Pan-cancer discovery of somatic mutations from RNA sequencing data.

Identification of somatic mutations (SMs) is essential for characterizing cancer genomes. While DNA-seq is the prevalent method for identifying SMs, RNA-seq provides an alternative strategy to discover tumor mutations in the transcribed genome. Here, we have developed a machine learning based pipeline to discover SMs based on RNA-seq data (designated as RNA-SMs). Subsequently, we have conducted a pan-cancer analysis to systematically identify RNA-SMs from over 8,000 tumors in The Cancer Genome Atlas (TCGA). In this way, we have identified over 105,000 novel SMs that had not been reported in previous TCGA studies. These novel SMs have significant clinical implications in designing targeted therapy for improved patient outcomes. Further, we have combined the SMs identified by both RNA-seq and DNA-seq analyses to depict an updated mutational landscape across 32 cancer types. This new online SM atlas, OncoDB ( https://oncodb.org ), offers a more complete view of gene mutations that underline the development and progression of various cancers.

Surgical options and clinical outcomes for high myopia.

PURPOSE OF REVIEW: Higher degrees of myopia are currently being treated with refractive surgery. However, there is limited characterization and outcomes data for this cohort. This article aims to review the literature on highly myopic patients who had refractive surgery and present a retrospective analysis of 149 patients (270 eyes) with high to extreme myopia (≤-5.0D SE) who underwent refractive surgery [laser-assisted subepithelial keratomileusis (LASIK), photorefractive keratectomy (PRK), or implantable collamer lense (ICL)] at a single practice. RECENT FINDINGS: There is substantial literature on the efficacy of LASIK, PRK, and phakic intraocular lenses for refractive error correction, but a dearth of studies on patients with high to extreme myopia undergoing different types of refractive surgery. Our study reveals that this cohort of patients has excellent outcomes with minimal complications. SUMMARY: Our study reveals that the average preoperative myopia was highest in ICL patients (-10.03D), followed by PRK (-7.21D), and LASIK (-7.04D) patients. Not surprisingly, eyes with high myopia and thin corneas were offered and elected ICLs for their procedure. Highly myopic patients achieved outcomes consistent with data reported in the literature- average postoperative uncorrected visual acuity was 20/20 for LASIK and ICL eyes and 20/25 for PRK eyes.

Leveraging Text-to-Text Pretrained Language Models for Question Answering in Chemistry.

In this study, we present a question answering (QA) system for chemistry, named Marie, with the use of a text-to-text pretrained language model to attain accurate data retrieval. The underlying data store is "The World Avatar" (TWA), a general world model consisting of a knowledge graph that evolves over time. TWA includes information about chemical species such as their chemical and physical properties, applications, and chemical classifications. Building upon our previous work on KGQA for chemistry, this advanced version of Marie leverages a fine-tuned Flan-T5 model to seamlessly translate natural language questions into SPARQL queries with no separate components for entity and relation linking. The developed QA system demonstrates competence in providing accurate results for complex queries that involve many relation hops as well as showcasing the ability to balance correctness and speed for real-world usage. This new approach offers significant advantages over the prior implementation that relied on knowledge graph embedding. Specifically, the updated system boasts high accuracy and great flexibility in accommodating changes and evolution of the data stored in the knowledge graph without necessitating retraining. Our evaluation results underscore the efficacy of the improved system, highlighting its superior accuracy and the ability in answering complex questions compared to its predecessor.

Mathematical model of rabies vaccination in the United States.

Rabies is one of the oldest viral diseases and it has been present on every continent except Antarctica. Within the U.S. human rabies cases are quite rare. In the eastern USA, raccoons are the main reservoir hosts and pet vaccination serves as an important barrier against human rabies exposure. In this paper, we develop a compartmental model for rabies transmission amongst raccoons and domestic pets. We find the disease-free equilibria, reproduction numbers for the raccoons and domestic pets. We also determine the vaccination coverage/rates, both for raccoons and pets, needed to achieve the elimination of rabies.

The effects of bivalent human papillomavirus (HPV) vaccination on high-risk anogenital HPV infection among sexually active female adolescents with and without perinatally acquired HIV.

