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  • 1
    In: JAMA Ophthalmology, American Medical Association (AMA), Vol. 140, No. 10 ( 2022-10-01), p. 936-
    Abstract: Presence of predominantly peripheral diabetic retinopathy (DR) lesions on ultra-widefield fluorescein angiography (UWF-FA) was associated with greater risk of DR worsening or treatment over 4 years. Whether baseline retinal nonperfusion assessment is additionally predictive of DR disease worsening is unclear. Objective To assess whether the extent and location of retinal nonperfusion identified on UWF-FA are associated with worsening in Diabetic Retinopathy Severity Scale (DRSS) score or DR treatment over time. Design, Setting, and Participants This cohort study was a prospective, multicenter, longitudinal observational study with data for 508 eyes with nonproliferative DR and gradable nonperfusion on UWF-FA at baseline. All images were graded at a centralized reading center; 200° ultra-widefield (UWF) color images were graded for DR at baseline and annually for 4 years. Baseline 200° UWF-FA images were graded for nonperfused area, nonperfusion index (NPI), and presence of predominantly peripheral lesions on UWF-FA (FA PPL). Interventions Treatment of DR or diabetic macular edema was at investigator discretion. Main Outcomes and Measures Association of baseline UWF-FA nonperfusion extent with disease worsening, defined as either 2 or more steps of DRSS worsening within Early Treatment Diabetic Retinopathy Study fields on UWF-color images or receipt of DR treatment. Results After adjusting for baseline DRSS, the risk of disease worsening over 4 years was higher in eyes with greater overall NPI (hazard ratio [HR] for 0.1-unit increase, 1.11; 95% CI, 1.02-1.21; P  = .02) and NPI within the posterior pole (HR for 0.1-unit increase, 1.35; 95% CI, 1.17-1.56; P   & amp;lt; .001) and midperiphery (HR for 0.1-unit increase, 1.08; 95% CI, 1.00-1.16; P  = .04). In a multivariable analysis adjusting for baseline DRSS score and baseline systemic risk factors, greater NPI (HR, 1.11; 95% CI, 1.02-1.22; P  = .02) and presence of FA PPL (HR, 1.89; 95% CI, 1.35-2.65; P   & amp;lt; .001) remained associated with disease worsening. Conclusions and Relevance This 4-year longitudinal study has demonstrated that both greater baseline retinal nonperfusion and FA PPL on UWF-FA are associated with higher risk of disease worsening, even after adjusting for baseline DRSS score and known systemic risk. These associations between disease worsening and retinal nonperfusion and FA PPL support the increased use of UWF-FA to complement color fundus photography in future efforts for DR prognosis, clinical care, and research.
    Type of Medium: Online Resource
    ISSN: 2168-6165
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2022
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  • 2
    In: Issues in Accounting Education, American Accounting Association, ( 2023-11-01), p. 1-28
    Abstract: ChatGPT, a language-learning model chatbot, has garnered considerable attention for its ability to respond to users’ questions. Using data from 14 countries and 186 institutions, we compare ChatGPT and student performance for 28,085 questions from accounting assessments and textbook test banks. As of January 2023, ChatGPT provides correct answers for 56.5 percent of questions and partially correct answers for an additional 9.4 percent of questions. When considering point values for questions, students significantly outperform ChatGPT with a 76.7 percent average on assessments compared to 47.5 percent for ChatGPT if no partial credit is awarded and 56.5 percent if partial credit is awarded. Still, ChatGPT performs better than the student average for 15.8 percent of assessments when we include partial credit. We provide evidence of how ChatGPT performs on different question types, accounting topics, class levels, open/closed assessments, and test bank questions. We also discuss implications for accounting education and research.
