Shared genetics linking sociability with the brain's default mode network.

The brain's default mode network (DMN) plays a role in social cognition, with altered DMN function being associated with social impairments across various neuropsychiatric disorders. In the present study, we examined the genetic relationship between sociability and DMN-related resting-state functional magnetic resonance imaging (rs-fMRI) traits. To this end, we used genome-wide association summary statistics for sociability and 31 activity and 64 connectivity DMN-related rs-fMRI traits (N=34,691-342,461). First, we examined global and local genetic correlations between sociability and the rs-fMRI traits. Second, to assess putatively causal relationships between the traits, we conducted bi-directional Mendelian randomisation (MR) analyses. Finally, we prioritised genes influencing both sociability and rs-fMRI traits by combining three methods: gene-expression eQTL MR analyses, the CELLECT framework using single-nucleus RNA-seq data, and network propagation in the context of a protein-protein interaction network. Significant local genetic correlations were found between sociability and two rs-fMRI traits, one representing spontaneous activity within the temporal cortex, the other representing connectivity between the frontal/cingulate and angular/temporal cortices. Sociability affected 12 rs-fMRI traits when allowing for weakly correlated genetic instruments. Combing all three methods for gene prioritisation, we defined 17 highly prioritised genes, with DRD2 and LINGO1 showing the most robust evidence across all analyses. By integrating genetic and transcriptomics data, our gene prioritisation strategy may serve as a blueprint for future studies. The prioritised genes could be explored as potential biomarkers for social dysfunction in the context of neuropsychiatric disorders and as drug target genes.

Driving Precision of Pediatric VTE Risk-stratification through Genetics.

This study addresses rising incidence of pediatric venous thromboembolism by validating a VTE phenotype and developing a polygenic risk score (PRS) using UK Biobank data. Our findings demonstrate predictive value of the PRS, enhancing VTE risk assessment in clinical settings. Future steps involve integrating the PRS into risk stratification models.

A systematic review of large language models and their implications in medical education.

INTRODUCTION: In the past year, the use of large language models (LLMs) has generated significant interest and excitement because of their potential to revolutionise various fields, including medical education for aspiring physicians. Although medical students undergo a demanding educational process to become competent health care professionals, the emergence of LLMs presents a promising solution to challenges like information overload, time constraints and pressure on clinical educators. However, integrating LLMs into medical education raises critical concerns and challenges for educators, professionals and students. This systematic review aims to explore LLM applications in medical education, specifically their impact on medical students' learning experiences. METHODS: A systematic search was performed in PubMed, Web of Science and Embase for articles discussing the applications of LLMs in medical education using selected keywords related to LLMs and medical education, from the time of ChatGPT's debut until February 2024. Only articles available in full text or English were reviewed. The credibility of each study was critically appraised by two independent reviewers. RESULTS: The systematic review identified 166 studies, of which 40 were found by review to be relevant to the study. Among the 40 relevant studies, key themes included LLM capabilities, benefits such as personalised learning and challenges regarding content accuracy. Importantly, 42.5% of these studies specifically evaluated LLMs in a novel way, including ChatGPT, in contexts such as medical exams and clinical/biomedical information, highlighting their potential in replicating human-level performance in medical knowledge. The remaining studies broadly discussed the prospective role of LLMs in medical education, reflecting a keen interest in their future potential despite current constraints. CONCLUSIONS: The responsible implementation of LLMs in medical education offers a promising opportunity to enhance learning experiences. However, ensuring information accuracy, emphasising skill-building and maintaining ethical safeguards are crucial. Continuous critical evaluation and interdisciplinary collaboration are essential for the appropriate integration of LLMs in medical education.

Use of drugs for hyperlipidaemia and diabetes and risk of primary and secondary brain tumours: nested case-control studies using the UK Clinical Practice Research Datalink (CPRD).