BACKGROUND: Females with perinatal HIV (PHIV) infection are at elevated risk for anogenital high-risk human papillomavirus (HR-HPV) infection. Limited data are available around the effect of the HPV vaccination after initiation of sexual activity among PHIV youth. This study aims to assess the impact of a bivalent HPV vaccination on the persistence of anogenital HR-HPV among sexually active female PHIV youth and matched HIV-negative controls aged 12-24years in Thailand and Vietnam. METHODS: During a 3-year study, prevalent, incident, and persistent HR-HPV infection were assessed at annual visits. A subset of participants received a bivalent HPV vaccine. Samples were taken for HPV testing from the vagina, cervix, and anus. HR-HPV persistence was defined as the detection of the same genotype(s) at any anogenital compartment over≥two consecutive visits. RESULTS: Of the 93 PHIV and 99 HIV-negative female youth enrolled in this study, 25 (27%) PHIV and 22 (22%) HIV-negative youth received a HPV vaccine. Persistent infection with any HR-HPV type was significantly lower among PHIV youth who received the vaccine compared to those who did not (33%vs 61%, P =0.02); a difference was not observed among HIV-negative youth (35%vs 50%, P =0.82). PHIV infection (adjusted prevalence ratio [aPR] 2.31, 95% CI 1.45-3.67) and not receiving a HPV vaccine (aPR, 1.19, 95%CI 1.06-1.33) were associated with persistent anogenital HR-HPV infection. CONCLUSIONS: Bivalent HPV vaccination after initiation of sexual activity was associated with reduced persistence of anogenital HR-HPV infection in Southeast Asian PHIV female youth, which may be related to vaccine cross-protection. Primary and catch-up HPV vaccinations should be prioritised for children and youth with HIV.

Effect of Feedback Modality on Simulated Surgical Skills Learning Using Automated Educational Systems- A Four-Arm Randomized Control Trial.

OBJECTIVE: To explore optimal feedback methodologies to enhance trainee skill acquisition in simulated surgical bimanual skills learning during brain tumor resections. HYPOTHESES: (1) Providing feedback results in better learning outcomes in teaching surgical technical skill when compared to practice alone with no tailored performance feedback. (2) Providing more visual and visuospatial feedback results in better learning outcomes when compared to providing numerical feedback. DESIGN: A prospective 4-parallel-arm randomized controlled trial. SETTING: Neurosurgical Simulation and Artificial Intelligence Learning Centre, McGill University, Canada. PARTICIPANTS: Medical students (n = 120) from 4 Quebec medical schools. RESULTS: Participants completed a virtually simulated tumor resection task 5 times while receiving 1 of 4 feedback based on their group allocation: (1) practice-alone without feedback, (2) numerical feedback, (3) visual feedback, and (4) visuospatial feedback. Outcome measures were participants' scores on 14-performance metrics and the number of expert benchmarks achieved during each task. There were no significant differences in the first task which determined baseline performance. A statistically significant interaction between feedback allocation and task repetition was found on the number of benchmarks achieved, F (10.558, 408.257)=3.220, p < 0.001. Participants in all feedback groups significantly improved their performance compared to baseline. The visual feedback group achieved significantly higher number of benchmarks than the practice-alone group by the third repetition of the task, p = 0.005, 95%CI [0.42 3.25]. Visual feedback and visuospatial feedback improved performance significantly by the second repetition of the task, p = 0.016, 95%CI [0.19 2.71] and p = 0.003, 95%CI [0.4 2.57], respectively. CONCLUSION: Simulations with autonomous visual computer assistance may be effective pedagogical tools in teaching bimanual operative skills via visual and visuospatial feedback information delivery.

Improving assessment and escalation of threatened haemodialysis access: results of a nursing-led program.

