such, the cost-effectiveness of the genetic testing smoking cessation program is uncertain. Further clinical research on smoking-cessation quit and relapse rates following genetic testing is needed to inform its cost-effectiveness.

Abstract Background Prostaglandin (PG) F2α is a key regulator of endometrial function and exerts its biological action after coupling with its heptahelical G protein-coupled receptor (FP receptor). In endometrial adenocarcinoma the FP receptor expression is elevated. We have shown previously that PGF2α-FP receptor signalling in endometrial adenocarcinoma cells can upregulate several angiogenic factors including fibroblast growth factor-2 (FGF2). In the present study, we investigated the paracrine effect of conditioned medium produced via PGF2α-FP receptor signalling in endometrial adenocarcinoma cells stably expressing the FP receptor (Ishikawa FPS cells), on endothelial cell function. Results Conditioned medium (CM) was collected from FPS cells after 24 hrs treatment with either vehicle (V CM) or 100 nM PGF2α (P CM). Treatment of human umbilical vein endothelial cells (HUVECs) with P CM significantly enhanced endothelial cell differentiation (network formation) and proliferation. Using chemical inhibitors of intracellular signalling, we found that P CM-stimulated endothelial cell network formation was mediated by secretion of endothelial PGF2α and activation of endothelial FP receptors, following FGF2-FGFR1 signalling, phosphorylation of ERK1/2 and induction of COX-2. Whereas, P CM stimulation of endothelial cell proliferation occurred independently of PGF2α secretion via an FGF2-FGFR1-ERK1/2 dependent mechanism involving activation of the mTOR pathway. Conclusions Taken together, we have shown a novel mechanism whereby epithelial prostaglandin F2α-FP signalling regulates endothelial cell network formation and proliferation. In addition we provide novel in vitro evidence to suggest that prostaglandin F2α can directly regulate endothelial cell network formation but not endothelial cell proliferation. These findings have relevance for pathologies where the FP receptor is aberrantly expressed, such as endometrial adenocarcinoma, and provide in vitro evidence to suggest that targeting the FP receptor could provide an anti-angiogenic approach to reducing tumour vasculature and growth.

Abstract Background Endometrial cancer is the most common gynaecological malignancy; risk factors include exposure to oestrogens and high body mass index. Expression of enzymes involved in biosynthesis of oestrogens and prostaglandins (PG) is often higher in endometrial cancers when compared with levels detected in normal endometrium. Oestrogens bind one of two receptors (ERα and ERβ) encoded by separate genes. The full-length receptors function as ligand-activated transcription factors; splice variant isoforms of ERβ lacking a ligand-binding domain have also been described. PGs act in an autocrine or paracrine manner by binding to specific G-protein coupled receptors. Methods We compared expression of ERs, progesterone receptor (PR) and cyclooxygenase-2 (COX-2) in stage 1 endometrial adenocarcinomas graded as well (G1), moderately (G2) or poorly (G3) differentiated (n ≥ 10 each group) using qRTPCR, single and double immunohistochemistry. We used endometrial adenocarcinoma cell lines to investigate the impact of PGF2α on expression of ERs and PR. Results Full length ERβ (ERβ1) and two ERβ variants (ERβ2, ERβ5) were expressed in endometrial cancers regardless of grade and the proteins were immunolocalised to the nuclei of cells in both epithelial and stromal compartments. Immunoexpression of COX-2 was most intense in cells that were ERαneg/low. Expression of PR in endometrial adenocarcinoma (Ishikawa) cell lines and tissues broadly paralleled that of ERα. Treatment of adenocarcinoma cells with PGF2α reduced expression of ERα but had no impact on ERβ1. Cells incubated with PGF2α were unable to increase expression of PR mRNA when they were incubated with E2. Conclusion We have demonstrated that ERβ5 protein is expressed in stage 1 endometrial adenocarcinomas. Expression of three ERβ variants, including the full-length protein is not grade-dependent and most cells in poorly differentiated cancers are ERβpos/ERαneg. We found evidence of a link between COX-2, its product PGF2α, and expression of ERα and PR that sheds new light on the cross talk between steroid and PG signalling pathways in this disease.