    Type of Medium: Online Resource
    ISSN: 0739-3172 , 1558-7983
    Language: English
    Publisher: American Accounting Association
    Publication Date: 2023
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  • 3
    In: JAMA Ophthalmology, American Medical Association (AMA), Vol. 140, No. 10 ( 2022-10-01), p. 946-
    Abstract: Ultra-widefield (UWF) imaging improves the ability to identify peripheral diabetic retinopathy (DR) lesions compared with standard imaging. Whether detection of predominantly peripheral lesions (PPLs) better predicts rates of disease worsening over time is unknown. Objective To determine whether PPLs identified on UWF imaging are associated with increased disease worsening beyond the risk associated with baseline Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) score. Design, Setting, and Participants This cohort study was a prospective, multicenter, longitudinal observational study conducted at 37 US and Canadian sites with 388 participants enrolled between February and December 2015. At baseline and annually through 4 years, 200° UWF-color images were obtained and graded for DRSS at a reading center. Baseline UWF-color and UWF-fluorescein angiography (FA) images were evaluated for the presence of PPL. Data were analyzed from May 2020 to June 2022. Interventions Treatment of DR or diabetic macular edema was at investigator discretion. Main Outcomes and Measures Predominantly peripheral lesions were defined as DR lesions with a greater extent outside vs inside the 7 standard ETDRS fields. Primary outcome was disease worsening defined as worsening 2 steps or more on the DRSS or receipt of DR treatment. Analyses were adjusted for baseline DRSS score and correlation between 2 study eyes of the same participant. Results Data for 544 study eyes with nonproliferative DR (NPDR) were analyzed (182 [50%] female participants; median age, 62 years; 68% White). The 4-year disease worsening rates were 45% for eyes with baseline mild NPDR, 40% for moderate NPDR, 26% for moderately severe NPDR, and 43% for severe NPDR. Disease worsening was not associated with color PPL at baseline (present vs absent: 38% vs 43%; HR, 0.78; 95% CI, 0.57-1.08; P  = .13) but was associated with FA PPL at baseline (present vs absent: 50% vs 31%; HR, 1.72; 95% CI, 1.25-2.36; P   & amp;lt; .001). Conclusions and Relevance Although no association was identified with color PPL, presence of FA PPL was associated with greater risk of disease worsening over 4 years, independent of baseline DRSS score. These results suggest that use of UWF-FA to evaluate retinas peripheral to standard ETDRS fields may improve the ability to predict disease worsening in NPDR eyes. These findings support use of UWF-FA for future DR staging systems and clinical care to more accurately determine prognosis in NPDR eyes.
    Type of Medium: Online Resource
    ISSN: 2168-6165
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2022
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  • 4
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2020
    In:  Human Reproduction Vol. 35, No. 5 ( 2020-05-01), p. 1013-1018
    In: Human Reproduction, Oxford University Press (OUP), Vol. 35, No. 5 ( 2020-05-01), p. 1013-1018
    Abstract: The majority of research within reproductive and gynecologic health, or investigating ART, is observational in design. One of the most critical challenges for observational studies is confounding, while one of the most important for discovery and inference is effect modification. In this commentary, we explain what confounding and effect modification are and why they matter. We present examples illustrating how failing to adjust for a confounder leads to invalid conclusions, as well as examples where adjusting for a factor that is not a confounder also leads to invalid or imprecise conclusions. Careful consideration of which factors may act as confounders or modifiers of the association of interest is critical to conducting sound research, particularly with complex observational studies in reproductive medicine.
    Type of Medium: Online Resource
    ISSN: 0268-1161 , 1460-2350
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
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  • 5
    In: Alimentary Pharmacology & Therapeutics, Wiley, Vol. 56, No. 11-12 ( 2022-12), p. 1556-1569
    Abstract: Factors influencing recurrence risk in primary Clostridioides difficile infection (CDI) are poorly understood, and tools predicting recurrence are lacking. Perturbations in bile acids (BAs) contribute to CDI pathogenesis and may be relevant to primary disease prognosis. Aims To define stool BA dynamics in patients with primary CDI and to explore signatures predicting recurrence Methods Weekly stool samples were collected from patients with primary CDI from the last day of anti‐CDI therapy until recurrence or, otherwise, through 8 weeks post‐completion. Ultra‐high performance liquid chromatography‐mass spectrometry was used to profile BAs. Stool bile salt hydrolase (BSH) activity was measured to determine primary BA bacterial deconjugation capacity. Multivariate and univariate models were used to define differential BA trajectories in patients with recurrence versus those without, and to assess faecal BAs as predictive markers for recurrence. Results Twenty (36%) of 56 patients (median age: 57, 64% male) had recurrence; 80% of recurrences occurred within the first 9 days post‐antibiotic treatment. Principal component analysis of stool BA profiles demonstrated clustering by recurrence status and post‐treatment timepoint. Longitudinal faecal BA trajectories showed recovery of secondary BAs and their derivatives only in patients without recurrence. BSH activity increased over time only among non‐relapsing patients ( β  = 0.056; likelihood ratio test p  = 0.018). A joint longitudinal‐survival model identified five stool BAs with area under the receiver operating characteristic curve 〉 0.73 for predicting recurrence within 9 days post‐CDI treatment. Conclusions Gut BA metabolism dynamics differ in primary CDI patients between those developing recurrence and those who do not. Individual BAs show promise as potential novel biomarkers to predict CDI recurrence.