OBJECTIVES: Previous studies have suggested that fibrates and glitazones may have a role in brain tumour prevention. We examined if there is support for these observations using primary care records from the UK Clinical Practice Research Datalink (CPRD). DESIGN: We conducted two nested case-control studies using primary and secondary brain tumours identified within CPRD between 2000 and 2016. We selected cases and controls among the population of individuals who had been treated with any anti-diabetic or anti-hyperlipidaemic medication to reduce confounding by indication. SETTING: Adults older than 18 years registered with a general practitioner in the UK contributing data to CPRD. RESULTS: We identified 7496 individuals with any brain tumour (4471 primary; 3025 secondary) in total. After restricting cases and controls to those prescribed any anti-diabetic or anti-hyperlipidaemic medication, there were 1950 cases and 7791 controls in the fibrate and 480 cases with 1920 controls in the glitazone analyses. Longer use of glitazones compared with all other anti-diabetic medications was associated with a reduced risk of primary (adjusted OR (aOR) 0.89 per year, 95% CI 0.80 to 0.98), secondary (aOR 0.87 per year, 95% CI 0.77 to 0.99) or combined brain tumours (aOR 0.88 per year, 95% CI 0.81 to 0.95). There was little evidence that fibrate exposure was associated with risk of either primary or secondary brain tumours. CONCLUSIONS: Longer exposure to glitazones was associated with reduced primary and secondary brain tumour risk. Further basic science and population-based research should explore this finding in greater detail, in terms of replication and mechanistic studies.

Competency-Based Education in RN to BSN Programs.

BACKGROUND: The call for nursing education reform has never been louder. National organizations recognize the urgent need to prepare nursing students to practice competently, moving away from traditional teaching and curricula and to competency-based education (CBE) strategies to prepare future nurses for independent clinical practice. PROBLEM: The 2021 American Association of Colleges of Nursing Essentials do not account for the competencies achieved in registered nurse (RN) associate degree and diploma programs. This presents a challenge for RN to bachelor of science in nursing (BSN) program administrators and faculty when designing curricula to meet the new Essentials . APPROACH: The Essentials crosswalk created by the National RN-Baccalaureate Faculty Forum serves as a foundational guide for the development of the template models discussed in this article. CONCLUSION: This article provides a template of instructional models for implementing CBE in RN to BSN programs.

Association between circulating inflammatory markers and adult cancer risk: a Mendelian randomization analysis.

