Questionnaire-based exposome-wide association studies for common diseases in the Personalized Environment and Genes Study.

The exposome collectively refers to all exposures, beginning in utero and continuing throughout life, and comprises not only standard environmental exposures such as point source pollution and ozone levels but also exposures from diet, medication, lifestyle factors, stress, and occupation. The exposome interacts with individual genetic and epigenetic characteristics to affect human health and disease, but large-scale studies that characterize the exposome and its relationships with human disease are limited. To address this gap, we used extensive questionnaire data from the diverse North Carolina-based Personalized Environment and Genes Study (PEGS, n = 9, 429) to evaluate exposure associations in relation to common diseases. We performed an exposome-wide association study (ExWAS) to examine single exposure models and their associations with 11 common complex diseases, namely allergic rhinitis, asthma, bone loss, fibroids, high cholesterol, hypertension, iron-deficient anemia, ovarian cysts, lower GI polyps, migraines, and type 2 diabetes. Across diseases, we found associations with lifestyle factors and socioeconomic status as well as asbestos, various dust types, biohazardous material, and textile-related exposures. We also found disease-specific associations such as fishing with lead weights and migraines. To differentiate between a replicated result and a novel finding, we used an AI-based literature search and database tool that allowed us to examine the current literature. We found both replicated findings, especially for lifestyle factors such as sleep and smoking across diseases, and novel findings, especially for occupational exposures and multiple diseases.

Interactive data sharing for multiple questionnaire-based exposome-wide association studies and exposome correlations in the Personalized Environment and Genes Study.

The correlations among individual exposures in the exposome, which refers to all exposures an individual encounters throughout life, are important for understanding the landscape of how exposures co-occur, and how this impacts health and disease. Exposome-wide association studies (ExWAS), which are analogous to genome-wide association studies (GWAS), are increasingly being used to elucidate links between the exposome and disease. Despite increased interest in the exposome, tools and publications that characterize exposure correlations and their relationships with human disease are limited, and there is a lack of data and results sharing in resources like the GWAS catalog. To address these gaps, we developed the PEGS Explorer web application to explore exposure correlations in data from the diverse North Carolina-based Personalized Environment and Genes Study (PEGS) that were rigorously calculated to account for differing data types and previously published results from ExWAS. Through globe visualizations, PEGS Explorer allows users to explore correlations between exposures found to be associated with complex diseases. The exposome data used for analysis includes not only standard environmental exposures such as point source pollution and ozone levels but also exposures from diet, medication, lifestyle factors, stress, and occupation. The web application addresses the lack of accessible data and results sharing, a major challenge in the field, and enables users to put results in context, generate hypotheses, and, importantly, replicate findings in other cohorts. PEGS Explorer will be updated with additional results as they become available, ensuring it is an up-to-date resource in exposome science.

Challenges in diagnosing pulmonary embolism in an adult with Fontan physiology: a case report.

Background: With the increasing longevity of congenital heart disease patients and limited number of adult congenital heart disease specialists, it is becoming increasingly imperative for general cardiologists to understand not only the unique physiology of Fontan patients but also imaging protocol considerations when treating this group of patients. Case summary: Here, we present a patient with a history of congenital tricuspid atresia status after the Fontan procedure who presented for gut translocation-related bacteraemia. Importantly, the patient was falsely diagnosed with pulmonary embolism resulting from inaccurate acquisition of computed tomography imaging. Discussion: This case illustrates the complex intricacies that clinicians should consider when facing the challenge of treating Fontan patients.

Development of a Chief Resident Medical Procedure Service: a 10-Year Experience.