    Type of Medium: Online Resource
    ISSN: 0269-2813 , 1365-2036
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2022
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  • 6
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2020
    In:  Open Forum Infectious Diseases Vol. 7, No. Supplement_1 ( 2020-12-31), p. S497-S498
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 7, No. Supplement_1 ( 2020-12-31), p. S497-S498
    Abstract: Treatment of Hepatitis C virus (HCV) infection for persons with Human Immunodeficiency Virus (HIV) is dependent on consistent outpatient follow-up. We sought to identify factors that are associated with lower HCV treatment rates in HIV/HCV co-infected patients followed at Rutgers Infectious Diseases Practice (IDP), an integrated urban clinic. Methods Retrospective chart reviews were conducted for HIV/HCV co-infected patients treated at IDP in Newark, New Jersey between January 2017 and July 2018. We assessed factors associated with lack of HCV treatment in this practice. Data collected included demographics, HIV disease markers, liver function tests, HCV treatment history and response. Factors with p & lt; 0.05, age and race were included in the multivariate analysis. Results We included 317 HIV/HCV co-infected patients with at least one visit between January 2017 and July 2018. Fifty eight percent were male, 79% black, 10% hispanic, 6% white, and 5% other; 21% reported heterosexual and 79% drug use (injection and non-injection) as their HIV risk factor The median CD4 was 522 cells/cm3, and 74% of patients had HIV viral load (VL) & lt; 40 copies/ml. HCV treatment was started at IDP in 142 (45%) and of those 87% were cured. Data are awaited on 6%. Univariate analyses showed those not treated for HCV were more likely to be born female (57% vs 42%), have a CD4 count & lt; 200 cells/cm3 (9% vs 27%), HIV VL & gt;40 copies/ml (43% vs 17%), currently (58% vs 30%) or previously (89% vs 74%) used drugs, and have a higher APRI score (0.43 vs 1.6). Multivariate logistic regression showed that patients with untreated HCV were more likely to be female (OR 2.93, p & lt; 0.001), report current drug/alcohol use (OR 2.43, p=0.004), and have HIV VL ≥40 copies/ml (OR 2.11, p & lt; 0.001). Table 1: Demographics/Risk Factors of Study Group Table 2: Laboratory Studies Table 3: Logistic Regression of Significant HCV Treatment Factors Conclusion Our results show that despite the availability of integrated treatment programs, concerted efforts need to be made for patients at high risk for not receiving HCV treatment, and who therefore remain at high risk for complications from HCV. Provider perceptions may play a role in withholding treatment for those with high HIV VL and current drug or alcohol use; whereas the rationale for why women were less likely to be treated is less clear and may be related to trauma and other factors not captured by this project that may negatively impact their access to care. Disclosures All Authors: No reported disclosures
    Type of Medium: Online Resource
    ISSN: 2328-8957
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
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  • 7
    In: Nature, Springer Science and Business Media LLC, Vol. 617, No. 7962 ( 2023-05-25), p. 764-768
    Abstract: Critical illness in COVID-19 is an extreme and clinically homogeneous disease phenotype that we have previously shown 1 to be highly efficient for discovery of genetic associations 2 . Despite the advanced stage of illness at presentation, we have shown that host genetics in patients who are critically ill with COVID-19 can identify immunomodulatory therapies with strong beneficial effects in this group 3 . Here we analyse 24,202 cases of COVID-19 with critical illness comprising a combination of microarray genotype and whole-genome sequencing data from cases of critical illness in the international GenOMICC (11,440 cases) study, combined with other studies recruiting hospitalized patients with a strong focus on severe and critical disease: ISARIC4C (676 cases) and the SCOURGE consortium (5,934 cases). To put these results in the context of existing work, we conduct a meta-analysis of the new GenOMICC genome-wide association