Abstract Background The use of electronic health records (EHRs) to support the organization and delivery of healthcare is evolving rapidly. However, little is known regarding potential variation in access to EHRs by provider type or care setting. This paper reports on observed variation in the perceptions of access to EHRs by a wide range of cancer care providers covering diverse cancer care settings in Ontario, Canada. Methods Perspectives were sought regarding EHR access and health record completeness for cancer patients as part of an internet survey of 5663 cancer care providers and administrators in Ontario. Data were analyzed using a multilevel logistic regression model. Provider type, location of work, and access to computer or internet were included as covariates in the model. Results A total of 1997 of 5663 (35%) valid responses were collected. Focusing on data from cancer care providers (N = 1247), significant variation in EHR access and health record completeness was observed between provider types, location of work, and level of computer access. Providers who worked in community hospitals were half as likely as those who worked in teaching hospitals to have access to their patients' EHRs (OR 0.45 95% CI: 0.24–0.85, p < 0.05) and were six times less likely to have access to other organizations' EHRs (OR 0.15 95% CI: 0.02–1.00, p < 0.05). Compared to surgeons, nurses (OR 3.47 95% CI: 1.80–6.68, p < 0.05), radiation therapists/physicists (OR 7.86 95% CI: 2.54–25.34, p < 0.05), and other clinicians (OR 4.92 95% CI: 2.15–11.27, p < 0.05) were more likely to report good access to their organization's EHRs. Conclusion Variability in access across different provider groups, organization types, and geographic locations illustrates the fragmented nature of EHR adoption in the cancer system. Along with focusing on technological aspects of EHR adoption within organizations, it is essential that there is cross-organizational and cross-provider access to EHRs to ensure patient continuity of care, system efficiency, and high quality care.

Abstract Background Growth hormone-releasing hormone (GHRH) plasmid-based therapy for the treatment of chronic renal failure and its complications was examined. Companion dogs (13.1 ± 0.8 years, 29.4 ± 5.01 kg) and cats (13.2 ± 0.9 years, 8.5 ± 0.37 kg) received a single 0.4 mg or 0.1 mg species-specific plasmid injection, respectively, intramuscularly followed by electroporation, and analyzed up to 75 days post-treatment; controls underwent electroporation without plasmid administration. Results Plasmid-treated animals showed an increase in body weight (dogs 22.5% and cats 3.2%) compared to control animals, and displayed improved quality of life parameters including significant increases in appetite, activity, mentation and exercise tolerance levels. Insulin-like growth factor I (IGF-I, the downstream effector of GHRH) levels were increased in the plasmid treated animals. Hematological parameters were also significantly improved. Protein metabolism changes were observed suggesting a shift from a catabolic to an anabolic state in the treated animals. Blood urea nitrogen and creatinine did not show any significant changes suggesting maintenance of kidney function whereas the control animal's renal function deteriorated. Treated animals survived longer than control animals with 70% of dogs and 80% of cats surviving until study day 75. Only 17% and 40% of the control dogs and cats, respectively, survived to day 75. Conclusion Improved quality of life, survival and general well-being indicate that further investigation is warranted, and show the potential of a plasmid-based therapy by electroporation in preventing and managing complications of renal insufficiency.

Abstract Background Previous studies demonstrated breast cancer tumor tissue samples could be classified into different subtypes based upon DNA microarray profiles. The most recent study presented evidence for the existence of five different subtypes: normal breast-like, basal, luminal A, luminal B, and ERBB2+. Results Based upon the analysis of 599 microarrays (five separate cDNA microarray datasets) using a novel approach, we present evidence in support of the most consistently identifiable subtypes of breast cancer tumor tissue microarrays being: ESR1+/ERBB2-, ESR1-/ERBB2-, and ERBB2+ (collectively called the ESR1/ERBB2 subtypes). We validate all three subtypes statistically and show the subtype to which a sample belongs is a significant predictor of overall survival and distant-metastasis free probability. Conclusion As a consequence of the statistical validation procedure we have a set of centroids which can be applied to any microarray (indexed by UniGene Cluster ID) to classify it to one of the ESR1/ERBB2 subtypes. Moreover, the method used to define the ESR1/ERBB2 subtypes is not specific to the disease. The method can be used to identify subtypes in any disease for which there are at least two independent microarray datasets of disease samples.