BACKGROUND: Lack of experienced faculty to supervise internal medicine (IM) residents is a significant barrier to establishing a medical procedure service (MPS). AIM: Describe the development and 10-year outcomes of an MPS led by IM chief residents. SETTING: University-based IM residency program affiliated with a county and Veterans Affairs hospital. PARTICIPANTS: Categorical IM interns (n=320) and 4th-year IM chief residents (n=48) from 2011 to 2022. PROGRAM DESCRIPTION: The MPS operated on weekdays, 8 am-5 pm. After training and sign-off by the MPS director, chief residents trained and supervised interns in ultrasound-guided procedures during a 4-week rotation. PROGRAM EVALUATION: From 2011 to 2022, our MPS received 5967 consults and 4465 (75%) procedures were attempted. Overall procedure success, complication, and major complication rates were 94%, 2.6%, and 0.6%, respectively. Success and complication rates for paracentesis (n=2285) were 99% and 1.1%, respectively; 99% and 4.2% for thoracentesis (n=1167); 76% and 4.5% for lumbar puncture (n=883); 83% and 1.2% for knee arthrocentesis (n=85); and 76% and 0% for central venous catheterization (n=45). The rotation was rated 4.6 out of 5 for overall learning quality. DISCUSSION: A chief resident-led MPS is a practical and safe approach for IM residency programs to establish an MPS when experienced attending physicians are unavailable.

How I Do It: The prostatic urethral lift for obstructive median lobes.

Millions of men in North America suffering from lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH) are managed on medical therapy. Most patients, however, report poor adherence, and yet relatively few pursue more definitive surgical solutions. The Prostatic Urethral Lift (PUL) was designed to address many of the patient-identified barriers to surgery, namely iatrogenic sexual dysfunction, incontinence, lengthy recovery and postoperative catheterization. Randomized studies and large real world multicenter and database studies have demonstrated safety and effectiveness of PUL when addressing lateral lobe disease. In recent years further technique and device development has led to the FDA approval for PUL addressing obstructive median lobes as well. At 12 months, PUL median lobe patients in a controlled trial and a large retrospective study experienced average IPSS improvement of 13.5 and 11.6 points, QoL improvement of 3.0 and 2.1 points, and Qmax improvement of 6.4 and 7.1 mL/sec, respectively. In the controlled setting, both ejaculatory and erectile function were preserved and postoperative catheterization rates, while higher than lateral lobe PUL rates, were similarly short lived with a mean duration of 1.2 days. We describe the current technique for performing PUL to address the obstructive median lobe and detail a new device, which can make it easier to alleviate obstruction due to trilobar anatomy.

Determining sustainability using the Environmental Performance Index and Human Development Index - An alternative approach to the Environmental Human Index through a holistic quantitative dynamic framework.

The Environmental Human Index (EHI) was recently proposed and demonstrated as a new sustainability assessment tool which uses data from the Environmental Performance Index (EPI) and the Human Development Index (HDI). However, the EHI has potential conceptual and operational issues in respect to its consistency with established concepts and principles of the coupled environment-human system and sustainability. Specifically, the thresholds of sustainability the EHI uses, the bias towards the anthroposphere, and the absence of unsustainability. These issues raise potential questions concerning the EHI's value and approach adopted to utilise the EPI and HDI data to determine potential or actual sustainability outcomes. Therefore, to demonstrate how the EPI and HDI can be used to determine sustainability outcomes, the Sustainability Dynamics Framework (SDF) is applied in respect to the case study of the United Kingdom 1995-2020. The results indicated strong sustainability occurring throughout the specified period, within a S-value range of [+0.503 ≤ S(t) ≤ +0.682]. The Pearson correlation analysis showed a significant negative relationship between E and HNI-values and between HNI and S-values, and a significant positive relationship between E and S-values. The Fourier analysis indicated a three-phase change in the nature of the environment-human system dynamics over the 1995-2020 period. The SDF application to the EPI and HDI data has shown the importance of using a consistent holistic conceptual and operational framework to determine and evaluate sustainability outcomes.

A rapid sustainability dynamic assessment of the USA and China 1995-2018.

The USA and China have the world's largest GDP and greenhouse gas emissions, as well as having a significant proportion of the world's total population. These form part of the triumvirate of influencing factors which potentially detrimentally impact upon sustainability. How the triumvirate factors have impacted upon the sustainability of the USA and China has not been adequately determined quantitatively or holistically. Understanding this can strongly indicate how significant levels of population, economic growth, and greenhouse gas emissions impacts and influences the indicated levels, nature, and dynamics of sustainability occurring. Therefore, to contribute towards developing understanding of the issues outlined, the Sustainability Dynamics Framework is applied to conduct a sustainability dynamic assessment for the USA and China 1995-2018. The results indicate both countries are consistently unsustainable due to significant levels of triumvirate-based factors, with differing dynamic trends, characteristics, and potential outcomes. The current static nature of the USA's environment-human system provides the opportunity for a managed co-evolutionary strategy. China's dynamic trends indicate a significant increasingly stressed environment-human system, which is at risk of a potential systemic crisis or collapse unless stringent corrective measures are implemented. In order for both countries to return to sustainability, there needs to be population mitigation to return them to optimum levels, and the use of contractionary policies and rapid decarbonation of their economies and societies. Unless this occurs, then their continued reticence to undertaking the urgent and necessary measures required not only risking their own future, but the world as well.

