Background
COVID-19 is caused by the SARS-CoV-2 virus and has strikingly heterogeneous clinical manifestations, with most individuals contracting mild disease but a substantial minority experiencing ...fulminant cardiopulmonary symptoms or death. The clinical covariates and the laboratory tests performed on a patient provide robust statistics to guide clinical treatment. Deep learning approaches on a data set of this nature enable patient stratification and provide methods to guide clinical treatment.
Objective
Here, we report on the development and prospective validation of a state-of-the-art machine learning model to provide mortality prediction shortly after confirmation of SARS-CoV-2 infection in the Mayo Clinic patient population.
Methods
We retrospectively constructed one of the largest reported and most geographically diverse laboratory information system and electronic health record of COVID-19 data sets in the published literature, which included 11,807 patients residing in 41 states of the United States of America and treated at medical sites across 5 states in 3 time zones. Traditional machine learning models were evaluated independently as well as in a stacked learner approach by using AutoGluon, and various recurrent neural network architectures were considered. The traditional machine learning models were implemented using the AutoGluon-Tabular framework, whereas the recurrent neural networks utilized the TensorFlow Keras framework. We trained these models to operate solely using routine laboratory measurements and clinical covariates available within 72 hours of a patient’s first positive COVID-19 nucleic acid test result.
Results
The GRU-D recurrent neural network achieved peak cross-validation performance with 0.938 (SE 0.004) as the area under the receiver operating characteristic (AUROC) curve. This model retained strong performance by reducing the follow-up time to 12 hours (0.916 SE 0.005 AUROC), and the leave-one-out feature importance analysis indicated that the most independently valuable features were age, Charlson comorbidity index, minimum oxygen saturation, fibrinogen level, and serum iron level. In the prospective testing cohort, this model provided an AUROC of 0.901 and a statistically significant difference in survival (P<.001, hazard ratio for those predicted to survive, 95% CI 0.043-0.106).
Conclusions
Our deep learning approach using GRU-D provides an alert system to flag mortality for COVID-19–positive patients by using clinical covariates and laboratory values within a 72-hour window after the first positive nucleic acid test result.
Systemic lupus erythematosus (SLE, MIM152700) is an autoimmune disease characterized by self-reactive antibodies resulting in systemic inflammation and organ failure. TNFAIP3, encoding the ...ubiquitin-modifying enzyme A20, is an established susceptibility locus for SLE. By fine mapping and genomic re-sequencing in ethnically diverse populations, we fully characterized the TNFAIP3 risk haplotype and identified a TT>A polymorphic dinucleotide (deletion T followed by a T to A transversion) associated with SLE in subjects of European (P = 1.58 × 10−8, odds ratio = 1.70) and Korean (P = 8.33 × 10−10, odds ratio = 2.54) ancestry. This variant, located in a region of high conservation and regulatory potential, bound a nuclear protein complex composed of NF-κB subunits with reduced avidity. Further, compared with the non-risk haplotype, the haplotype carrying this variant resulted in reduced TNFAIP3 mRNA and A20 protein expression. These results establish this TT>A variant as the most likely functional polymorphism responsible for the association between TNFAIP3 and SLE.
TNFAIP3 encodes the ubiquitin-modifying enzyme, A20, a key regulator of inflammatory signaling pathways. We previously reported association between TNFAIP3 variants and systemic lupus erythematosus ...(SLE). To further localize the risk variant(s), we performed a meta-analysis using genetic data available from two Caucasian case-control datasets (1453 total cases, 3381 total control subjects) and 713 SLE trio families. The best result was found at rs5029939 (P=1.67 x 10(-14), odds ratio=2.09, 95% confidence interval 1.68-2.60). We then imputed single nucleotide polymorphisms (SNPs) from the CEU Phase II HapMap using genotypes from 431 SLE cases and 2155 control subjects. Imputation identified 11 SNPs in addition to three observed SNPs, which together, defined a 109 kb SLE risk segment surrounding TNFAIP3. When evaluating whether the rs5029939 risk allele was associated with SLE clinical manifestations, we observed that heterozygous carriers of the TNFAIP3 risk allele at rs5029939 have a twofold increased risk of developing renal or hematologic manifestations compared to homozygous non-risk subjects. In summary, our study strengthens the genetic evidence that variants in the region of TNFAIP3 influence risk for SLE, particularly in patients with renal and hematologic manifestations, and narrows the risk effect to a 109 kb DNA segment that spans the TNFAIP3 gene.