BACKGROUND: Tumour-promoting inflammation is a "hallmark" of cancer and conventional epidemiological studies have reported links between various inflammatory markers and cancer risk. The causal nature of these relationships and, thus, the suitability of these markers as intervention targets for cancer prevention is unclear. METHODS: We meta-analysed 6 genome-wide association studies of circulating inflammatory markers comprising 59,969 participants of European ancestry. We then used combined cis-Mendelian randomization and colocalisation analysis to evaluate the causal role of 66 circulating inflammatory markers in risk of 30 adult cancers in 338,294 cancer cases and up to 1,238,345 controls. Genetic instruments for inflammatory markers were constructed using genome-wide significant (P < 5.0 × 10-8) cis-acting SNPs (i.e., in or ±250 kb from the gene encoding the relevant protein) in weak linkage disequilibrium (LD, r2 < 0.10). Effect estimates were generated using inverse-variance weighted random-effects models and standard errors were inflated to account for weak LD between variants with reference to the 1000 Genomes Phase 3 CEU panel. A false discovery rate (FDR)-corrected P-value ("q-value") <0.05 was used as a threshold to define "strong evidence" to support associations and 0.05 ≤ q-value < 0.20 to define "suggestive evidence". A colocalisation posterior probability (PPH4) >70% was employed to indicate support for shared causal variants across inflammatory markers and cancer outcomes. Findings were replicated in the FinnGen study and then pooled using meta-analysis. FINDINGS: We found strong evidence to support an association of genetically-proxied circulating pro-adrenomedullin concentrations with increased breast cancer risk (OR: 1.19, 95% CI: 1.10-1.29, q-value = 0.033, PPH4 = 84.3%) and suggestive evidence to support associations of interleukin-23 receptor concentrations with increased pancreatic cancer risk (OR: 1.42, 95% CI: 1.20-1.69, q-value = 0.055, PPH4 = 73.9%), prothrombin concentrations with decreased basal cell carcinoma risk (OR: 0.66, 95% CI: 0.53-0.81, q-value = 0.067, PPH4 = 81.8%), and interleukin-1 receptor-like 1 concentrations with decreased triple-negative breast cancer risk (OR: 0.92, 95% CI: 0.88-0.97, q-value = 0.15, PPH4 = 85.6%). These findings were replicated in pooled analyses with the FinnGen study. Though suggestive evidence was found to support an association of macrophage migration inhibitory factor concentrations with increased bladder cancer risk (OR: 2.46, 95% CI: 1.48-4.10, q-value = 0.072, PPH4 = 76.1%), this finding was not replicated when pooled with the FinnGen study. For 22 of 30 cancer outcomes examined, there was little evidence (q-value ≥0.20) that any of the 66 circulating inflammatory markers examined were associated with cancer risk. INTERPRETATION: Our comprehensive joint Mendelian randomization and colocalisation analysis of the role of circulating inflammatory markers in cancer risk identified potential roles for 4 circulating inflammatory markers in risk of 4 site-specific cancers. Contrary to reports from some prior conventional epidemiological studies, we found little evidence of association of circulating inflammatory markers with the majority of site-specific cancers evaluated. FUNDING: Cancer Research UK (C68933/A28534, C18281/A29019, PPRCPJT∖100005), World Cancer Research Fund (IIG_FULL_2020_022), National Institute for Health Research (NIHR202411, BRC-1215-20011), Medical Research Council (MC_UU_00011/1, MC_UU_00011/3, MC_UU_00011/6, and MC_UU_00011/4), Academy of Finland Project 326291, European Union's Horizon 2020 grant agreement no. 848158 (EarlyCause), French National Cancer Institute (INCa SHSESP20, 2020-076), Versus Arthritis (21173, 21754, 21755), National Institutes of Health (U19 CA203654), National Cancer Institute (U19CA203654).

Creation of an Enhanced Primary Care Registered Nurse Preceptor Role: A Pilot Project.

Historically, community health nursing education has not encompassed clinical sites in primary care. Primary care can be an important domain of community health nursing education. However, student practicum opportunities are limited by the number of and underutilization of RNs practicing at the full scope of their licensure (including assessment, client education, care planning and evaluation of care interventions) who can serve as student preceptors, especially in rural areas. This article describes the creation and implementation of the Enhanced Primary Care Registered Nurse (EPCRN) role in rural primary care clinics, as well as evaluates student perceptions of the EPCRN-precepted clinical experience. One nursing school used a federal training award to create the role of Enhanced Primary Care Registered Nurses (EPCRNs) to practice in federally-designated Rural Health Clinics. The EPCRNs worked in the Rural Health Clinics performing patient care and also functioned as student preceptors. Student experiences were evaluated through quantitative and qualitative methods, namely the Clinical Learning Experience, Supervision, and Nurse Teacher (CLES+T) scale and focus groups. This pilot project demonstrated positive pre-licensure student experience feedback as well as role value and sustainability for the health system. This pilot served as an example of a process for EPCRN role design within a primary care clinic site. It also demonstrated the importance of innovative, sustainable academic-practice partnerships.

Developing and evaluating pediatric phecodes (Peds-Phecodes) for high-throughput phenotyping using electronic health records.