Postincident Interpersonal Difficulty Among Adolescent Victims of Violent Crime.

Adolescents are exposed to high levels of violence in the United States. Exposure to violence at this point in the life course can have both short- and long-term consequences for young victims that include socioemotional distress and depression, substance abuse, and delinquency. Prior research indicates that positive, productive, and supportive reactions on the parts of those close to targets of violence attenuate feelings of distress and social anomie that many victims report. However, less attention has been devoted to the attributes of criminal violence that may stress the postincident interpersonal relationships of victims and their family members, friends, or peers. The disquieting effects of violence and bodily injury may influence how victims characterize their social connections in the wake of violent crime. This study uses data from the National Crime Victimization Survey (N = 1,652) to assess whether characteristics of violent acts and victims predict reports of postincident interpersonal difficulties made by violent crime victims aged 12 to 20. The findings are that more severe forms or levels of violence (e.g., robberies and sexual assaults) and reports of physical injuries are linked to perceptions of relationship difficulties with members of social networks by adolescent victims of violent crime. This study makes a contribution to our understanding of victimization by identifying levels of violence and injury as independent stressors on victims' perceptions of their relationships and as relevant components of how younger victims see themselves or are perceived by others. It also represents a direct test of whether attributes of violent acts undermine adolescents' perceptions of the quality of their relationships. The results of the study could also aid in the development of interventions that better address the needs of both young victims and their supporters.

Risk and Protective Factors in the COVID-19 Pandemic: A Rapid Evidence Map.

Background: Given the worldwide spread of the 2019 Novel Coronavirus (COVID-19), there is an urgent need to identify risk and protective factors and expose areas of insufficient understanding. Emerging tools, such as the Rapid Evidence Map (rEM), are being developed to systematically characterize large collections of scientific literature. We sought to generate an rEM of risk and protective factors to comprehensively inform areas that impact COVID-19 outcomes for different sub-populations in order to better protect the public. Methods: We developed a protocol that includes a study goal, study questions, a PECO statement, and a process for screening literature by combining semi-automated machine learning with the expertise of our review team. We applied this protocol to reports within the COVID-19 Open Research Dataset (CORD-19) that were published in early 2020. SWIFT-Active Screener was used to prioritize records according to pre-defined inclusion criteria. Relevant studies were categorized by risk and protective status; susceptibility category (Behavioral, Physiological, Demographic, and Environmental); and affected sub-populations. Using tagged studies, we created an rEM for COVID-19 susceptibility that reveals: (1) current lines of evidence; (2) knowledge gaps; and (3) areas that may benefit from systematic review. Results: We imported 4,330 titles and abstracts from CORD-19. After screening 3,521 of these to achieve 99% estimated recall, 217 relevant studies were identified. Most included studies concerned the impact of underlying comorbidities (Physiological); age and gender (Demographic); and social factors (Environmental) on COVID-19 outcomes. Among the relevant studies, older males with comorbidities were commonly reported to have the poorest outcomes. We noted a paucity of COVID-19 studies among children and susceptible sub-groups, including pregnant women, racial minorities, refugees/migrants, and healthcare workers, with few studies examining protective factors. Conclusion: Using rEM analysis, we synthesized the recent body of evidence related to COVID-19 risk and protective factors. The results provide a comprehensive tool for rapidly elucidating COVID-19 susceptibility patterns and identifying resource-rich/resource-poor areas of research that may benefit from future investigation as the pandemic evolves.

An integrated chemical environment with tools for chemical safety testing.