Abstract Background Blood is a complex tissue comprising numerous cell types with distinct functions and corresponding gene expression profiles. We attempted to define the cell type specific gene expression patterns for the major constituent cells of blood, including B-cells, CD4+ T-cells, CD8+ T-cells, lymphocytes and granulocytes. We did this by comparing the global gene expression profiles of purified B-cells, CD4+ T-cells, CD8+ T-cells, granulocytes, and lymphocytes using cDNA microarrays. Results Unsupervised clustering analysis showed that similar cell populations from different donors share common gene expression profiles. Supervised analyses identified gene expression signatures for B-cells (427 genes), T-cells (222 genes), CD8+ T-cells (23 genes), granulocytes (411 genes), and lymphocytes (67 genes). No statistically significant gene expression signature was identified for CD4+ cells. Genes encoding cell surface proteins were disproportionately represented among the genes that distinguished among the lymphocyte subpopulations. Lymphocytes were distinguishable from granulocytes based on their higher levels of expression of genes encoding ribosomal proteins, while granulocytes exhibited characteristic expression of various cell surface and inflammatory proteins. Conclusion The genes comprising the cell-type specific signatures encompassed many of the genes already known to be involved in cell-type specific processes, and provided clues that may prove useful in discovering the functions of many still unannotated genes. The most prominent feature of the cell type signature genes was the enrichment of genes encoding cell surface proteins, perhaps reflecting the importance of specialized systems for sensing the environment to the physiology of resting leukocytes.

Abstract Background Antimicrobial usage is considered the most important factor promoting the emergence, selection and dissemination of antimicrobial-resistant microorganisms in both veterinary and human medicine. The aim of this study was to investigate the prevalence and genetic basis of tetracycline resistance in faecal Escherichia coli isolates from healthy broiler chickens and compare these data with isolates obtained from hospitalized patients in Jamaica. Results Eighty-two E. coli strains isolated from faecal samples of broiler chickens and urine and wound specimens of hospitalized patients were analyzed by agar disc diffusion to determine their susceptibility patterns to 11 antimicrobial agents. Tetracycline resistance determinants were investigated by plasmid profiling, transformations, and amplification of plasmid-borne resistance genes. Tetracycline resistance occurred at a frequency of 82.4% in avian isolates compared to 43.8% in human isolates. In addition, among avian isolates there was a trend towards higher resistance frequencies to kanamycin and nalidixic acid (p < 0.05), while a greater percentage of human isolates were resistant to chloramphenicol and gentamicin (p < 0.05). Multiple drug resistance was found in isolates from both sources and was usually associated with tetracycline resistance. Tetracycline-resistant isolates from both avian and human sources contained one or several plasmids, which were transmissible by transformation of chemically-competent E. coli. Tetracycline resistance was mediated by efflux genes tetB and/or tetD. Conclusion The present study highlights the prevalence of multiple drug resistant E. coli among healthy broiler chickens in Jamaica, possibly associated with expression of tetracycline resistance. While there did not appear to be a common source for multiple drug resistance in the strains from avian or human origin, the genes encoding resistance are similar. These results suggest that genes are disseminated in the environment and warrant further investigation of the possibility for avian sources acting as reservoirs for tetracycline resistance.

Abstract Background Much of the microarray data published at Stanford is based on mouse and human arrays produced under controlled and monitored conditions at the Brown and Botstein laboratories and at the Stanford Functional Genomics Facility (SFGF). Nevertheless, as large datasets based on the Stanford Human array began to accumulate, a small but significant number of discrepancies were detected that required a serious attempt to track down the original source of error. Due to a controlled process environment, sufficient data was available to accurately track the entire process leading to up to the final expression data. In this paper, we describe our statistical methods to detect the inconsistencies in microarray data that arise from process errors, and discuss our technique to locate and fix these errors. Results To date, the Brown and Botstein laboratories and the Stanford Functional Genomics Facility have together produced 40,000 large-scale (10–50,000 feature) cDNA microarrays. By applying the heuristic described here, we have been able to check most of these arrays for misidentified features, and have been able to confidently apply fixes to the data where needed. Out of the 265 million features checked in our database, problems were detected and corrected on 1.3 million of them. Conclusion Process errors in any genome scale high throughput production regime can lead to subsequent errors in data analysis. We show the value of tracking multi-step high throughput operations by using this knowledge to detect and correct misidentified data on gene expression microarrays.

Abstract Background A central challenge in the molecular diagnosis and treatment of cancer is to define a set of molecular features that, taken together, distinguish a given cancer, or type of cancer, from all normal cells and tissues. Results Discriminative margin clustering is a new technique for analyzing high dimensional quantitative datasets, specially applicable to gene expression data from microarray experiments related to cancer. The goal of the analysis is find highly specialized sub-types of a tumor type which are similar in having a small combination of genes which together provide a unique molecular portrait for distinguishing the sub-type from any normal cell or tissue. Detection of the products of these genes can then, in principle, provide a basis for detection and diagnosis of a cancer, and a therapy directed specifically at the distinguishing constellation of molecular features can, in principle, provide a way to eliminate the cancer cells, while minimizing toxicity to any normal cell. Conclusions The new methodology yields highly specialized tumor subtypes which are similar in terms of potential diagnostic markers.

