11 research outputs found
Finishing the euchromatic sequence of the human genome
The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead
Predicting COVID-19 mortality with electronic medical records
This study aims to predict death after COVID-19 using only the past medical information routinely collected in electronic health records (EHRs) and to understand the differences in risk factors across age groups. Combining computational methods and clinical expertise, we curated clusters that represent 46 clinical conditions as potential risk factors for death after a COVID-19 infection. We trained age-stratified generalized linear models (GLMs) with component-wise gradient boosting to predict the probability of death based on what we know from the patients before they contracted the virus. Despite only relying on previously documented demographics and comorbidities, our models demonstrated similar performance to other prognostic models that require an assortment of symptoms, laboratory values, and images at the time of diagnosis or during the course of the illness. In general, we found age as the most important predictor of mortality in COVID-19 patients. A history of pneumonia, which is rarely asked in typical epidemiology studies, was one of the most important risk factors for predicting COVID-19 mortality. A history of diabetes with complications and cancer (breast and prostate) were notable risk factors for patients between the ages of 45 and 65 years. In patients aged 65–85 years, diseases that affect the pulmonary system, including interstitial lung disease, chronic obstructive pulmonary disease, lung cancer, and a smoking history, were important for predicting mortality. The ability to compute precise individual-level risk scores exclusively based on the EHR is crucial for effectively allocating and distributing resources, such as prioritizing vaccination among the general population
Improvements of Fibrosis and Disease Activity Are Associated With Improvement of Patient‐Reported Outcomes in Patients With Advanced Fibrosis Due to Nonalcoholic Steatohepatitis
Patient-reported outcomes (PROs) are important endpoints for clinical trials. The impact of investigational drugs on PROs of patients with advanced nonalcoholic steatohepatitis (NASH) was investigated. Patients with NASH with bridging fibrosis or compensated cirrhosis were enrolled in a phase 2, randomized, placebo-controlled study of selonsertib, firsocostat, or cilofexor, alone or in two-drug combinations (NCT03449446). PROs included Short Form 36 (SF-36), Chronic Liver Disease Questionnaire (CLDQ)-NASH, EuroQol Five Dimension (EQ-5D), Work Productivity and Impairment (WPAI), and 5-D Itch before and during treatment. A total of 392 patients with NASH (mean ± SD, 60 ± 9 years old; 35% men; 89% white; 72% diabetes; and 56% compensated cirrhosis) were included. Baseline Physical Functioning (PF) and Bodily Pain of SF-36 and Fatigue and Worry of CLDQ-NASH were significantly lower in patients with cirrhosis (total CLDQ-NASH score mean ± SD, 4.91 ± 1.06 with cirrhosis vs. 5.16 ± 1.14 without cirrhosis; P < 0.05). Lower baseline PRO scores were independently associated with age, female sex, greater body mass index, diabetes, clinically overt fatigue, and comorbidities (all P < 0.05). After 48 weeks of treatment, patients with ≥1-stage fibrosis improvement without worsening of NASH experienced improvement in EQ-5D and five out of six CLDQ-NASH domains (P < 0.05). Patients with ≥2-point decrease in their nonalcoholic fatty liver disease activity score (NAS) also had improvements in PF and Role Physical scores and all domains of CLDQ-NASH (P < 0.05). Progression to cirrhosis was associated with a decrease in PF scores of SF-36 (P ≤ 0.05). Fibrosis regression was independently associated with greater improvements in PF and EQ-5D scores, while NAS improvement was associated with improvement in fatigue and pruritus (all P < 0.05). Conclusion: Patients with advanced NASH experienced improvement in their PROs after fibrosis regression or improvement in disease activity
A retrospective cohort analysis leveraging augmented intelligence to characterize long COVID in the electronic health record: A precision medicine framework.