Moving toward species-relevant chemical safety assessments and away from animal testing requires access to reliable data to develop and build confidence in new approaches. The Integrated Chemical Environment (ICE) provides tools and curated data centered around chemical safety assessment. This article describes updates to ICE, including improved accessibility and interpretability of in vitro data via mechanistic target mapping and enhanced interactive tools for in vitro to in vivo extrapolation (IVIVE). Mapping of in vitro assay targets to toxicity endpoints of regulatory importance uses literature-based mode-of-action information and controlled terminology from existing knowledge organization systems to support data interoperability with external resources. The most recent ICE update includes Tox21 high-throughput screening data curated using analytical chemistry data and assay-specific parameters to eliminate potential artifacts or unreliable activity. Also included are physicochemical/ADME parameters for over 800,000 chemicals predicted by quantitative structure-activity relationship models. These parameters are used by the new ICE IVIVE tool in combination with the U.S. Environmental Protection Agency's httk R package to estimate in vivo exposures corresponding to in vitro bioactivity concentrations from stored or user-defined assay data. These new ICE features allow users to explore the applications of an expanded data space and facilitate building confidence in non-animal approaches.

SWIFT-Active Screener: Accelerated document screening through active learning and integrated recall estimation.

BACKGROUND: In the screening phase of systematic review, researchers use detailed inclusion/exclusion criteria to decide whether each article in a set of candidate articles is relevant to the research question under consideration. A typical review may require screening thousands or tens of thousands of articles in and can utilize hundreds of person-hours of labor. METHODS: Here we introduce SWIFT-Active Screener, a web-based, collaborative systematic review software application, designed to reduce the overall screening burden required during this resource-intensive phase of the review process. To prioritize articles for review, SWIFT-Active Screener uses active learning, a type of machine learning that incorporates user feedback during screening. Meanwhile, a negative binomial model is employed to estimate the number of relevant articles remaining in the unscreened document list. Using a simulation involving 26 diverse systematic review datasets that were previously screened by reviewers, we evaluated both the document prioritization and recall estimation methods. RESULTS: On average, 95% of the relevant articles were identified after screening only 40% of the total reference list. In the 5 document sets with 5,000 or more references, 95% recall was achieved after screening only 34% of the available references, on average. Furthermore, the recall estimator we have proposed provides a useful, conservative estimate of the percentage of relevant documents identified during the screening process. CONCLUSION: SWIFT-Active Screener can result in significant time savings compared to traditional screening and the savings are increased for larger project sizes. Moreover, the integration of explicit recall estimation during screening solves an important challenge faced by all machine learning systems for document screening: when to stop screening a prioritized reference list. The software is currently available in the form of a multi-user, collaborative, online web application.

Putting veterans with heart failure FIRST improves follow-up and reduces readmissions.

Background: Despite improvements in length of stay and mortality, congestive heart failure (CHF) remains the most common cause of 30-day readmissions to the hospital. Though multiple studies have found that early follow-up after discharge (eg, within 7 days) is critical to improving 30-day readmissions, implementation strategies are challenging in resource-limited settings. Here we present a quality improvement initiative aimed at improving early follow-up while maximising available resources. Methods: This was a medical resident-driven initiative. A process map of the discharge and follow-up appointment process was created that identified multiple areas for improvement. Based on these findings, a two-part intervention was implemented. First, heart failure discharge education with focus on early follow-up was disseminated to providers throughout the internal medicine department. Subsequently, improved identification of high-risk patients (Failure Intervention Risk StratificationTool) and innovative use of the existing electronic medical record (EMR) were employed to sustain and improve on gains from the first set of interventions. Results: We increased our 7-day follow-up rate from 47% to 57% (p=0.429) and decreased the average time to follow-up from 17.6 days to 8.7 days (p=0.016) following the first intervention. The percentage of patients readmitted within 30 days after discharge at baseline (2012-2013) and following the first intervention (education and standardisation of follow-up scheduling) and second intervention (risk stratification, intensive follow-up and EMR change) was 25% and 21%, respectively. Thirty-day mortality rate decreased from 10% in 2011 to 7.16% in December 2015. Conclusion: Close hospital discharge follow-up and identification of high-risk patients with CHF are useful approaches to reduce readmissions. Using the existing EMR tool for identifying high-risk patients and improving adherence to best practices is an effective intervention. In patients with CHF these strategies improved time to follow-up and 30-day readmissions while decreasing mortality.