BACKGROUND: Optimal vascular access is critical to successful haemodialysis. Acute thrombosis of haemodialysis access often leads to unplanned hospital admissions and interventions to restore patency. Western Health is a large health service in Victoria, Australia. During the period February 2019 to January 2020, the rate of arteriovenous fistula (AVF) and arteriovenous graft (AVG) at Western Health satellite dialysis units was 0.33 episodes per 1000 patient-days, higher than the reported rate in the literature of 0.24 events per 1000 patient-days, and was associated with a cumulative total of 139 days of inpatient stay (2.2 per 1000 patient-days). METHODS: The above results prompted creation of an education and escalation pathway for threatened haemodialysis access, based upon clinical markers of vascular access stenosis or imminent thrombosis assessed by nursing staff in satellite haemodialysis centres. In the period February 2020 to January 2021, the education and escalation pathway was implemented. We assessed referrals via the pathway, rates of AVF/AVG thrombosis and associated hospital length of stay in the following 12-month period (February 2021 to January 2022). RESULTS: Following introduction of the pathway, rates of AVF/AVG thrombosis declined to 0.15 per 1000 patient-days (p = 0.02), associated with a decline in attributable cumulative inpatient stay to 55 days (0.69 per 1000 patient-days). CONCLUSIONS: Our program demonstrates that the majority of thrombosed vascular access can be predicted and potentially averted with vigilant and well-practiced routine clinical assessment by trained nursing staff. Our nursing-led education and escalation program successfully identified vascular access at risk of imminent thrombosis, reduced rates of acute thrombosis and associated healthcare costs. Despite these improvements, there are still disparities in outcomes for patients with thrombosed vascular access, with regards to length of stay and requirement for insertion of a temporary central venous catheter (CVC) for urgent dialysis whilst awaiting intervention, and these are areas for further investigation and improvement.

Refractive lens exchange - who is getting it, what are they getting, how are they doing?

PURPOSE OF REVIEW: The purpose of this article is to provide a review of the literature on refractive lens exchange and present a retrospective analysis of 55 patients who underwent refractive lens exchange at a single practice. RECENT FINDINGS: Our study substantiates refractive lens exchange as an important option for presbyopic patients, hyperopic patients or patients with extremely high refractive error who desire spectacle independence. SUMMARY: Our study reveals that the refractive lens exchange population is younger than the average cataract population and their primary motivations are to resolve hyperopic or myopic refractive errors, gain spectacle independence, and address near vision loss. A variety of presbyopia-addressing intraocular lens options are available and we present our experience with multifocal, extended depth-of-focus, light-adjustable, and monofocal lenses.

A Systematic Review and Meta-Analysis on the Real-World Effectiveness of COVID-19 Vaccines against Infection, Symptomatic and Severe COVID-19 Disease Caused by the Omicron Variant (B.1.1.529).

Real-world data on the effectiveness of COVID-19 vaccines against the Omicron variant (B.1.1.529) is limited. This systematic review aimed to investigate the real-world effectiveness and durability of protection conferred by primary course and booster vaccines against confirmed Omicron infection, and severe outcomes. We systematically searched literature up to 1 August 2022. Meta-analysis was performed with the DerSimonian-Laird random-effects model to estimate the pooled vaccine effectiveness (VE). Overall, 28 studies were included representing 11 million individuals. The pooled VE against Omicron infection was 20.4% (95%CI: 12.1-28.7%) and 23.4% (95%CI: 13.5-33.3%) against symptomatic infection with variation based on vaccine type and age groups. VE sharply declined from 28.1% (95%CI: 19.1-37.1%) at three months to 3.9% (95%CI: -24.8-32.7%) at six months. Similar trends were observed for symptomatic Omicron infection. A booster dose restored protection against Omicron infection up to 51.1% (95%CI: 43.8-58.3%) and 57.3% (95%CI: 54.0-60.5%) against symptomatic infection within three months; however, this waned to 32.8% (95%CI: 16.8-48.7%) within six months. VE against severe Omicron infection following the primary course was 63.6% (95%CI: 57.5-69.7%) at three months, decreased to 49% (95%CI: 35.7-63.4%) within six months, and increased to 86% after the first or second booster dose.

Interruptions to HIV Care Delivery During Pandemics and Natural Disasters: A Qualitative Study of Challenges and Opportunities From Frontline Healthcare Providers in Western Kenya.