study (GWAS) results with previously published data. We find 49 genome-wide significant associations, of which 16 have not been reported previously. To investigate the therapeutic implications of these findings, we infer the structural consequences of protein-coding variants, and combine our GWAS results with gene expression data using a monocyte transcriptome-wide association study (TWAS) model, as well as gene and protein expression using Mendelian randomization. We identify potentially druggable targets in multiple systems, including inflammatory signalling ( JAK1 ), monocyte–macrophage activation and endothelial permeability ( PDE4A ), immunometabolism ( SLC2A5 and AK5 ), and host factors required for viral entry and replication ( TMPRSS2 and RAB2A ).
    Type of Medium: Online Resource
    ISSN: 0028-0836 , 1476-4687
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    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
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  • 8
    In: Nature, Springer Science and Business Media LLC, Vol. 619, No. 7971 ( 2023-07-27), p. E61-E61
    Type of Medium: Online Resource
    ISSN: 0028-0836 , 1476-4687
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    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
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  • 9
    In: Nature, Springer Science and Business Media LLC, Vol. 600, No. 7889 ( 2021-12-16), p. 472-477
    Abstract: The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-19 1,2 , host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases 3–7 . They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.
    Type of Medium: Online Resource
    ISSN: 0028-0836 , 1476-4687
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    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
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    detail.hit.zdb_id: 1413423-8
    SSG: 11
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  • 10
    In: British Journal of Surgery, Oxford University Press (OUP), Vol. 106, No. 2 ( 2019-01-08), p. e73-e80
    Abstract: The Clavien–Dindo classification is perhaps the most widely used approach for reporting postoperative complications in clinical trials. This system classifies complication severity by the treatment provided. However, it is unclear whether the Clavien–Dindo system can be used internationally in studies across differing healthcare systems in high- (HICs) and low- and middle-income countries (LMICs). Methods This was a secondary analysis of the International Surgical Outcomes Study (ISOS), a prospective observational cohort study of elective surgery in adults. Data collection occurred over a 7-day period. Severity of complications was graded using Clavien–Dindo and the simpler ISOS grading (mild, moderate or severe, based on guided investigator judgement). Severity grading was compared using the intraclass correlation coefficient (ICC). Data are presented as frequencies and ICC values (with 95 per cent c.i.). The analysis was stratified by income status of the country, comparing HICs with LMICs. Results A total of 44 814 patients were recruited from 474 hospitals in 27 countries (19 HICs and 8 LMICs). Some 7508 patients (16·8 per cent) experienced at least one postoperative complication, equivalent to 11 664 complications in total. Using the ISOS classification, 5504 of 11 664 complications (47·2 per cent) were graded as mild, 4244 (36·4 per cent) as moderate and 1916 (16·4 per cent) as severe. Using Clavien–Dindo, 6781 of 11 664 complications (58·1 per cent) were graded as I or II, 1740 (14·9 per cent) as III, 2408 (20·6 per cent) as IV and 735 (6·3 per cent) as V. Agreement between classification systems was poor overall (ICC 0·41, 95 per cent c.i. 0·20 to 0·55), and in LMICs (ICC 0·23, 0·05 to 0·38) and HICs (ICC 0·46, 0·25 to 0·59). Conclusion Caution is recommended when using a treatment approach to grade complications in global surgery studies, as this may introduce bias unintentionally.
    Type of Medium: Online Resource
    ISSN: 0007-1323 , 1365-2168
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
    detail.hit.zdb_id: 2006309-X
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