BMDExpress 2: enhanced transcriptomic dose-response analysis workflow.

SUMMARY: A new version (version 2) of the genomic dose-response analysis software, BMDExpress, has been created. The software addresses the increasing use of transcriptomic dose-response data in toxicology, drug design, risk assessment and translational research. In this new version, we have implemented additional statistical filtering options (e.g. Williams' trend test), curve fitting models, Linux and Macintosh compatibility and support for additional transcriptomic platforms with up-to-date gene annotations. Furthermore, we have implemented extensive data visualizations, on-the-fly data filtering, and a batch-wise analysis workflow. We have also significantly re-engineered the code base to reflect contemporary software engineering practices and streamline future development. The first version of BMDExpress was developed in 2007 to meet an unmet demand for easy-to-use transcriptomic dose-response analysis software. Since its original release, however, transcriptomic platforms, technologies, pathway annotations and quantitative methods for data analysis have undergone a large change necessitating a significant re-development of BMDExpress. To that end, as of 2016, the National Toxicology Program assumed stewardship of BMDExpress. The result is a modernized and updated BMDExpress 2 that addresses the needs of the growing toxicogenomics user community. AVAILABILITY AND IMPLEMENTATION: BMDExpress 2 is available at https://github.com/auerbachs/BMDExpress-2/releases. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

An Integrated Chemical Environment to Support 21st-Century Toxicology.

SUMMARY: Access to high-quality reference data is essential for the development, validation, and implementation of in vitro and in silico approaches that reduce and replace the use of animals in toxicity testing. Currently, these data must often be pooled from a variety of disparate sources to efficiently link a set of assay responses and model predictions to an outcome or hazard classification. To provide a central access point for these purposes, the National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods developed the Integrated Chemical Environment (ICE) web resource. The ICE data integrator allows users to retrieve and combine data sets and to develop hypotheses through data exploration. Open-source computational workflows and models will be available for download and application to local data. ICE currently includes curated in vivo test data, reference chemical information, in vitro assay data (including Tox21TM/ToxCast™ high-throughput screening data), and in silico model predictions. Users can query these data collections focusing on end points of interest such as acute systemic toxicity, endocrine disruption, skin sensitization, and many others. ICE is publicly accessible at https://ice.ntp.niehs.nih.gov. https://doi.org/10.1289/EHP1759.

SWIFT-Review: a text-mining workbench for systematic review.

BACKGROUND: There is growing interest in using machine learning approaches to priority rank studies and reduce human burden in screening literature when conducting systematic reviews. In addition, identifying addressable questions during the problem formulation phase of systematic review can be challenging, especially for topics having a large literature base. Here, we assess the performance of the SWIFT-Review priority ranking algorithm for identifying studies relevant to a given research question. We also explore the use of SWIFT-Review during problem formulation to identify, categorize, and visualize research areas that are data rich/data poor within a large literature corpus. METHODS: Twenty case studies, including 15 public data sets, representing a range of complexity and size, were used to assess the priority ranking performance of SWIFT-Review. For each study, seed sets of manually annotated included and excluded titles and abstracts were used for machine training. The remaining references were then ranked for relevance using an algorithm that considers term frequency and latent Dirichlet allocation (LDA) topic modeling. This ranking was evaluated with respect to (1) the number of studies screened in order to identify 95 % of known relevant studies and (2) the "Work Saved over Sampling" (WSS) performance metric. To assess SWIFT-Review for use in problem formulation, PubMed literature search results for 171 chemicals implicated as EDCs were uploaded into SWIFT-Review (264,588 studies) and categorized based on evidence stream and health outcome. Patterns of search results were surveyed and visualized using a variety of interactive graphics. RESULTS: Compared with the reported performance of other tools using the same datasets, the SWIFT-Review ranking procedure obtained the highest scores on 11 out of 15 of the public datasets. Overall, these results suggest that using machine learning to triage documents for screening has the potential to save, on average, more than 50 % of the screening effort ordinarily required when using un-ordered document lists. In addition, the tagging and annotation capabilities of SWIFT-Review can be useful during the activities of scoping and problem formulation. CONCLUSIONS: Text-mining and machine learning software such as SWIFT-Review can be valuable tools to reduce the human screening burden and assist in problem formulation.