Abstract Background In asthma and other allergic disorders, the activation of mast cells by IgE and antigen induces the cells to release histamine and other mediators of inflammation, as well as to produce certain cytokines and chemokines. To search for new mast cell products, we used complementary DNA microarrays to analyze gene expression in human umbilical cord blood-derived mast cells stimulated via the high-affinity IgE receptor (FcεRI). Results One to two hours after FcεRI-dependent stimulation, more than 2,400 genes (about half of which are of unknown function) exhibited 2–200 fold changes in expression. The transcriptional program included changes in the expression of IL-11 and at least 30 other cytokines and chemokines. Human mast cells secreted 130–529 pg of IL-11/106 cells by 6 h after stimulation with anti-IgE. Conclusion Our initial analysis of the transcriptional program induced in in vitro-derived human mast cells stimulated via the FcεRI has identified many products that heretofore have not been associated with this cell type, but which may significantly influence mast cell function in IgE-associated host responses. We also have demonstrated that mast cells stimulated via the FcεRI can secrete IL-11. Based on the previously reported biological effects of IL-11, our results suggest that production of IL-11 may represent one link between IgE-dependent mast cell activation in subjects with allergic asthma and the development of a spectrum of structural changes in the airways of these individuals; such changes, collectively termed "airway remodeling," can constitute an important long term consequence of asthma.

Objectives: The expansion of over-the-counter (OTC) hearing aids has raised inquiries regarding primary care physicians' (PCP) knowledge, perspective, and perceived roles. We aimed to understand PCP perspectives on OTC hearing aids via nationwide online surveys., Methods: RedCap survey was distributed to PCPs via online forums and public mailing lists. Outcomes included PCPs' attitudes toward, perceived role surrounding, confidence managing, and knowledge of OTC hearing aids. Regression analyses were performed to identify associated factors including demographics and practice characteristics., Results: Cohort included 111 PCPs primarily working in non-rural (83.8%) outpatient academic medical centers (47.5%), with a mean (SD) of 16.9 (11.6) years practicing. Most reported unfamiliarity (61.3%) with OTC hearing aids but viewed them positively (91.9%). They often perceived themselves as poor sources of OTC hearing aid information (63.1%) but desired involvement (90.1%) and believed associated knowledge is important (98.2%). Rural practice environment was associated with less familiarity toward OTC hearing aids (β = -0.72, [95% CI -1.40 to -0.04]). Respondents answered 5.0 (2.4) of 10 OTC hearing aid knowledge questions correctly. Using 5-point Likert scale, participants reported most confidence recognizing signs/symptoms of hearing loss 3.71 (0.84), but less confidence educating 1.68 (0.96) about and determining candidacy 1.72 (1.05) for OTC hearing aids. Participants reported continuing medical education courses and published guidelines would effectively improve their OTC hearing aid knowledge., Conclusion: PCPs displayed positive attitudes toward OTC hearing aids and valued involvement. Addressing unfamiliarity/knowledge gaps surrounding OTC hearing aids through courses and published guidelines may help clarify misconceptions and promote hearing health care., Level of Evidence: NA Laryngoscope, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Electrolytes (sodium, potassium, calcium, magnesium, chloride, phosphate) are