OBJECTIVE: Pediatric patients have different diseases and outcomes than adults; however, existing phecodes do not capture the distinctive pediatric spectrum of disease. We aim to develop specialized pediatric phecodes (Peds-Phecodes) to enable efficient, large-scale phenotypic analyses of pediatric patients. MATERIALS AND METHODS: We adopted a hybrid data- and knowledge-driven approach leveraging electronic health records (EHRs) and genetic data from Vanderbilt University Medical Center to modify the most recent version of phecodes to better capture pediatric phenotypes. First, we compared the prevalence of patient diagnoses in pediatric and adult populations to identify disease phenotypes differentially affecting children and adults. We then used clinical domain knowledge to remove phecodes representing phenotypes unlikely to affect pediatric patients and create new phecodes for phenotypes relevant to the pediatric population. We further compared phenome-wide association study (PheWAS) outcomes replicating known pediatric genotype-phenotype associations between Peds-Phecodes and phecodes. RESULTS: The Peds-Phecodes aggregate 15 533 ICD-9-CM codes and 82 949 ICD-10-CM codes into 2051 distinct phecodes. Peds-Phecodes replicated more known pediatric genotype-phenotype associations than phecodes (248 vs 192 out of 687 SNPs, P < .001). DISCUSSION: We introduce Peds-Phecodes, a high-throughput EHR phenotyping tool tailored for use in pediatric populations. We successfully validated the Peds-Phecodes using genetic replication studies. Our findings also reveal the potential use of Peds-Phecodes in detecting novel genotype-phenotype associations for pediatric conditions. We expect that Peds-Phecodes will facilitate large-scale phenomic and genomic analyses in pediatric populations. CONCLUSION: Peds-Phecodes capture higher-quality pediatric phenotypes and deliver superior PheWAS outcomes compared to phecodes.

Developing and Evaluating Pediatric Phecodes (Peds-Phecodes) for High-Throughput Phenotyping Using Electronic Health Records.

Objective: Pediatric patients have different diseases and outcomes than adults; however, existing phecodes do not capture the distinctive pediatric spectrum of disease. We aim to develop specialized pediatric phecodes (Peds-Phecodes) to enable efficient, large-scale phenotypic analyses of pediatric patients. Materials and Methods: We adopted a hybrid data- and knowledge-driven approach leveraging electronic health records (EHRs) and genetic data from Vanderbilt University Medical Center to modify the most recent version of phecodes to better capture pediatric phenotypes. First, we compared the prevalence of patient diagnoses in pediatric and adult populations to identify disease phenotypes differentially affecting children and adults. We then used clinical domain knowledge to remove phecodes representing phenotypes unlikely to affect pediatric patients and create new phecodes for phenotypes relevant to the pediatric population. We further compared phenome-wide association study (PheWAS) outcomes replicating known pediatric genotype-phenotype associations between Peds-Phecodes and phecodes. Results: The Peds-Phecodes aggregate 15,533 ICD-9-CM codes and 82,949 ICD-10-CM codes into 2,051 distinct phecodes. Peds-Phecodes replicated more known pediatric genotype-phenotype associations than phecodes (248 versus 192 out of 687 SNPs, p<0.001). Discussion: We introduce Peds-Phecodes, a high-throughput EHR phenotyping tool tailored for use in pediatric populations. We successfully validated the Peds-Phecodes using genetic replication studies. Our findings also reveal the potential use of Peds-Phecodes in detecting novel genotype-phenotype associations for pediatric conditions. We expect that Peds-Phecodes will facilitate large-scale phenomic and genomic analyses in pediatric populations. Conclusion: Peds-Phecodes capture higher-quality pediatric phenotypes and deliver superior PheWAS outcomes compared to phecodes.

Revolutionizing Healthcare with ChatGPT: An Early Exploration of an AI Language Model's Impact on Medicine at Large and its Role in Pediatric Surgery.

BACKGROUND: ChatGPT, a natural language processing model, has shown great promise in revolutionizing the field of medicine. This paper presents a comprehensive evaluation of the transformative potential of OpenAI's ChatGPT on healthcare and scientific research, with an exploration on its prospective capacity to impact the field of pediatric surgery. METHODS: Through an extensive review of the literature, we illuminate ChatGPT's applications in clinical healthcare and medical research while presenting the ethical considerations surrounding its use. RESULTS: Our review reveals the exciting work done so far evaluating the numerous potential uses of ChatGPT in clinical medicine and medical research, but it also shows that significant research and advancements in natural language processing models are still needed. CONCLUSION: ChatGPT has immense promise in transforming how we provide healthcare and how we conduct research. Currently, further robust research on the safety, effectiveness, and ethical considerations of ChatGPT is greatly needed. LEVEL OF STUDY: V.