Targeted focal therapy for the management of organ confined prostate cancer.

PURPOSE: Patients currently diagnosed with low risk prostate cancer are often overtreated and experience complications, resulting in detriment to quality of life. Targeted focal therapy is a minimally invasive procedure designed to ablate tumor foci while minimizing collateral damage to maintain quality of life. MATERIALS AND METHODS: This institutional review board approved, prospective study was done to assess the safety and efficacy of targeted focal therapy using cryotherapy in men 40 to 85 years old diagnosed with low risk, organ confined prostate cancer at our institution between 2006 and 2009. Low risk, organ confined prostate cancer was defined as Gleason score 7 or less (3 + 4) on transrectal ultrasound biopsy, tumor burden 50% or less and prostate specific antigen less than 10 ng/dl. Patients were evaluated for eligibility after undergoing 3-dimensional mapping biopsy. Median followup was 28 months (IQR 26-31). RESULTS: A total of 62 men with low risk disease met study inclusion criteria. At 1 year biopsy was negative in 50 of 62 patients (81%). All 12 men who tested positive on repeat biopsy had a Gleason score of 3 + 3 = 6 with 1 or 2 positive cores. The median prostate specific antigen change was a 3.0 ng/dl decrease (p <0.01). The median American Urological Association symptom score change was a 1.5-point decrease (p <0.01). No significant change was observed in Sexual Health Inventory for Men score (p = 0.6). No urinary incontinence episodes and no severe side effects were noted. CONCLUSIONS: Targeted focal therapy in carefully selected patients provides a feasible, practical option for treating low risk prostate cancer with minimal impact on quality of life.

Validation of the Urgency, Weak stream, Incomplete emptying, and Nocturia (UWIN) score compared with the American Urological Association Symptoms Score in assessing lower urinary tract symptoms in the clinical setting.

OBJECTIVE: To validate the Urgency, Weak stream, Incomplete emptying, and Nocturia (UWIN) survey for patients with lower urinary tract symptoms (LUTS) by comparison with the American Urological Association Symptoms Score (AUA-SS). The hypothesis is that the UWIN will perform as well as the AUA-SS in assessing LUTS symptoms and quality of life. The AUA-SS is complex for many patients and can be misunderstood. The UWIN questionnaire was developed to serve as a simpler and shorter version of the AUA-SS, with the intent of improving accuracy and minimizing error in assessing LUTS. The UWIN consists of 4 questions scored 0-3 to give a maximum score of 12. METHODS: We screened 700 patients in the urology clinic between 2011 and 2012. We enrolled 593 patients who completed the AUA-SS survey and UWIN in the same clinic visit. The AUA-SS and UWIN responses were evaluated using Spearman correlation coefficients and Bland-Altman graphs. RESULTS: Correlation coefficients were calculated between the corresponding AUA-SS and UWIN items on 593 matched surveys, demonstrating a strong correlation coefficient of 0.81 or greater for each question, which was statistically significant (P <.0001). The correlation coefficient between the total scores of the AUA and UWIN was 0.89 (P <.01). A second analysis was performed using Bland-Altman plots between AUA-SS and UWIN including total score, quality of life, and categories, which showed a good agreement. CONCLUSION: The UWIN appears to provide results comparable to the AUA-SS, while using a simpler format and taking less time to complete.

Daptomycin-induced acute eosinophilic pneumonia: analysis of the current data and illustrative case reports.

Acute eosinophilic pneumonia (AEP) is a rare but important complication of daptomycin therapy. We describe 2 cases of daptomycin-associated AEP, compile available data from another 22 published cases, and propose a revised set of diagnostic criteria.

Male primary retroperitoneal mucinous cystadenoma.

Primary retroperitoneal mucinous cystadenoma of borderline malignancy is a rare disease, especially in male patients. Often these tumors are not incidentally found due to abdominal symptoms. We present the radiologic abdominal computed tomography scan, surgical, and pathologic images of this unique, rare condition in a male patient. Surgical treatment is recommended to establish diagnosis and treatment.