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  • 1
    Online Resource
    Online Resource
    Plasma Vascular Endothelial Growth Factor Concentrations after Intravitreous Anti–Vascular Endothelial Growth Factor Therapy for Diabetic Macular Edema
    Elsevier BV ; 2018
    In:  Ophthalmology Vol. 125, No. 7 ( 2018-07), p. 1054-1063
    Details
    In: Ophthalmology, Elsevier BV, Vol. 125, No. 7 ( 2018-07), p. 1054-1063
    Type of Medium: Online Resource
    ISSN: 0161-6420
    URL: Article
    DOI: 10.1016/j.ophtha.2018.01.019
    RVK:
    XA 10000
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2018
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  • 2
    Online Resource
    Online Resource
    Four-Year Visual Outcomes in the Protocol W Randomized Trial of Intravitreous Aflibercept for Prevention of Vision-Threatening Complications of Diabetic Retinopathy
    American Medical Association (AMA) ; 2023
    In:  JAMA Vol. 329, No. 5 ( 2023-02-07), p. 376-
    Details
    In: JAMA, American Medical Association (AMA), Vol. 329, No. 5 ( 2023-02-07), p. 376-
    Abstract: Anti–vascular endothelial growth factor (VEGF) injections in eyes with nonproliferative diabetic retinopathy (NPDR) without center-involved diabetic macular edema (CI-DME) reduce development of vision-threatening complications from diabetes over at least 2 years, but whether this treatment has a longer-term benefit on visual acuity is unknown. Objective To compare the primary 4-year outcomes of visual acuity and rates of vision-threatening complications in eyes with moderate to severe NPDR treated with intravitreal aflibercept compared with sham. The primary 2-year analysis of this study has been reported. Design, Setting, and Participants Randomized clinical trial conducted at 64 clinical sites in the US and Canada from January 2016 to March 2018, enrolling 328 adults (399 eyes) with moderate to severe NPDR (Early Treatment Diabetic Retinopathy Study [ETDRS] severity level 43-53) without CI-DME. Interventions Eyes were randomly assigned to 2.0 mg aflibercept (n = 200) or sham (n = 199). Eight injections were administered at defined intervals through 2 years, continuing quarterly through 4 years unless the eye improved to mild NPDR or better. Aflibercept was given in both groups to treat development of high-risk proliferative diabetic retinopathy (PDR) or CI-DME with vision loss. Main Outcomes and Measures Development of PDR or CI-DME with vision loss (≥10 letters at 1 visit or ≥5 letters at 2 consecutive visits) and change in visual acuity (best corrected ETDRS letter score) from baseline to 4 years. Results Among participants (mean age 56 years; 42.4% female; 5% Asian, 15% Black, 32% Hispanic, 45% White), the 4-year cumulative probability of developing PDR or CI-DME with vision loss was 33.9% with aflibercept vs 56.9% with sham (adjusted hazard ratio, 0.40 [97.5% CI, 0.28 to 0.57] ; P   & amp;lt; .001). The mean (SD) change in visual acuity from baseline to 4 years was −2.7 (6.5) letters with aflibercept and −2.4 (5.8) letters with sham (adjusted mean difference, −0.5 letters [97.5% CI, −2.3 to 1.3]; P  = .52). Antiplatelet Trialists’ Collaboration cardiovascular/cerebrovascular event rates were 9.9% (7 of 71) in bilateral participants, 10.9% (14 of 129) in unilateral aflibercept participants, and 7.8% (10 of 128) in unilateral sham participants. Conclusions and Relevance Among patients with NPDR but without CI-DME, at 4 years treatment with aflibercept vs sham, initiating aflibercept treatment only if vision-threatening complications developed, resulted in statistically significant anatomic improvement but no improvement in visual acuity. Aflibercept as a preventive strategy, as used in this trial, may not be generally warranted for patients with NPDR without CI-DME. Trial Registration ClinicalTrials.gov Identifier: NCT02634333
    Type of Medium: Online Resource
    ISSN: 0098-7484
    URL: Article