Systemic Lupus Erythematosus (SLE, OMIM 152700) is an autoimmune disease characterized by self-reactive antibodies resulting in systemic inflammation and organ failure.
TNFAIP3
, encoding the ...ubiquitin-modifying enzyme A20, is an established susceptibility locus for SLE. By fine mapping and genomic resequencing in ethnically diverse populations we fully characterized the
TNFAIP3
risk haplotype and isolated a novel TT>A polymorphic dinucleotide associated with SLE in subjects of European (
P
= 1.58 × 10
−8
; odds ratio (OR) = 1.70) and Korean (
P
= 8.33 × 10
−10
; OR = 2.54) ancestry. This variant, located in a region of high conservation and regulatory potential, bound a nuclear protein complex comprised of NF-κB subunits with reduced avidity. Furthermore, compared with the non-risk haplotype, the haplotype carrying this variant resulted in reduced
TNFAIP3
mRNA and A20 protein expression. These results establish this TT>A variant as the most likely functional polymorphism responsible for the association between
TNFAIP3
and SLE.
Many factors contribute to the poor survival of malignant brain tumor patients, some of which are not easily remedied. However, one contributor to the lack of progress that may be modifiable is poor ...clinical trial accrual. Surveys of brain tumor patients and neuro-oncology providers suggest that clinicians do a poor job of discussing clinical trials with patients and referring patients for clinical trials. Yet, data from the Cancer Action Network of the American Cancer Society suggest that most eligible oncology patients asked to enroll on a clinical trial will agree to do so. To this end, the Society for Neuro-Oncology (SNO) in collaboration with the Response Assessment in Neuro-Oncology (RANO) Working Group, patient advocacy groups, clinical trial cooperative groups, including the Adult Brain Tumor Consortium (ABTC), and other partners are working together with the intent to double clinical trial accrual over the next 5 years. Here we describe the factors contributing to poor clinical trial accrual in neuro-oncology and offer possible solutions.
The number of medical center-based farmers markets has increased in the past decade, but little is known about how such organizations contribute to the preventive health goals of the patient-centered ...medical home.
In 2010, we started a seasonal farmers market at Penn State Hershey Medical Center to help support the institution's commitment to the medical home.
We obtained descriptive data on the farmers market from hospital and market records and tracking information on the market's Facebook and Twitter sites. We computed summary measures to characterize how the market has begun to meet the 6 standards of the 2011 National Committee for Quality Assurance's report on the medical home.
During the 2010 and 2011 seasons, 146 medical center volunteers from 40 departments formed 23 interprofessional teams that spent an average of 551 volunteer hours per season at the market, providing health screenings (n = 695) and speaking to customers (n = 636) about preventive health. Fifty-five nonmedical community health partners provided 208 hours of service at the market alongside medical center staff. Market programming contributed to 5 regional preventive health partnerships and created opportunities for interprofessional mentoring, student leadership, data management, development of social media skills, and grant-writing experience. The market contributed to all 6 medical home standards outlined by the National Committee for Quality Assurance.
Medical center markets can support medical home standards. With systematic tracking of the health effects and integration with electronic medical health records, markets hold potential to contribute to comprehensive patient-centered care.