During public health crises, people living with HIV (PLWH) may become disengaged from care. The goal of this study was to understand the impact of the COVID-19 pandemic and recent flooding disasters on HIV care delivery in western Kenya. We conducted ten individual in-depth interviews with HIV providers across four health facilities. We used an iterative and integrated inductive and deductive data analysis approach to generate four themes. First, increased structural interruptions created exacerbating strain on health facilities. Second, there was increased physical and psychosocial burnout among providers. Third, patient uptake of services along the HIV continuum decreased, particularly among vulnerable patients. Finally, existing community-based programs and teleconsultations could be adapted to provide differentiated HIV care. Community-centric care programs, with an emphasis on overcoming the social, economic, and structural barriers will be crucial to ensure optimal care and limit the impact of public health disruptions on HIV care globally.

Factors Associated with Morbidity and Mortality Among Sexually Active Asian Adolescents and Young Adults with Perinatally Acquired HIV.

We assessed morbidity and mortality among Thai and Vietnamese adolescents and young adults with perinatally acquired human immunodeficiency virus (PHIV) compared with matched HIV-negative peers, 12-24 years of age. Data on serious adverse events (SAEs) were prospectively collected between 2013 and 2018 according to U.S. NIH Division of AIDS criteria. Of 288 youth, 142 had PHIV and 146 were HIV negative. At enrollment, the overall median age was 19 (interquartile range [IQR] 17-20) years, 67% were female, and 95% were Thai. Almost all PHIV youth (99%) were receiving antiretroviral therapy; 50% self-reported adherence ≥95%. Median CD4 was 579 (IQR 404-800) cells/mm3, and 24% had HIV-RNA ≥1,000 copies/mL. During follow-up, 31 (22%) PHIV youth and 9 (6%) HIV-negative youth had at least one SAE. The overall crude SAE rate was 4.66 (3.42-6.35) per 100 person-years (PY); 7.22 (5.08-10.26) per 100 PY among youth with PHIV and 2.10 (1.09-4.03) per 100 PY in HIV-negative youth (p < .001). All seven deaths that occurred were among those with PHIV and primarily due to opportunistic infections (e.g., pneumocystis pneumonia, tuberculous meningitis). In multivariate analyses, having PHIV, being <20 years of age, and having anogenital high-risk human papillomavirus (HPV) infection with types 16 and/or 18 increased risk of SAEs. Among PHIV youth, CD4 count <350 cells/mm3, HIV-RNA ≥1,000 copies/mL, advanced WHO stages, and having anogenital HPV 16 and/or 18 infection predicted higher incidence of SAEs; no prior use of alcohol was protective. These data emphasize the need for tailored interventions for adolescents with PHIV to prevent long-term morbidity and mortality.

SARS-CoV-2 Envelope-mediated Golgi pH dysregulation interferes with ERAAP retention in cells.

Endoplasmic reticulum (ER) aminopeptidase associated with antigen processing (ERAAP) trims peptide precursors in the ER for presentation by major histocompatibility (MHC)-I molecules to surveying CD8+ T-cells. This function allows ERAAP to regulate the nature and quality of the peptide repertoire and, accordingly, the resulting immune responses. We recently showed that infection with murine cytomegalovirus leads to a dramatic loss of ERAAP levels in infected cells. In mice, this loss is associated with the activation of QFL T-cells, a subset of T-cells that monitor ERAAP integrity and eliminate cells experiencing ERAAP dysfunction. In this study, we aimed to identify host factors that regulate ERAAP expression level and determine whether these could be manipulated during viral infections. We performed a CRISPR knockout screen and identified ERp44 as a factor promoting ERAAP retention in the ER. ERp44's interaction with ERAAP is dependent on the pH gradient between the ER and Golgi. We hypothesized that viruses that disrupt the pH of the secretory pathway interfere with ERAAP retention. Here, we demonstrate that expression of the Envelope (E) protein from Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) leads to Golgi pH neutralization and consequently decrease of ERAAP intracellular levels. Furthermore, SARS-CoV-2-induced ERAAP loss correlates with its release into the extracellular environment. ERAAP's reliance on ERp44 and a functioning ER/Golgi pH gradient for proper localization and function led us to propose that ERAAP serves as a sensor of disturbances in the secretory pathway during infection and disease.