    DOI: 10.1001/jama.2022.25029
    RVK:
    XA 10000
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2023
    detail.hit.zdb_id: 2958-0
    detail.hit.zdb_id: 2018410-4
    SSG: 5,21
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  • 3
    Online Resource
    Online Resource
    Lapses in Care Among Patients Assigned to Ranibizumab for Proliferative Diabetic Retinopathy : A Post Hoc Analysis of a Randomized Clinical Trial
    American Medical Association (AMA) ; 2021
    In:  JAMA Ophthalmology Vol. 139, No. 12 ( 2021-12-01), p. 1266-
    Details
    In: JAMA Ophthalmology, American Medical Association (AMA), Vol. 139, No. 12 ( 2021-12-01), p. 1266-
    Type of Medium: Online Resource
    ISSN: 2168-6165
    URL: Article
    DOI: 10.1001/jamaophthalmol.2021.4103
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2021
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  • 4
    Online Resource
    Online Resource
    Cost-effectiveness of Aflibercept Monotherapy vs Bevacizumab First Followed by Aflibercept If Needed for Diabetic Macular Edema
    American Medical Association (AMA) ; 2023
    In:  JAMA Ophthalmology Vol. 141, No. 3 ( 2023-03-01), p. 268-
    Details
    In: JAMA Ophthalmology, American Medical Association (AMA), Vol. 141, No. 3 ( 2023-03-01), p. 268-
    Abstract: The DRCR Retina Network Protocol AC showed no significant difference in visual acuity outcomes over 2 years between treatment with aflibercept monotherapy and bevacizumab first with switching to aflibercept for suboptimal response in treating diabetic macular edema (DME). Understanding the estimated cost and cost-effectiveness of these approaches is important. Objective To evaluate the cost and cost-effectiveness of aflibercept monotherapy vs bevacizumab-first strategies for DME treatment. Design, Setting, and Participants This economic evaluation was a preplanned secondary analysis of a US randomized clinical trial of participants aged 18 years or older with center-involved DME and best-corrected visual acuity of 20/50 to 20/320 enrolled from December 15, 2017, through November 25, 2019. Interventions Aflibercept monotherapy or bevacizumab first, switching to aflibercept in eyes with protocol-defined suboptimal response. Main Outcomes and Measures Between February and July 2022, the incremental cost-effectiveness ratio (ICER) in cost per quality-adjusted life-year (QALY) over 2 years was assessed. Efficacy and resource utilization data from the randomized clinical trial were used with health utility mapping from the literature and Medicare unit costs. Results This study included 228 participants (median age, 62 [range, 34-91 years; 116 [51%] female and 112 [49%] male; 44 [19%] Black or African American, 60 [26%] Hispanic or Latino, and 117 [51%] White) with 1 study eye. The aflibercept monotherapy group included 116 participants, and the bevacizumab-first group included 112, of whom 62.5% were eventually switched to aflibercept. Over 2 years, the cost of aflibercept monotherapy was $26 504 (95% CI, $24 796-$28 212) vs $13 929 (95% CI, $11 984-$15 874) for the bevacizumab-first group, a difference of $12 575 (95% CI, $9987-$15 163). The aflibercept monotherapy group gained 0.015 (95% CI, −0.011 to 0.041) QALYs using the better-seeing eye and had an ICER of $837 077 per QALY gained compared with the bevacizumab-first group. Aflibercept could be cost-effective with an ICER of $100 000 per QALY if the price per dose were $305 or less or the price of bevacizumab was $1307 per dose or more. Conclusions and Relevance Variability in individual needs will influence clinician and patient decisions about how to treat specific eyes with DME. While the bevacizumab-first group costs still averaged approximately $14 000 over 2 years, this approach, as used in this study, may confer substantial cost savings on a societal level without sacrificing visual acuity gains over 2 years compared with aflibercept monotherapy.
