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Abstract Background Racial/ethnic disparities in the HIV care continuum have been well documented in the US, with especially striking inequalities in viral suppression rates between White and Black persons with HIV (PWH). The South is considered an epicenter of the HIV epidemic in the US, with the largest population of PWH living in Florida. It is unclear whether any disparities in viral suppression or immune reconstitution—a clinical outcome highly correlated with overall prognosis—have changed over time or are homogenous geographically. In this analysis, we 1) investigate longitudinal trends in viral suppression and immune reconstitution among PWH in Florida, 2) examine the impact of socio-ecological factors on the association between race/ethnicity and clinical outcomes, 3) explore spatial and temporal variations in disparities in clinical outcomes. Methods Data were obtained from the Florida Department of Health for 42,369 PWH enrolled in the Ryan White program during 2008-2020. We linked the data to county-level socio-ecological variables available from County Health Rankings. GEE models were fit to assess the effect of race/ethnicity on immune reconstitution and viral suppression longitudinally. Poisson Bayesian hierarchical models were fit to analyze geographic variations in racial/ethnic disparities while adjusting for socio-ecological factors. Results Proportions of PWH who experienced viral suppression and immune reconstitution rose by 60% and 45%, respectively, from 2008-2020. Odds of immune reconstitution and viral suppression were significantly higher among White [odds ratio =2.34, 95% credible interval=2.14-2.56; 1.95 (1.85-2.05)], and Hispanic [1.70 (1.54-1.87); 2.18(2.07-2.31)] PWH, compared with Black PWH. These findings remained unchanged after accounting for socio-ecological factors. Rural and urban counties in north-central Florida saw the largest racial/ethnic disparities. Conclusions There is persistent, spatially heterogeneous, racial/ethnic disparity in HIV clinical outcomes in Florida. This disparity could not be explained by socio-ecological factors, suggesting that further research on modifiable factors that can improve HIV outcomes among Black and Hispanic PWH in Florida is needed.

Abstract Background Prognostic models of hospital-induced delirium, that include potential predisposing and precipitating factors, may be used to identify vulnerable patients and inform the implementation of tailored preventive interventions. It is recommended that, in prediction model development studies, candidate predictors are selected on the basis of existing knowledge, including knowledge from clinical practice. The purpose of this article is to describe the process of identifying and operationalizing candidate predictors of hospital-induced delirium for application in a prediction model development study using a practice-based approach. Methods This study is part of a larger, retrospective cohort study that is developing prognostic models of hospital-induced delirium for medical-surgical older adult patients using structured data from administrative and electronic health records. First, we conducted a review of the literature to identify clinical concepts that had been used as candidate predictors in prognostic model development-and-validation studies of hospital-induced delirium. Then, we consulted a multidisciplinary task force of nine members who independently judged whether each clinical concept was associated with hospital-induced delirium. Finally, we mapped the clinical concepts to the administrative and electronic health records and operationalized our candidate predictors. Results In the review of 34 studies, we identified 504 unique clinical concepts. Two-thirds of the clinical concepts (337/504) were used as candidate predictors only once. The most common clinical concepts included age (31/34), sex (29/34), and alcohol use (22/34). 96% of the clinical concepts (484/504) were judged to be associated with the development of hospital-induced delirium by at least two members of the task force. All of the task force members agreed that 47 or 9% of the 504 clinical concepts were associated with hospital-induced delirium. Conclusions Heterogeneity among candidate predictors of hospital-induced delirium in the literature suggests a still evolving list of factors that contribute to the development of this complex phenomenon. We demonstrated a practice-based approach to variable selection for our model development study of hospital-induced delirium. Expert judgement of variables enabled us to categorize the variables based on the amount of agreement among the experts and plan for the development of different models, including an expert-model and data-driven model.

Abstract Background Integrase strand transferase inhibitors (INSTI), including raltegravir (RAL), elvitegravir (ELV), and dolutegravir (DTG), have demonstrated better efficacy and tolerability than other combination antiretroviral therapy (cART) classes in clinical trials; however, studies of sustainability of INSTI-containing therapy in the long-term are sparse. The purpose of this study was to provide an epidemiological overview comparing the outcome performance of different INSTI-based regimens longitudinally, including the metrics of efficacy, safety, convenience, and durability among a large, nationally representative cohort of persons living with HIV in Italy. Methods We selected subjects in the MaSTER cohort (an Italian multicenter, hospital-based cohort established in the mid-1990s that currently has enrolled over 24,000 PLWH) who initiated an INSTI-based regimen either when naïve or following a regimen switch. Cox proportional hazards regression models were fitted to evaluate associations between therapy interruptions and age, sex, nationality, transmission risk group, viral suppression status, CD4 + T-cell count, diagnosis year, cART status (naïve or experienced), and hepatitis coinfection. Results were stratified by cART INSTI type. Results There were 8173 participants who initiated an INSTI-based cART regimen in the MaSTER cohort between 2009 and 2017. The population was majority male (72.6%), of Italian nationality (88.6%), and cART-experienced (83.0%). Mean age was 49.7 (standard deviation: 13.9) years. In total, interruptions of the 1st INSTI-based treatment were recorded in 34% of cases. The most frequently cited reason for interruption among all three drug types was safety problems. In the survival analysis, past history of cART use was associated with higher hazards of interruption due to poor efficacy for all three drug types when compared to persons who were cART naïve. Non-viral suppression and CD4 + T-cell count