required in specific amounts for proper functioning of the human body. Although the body has different organ systems, such as the kidneys, that regulate electrolyte levels in the blood, electrolyte abnormalities occur frequently in people with eating disorders. The objective of this review will be to examine the association between electrolyte imbalances and adverse outcomes in people with eating disorders., Methods: A systematic review of studies on eating and electrolyte disorders shall be conducted. Electronic searches shall be done in the Ovid MEDLINE, EMBASE, and PsycINFO databases. Selected studies shall include randomized control trials (RCTs), non-randomized controlled trials, and cross-sectional studies published in English or French. Quality appraisal of studies and a narrative synthesis of extracted data shall be conducted., Discussion: This review will synthesize existing evidence on electrolyte abnormalities in people with eating disorders. It will identify the type of electrolyte imbalances, their impact, and outcomes in people with eating disorders. We anticipate that information that will be useful to policy makers and clinicians in designing better policies to prevent eating disorders and or manage people with eating disorders shall be elucidated in this study., Dissemination: The final manuscript will be submitted for publication in a journal., Review Registration: This protocol has been registered with the International Prospective Register of Systematic Reviews (PROSPERO); registration number CRD42023477497., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Buh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Social determinants of health are non-medical factors that impact health. For patients with chronic kidney disease (CKD) progressing to kidney failure, the influence of social determinants of health on dialysis modality selection (haemodialysis vs. peritoneal dialysis (PD)) is incompletely understood., Methods: Retrospective cohort study of 981 consecutive patients with advanced CKD referred to the Ottawa Hospital Multi-Care Kidney Clinic (Canada) who progressed to dialysis from 2010 to 2021. Multivariable logistic regression was used to measure odds ratios (OR) for the associations between social determinants of health (education, employment, marital status and residence) and modality of dialysis initiation., Results: The mean age and estimated glomerular filtration rate were 64 and 18 mL/min/1.73 m 2 , respectively. Not having a high school degree was associated with lower odds of initiating dialysis via PD compared to having a college degree (29% vs. 48%, OR 0.55 (95% confidence interval (CI) 0.34-0.88)). Unemployment was associated with lower odds of initiating dialysis via PD compared to active employment (38% vs. 62%, OR 0.40 (95% CI 0.27-0.60)). Being single was associated with lower odds of initiating dialysis via PD compared to being married (35% vs. 48%, adjusted OR 0.52 (95% CI 0.39-0.70)). Living alone at home was associated with lower odds of initiating dialysis via PD compared to living at home with family (33% vs. 47%, adjusted OR 0.55 (95% CI 0.39-0.78))., Conclusions: Social determinants of health including education, employment, marital status and residence are associated with dialysis modality selection. Addressing these 'upstream' social factors may allow for more equitable outcomes during the transition from advanced CKD to kidney failure., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: AA has received speaker fees from AstraZeneca and holds research grants from Otsuka. MMS has received speaker fees from AstraZeneca. All other authors declare no conflicts of interest.