Association between circulating inflammatory markers and adult cancer risk: a Mendelian randomization analysis.

Background: Tumour-promoting inflammation is a "hallmark" of cancer and conventional epidemiological studies have reported links between various inflammatory markers and cancer risk. The causal nature of these relationships and, thus, the suitability of these markers as intervention targets for cancer prevention is unclear. Methods: We meta-analysed 6 genome-wide association studies of circulating inflammatory markers comprising 59,969 participants of European ancestry. We then used combined cis-Mendelian randomization and colocalisation analysis to evaluate the causal role of 66 circulating inflammatory markers in risk of 30 adult cancers in 338,162 cancer cases and up to 824,556 controls. Genetic instruments for inflammatory markers were constructed using genome-wide significant (P < 5.0 x 10-8) cis-acting SNPs (i.e. in or ±250 kb from the gene encoding the relevant protein) in weak linkage disequilibrium (LD, r2 < 0.10). Effect estimates were generated using inverse-variance weighted random-effects models and standard errors were inflated to account for weak LD between variants with reference to the 1000 Genomes Phase 3 CEU panel. A false discovery rate (FDR)-corrected P-value ("q-value") < 0.05 was used as a threshold to define "strong evidence" to support associations and 0.05 ≤ q-value < 0.20 to define "suggestive evidence". A colocalisation posterior probability (PPH4) > 70% was employed to indicate support for shared causal variants across inflammatory markers and cancer outcomes. Results: We found strong evidence to support an association of genetically-proxied circulating pro-adrenomedullin concentrations with increased breast cancer risk (OR 1.19, 95% CI 1.10-1.29, q-value=0.033, PPH4=84.3%) and suggestive evidence to support associations of interleukin-23 receptor concentrations with increased pancreatic cancer risk (OR 1.42, 95% CI 1.20-1.69, q-value=0.055, PPH4=73.9%), prothrombin concentrations with decreased basal cell carcinoma risk (OR 0.66, 95% CI 0.53-0.81, q-value=0.067, PPH4=81.8%), macrophage migration inhibitory factor concentrations with increased bladder cancer risk (OR 1.14, 95% CI 1.05-1.23, q-value=0.072, PPH4=76.1%), and interleukin-1 receptor-like 1 concentrations with decreased triple-negative breast cancer risk (OR 0.92, 95% CI 0.88-0.97, q-value=0.15), PPH4=85.6%). For 22 of 30 cancer outcomes examined, there was little evidence (q-value ≥ 0.20) that any of the 66 circulating inflammatory markers examined were associated with cancer risk. Conclusion: Our comprehensive joint Mendelian randomization and colocalisation analysis of the role of circulating inflammatory markers in cancer risk identified potential roles for 5 circulating inflammatory markers in risk of 5 site-specific cancers. Contrary to reports from some prior conventional epidemiological studies, we found little evidence of association of circulating inflammatory markers with the majority of site-specific cancers evaluated.

Lowering of Circulating Sclerostin May Increase Risk of Atherosclerosis and Its Risk Factors: Evidence From a Genome-Wide Association Meta-Analysis Followed by Mendelian Randomization.