    Type of Medium: Online Resource
    ISSN: 2168-6165
    URL: Article
    DOI: 10.1001/jamaophthalmol.2022.6142
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2023
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  • 5
    Online Resource
    Online Resource
    Drosophila Muller F Elements Maintain a Distinct Set of Genomic Properties Over 40 Million Years of Evolution
    Oxford University Press (OUP) ; 2015
    In:  G3 Genes|Genomes|Genetics Vol. 5, No. 5 ( 2015-05-01), p. 719-740
    Details
    In: G3 Genes|Genomes|Genetics, Oxford University Press (OUP), Vol. 5, No. 5 ( 2015-05-01), p. 719-740
    Abstract: The Muller F element (4.2 Mb, ~80 protein-coding genes) is an unusual autosome of Drosophila melanogaster; it is mostly heterochromatic with a low recombination rate. To investigate how these properties impact the evolution of repeats and genes, we manually improved the sequence and annotated the genes on the D. erecta, D. mojavensis, and D. grimshawi F elements and euchromatic domains from the Muller D element. We find that F elements have greater transposon density (25–50%) than euchromatic reference regions (3–11%). Among the F elements, D. grimshawi has the lowest transposon density (particularly DINE-1: 2% vs. 11–27%). F element genes have larger coding spans, more coding exons, larger introns, and lower codon bias. Comparison of the Effective Number of Codons with the Codon Adaptation Index shows that, in contrast to the other species, codon bias in D. grimshawi F element genes can be attributed primarily to selection instead of mutational biases, suggesting that density and types of transposons affect the degree of local heterochromatin formation. F element genes have lower estimated DNA melting temperatures than D element genes, potentially facilitating transcription through heterochromatin. Most F element genes (~90%) have remained on that element, but the F element has smaller syntenic blocks than genome averages (3.4–3.6 vs. 8.4–8.8 genes per block), indicating greater rates of inversion despite lower rates of recombination. Overall, the F element has maintained characteristics that are distinct from other autosomes in the Drosophila lineage, illuminating the constraints imposed by a heterochromatic milieu.
    Type of Medium: Online Resource
    ISSN: 2160-1836
    URL: Article
    DOI: 10.1534/g3.114.015966
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2015
    detail.hit.zdb_id: 2629978-1
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  • 6
    Online Resource
    Online Resource
    Development of a Definition of Postacute Sequelae of SARS-CoV-2 Infection
    American Medical Association (AMA) ; 2023
    In:  JAMA Vol. 329, No. 22 ( 2023-06-13), p. 1934-
    Details
    In: JAMA, American Medical Association (AMA), Vol. 329, No. 22 ( 2023-06-13), p. 1934-
    Abstract: SARS-CoV-2 infection is associated with persistent, relapsing, or new symptoms or other health effects occurring after acute infection, termed postacute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID . Characterizing PASC requires analysis of prospectively and uniformly collected data from diverse uninfected and infected individuals. Objective To develop a definition of PASC using self-reported symptoms and describe PASC frequencies across cohorts, vaccination status, and number of infections. Design, Setting, and Participants Prospective observational cohort study of adults with and without SARS-CoV-2 infection at 85 enrolling sites (hospitals, health centers, community organizations) located in 33 states plus Washington, DC, and Puerto Rico. Participants who were enrolled in the RECOVER adult cohort before April 10, 2023, completed a symptom survey 6 months or more after acute symptom onset or test date. Selection included population-based, volunteer, and convenience sampling. Exposure SARS-CoV-2 infection. Main Outcomes and Measures PASC and 44 participant-reported symptoms (with severity thresholds). Results A total of 9764 participants (89% SARS-CoV-2 infected; 71% female; 16% Hispanic/Latino; 15% non-Hispanic Black; median age, 47 years [IQR, 35-60]) met selection criteria. Adjusted odds ratios were 1.5 or greater (infected vs uninfected participants) for 37 symptoms. Symptoms contributing to PASC score included postexertional malaise, fatigue, brain fog, dizziness, gastrointestinal symptoms, palpitations, changes in sexual desire or capacity, loss of or change in smell or taste, thirst, chronic cough, chest pain, and abnormal movements. Among 2231 participants first infected on or after December 1, 2021, and enrolled within 30 days of infection, 224 (10% [95% CI, 8.8%-11%] ) were PASC positive at 6 months. Conclusions and Relevance A definition of PASC was developed based on symptoms in a prospective cohort study. As a first step to providing a framework for other investigations, iterative refinement that further incorporates other clinical features is needed to support actionable definitions of PASC.