Infants less than 1 year old diagnosed with KMT2A-rearranged (KMT2A-r) acute lymphoblastic leukemia (ALL) are at high risk of remission failure, relapse, and death due to leukemia, despite intensive therapies. Infant KMT2A-r ALL blasts are characterized by DNA hypermethylation. Epigenetic priming with DNA methyltransferase inhibitors increases the cytotoxicity of chemotherapy in preclinical studies. The Children's Oncology Group trial AALL15P1 tested the safety and tolerability of five days of azacitidine immediately prior to the start of chemotherapy on day six, in four post-induction chemotherapy courses for infants with newly diagnosed KMT2A-r ALL. The treatment was welltolerated, with only two of 31 evaluable patients (6.5%) experiencing dose-limiting toxicity. Whole genome bisulfite sequencing of peripheral blood mononuclear cells (PBMCs) demonstrated decreased DNA methylation in 87% of samples tested following five days of azacitidine. Event-free survival was similar to prior studies of newly diagnosed infant ALL. Azacitidine is safe and results in decreased DNA methylation of PBMCs in infants with KMT2A-r ALL, but the incorporation of azacitidine to enhance cytotoxicity did not impact survival. Clinicaltrials.gov identifier: NCT02828358.

Atherosclerosis differs across major arteries. Although the biological basis is not fully understood, limited evidence of genetic differences has been documented. This study, therefore, was aimed to identify differentially expressed genes between clinically relevant major arteries and investigate their enrichment in endothelial dysfunction-related gene sets. A bioinformatic analysis of publicly available gene-level read counts for coronary, aortic, and tibial arteries was performed. Differential gene expression was conducted with DeSeq2 at a false discovery rate of 0.05. Differentially expressed genes were then subjected to over-representation analysis and active-subnetwork-oriented enrichment analysis, both at a false discovery rate of 0.005. Enriched terms common to both analyses were categorized for each contrast into immunity/inflammation-, membrane biology-, lipid metabolism-, and coagulation-related terms, and the top differentially expressed genes validated against Swiss Institute of Bioinformatics' Bgee database. There was mostly upregulation of differentially expressed genes for the coronary/tibial and aorta/tibial contrasts, but milder changes for the coronary/aorta contrast. Transcriptomic differences between coronary or aortic versus tibial samples largely involved immunity/inflammation-, membrane biology-, lipid metabolism-, and coagulation-related genes, suggesting potential to modulate endothelial dysfunction and atherosclerosis. These results imply atheroprone coronary and aortic environments compared with tibial artery tissue, which may explain observed relative inter-artery atherosclerosis risk., Competing Interests: The author declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Background: Equity, diversity and inclusion (EDI) in the healthcare field are crucial in meeting the healthcare needs of a progressively diverse society. In fact, a diverse healthcare workforce enables culturally sensitive care, promotes health equity and enhances the understanding of various needs and patients' viewpoints, potentially resulting in more effective patient treatment and improved patient outcomes. Despite this, information on the effectiveness of policies or programmes promoting EDI in health institutions is scarce. The objective of this systematic review is to assess the effects and outcomes of EDI programmes in healthcare institutions., Methods: We will conduct Preferred Reporting Items for Systematic Reviews and Meta-Analyses-compliant systematic review of studies on EDI programmes and describe their effects and outcomes in healthcare institutions. We will search PubMed, Scopus, Web of Science, CINAHL and PsycINFO databases. Selected studies will include randomised control trials (RCTs), non-RCTs and cross-sectional studies published either in English or French. Quality appraisal of studies and a narrative synthesis of extracted data will be conducted as well as a meta-analysis if possible. The quality of evidence in this review will be assessed by the Grades of Recommendation, Assessment, Development and Evaluation., Anticipated Results: We anticipate that this systematic review will reveal information on the effect of EDI programmes and their outcomes in healthcare institutions. We expect this information will provide insights that will lead to improvements in designing EDI policies and programmes in healthcare institutions., Ethics and Dissemination: No ethical clearance is required for this study as no primary data will be collected. The final manuscript will be submitted to a journal for publication. In addition to this, the results of the study will also be disseminated through conference presentations to inform the research and clinical practice., Review Registration: This protocol has been registered with the International Prospective Register of Systematic Reviews; registration number CRD42024502781., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The substitution of p-block heteroatoms into polyaromatic hydrocarbons offers the potential for introducing enhanced molecular properties and advancing material development for electro-optical applications. Using density functional theory, we characterize the substitution of boron and nitrogen atoms into a 2,3,6,7,10,11-hexakis(hexathiol)triphenylene (TTP) core, a precursor for a material with a discotic liquid crystal phase, to determine the strength of exciton dissociation and the influence doping has on the formation of a heterojunction with graphene. The substitution of nitrogen and boron into the TTP motif enables tunability of both electron and hole coupling between hetero- and homodyads. The coupling is found to far exceed that of TTP and varied transport behavior with different combinations of doped cores of nitrogen-TTP and boron-TTP is reported. Heterodyads of nitrogen-TTP with boron-TTP appear to be ambipolar in electron/hole coupling, whereas heterodyads of boron- or nitrogen-TTP with TTP form strong electron coupling dyads and homodyads of nitrogen-TTP and boron-TTP form strong hole coupling. Finally, we describe the heterojunction of nitrogen- or boron-TTP with monolayer graphene and observe Ohmic contacts with large hole transport barriers. The presence of induced dipoles occurs at the interface in all heterojunctions, suggesting the possibility of tuning the junction with external potentials and improving exciton dissociation.