OBJECTIVE: In this study, we aimed to establish the causal effects of lowering sclerostin, target of the antiosteoporosis drug romosozumab, on atherosclerosis and its risk factors. METHODS: A genome-wide association study meta-analysis was performed of circulating sclerostin levels in 33,961 European individuals. Mendelian randomization (MR) was used to predict the causal effects of sclerostin lowering on 15 atherosclerosis-related diseases and risk factors. RESULTS: We found that 18 conditionally independent variants were associated with circulating sclerostin. Of these, 1 cis signal in SOST and 3 trans signals in B4GALNT3, RIN3, and SERPINA1 regions showed directionally opposite signals for sclerostin levels and estimated bone mineral density. Variants with these 4 regions were selected as genetic instruments. MR using 5 correlated cis-SNPs suggested that lower sclerostin increased the risk of type 2 diabetes mellitus (DM) (odds ratio [OR] 1.32 [95% confidence interval (95% CI) 1.03-1.69]) and myocardial infarction (MI) (OR 1.35 [95% CI 1.01-1.79]); sclerostin lowering was also suggested to increase the extent of coronary artery calcification (CAC) (ß = 0.24 [95% CI 0.02-0.45]). MR using both cis and trans instruments suggested that lower sclerostin increased hypertension risk (OR 1.09 [95% CI 1.04-1.15]), but otherwise had attenuated effects. CONCLUSION: This study provides genetic evidence to suggest that lower levels of sclerostin may increase the risk of hypertension, type 2 DM, MI, and the extent of CAC. Taken together, these findings underscore the requirement for strategies to mitigate potential adverse effects of romosozumab treatment on atherosclerosis and its related risk factors.

Infectious Complications and Antibiotic Use in Gastroschisis.

Background: Gastroschisis is a challenging neonatal condition often with prolonged hospitalizations, need for parenteral nutrition, infectious complications, and can even result in death. Infection is reported to occur in up to two-thirds of patients with gastroschisis and is a strong risk factor for increased morbidity and mortality. Increased days with a central venous catheter, complex gastroschisis, and delayed abdominal wall closure have been consistently found to be associated with increased risk of infection, whereas sutureless gastroschisis closure has been associated with fewer infections. Although one of the most common complications of gastroschisis is infection, the use of antibiotic agents varies widely with variability in the literature to guide management. Antibiotic usage should be selective and short-term, especially in neonates with simple gastroschisis regardless of method for abdominal wall closure. Conclusions: Future initiatives should focus on development of evidence-based guidelines on the care of these patients with the goal of reducing variability and improve outcomes within and across institutions.

Evidence-informed framework for gender transformative continuing education interventions for midwives and midwifery associations.

INTRODUCTION: Continuing education for midwives is an important investment area to improve the quality of sexual and reproductive health services. Interventions must take into account and provide solutions for the systemic barriers and gender inequities faced by midwives. Our objective was to generate concepts and a theoretical framework of the range of factors and gender transformative considerations for the development of continuing education interventions for midwives. METHODS: A critical interpretive synthesis complemented by key informant interviews, focus groups, observations and document review was applied. Three electronic bibliographic databases (CINAHL, EMBASE and MEDLINE) were searched from July 2019 to September 2020 and were again updated in June 2021. A coding structure was created to guide the synthesis across the five sources of evidence. RESULTS: A total of 4519 records were retrieved through electronic searches and 103 documents were included in the critical interpretive synthesis. Additional evidence totalled 31 key informant interviews, 5 focus groups (Democratic Republic of Congo and Tanzania), 24 programme documents and field observations in the form of notes. The resulting theoretical framework outlines the key considerations including gender, the role of the midwifery association, political and health systems and external forces along with key enabling elements for the design, implementation and evaluation of gender transformative continuing education interventions. CONCLUSION: Investments in gender transformative continuing education for midwives, led by midwifery associations, can lead to the improvement of midwifery across all United Nations' target areas including governance, health workforce, health system arrangements and education.

Quantifying the phenome-wide disease burden of obesity using electronic health records and genomics.

OBJECTIVE: High BMI is associated with many comorbidities and mortality. This study aimed to elucidate the overall clinical risk of obesity using a genome- and phenome-wide approach. METHODS: This study performed a phenome-wide association study of BMI using a clinical cohort of 736,726 adults. This was followed by genetic association studies using two separate cohorts: one consisting of 65,174 adults in the Electronic Medical Records and Genomics (eMERGE) Network and another with 405,432 participants in the UK Biobank. RESULTS: Class 3 obesity was associated with 433 phenotypes, representing 59.3% of all billing codes in individuals with severe obesity. A genome-wide polygenic risk score for BMI, accounting for 7.5% of variance in BMI, was associated with 296 clinical diseases, including strong associations with type 2 diabetes, sleep apnea, hypertension, and chronic liver disease. In all three cohorts, 199 phenotypes were associated with class 3 obesity and polygenic risk for obesity, including novel associations such as increased risk of renal failure, venous insufficiency, and gastroesophageal reflux. CONCLUSIONS: This combined genomic and phenomic systematic approach demonstrated that obesity has a strong genetic predisposition and is associated with a considerable burden of disease across all disease classes.