Abstract Background Metagenomic data can be used to profile high-importance genes within microbiomes. However, current metagenomic workflows produce data that suffer from low sensitivity and an inability to accurately reconstruct partial or full genomes, particularly those in low abundance. These limitations preclude colocalization analysis, i.e., characterizing the genomic context of genes and functions within a metagenomic sample. Genomic context is especially crucial for functions associated with horizontal gene transfer (HGT) via mobile genetic elements (MGEs), for example antimicrobial resistance (AMR). To overcome this current limitation of metagenomics, we present a method for comprehensive and accurate reconstruction of antimicrobial resistance genes (ARGs) and MGEs from metagenomic DNA, termed target-enriched long-read sequencing (TELSeq). Results Using technical replicates of diverse sample types, we compared TELSeq performance to that of non-enriched PacBio and short-read Illumina sequencing. TELSeq achieved much higher ARG recovery (>1,000-fold) and sensitivity than the other methods across diverse metagenomes, revealing an extensive resistome profile comprising many low-abundance ARGs, including some with public health importance. Using the long reads generated by TELSeq, we identified numerous MGEs and cargo genes flanking the low-abundance ARGs, indicating that these ARGs could be transferred across bacterial taxa via HGT. Conclusions TELSeq can provide a nuanced view of the genomic context of microbial resistomes and thus has wide-ranging applications in public, animal, and human health, as well as environmental surveillance and monitoring of AMR. Thus, this technique represents a fundamental advancement for microbiome research and application. Video abstract

Abstract Background Identification of motifs and quantification of their occurrences are important for the study of genetic diseases, gene evolution, transcription sites, and other biological mechanisms. Exact formulae for estimating count distributions of motifs under Markovian assumptions have high computational complexity and are impractical to be used on large motif sets. Approximated formulae, e.g. based on compound Poisson, are faster, but reliable p value calculation remains challenging. Here, we introduce ‘motif_prob’, a fast implementation of an exact formula for motif count distribution through progressive approximation with arbitrary precision. Our implementation speeds up the exact calculation, usually impractical, making it feasible and posit to substitute currently employed heuristics. Results We implement motif_prob in both Perl and C+ + languages, using an efficient error-bound iterative process for the exact formula, providing comparison with state-of-the-art tools (e.g. MoSDi) in terms of precision, run time benchmarks, along with a real-world use case on bacterial motif characterization. Our software is able to process a million of motifs (13–31 bases) over genome lengths of 5 million bases within the minute on a regular laptop, and the run times for both the Perl and C+ + code are several orders of magnitude smaller (50–1000× faster) than MoSDi, even when using their fast compound Poisson approximation (60–120× faster). In the real-world use cases, we first show the consistency of motif_prob with MoSDi, and then how the p-value quantification is crucial for enrichment quantification when bacteria have different GC content, using motifs found in antimicrobial resistance genes. The software and the code sources are available under the MIT license at https://github.com/DataIntellSystLab/motif_prob . Conclusions The motif_prob software is a multi-platform and efficient open source solution for calculating exact frequency distributions of motifs. It can be integrated with motif discovery/characterization tools for quantifying enrichment and deviation from expected frequency ranges with exact p values, without loss in data processing efficiency.

Abstract Background To reduce cancer mortality and improve cancer outcomes, it is critical to understand the various cancer risk factors (RFs) across different domains (e.g., genetic, environmental, and behavioral risk factors) and levels (e.g., individual, interpersonal, and community levels). However, prior research on RFs of cancer outcomes, has primarily focused on individual level RFs due to the lack of integrated datasets that contain multi-level, multi-domain RFs. Further, the lack of a consensus and proper guidance on systematically identify RFs also increase the difficulty of RF selection from heterogenous data sources in a multi-level integrative data analysis (mIDA) study. More importantly, as mIDA studies require integrating heterogenous data sources, the data integration processes in the limited number of existing mIDA studies are inconsistently performed and poorly documented, and thus threatening transparency and reproducibility. Methods Informed by the National Institute on Minority Health and Health Disparities (NIMHD) research framework, we (1) reviewed existing reporting guidelines from the Enhancing the QUAlity and Transparency Of health Research (EQUATOR) network and (2) developed a theory-driven reporting guideline to guide the RF variable selection, data source selection, and data integration process. Then, we developed an ontology to standardize the documentation of the RF selection and data integration process in mIDA studies. Results We summarized the review results and created a reporting guideline—ATTEST—for reporting the variable selection and data source selection and integration process. We provided an ATTEST check list to help researchers to annotate and clearly document each step of their mIDA studies to ensure the transparency and reproducibility. We used the ATTEST to report two mIDA case studies and further transformed annotation results into sematic triples, so that the relationships among variables, data sources and integration processes are explicitly standardized and modeled using the classes and properties from OD-ATTEST. Conclusion Our ontology-based reporting guideline solves some key challenges in current mIDA studies for cancer outcomes research, through providing (1) a theory-driven guidance for multi-level and multi-domain RF variable and data source selection; and (2) a standardized documentation of the data selection and integration processes powered by an ontology, thus a way to enable sharing of mIDA study reports among researchers.