Background: Distributed Medical Education (DME), a decentralized model focused on smaller cities and communities, has been implemented worldwide to bridge the gap in psychiatric education. Faculty engagement in teaching activities such as clinical teaching, supervision, and examinations is a crucial aspect of DME sites. Implementing or expanding DME sites requires careful consideration to identify enablers that contribute to success and barriers that need to be addressed. This study aims to examine enablers, barriers, and factors influencing psychiatrists' willingness to start or continue participating in teaching activities within Dalhousie University's Faculty of Medicine DME sites in two provinces in Atlantic Canada., Methodology: This cross-sectional study was conducted as part of an environmental scan of Dalhousie Faculty of Medicine's DME programs in Nova Scotia (NS) and New Brunswick (NB), Canada. In February 2023, psychiatrists from seven administrative health zones in these provinces anonymously participated in an online survey. The survey, created with OPINIO, collected data on sociodemographic factors, practice-related characteristics, medical education, and barriers to teaching activities. Five key outcomes were assessed, which included psychiatrists' willingness to engage in (i) clinical training and supervision, (ii) lectures or skills-based teaching, (iii) skills-based examinations, (iv) training and supervision of Canadian-trained psychiatrists, and (v) training and supervision of internationally trained psychiatrists. The study employed various statistical analyses, including descriptive analysis, chi-square tests, and logistic regression, to identify potential predictors associated with each outcome variable., Results: The study involved 60 psychiatrists, primarily male (69%), practicing in NS (53.3%), with international medical education (69%), mainly working in outpatient services (41%). Notably, 60.3% lacked formal medical education training, yet they did not perceive the lack of training as a significant barrier, but lack of protected time as the main one. Despite this, there was a strong willingness to engage in teaching activities, with an average positive response rate of 81.98%. The lack of protected time for teaching/training was a major barrier reported by study participants. Availability to take the Royal College of Physicians and Surgeons of Canada Competency by Design training was the main factor associated with psychiatrists' willingness to participate in the five teaching activities investigated in this study: willingness to participate in clinical training and supervision of psychiatry residents (p = .01); provision of lectures or skills-based teaching for psychiatry residents (p < .01); skills-based examinations of psychiatry residents (p < .001); training/supervision of Canadian-trained psychiatrists (p < .01); and training and supervision of internationally trained psychiatrists (p < .01)., Conclusion: The study reveals a nuanced picture regarding psychiatrists' engagement in teaching activities at DME sites. Despite a significant association between interest in formal medical education training and willingness to participate in teaching activities, clinicians do not consider the lack of formal training as a barrier. Addressing this complexity requires thoughtful strategies, potentially involving resource allocation, policy modifications, and adjustments to incentive structures by relevant institutions., (© 2024. The Author(s).)

Improvements in survival have been made over the past two decades for childhood acute myeloid leukemia (AML), but the approximately 40% of patients who relapse continue to have poor outcomes. A combination of checkpoint-inhibitor nivolumab and azacitidine has demonstrated improvements in median survival in adults with AML. This phase I/II study with nivolumab and azacitidine in children with relapsed/refractory AML (NCT03825367) was conducted through the Therapeutic Advances in Childhood Leukemia & Lymphoma consortium. Thirteen patients, median age 13.7 years, were enrolled. Patients had refractory disease with multiple reinduction attempts. Twelve evaluable patients were treated at the recommended phase II dose (established at dose level 1, 3 mg/kg/dose). Four patients (33%) maintained stable disease. This combination was well tolerated, with no dose-limiting toxicities observed. Grade 3-4 adverse events (AEs) were primarily hematological. Febrile neutropenia was the most common AE ≥ grade 3. A trend to improved quality of life was noted. Increases in CD8+ T cells and reductions in CD4+/CD8+ T cells and demethylation were observed. The combination was well tolerated and had an acceptable safety profile in pediatric patients with relapsed/refractory AML. Future studies might explore this combination for the maintenance of remission in children with AML at high risk of relapse.

Introduction: Intraperitoneal (IP) vancomycin is often first-line empiric therapy and then maintenance therapy for peritoneal dialysis (PD) peritonitis. However, how vancomycin serum levels correlate with clinical outcomes remains unclear., Methods: We conducted a retrospective single-center adult cohort study of 98 patients with PD peritonitis treated with IP vancomycin between January 2016 and May 2022. The association between nadir vancomycin level and cure was evaluated in a logistic regression model, first unadjusted and then adjusted for age, sex, weight, glomerular filtration rate (GFR), and total number of days on PD. Vancomycin was assessed both as a continuous exposure (per 1 mg/l increase) and as a categorical exposure (<15 mg/l vs. ≥15 mg/l). A receiver operating characteristic curve (ROC) was created to explore nadir vancomycin level thresholds in an attempt to identify an optimal target level during treatment., Results: Of the patients, 81% achieved cure, and patients with nadir vancomycin level ≥15 mg/l were 7.5 times more likely to experience cure compared to those with a nadir level <15 mg/l (odds ratio [OR] 7.58, 95% confidence interval [CI] 1.71-33.57, P  = 0.008). Weight, GFR, days on PD, sex, and age were not independently associated with outcome. The vancomycin level with the greatest discriminatory capacity for cure on the ROC analysis was 14.4 mg/l., Conclusion: Increasing IP vancomycin serum levels are associated with increased odds of cure; and maintaining vancomycin serum levels above 14-15 mg/l throughout the course of PD peritonitis treatment is likely to improve clinical outcomes., (© 2023 International Society of Nephrology. Published by Elsevier Inc.)