Integrating community-based HIV and non-communicable disease care with microfinance groups: a feasibility study in Western Kenya.

BACKGROUND: The Harambee study is a cluster randomized trial in Western Kenya that tests the effect, mechanisms, and cost-effectiveness of integrating community-based HIV and non-communicable disease care within microfinance groups on chronic disease treatment outcomes. This paper documents the stages of our feasibility study conducted in preparation for the Harambee trial, which include (1) characterizing the target population and gauging recruitment capacity, (2) determining community acceptability of the integrated intervention and study procedures, and (3) identifying key implementation considerations prior to study start. METHODS: Feasibility research took place between November 2019 and February 2020 in Western Kenya. Mixed methods data collection included surveys administered to 115 leaders of 105 community-based microfinance groups, 7 in-person meetings and two workshops with stakeholders from multiple sectors of the health system, and ascertainment of field notes and geographic coordinates for group meeting locations and HIV healthcare facilities. Quantitative survey data were analyzed using STATA IC/13. Longitude and latitude coordinates were mapped to county boundaries using Esri ArcMap. Qualitative data obtained from stakeholder meetings and field notes were analyzed thematically. RESULTS: Of the 105 surveyed microfinance groups, 77 met eligibility criteria. Eligible groups had been in existence from 6 months to 18 years and had an average of 22 members. The majority (64%) of groups had at least one member who owned a smartphone. The definition of "active" membership and model of saving and lending differed across groups. Stakeholders perceived the community-based intervention and trial procedures to be acceptable given the minimal risks to participants and the potential to improve HIV treatment outcomes while facilitating care integration. Potential challenges identified by stakeholders included possible conflicts between the trial and existing community-based interventions, fear of group disintegration prior to trial end, clinicians' inability to draw blood for viral load testing in the community, and deviations from standard care protocols. CONCLUSIONS: This study revealed that it was feasible to recruit the number of microfinance groups necessary to ensure that our clinical trial was sufficient powered. Elicitation of stakeholder feedback confirmed that the planned intervention was largely acceptable and was critical to identifying challenges prior to implementation. TRIAL REGISTRATION: The original trial was prospectively registered with ClinicalTrials.gov (NCT04417127) on 4 June 2020.

Strategies Australian junior doctors use to maintain their mental, physical and social well-being: a qualitative study.

OBJECTIVES: This study aimed to uncover the strategies that junior doctors implement to maintain their mental, physical and social well-being, and the barriers they experience in practising these strategies. PARTICIPANTS: Fifteen junior doctors in their postgraduate year 1 or 2 currently practising in Australia were recruited. OUTCOME MEASURES: Semistructured interviews were conducted, and the transcripts underwent thematic analysis. RESULTS: Three key themes emerged from thematic analysis, namely: well-being strategies, barriers to well-being and and future interventions. Exercise, a healthy and balanced diet, quality sleep, and workplace organisations were frequently reported well-being strategies. High workload, unpredictable routines, lack of familiarity with the healthcare system and ongoing stigma surrounding mental health were seen as barriers to well-being. Suggested interventions included increased control over rosters, subsidised access to facilities such as gyms and increased internship preparedness programmes organised by the medical schools. CONCLUSIONS: The findings from this study may assist in developing more personalised and targeted methods to help junior doctors maintain their mental, physical and social well-being. Future studies may address the structural and systemic changes required to develop a workforce that fosters the well-being of junior doctors and reduces the institutional barriers to practising well-being strategies.

Association Between Right Ventricular Dysfunction and Adverse Outcomes in Peripartum Cardiomyopathy: Insights From the BRO-HF Quebec Cohort Study.