Physical and psychological symptoms lasting months following an acute COVID-19 infection are now recognized as post-acute sequelae of COVID-19 (PASC). Accurate tools for identifying such patients could enhance screening capabilities for the recruitment for clinical trials, improve the reliability of disease estimates, and allow for more accurate downstream cohort analysis. In this retrospective cohort study, we analyzed the EHR of hospitalized COVID-19 patients across three healthcare systems to develop a pipeline for better identifying patients with persistent PASC symptoms (dyspnea, fatigue, or joint pain) after their SARS-CoV-2 infection. We implemented distributed representation learning powered by the Machine Learning for modeling Health Outcomes (MLHO) to identify novel EHR features that could suggest PASC symptoms outside of typical diagnosis codes. MLHO applies an entropy-based feature selection and boosting algorithms for representation mining. These improved definitions were then used for estimating PASC among hospitalized patients. 30,422 hospitalized patients were diagnosed with COVID-19 across three healthcare systems between March 13, 2020 and February 28, 2021. The mean age of the population was 62.3 years (SD, 21.0 years) and 15,124 (49.7%) were female. We implemented the distributed representation learning technique to augment PASC definitions. These definitions were found to have positive predictive values of 0.73, 0.74, and 0.91 for dyspnea, fatigue, and joint pain, respectively. We estimated that 25 percent (CI 95%: 6-48), 11 percent (CI 95%: 6-15), and 13 percent (CI 95%: 8-17) of hospitalized COVID-19 patients will have dyspnea, fatigue, and joint pain, respectively, 3 months or longer after a COVID-19 diagnosis. We present a validated framework for screening and identifying patients with PASC in the EHR and then use the tool to estimate its prevalence among hospitalized COVID-19 patients
Distinguishing Admissions Specifically for COVID-19 From Incidental SARS-CoV-2 Admissions: National Retrospective Electronic Health Record Study
BackgroundAdmissions are generally classified as COVID-19 hospitalizations if the patient has a positive SARS-CoV-2 polymerase chain reaction (PCR) test. However, because 35% of SARS-CoV-2 infections are asymptomatic, patients admitted for unrelated indications with an incidentally positive test could be misclassified as a COVID-19 hospitalization. Electronic health record (EHR)–based studies have been unable to distinguish between a hospitalization specifically for COVID-19 versus an incidental SARS-CoV-2 hospitalization. Although the need to improve classification of COVID-19 versus incidental SARS-CoV-2 is well understood, the magnitude of the problems has only been characterized in small, single-center studies. Furthermore, there have been no peer-reviewed studies evaluating methods for improving classification.
ObjectiveThe aims of this study are to, first, quantify the frequency of incidental hospitalizations over the first 15 months of the pandemic in multiple hospital systems in the United States and, second, to apply electronic phenotyping techniques to automatically improve COVID-19 hospitalization classification.
MethodsFrom a retrospective EHR-based cohort in 4 US health care systems in Massachusetts, Pennsylvania, and Illinois, a random sample of 1123 SARS-CoV-2 PCR-positive patients hospitalized from March 2020 to August 2021 was manually chart-reviewed and classified as “admitted with COVID-19” (incidental) versus specifically admitted for COVID-19 (“for COVID-19”). EHR-based phenotyping was used to find feature sets to filter out incidental admissions.
ResultsEHR-based phenotyped feature sets filtered out incidental admissions, which occurred in an average of 26% of hospitalizations (although this varied widely over time, from 0% to 75%). The top site-specific feature sets had 79%-99% specificity with 62%-75% sensitivity, while the best-performing across-site feature sets had 71%-94% specificity with 69%-81% sensitivity.
ConclusionsA large proportion of SARS-CoV-2 PCR-positive admissions were incidental. Straightforward EHR-based phenotypes differentiated admissions, which is important to assure accurate public health reporting and research
Safety and efficacy of combination therapies including cilofexor/ firsocostat in patients with bridging fibrosis and cirrhosis due to NASH: Results of the phase 2b ATLAS trial
International electronic health record-derived post-acute sequelae profiles of COVID-19 patients
10.1038/s41746-022-00623-8NPJ DIGITAL MEDICINE5
Characterization of long COVID temporal sub-phenotypes by distributed representation learning from electronic health record data: a cohort studyResearch in Context
Summary: Background: Characterizing Post-Acute Sequelae of COVID (SARS-CoV-2 Infection), or PASC has been challenging due to the multitude of sub-phenotypes, temporal attributes, and definitions. Scalable characterization of PASC sub-phenotypes can enhance screening capacities, disease management, and treatment planning. Methods: We conducted a retrospective multi-centre observational cohort study, leveraging longitudinal electronic health record (EHR) data of 30,422 patients from three healthcare systems in the Consortium for the Clinical Characterization of COVID-19 by EHR (4CE). From the total cohort, we applied a deductive approach on 12,424 individuals with follow-up data and developed a distributed representation learning process for providing augmented definitions for PASC sub-phenotypes. Findings: Our framework characterized seven PASC sub-phenotypes. We estimated that on average 15.7% of the hospitalized COVID-19 patients were likely to suffer from at least one PASC symptom and almost 5.98%, on average, had multiple symptoms. Joint pain and dyspnea had the highest prevalence, with an average prevalence of 5.45% and 4.53%, respectively. Interpretation: We provided a scalable framework to every participating healthcare system for estimating PASC sub-phenotypes prevalence and temporal attributes, thus developing a unified model that characterizes augmented sub-phenotypes across the different systems. Funding: Authors are supported by National Institute of Allergy and Infectious Diseases, National Institute on Aging, National Center for Advancing Translational Sciences, National Medical Research Council, National Institute of Neurological Disorders and Stroke, European Union, National Institutes of Health, National Center for Advancing Translational Sciences