Purpose: Blinatumomab, a bispecific T-cell engager immunotherapy, is efficacious in relapsed/refractory B-cell ALL (B-ALL) and has a favorable toxicity profile. One aim of the Children's Oncology Group AALL1331 study was to compare survival of patients with low-risk (LR) first relapse of B-ALL treated with chemotherapy alone or chemotherapy plus blinatumomab., Patients and Methods: After block 1 reinduction, patients age 1-30 years with LR first relapse of B-ALL were randomly assigned to block 2/block 3/two continuation chemotherapy cycles/maintenance (arm C) or block 2/two cycles of continuation chemotherapy intercalated with three blinatumomab blocks/maintenance (arm D). Patients with CNS leukemia received 18 Gy cranial radiation during maintenance and intensified intrathecal chemotherapy. The primary and secondary end points were disease-free survival (DFS) and overall survival (OS)., Results: The 4-year DFS/OS for the 255 LR patients accrued between December 2014 and September 2019 were 61.2% ± 5.0%/90.4% ± 3.0% for blinatumomab versus 49.5% ± 5.2%/79.6% ± 4.3% for chemotherapy ( P = .089/ P = .11). For bone marrow (BM) ± extramedullary (EM) (BM ± EM; n = 174) relapses, 4-year DFS/OS were 72.7% ± 5.8%/97.1% ± 2.1% for blinatumomab versus 53.7% ± 6.7%/84.8% ± 4.8% for chemotherapy ( P = .015/ P = .020). For isolated EM (IEM; n = 81) relapses, 4-year DFS/OS were 36.6% ± 8.2%/76.5% ± 7.5% for blinatumomab versus 38.8% ± 8.0%/68.8% ± 8.6% for chemotherapy ( P = .62/ P = .53). Blinatumomab was well tolerated and patients had low adverse event rates., Conclusion: For children, adolescents, and young adults with B-ALL in LR first relapse, there was no statistically significant difference in DFS or OS between the blinatumomab and standard chemotherapy arms overall. However, blinatumomab significantly improved DFS and OS for the two thirds of patients with BM ± EM relapse, establishing a new standard of care for this population. By contrast, similar outcomes and poor DFS for both arms were observed in the one third of patients with IEM; new treatment approaches are needed for these patients (ClinicalTrials.gov identifier: NCT02101853).

Aims: Oncology stakeholders' view on shared decision making (SDM) in Aotearoa New Zealand is not well described in the literature. This study aimed to explore the perspectives of patients, clinicians and other cancer care stakeholders on shared decision making, and how and why shared decision making in cancer care can be viable and appropriate for patients and healthcare providers., Methods: Non-random, purposive sampling, combined with advertisement and snowball recruitment identified patient, whānau and healthcare provider participants for qualitative interviews. One-hour, semi-structured interviews were conducted to elicit perspectives on SDM. Data was analysed using Directed Content Analysis., Results: Thirty-one participants were interviewed. SDM conceptualisations primarily concerned the sharing of information. Participants' stories highlighted patients' and whānau willingness to participate in making decisions about their care, to hold authority in this process, and to have their needs and preferences considered beyond the biomedical model. Patients and clinicians identified a range of factors moderating the extent of SDM, creating a gap between SDM expectations and practice., Conclusions: These data highlight the complexity of information needs in cancer care, and the discrepancy between patients' and their whānau and clinicians' views. This study increases our understanding of cancer stakeholders' expectations of SDM by highlighting various views on the meaning of SDM, informational needs and decision making engagement level. These findings can aid clinicians in creating space for patients to exercise their right to self-determination/rangatiratanga of health and wellbeing. Future work should explore approaches and implementations of SDM to facilitate an equitable experience of cancer care., Competing Interests: Nil, (© PMA.)

This study aimed to identify country-level predictors of COVID-19 mortality, after controlling for diverse potential factors, and utilizing current worldwide mortality data. COVID-19 deaths, as well as geographic, demographic, socioeconomic, healthcare, population health, and pandemic-related variables, were obtained for 152 countries. Continuous variables were examined with Spearman's correlation, categorical variables with ANOVA or Welch's Heteroscedastic F Test, and country-level independent predictors of COVID-19 mortality identified by weighted generalized additive models. This study identified independent mortality predictors in six limited models, comprising groups of related variables. However, in the full model, only WHO region, percent of population ≥ 65 years, Corruption Perception Index, hospital beds/100,000 population, and COVID-19 cases/100,000 population were predictive of mortality, with model accounting for 80.7% of variance. These findings suggest areas for focused intervention in the event of similar future public health emergencies, including prioritization of the elderly, optimizing healthcare capacity, and improving deficient health sector-related governance., (© 2023. The Author(s).)