Evaluating the efficacy and mechanism of metformin targets on reducing Alzheimer's disease risk in the general population: a Mendelian randomisation study.

AIMS/HYPOTHESIS: Metformin use has been associated with reduced incidence of dementia in diabetic individuals in observational studies. However, the causality between the two in the general population is unclear. This study uses Mendelian randomisation (MR) to investigate the causal effect of metformin targets on Alzheimer's disease and potential causal mechanisms in the brain linking the two. METHODS: Genetic proxies for the effects of metformin drug targets were identified as variants in the gene for the corresponding target that associated with HbA1c level (N=344,182) and expression level of the corresponding gene (N≤31,684). The cognitive outcomes were derived from genome-wide association studies comprising 527,138 middle-aged Europeans, including 71,880 with Alzheimer's disease or Alzheimer's disease-by-proxy. MR estimates representing lifelong metformin use on Alzheimer's disease and cognitive function in the general population were generated. Effect of expression level of 22 metformin-related genes in brain cortex (N=6601 donors) on Alzheimer's disease was further estimated. RESULTS: Genetically proxied metformin use, equivalent to a 6.75 mmol/mol (1.09%) reduction on HbA1c, was associated with 4% lower odds of Alzheimer's disease (OR 0.96 [95% CI 0.95, 0.98], p=1.06×10-4) in non-diabetic individuals. One metformin target, mitochondrial complex 1 (MCI), showed a robust effect on Alzheimer's disease (OR 0.88, p=4.73×10-4) that was independent of AMP-activated protein kinase. MR of expression in brain cortex tissue showed that decreased MCI-related gene (NDUFA2) expression was associated with lower Alzheimer's disease risk (OR 0.95, p=4.64×10-4) and favourable cognitive function. CONCLUSIONS/INTERPRETATION: Metformin use may cause reduced Alzheimer's disease risk in the general population. Mitochondrial function and the NDUFA2 gene are plausible mechanisms of action in dementia protection.

The lasting effects of historical racial divides in nursing education: A case study examining holistic admission policies development.

BACKGROUND: Historically, in the United States, nursing programs reflected practices that systematically discriminated against Black students and nurses. OBJECTIVES: The authors investigated historical nursing school admission policies to determine if racist practices existed that impeded Black students' ability to access formal nurse training programs. This study further examined whether those historical discriminating practices continue to exist in schools of nursing today and if admission policies in a Southern School of Nursing contributed to inequitable admission of students. Current recommendations for increasing diversity, equity and inclusion in nursing schools will be addressed. METHODS: This study combines social-historical archival research with a case study of the racial breakdown of applied versus admitted nursing students at a Southern university. RESULTS: School of Nursing admission data (2019-2021) demonstrate discrepancies in the distribution of admitted students by race, reflecting the ongoing effects of systematic discrimination. CONCLUSIONS: In the United States, the nursing profession is pursuing strategies to promote diversity, equity, and inclusion. However, the lingering effects of policies that systematically built barriers keeping underrepresented groups from earning a nursing education persist. Holistic admission is one way that nursing programs can address this inequity.

Trans-ethnic Mendelian-randomization study reveals causal relationships between cardiometabolic factors and chronic kidney disease.