    Type of Medium: Online Resource
    ISSN: 0098-7484
    URL: Article
    DOI: 10.1001/jama.2023.8823
    RVK:
    XA 10000
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2023
    detail.hit.zdb_id: 2958-0
    detail.hit.zdb_id: 2018410-4
    SSG: 5,21
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  • 7
    Online Resource
    Online Resource
    Association of Ultra-Widefield Fluorescein Angiography–Identified Retinal Nonperfusion and the Risk of Diabetic Retinopathy Worsening Over Time
    American Medical Association (AMA) ; 2022
    In:  JAMA Ophthalmology Vol. 140, No. 10 ( 2022-10-01), p. 936-
    Details
    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
    URL: Article
    DOI: 10.1001/jamaophthalmol.2022.3130
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2022
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  • 8
    Online Resource
    Online Resource
    Evaluation of a National Quality Improvement Collaborative for Improving Cancer Screening
    American Medical Association (AMA) ; 2022
    In:  JAMA Network Open Vol. 5, No. 11 ( 2022-11-16), p. e2242354-
    Details
    In: JAMA Network Open, American Medical Association (AMA), Vol. 5, No. 11 ( 2022-11-16), p. e2242354-
    Abstract: Cancer screening deficits during the first year of the COVID-19 pandemic were found to persist into 2021. Cancer-related deaths over the next decade are projected to increase if these deficits are not addressed. Objective To assess whether participation in a nationwide quality improvement (QI) collaborative, Return-to-Screening, was associated with restoration of cancer screening. Design, Setting, and Participants Accredited cancer programs electively enrolled in this QI study. Project-specific targets were established on the basis of differences in mean monthly screening test volumes (MTVs) between representative prepandemic (September 2019 and January 2020) and pandemic (September 2020 and January 2021) periods to restore prepandemic volumes and achieve a minimum of 10% increase in MTV. Local QI teams implemented evidence-based screening interventions from June to November 2021 (intervention period), iteratively adjusting interventions according to their MTVs and target. Interrupted time series analyses was used to identify the intervention effect. Data analysis was performed from January to April 2022. Exposures Collaborative QI support included provision of a Return-to-Screening plan-do-study-act protocol, evidence-based screening interventions, QI education, programmatic coordination, and calculation of screening deficits and targets. Main Outcomes and Measures The primary outcome was the proportion of QI projects reaching target MTV and counterfactual differences in the aggregate number of screening tests across time periods. Results Of 859 cancer screening QI projects (452 for breast cancer, 134 for colorectal cancer, 244 for lung cancer, and 29 for cervical cancer) conducted by 786 accredited cancer programs, 676 projects (79%) reached their target MTV. There were no hospital characteristics associated with increased likelihood of reaching target MTV except for disease site (lung vs breast, odds ratio, 2.8; 95% CI, 1.7 to 4.7). During the preintervention period (April to May 2021), there was a decrease in the mean MTV (slope, −13.1 tests per month; 95% CI, −23.1 to −3.2 tests per month). Interventions were associated with a significant immediate (slope, 101.0 tests per month; 95% CI, 49.1 to 153.0 tests per month) and sustained (slope, 36.3 tests per month; 95% CI, 5.3 to 67.3 tests per month) increase in MTVs relative to the preintervention trends. Additional screening tests were performed during the intervention period compared with the prepandemic period (170 748 tests), the pandemic period (210 450 tests), and the preintervention period (722 427 tests). Conclusions and Relevance In this QI study, participation in a national Return-to-Screening collaborative with a multifaceted QI intervention was associated with improvements in cancer screening. Future collaborative QI endeavors leveraging accreditation infrastructure may help address other gaps in cancer care.
    Type of Medium: Online Resource
    ISSN: 2574-3805
    URL: Article
    DOI: 10.1001/jamanetworkopen.2022.42354
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2022
    detail.hit.zdb_id: 2931249-8
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  • 9
    Online Resource
    Online Resource
    Association of Predominantly Peripheral Lesions on Ultra-Widefield Imaging and the Risk of Diabetic Retinopathy Worsening Over Time
    American Medical Association (AMA) ; 2022
    In:  JAMA Ophthalmology Vol. 140, No. 10 ( 2022-10-01), p. 946-
    Details
    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
    URL: Article
    DOI: 10.1001/jamaophthalmol.2022.3131
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2022
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  • 10
    Online Resource
    Online Resource
    Global urban environmental change drives adaptation in white clover
    American Association for the Advancement of Science (AAAS) ; 2022
    In:  Science Vol. 375, No. 6586 ( 2022-03-18), p. 1275-1281
    Details
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 375, No. 6586 ( 2022-03-18), p. 1275-1281
    Abstract: A widespread adaptive change in antiherbivore response is seen in a common plant species in urban environments across 160 cities.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    URL: Article
    DOI: 10.1126/science.abk0989
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2022
    detail.hit.zdb_id: 128410-1
    detail.hit.zdb_id: 2066996-3
    detail.hit.zdb_id: 2060783-0
    SSG: 11
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