BACKGROUND: Widespread screening and treatment of hepatitis C virus (HCV) is required to decrease late-stage liver disease and liver cancer. Clinical practice guidelines and Canadian Task Force on ...Preventative Health Care recommendations differ on the value of one-time birth cohort (1945–75) HCV screening in Canada. To assess the utility of this approach, we conducted a real-world analysis of HCV antibody (Ab) prevalence among birth cohort individuals seen in different clinical contexts. METHODS: Cross-sectional study of individuals born between 1945 and 1975 who completed HCV Ab testing at multiple participating centres in Ontario, Canada between January 2016 and December 2020. Differences in prevalence were compared by year of birth, gender, and setting. RESULTS: Among 16,672 birth cohort individuals tested, HCV Ab prevalence was 3.2%. Prevalence was higher among younger individuals which increased from 0.9% among those born between 1945 and 1956 to 4.6% among those born between 1966 and 1975. Prevalence was higher among males (4.4%) compared with females (2.0%) and differed by test site. In primary care, the prevalence was 0.5%, whereas the prevalence was highest among those tested at drug treatment centres (28.7%) and through community outreach (14.0%). CONCLUSIONS: HCV Ab prevalence remains high in the 1945–1975 birth cohort. These data highlight the need to re-evaluate existing Canadian Preventative Task Force recommendations, to consider incorporating one-time birth cohort and/or other population-based approaches to HCV screening into the clinical workflow as a preventative health measure, and to increase training among community providers to screen for and treat HCV.
Effective treatment regimens for pulmonary tuberculosis are difficult to assess because of the slow growth rate of Mycobacterium tuberculosis in culture and its protracted clearance from sputum. A ...rapid method that reflects effective antimicrobial activity would markedly advance evaluation of treatment and promote the assessment of new antituberculosis drugs. Conventional methods measure the progressive reduction of numbers of acid-fast bacilli in the sputum smear and the clearance of organisms in sputum culture. In this study, we measured levels of M. tuberculosis 85B (alpha antigen) messenger RNA (mRNA), 16S ribosomal RNA (rRNA), and IS6110 DNA in patients' sputa to ascertain whether they could serve as potential surrogate markers of response to chemotherapy. Sputum specimens were sequentially collected for up to a year from 19 smear-positive pulmonary tuberculosis patients receiving an optimal drug treatment regimen. Nucleic acids were isolated from these specimens, and two M. tuberculosis molecular targets (mRNA, DNA) were quantified, using the ABI Prism 7700 Sequence Detection System. The Mycobacterium genus-specific 16S rRNA was quantified with a limiting dilution RT-PCR assay. Results show that levels of 85B mRNA declined after initiation of therapy, as did viable M. tuberculosis colony counts, with 90% of patients becoming negative for both markers after 2 mo of treatment. The rapid disappearance of M. tuberculosis mRNA from sputum suggests that it is a good indicator of microbial viability and a useful marker for rapid assessment of response to chemotherapy.
The first EdGEO Nova Scotia Workshop, "The Earth Sciences: New Resources for Teachers", was held in Halifax, 22-23 August 1994. The enthusiastic response of those attending encouraged the local ...committee to continue the program, with equally successful workshops in Sydney (1995), Wolfville (1996) and Bridgewater (1997). Each workshop highlights earth science resources available to K-12 grade teachers and how these can be used in the classroom. The program, which emphasizes hands-on activities, includes: identifying rocks and minerals common in Nova Scotia, use of the Nova Scotia Museum's mining and fossil kits, accessing the Internet and especially AGS's EarthNet, improvising in the classroom, and ideas for explaining the concept of geological time to young students. The highlight of each Workshop has to be the field trip, which is always to local sites. For Bridgewater, we visited a local quarry, Broad Cove, Crescent Beach, and The Ovens Natural Park, where we panned for gold. After the excitement of the half-day trip, everyone really enjoyed the evening's talk on the geology of Nova Scotia. What were the teachers' reactions to the day and a half of intense activity? I quote from some of the evaluation sheets: "All the handouts are fantastic", "Excellent resources, excellent and enthusiastic resource people", "Without a doubt, the best workshop I have ever attended". The 1998 workshop will be in Truro on 17-18 August. Because of the rapidly evolving format, this workshop will be titled, "Experience the Excitement of Earth Science". Handouts will include a rock and mineral kit, a fossil kit, four videos and video guides, maps, books, lesson plans, posters, and leaflets. The success of the EdGEO program is dependent upon funding from the National EdGEO Workshop Committee and the Geological Survey of Canada. The Nova Scotia Department of Natural Resources, Saint Mary's University, the Nova Scotia Museum and GSC allow staff to participate in the workshops and provide numerous resources. And the volunteers are all enthusiasts. Why don't you consider becoming involved? Your commitment will help further interest in the earth sciences where it's most important, in the schools throughout our province.
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