Background: Peripartum cardiomyopathy (PPCM) is associated with severe morbidity and mortality, and the significance of right ventricular (RV) involvement is unclear. We sought to determine whether RV systolic dysfunction or dilatation is associated with adverse clinical outcomes in women with PPCM. Methods: We conducted a multicentre retrospective cohort study examining the association between echocardiographic RV systolic dysfunction or dilatation at the time of PPCM diagnosis and clinical outcomes. Clinical endpoints of interest were the need for mechanical support, recovery of left ventricular ejection fraction at follow-up, and a combined endpoint of hospitalization for heart failure, cardiac transplant, or death. Results: A total of 67 women, median age 30 years (interquartile range: 7), were diagnosed with PPCM between 1994 and 2015 in 17 participating centres. Twin pregnancies occurred in 11%; 62% of women were multiparous; and 24% had preeclampsia. RV systolic function was impaired in 18 (27%) and dilated in 8 (12%). Seven women required ventricular assistance, and 8 experienced the composite outcome during follow-up (25 [interquartile range 61] months). RV dysfunction was associated with the need for mechanical support (odds ratio 10.10 (95% confidence interval: 1.86-54.81), P = 0.007), but neither RV dysfunction nor dilatation was associated with left ventricular ejection fraction recovery, the need for cardiac transplant, heart failure hospitalization, or death. Conclusions: RV dysfunction is associated with the need for mechanical support in women with PPCM. These findings may improve risk stratification of complications and clinical management.

Introduction: La cardiomyopathie du péripartum (CMP-PP) est associée à la morbidité grave et à la mortalité, mais on ignore l'importance de l'atteinte ventriculaire droite (VD). Nous avons cherché à déterminer si la dysfonction systolique ou la dilatation VD sont associées aux résultats cliniques défavorables chez les femmes atteintes de CMP-PP. Méthodes: Nous avons mené une étude de cohorte rétrospective multicentrique sur l'association entre la dysfonction systolique ou la dilatation VD à l'échographie au moment du diagnostic de CMP-PP et les résultats cliniques. Les critères cliniques d'intérêt étaient la nécessité d'une assistance mécanique, la récupération de la fraction d'éjection ventriculaire gauche (FEVG) au suivi et un critère combiné d'hospitalisation liée à l'insuffisance cardiaque (IC), la transplantation cardiaque ou la mort. Résultats: Un total de 67 femmes, dont l'âge médian était de 30 ans (écart interquartile [EI] : 7), ont reçu un diagnostic de CMP-PP entre 1994 et 2015 dans 17 centres participants. Les grossesses gémellaires sont survenues chez 11 % ; 62 % de femmes étaient multipares ; et 24 % souffraient de prééclampsie. La fonction systolique VD était compromise chez 18 (27 %) femmes et le VD, dilaté, chez huit (12 %) femmes. Sept femmes ont eu besoin d'une assistance ventriculaire, et huit ont subi le critère composite durant le suivi (25 [EI : 61] mois). La dysfonction VD a été associée à la nécessité d'une assistance mécanique (rapport de cotes 10,10 [intervalle de confiance à 95 % : 1,86-54,81], P = 0,007), mais ni la dysfonction ni la dilatation VD n'ont été associées à la récupération de la FEVG, à la nécessité d'une transplantation cardiaque, à une hospitalisation liée à l'IC ou à la mort. Conclusions: La dysfonction VD est associée à la nécessité d'une assistance mécanique chez les femmes atteintes de CMP-PP. Ces conclusions peuvent permettre d'améliorer la stratification des risques de complications et la prise en charge clinique.

Community-based medication delivery program for antihypertensive medications improves adherence and reduces blood pressure.