Abstract Background Dietary supplements (DSs) are widely used. However, consumers know little about the safety and efficacy of DSs. There is a growing interest in accessing health information online; however, health information, especially online information on DSs, is scattered with varying levels of quality. In our previous work, we prototyped a web application, ALOHA, with interactive graph-based visualization to facilitate consumers’ browsing of the integrated DIetary Supplement Knowledge base (iDISK) curated from scientific resources, following an iterative user-centered design (UCD) process. Methods Following UCD principles, we carried out two design iterations to enrich the functionalities of ALOHA and enhance its usability. For each iteration, we conducted a usability assessment and design session with a focus group of 8–10 participants and evaluated the usability with a modified System Usability Scale (SUS). Through thematic analysis, we summarized the identified usability issues and conducted a heuristic evaluation to map them to the Gerhardt-Powals’ cognitive engineering principles. We derived suggested improvements from each of the usability assessment session and enhanced ALOHA accordingly in the next design iteration. Results The SUS score in the second design iteration decreased to 52.2 ± 11.0 from 63.75 ± 7.2 in our original work, possibly due to the high number of new functionalities we introduced. By refining existing functionalities to make the user interface simpler, the SUS score increased to 64.4 ± 7.2 in the third design iteration. All participants agreed that such an application is urgently needed to address the gaps in how DS information is currently organized and consumed online. Moreover, most participants thought that the graph-based visualization in ALOHA is a creative and visually appealing format to obtain health information. Conclusions In this study, we improved a novel interactive visualization platform, ALOHA, for the general public to obtain DS-related information through two UCD design iterations. The lessons learned from the two design iterations could serve as a guide to further enhance ALOHA and the development of other knowledge graph-based applications. Our study also showed that graph-based interactive visualization is a novel and acceptable approach to end-users who are interested in seeking online health information of various domains.

Abstract Background Nowadays, trendy research in biomedical sciences juxtaposes the term ‘precision’ to medicine and public health with companion words like big data, data science, and deep learning. Technological advancements permit the collection and merging of large heterogeneous datasets from different sources, from genome sequences to social media posts or from electronic health records to wearables. Additionally, complex algorithms supported by high-performance computing allow one to transform these large datasets into knowledge. Despite such progress, many barriers still exist against achieving precision medicine and precision public health interventions for the benefit of the individual and the population. Main body The present work focuses on analyzing both the technical and societal hurdles related to the development of prediction models of health risks, diagnoses and outcomes from integrated biomedical databases. Methodological challenges that need to be addressed include improving semantics of study designs: medical record data are inherently biased, and even the most advanced deep learning’s denoising autoencoders cannot overcome the bias if not handled a priori by design. Societal challenges to face include evaluation of ethically actionable risk factors at the individual and population level; for instance, usage of gender, race, or ethnicity as risk modifiers, not as biological variables, could be replaced by modifiable environmental proxies such as lifestyle and dietary habits, household income, or access to educational resources. Conclusions Data science for precision medicine and public health warrants an informatics-oriented formalization of the study design and interoperability throughout all levels of the knowledge inference process, from the research semantics, to model development, and ultimately to implementation.

Abstract Background Kidney stone (KS) disease has high, increasing prevalence in the United States and poses a massive economic burden. Diagnostics algorithms of KS only use a few variables with a limited sensitivity and specificity. In this study, we tested a big data approach to infer and validate a ‘multi-domain’ personalized diagnostic acute care algorithm for KS (DACA-KS), merging demographic, vital signs, clinical, and laboratory information. Methods We utilized a large, single-center database of patients admitted to acute care units in a large tertiary care hospital. Patients diagnosed with KS were compared to groups of patients with acute abdominal/flank/groin pain, genitourinary diseases, and other conditions. We analyzed multiple information domains (several thousands of variables) using a collection of statistical and machine learning models with feature selectors. We compared sensitivity, specificity and area under the receiver operating characteristic (AUROC) of our approach with the STONE score, using cross-validation. Results Thirty eight thousand five hundred and ninety-seven distinct adult patients were admitted to critical care between 2001 and 2012, of which 217 were diagnosed with KS, and 7446 with acute pain (non-KS). The multi-domain approach using logistic regression yielded an AUROC of 0.86 and a sensitivity/specificity of 0.81/0.82 in cross-validation. Increase in performance was obtained by fitting a super-learner, at the price of lower interpretability. We discussed in detail comorbidity and lab marker variables independently associated with KS (e.g. blood chloride, candidiasis, sleep disorders). Conclusions Although external validation is warranted, DACA-KS could be integrated into electronic health systems; the algorithm has the potential used as an effective tool to help nurses and healthcare personnel during triage or clinicians making a diagnosis, streamlining patients’ management in acute care.