BACKGROUND: This study was to systematically test whether previously reported risk factors for chronic kidney disease (CKD) are causally related to CKD in European and East Asian ancestries using Mendelian randomization. METHODS: A total of 45 risk factors with genetic data in European ancestry and 17 risk factors in East Asian participants were identified as exposures from PubMed. We defined the CKD by clinical diagnosis or by estimated glomerular filtration rate of <60 ml/min/1.73 m2. Ultimately, 51 672 CKD cases and 958 102 controls of European ancestry from CKDGen, UK Biobank and HUNT, and 13 093 CKD cases and 238 118 controls of East Asian ancestry from Biobank Japan, China Kadoorie Biobank and Japan-Kidney-Biobank/ToMMo were included. RESULTS: Eight risk factors showed reliable evidence of causal effects on CKD in Europeans, including genetically predicted body mass index (BMI), hypertension, systolic blood pressure, high-density lipoprotein cholesterol, apolipoprotein A-I, lipoprotein(a), type 2 diabetes (T2D) and nephrolithiasis. In East Asians, BMI, T2D and nephrolithiasis showed evidence of causality on CKD. In two independent replication analyses, we observed that increased hypertension risk showed reliable evidence of a causal effect on increasing CKD risk in Europeans but in contrast showed a null effect in East Asians. Although liability to T2D showed consistent effects on CKD, the effects of glycaemic phenotypes on CKD were weak. Non-linear Mendelian randomization indicated a threshold relationship between genetically predicted BMI and CKD, with increased risk at BMI of >25 kg/m2. CONCLUSIONS: Eight cardiometabolic risk factors showed causal effects on CKD in Europeans and three of them showed causality in East Asians, providing insights into the design of future interventions to reduce the burden of CKD.

Enhancing the Prelicensure Clinical Learning Experience: A Student-Centered Learning Approach.

BACKGROUND: Studies of the clinical learning environment document the importance of the student's clinical learning process. PURPOSE: The aim of this study was to gather information on students' perceptions of their learning in the clinical environment. METHODS: A mixed-method strategy was used to explore nursing students' (N = 194) perceptions of their clinical learning experiences. Data were collected using the Clinical Learning Environment Inventory (CLEI) survey and open-ended questions. RESULTS: The results showed that significant CLEI factors were affordances and engagement, student-centeredness, valuing nurses' work, and fostering workplace learning and that these factors were important to prelicensure nursing students' learning in the clinical environment. In addition, the thematic concepts that enhanced their learning were clinical faculty who exhibited strong communication, encouraged and challenged learners, and were readily available. CONCLUSIONS: Clinical faculty in the clinical environment must be competent and able to support the prelicensure nursing student learner.

A pilot study to determine the incidence, type, and severity of non-routine events in neonates undergoing gastrostomy tube placement.

BACKGROUND: Non-routine events (NRE) are defined as any suboptimal occurrences in a process being measured in the opinion of the reporter and comes from the field of human factors engineering. These typically occur well up-stream of an adverse event and NRE measurement has not been applied to the complex context of neonatal surgery. We sought to apply this novel safety event measurement methodology to neonates in the NICU undergoing gastrostomy tube placement. METHODS: A prospective pilot study was conducted between November 2016 and August 2020 in the Level IV NICU and the pediatric operating rooms of an urban academic children's hospital to determine the incidence, severity, impact, and contributory factors of clinician-reported non-routine events (NREs, i.e., deviations from optimal care) and 30-day NSQIP occurrences in neonates receiving a G-tube. RESULTS: Clinicians reported at least one NRE in 32 of 36 (89%) G-tube cases, averaging 3.0 (Standard deviation: 2.5) NRE reports per case. NSQIP-P review identified 7 cases (19%) with NSQIP-P occurrences and each of these cases had multiple reported NREs. One case in which NREs were not reported was without NSQIP-P occurrences. The odds ratio of having a NSQIP-P occurrence with the presence of an NRE was 0.695 (95% CI 0.06-17.04). CONCLUSION: Despite being considered a "simple" operation, >80% of neonatal G-tube placement operations had at least one reported NRE by an operative team member. In this pilot study, NRE occurrence was not significantly associated with the subsequent reporting of an NSQIP-P occurrence. Understanding contributory factors of NREs that occur in neonatal surgery may promote surgical safety efforts and should be evaluated in larger and more diverse populations. LEVEL OF EVIDENCE: IV.