Non-adherence to antihypertensive medications is a major cause of uncontrolled hypertension, leading to cardiovascular morbidity and mortality. Ensuring consistent medication possession is crucial in addressing non-adherence. Community-based medication delivery is a strategy that may improve medication possession, adherence, and blood pressure (BP) reduction. Our program in Kenya piloted a community medication delivery program, coupled with blood pressure monitoring and adherence evaluation. Between September 2019 and March 2020, patients who received hypertension care from our chronic disease management program also received community-based delivery of antihypertensive medications. We calculated number of days during which each patient had possession of medications and analyzed the relationship between successful medication delivery and self-reported medication adherence and BP. A total of 128 patient records (80.5% female) were reviewed. At baseline, mean systolic blood pressure (SBP) was 155.7 mmHg and mean self-reported adherence score was 2.7. Sixty-eight (53.1%) patients received at least 1 successful medication delivery. Our pharmacy dispensing records demonstrated that medication possession was greater among patients receiving medication deliveries. Change in self-reported medication adherence from baseline worsened in patients who did not receive any medication delivery (+0.5), but improved in patients receiving 1 delivery (-0.3) and 2 or more deliveries (-0.8). There was an SBP reduction of 1.9, 6.1, and 15.5 mmHg among patients who did not receive any deliveries, those who received 1 delivery, and those who received 2 or more medication deliveries, respectively. Adjusted mixed-effect model estimates revealed that mean SBP reduction and self-reported medication adherence were improved among individuals who successfully received medication deliveries, compared to those who did not. A community medication delivery program in western Kenya was shown to be implementable and enhanced medication possession, reduced SBP, and significantly improved self-reported adherence. This is a promising strategy to improve health outcomes for patients with uncontrolled hypertension that warrants further investigation.

Development and validation of algorithms to identify patients with chronic kidney disease and related chronic diseases across the Northern Territory, Australia.

BACKGROUND: Electronic health records can be used for population-wide identification and monitoring of disease. The Territory Kidney Care project developed algorithms to identify individuals with chronic kidney disease (CKD) and several commonly comorbid chronic diseases. This study aims to describe the development and validation of our algorithms for CKD, diabetes, hypertension, and cardiovascular disease. A secondary aim of the study was to describe data completeness of the Territory Kidney Care database. METHODS: The Territory Kidney Care database consolidates electronic health records from multiple health services including public hospitals (n = 6) and primary care health services (> 60) across the Northern Territory, Australia. Using the database (n = 48,569) we selected a stratified random sample of patients (n = 288), which included individuals with mild to end-stage CKD. Diagnostic accuracy of the algorithms was tested against blinded manual chart reviews. Data completeness of the database was also described. RESULTS: For CKD defined as CKD stage 1 or higher (eGFR of any level with albuminuria or persistent eGFR < 60 ml/min/1.732, including renal replacement therapy) overall algorithm sensitivity was 93% (95%CI 89 to 96%) and specificity was 73% (95%CI 64 to 82%). For CKD defined as CKD stage 3a or higher (eGFR < 60 ml/min/1.732) algorithm sensitivity and specificity were 93% and 97% respectively. Among the CKD 1 to 5 staging algorithms, the CKD stage 5 algorithm was most accurate with > 99% sensitivity and specificity. For related comorbidities - algorithm sensitivity and specificity results were 75% and 97% for diabetes; 85% and 88% for hypertension; and 79% and 96% for cardiovascular disease. CONCLUSIONS: We developed and validated algorithms to identify CKD and related chronic diseases within electronic health records. Validation results showed that CKD algorithms have a high degree of diagnostic accuracy compared to traditional administrative codes. Our highly accurate algorithms present new opportunities in early kidney disease detection, monitoring, and epidemiological research.

Strategies to Improve Women's Leadership Preparation for Early Career Global Health Professionals: Suggestions from Two Working Groups.

Background: Despite advances in gender equality, women still experience inequitable gaps in global health leadership, and barriers to women's advancement as leaders in global health have been well described in the literature. In 2021, the Johns Hopkins Center for Global Health conducted two virtual working groups for emerging women leaders to share challenges and suggest solutions to advance women's leadership in global health. In this paper, we present emerging themes from the working groups, provide a framework for the results, and discuss strategies for advancing women's leadership in global health. Objectives: The objective of this paper is to synthesize and share the themes of the two working group sessions to provide strategies for improving women's leadership training and opportunities in the field of global health. Methods: Approximately 182 women in the global health field participated in two virtual working group sessions hosted by the Johns Hopkins Center for Global Health using the Zoom platform. Participants were divided into virtual breakout rooms and discussed pre-assigned topics related to women's leadership in global health. The participants then returned to share their ideas in a plenary session. Notes from the breakout rooms and transcripts from the plenary session were analyzed through a participatory and iterative thematic analysis approach. Findings: We found that the working group participants identified two overarching themes that were critical for emerging women leaders to find success in global health leadership. First, the acquisition of individual essential skills is necessary to advance in their careers. Second, the institutional environments should be setup to encourage and enable women to enter and succeed in leadership roles. The participants also shared suggestions for improving women's leadership opportunities such as including the use of virtual technologies to increase training and networking opportunities, intersectionality in mentorship and sponsorship, combatting impostor syndrome, and the importance of work-life balance. Conclusions: Investing in women and their leadership potential has the promise to improve health and wealth at the individual, institutional, and community levels. This manuscript offers lessons and proposes solutions for increasing women's leadership through improving individual level essential skills and fostering environments in which women leaders can emerge and thrive.

Artificial Neural Network Approach to Competency-Based Training Using a Virtual Reality Neurosurgical Simulation.

BACKGROUND: The methodology of assessment and training of surgical skills is evolving to deal with the emergence of competency-based training. Artificial neural networks (ANNs), a branch of artificial intelligence, can use newly generated metrics not only for assessment performance but also to quantitate individual metric importance and provide new insights into surgical expertise. OBJECTIVE: To outline the educational utility of using an ANN in the assessment and quantitation of surgical expertise. A virtual reality vertebral osteophyte removal during a simulated surgical spine procedure is used as a model to outline this methodology. METHODS: Twenty-one participants performed a simulated anterior cervical diskectomy and fusion on the Sim-Ortho virtual reality simulator. Participants were divided into 3 groups, including 9 postresidents, 5 senior residents, and 7 junior residents. Data were retrieved from the osteophyte removal component of the scenario, which involved using a simulated burr. The data were manipulated to initially generate 83 performance metrics spanning 3 categories (safety, efficiency, and motion) of which only the most relevant metrics were used to train and test the ANN. RESULTS: The ANN model was trained on 6 safety metrics to a testing accuracy of 83.3%. The contributions of these performance metrics to expertise were revealed through connection weight products and outlined 2 identifiable learning patterns of technical skills. CONCLUSION: This study outlines the potential utility of ANNs which allows a deeper understanding of the composites of surgical expertise and may contribute to the paradigm shift toward competency-based surgical training.

Aerobic vaginitis in the third trimester and its impact on pregnancy outcomes.

BACKGROUND: Aerobic vaginitis (AV) is a vaginal inflammation characterized by disruption of the lactobacillus microbiota and increased counts of different aerobic bacteria. AV may result in severe complications, especially during pregnancy, including preterm delivery, neonatal and maternal infections. This study aimed to determine the prevalence of AV in the third trimester of pregnancy, and the relationship between AV and pregnancy outcomes.  METHODS: A cross-sectional descriptive study included 323 pregnant women attending for routine antenatal care in the Hue University Hospital. Vaginal samples collected at the third trimester of pregnancy were evaluated for AV according to the scoring system of Donders and cultured for identification of predominant bacteria. Pregnancy was followed to its end, and pregnancy outcomes were recorded for both mothers and infants. RESULTS: The proportion of pregnant women diagnosed with AV in the third trimester was found to be 15.5%, with the vast majority of the cases (84%) displaying the light AV and 16% the moderate AV. The vaginal cultures in the women with AV revealed most frequently Streptococcus agalactiae (6%), followed by Enterococcus spp (4%), Staphylococcus aureus (4%), and Acinetobacter baumannii (2%). In addition, AV during the last trimester of pregnancy was associated with an increased risk of puerperal sepsis (OR 8.65, 95% CI: 1.41-53.16, p = 0.020) and there was a slightly increased risk for neonatal infections, which was statistically insignificant. CONCLUSIONS: The proportion of AV is relatively high in Vietnamese pregnant women. Since it is associated with an increased risk of puerperal sepsis, it needs to be diagnosed and treated before delivery.