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  • American Medical Association (AMA)  (34)
  • 1
    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
    RVK:
    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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  • 2
    In: JAMA Network Open, American Medical Association (AMA), Vol. 6, No. 7 ( 2023-07-13), p. e2323349-
    Abstract: Current data identifying COVID-19 risk factors lack standardized outcomes and insufficiently control for confounders. Objective To identify risk factors associated with COVID-19, severe COVID-19, and SARS-CoV-2 infection. Design, Setting, and Participants This secondary cross-protocol analysis included 4 multicenter, international, randomized, blinded, placebo-controlled, COVID-19 vaccine efficacy trials with harmonized protocols established by the COVID-19 Prevention Network. Individual-level data from participants randomized to receive placebo within each trial were combined and analyzed. Enrollment began July 2020 and the last data cutoff was in July 2021. Participants included adults in stable health, at risk for SARS-CoV-2, and assigned to the placebo group within each vaccine trial. Data were analyzed from April 2022 to February 2023. Exposures Comorbid conditions, demographic factors, and SARS-CoV-2 exposure risk at the time of enrollment. Main Outcomes and Measures Coprimary outcomes were COVID-19 and severe COVID-19. Multivariate Cox proportional regression models estimated adjusted hazard ratios (aHRs) and 95% CIs for baseline covariates, accounting for trial, region, and calendar time. Secondary outcomes included severe COVID-19 among people with COVID-19, subclinical SARS-CoV-2 infection, and SARS-CoV-2 infection. Results A total of 57 692 participants (median [range] age, 51 [18-95] years; 11 720 participants [20.3%] aged ≥65 years; 31 058 participants [53.8%] assigned male at birth) were included. The analysis population included 3270 American Indian or Alaska Native participants (5.7%), 7849 Black or African American participants (13.6%), 17 678 Hispanic or Latino participants (30.6%), and 40 745 White participants (70.6%). Annualized incidence was 13.9% (95% CI, 13.3%-14.4%) for COVID-19 and 2.0% (95% CI, 1.8%-2.2%) for severe COVID-19. Factors associated with increased rates of COVID-19 included workplace exposure (high vs low: aHR, 1.35 [95% CI, 1.16-1.58]; medium vs low: aHR, 1.41 [95% CI, 1.21-1.65] ; P   & amp;lt; .001) and living condition risk (very high vs low risk: aHR, 1.41 [95% CI, 1.21-1.66]; medium vs low risk: aHR, 1.19 [95% CI, 1.08-1.32] ; P   & amp;lt; .001). Factors associated with decreased rates of COVID-19 included previous SARS-CoV-2 infection (aHR, 0.13 [95% CI, 0.09-0.19]; P   & amp;lt; .001), age 65 years or older (aHR vs age & amp;lt;65 years, 0.57 [95% CI, 0.50-0.64]; P   & amp;lt; .001) and Black or African American race (aHR vs White race, 0.78 [95% CI, 0.67-0.91]; P  = .002). Factors associated with increased rates of severe COVID-19 included race (American Indian or Alaska Native vs White: aHR, 2.61 [95% CI, 1.85-3.69]; multiracial vs White: aHR, 2.19 [95% CI, 1.50-3.20] ; P   & amp;lt; .001), diabetes (aHR, 1.54 [95% CI, 1.14-2.08]; P  = .005) and at least 2 comorbidities (aHR vs none, 1.39 [95% CI, 1.09-1.76]; P  = .008). In analyses restricted to participants who contracted COVID-19, increased severe COVID-19 rates were associated with age 65 years or older (aHR vs & amp;lt;65 years, 1.75 [95% CI, 1.32-2.31]; P   & amp;lt; .001), race (American Indian or Alaska Native vs White: aHR, 1.98 [95% CI, 1.38-2.83]; Black or African American vs White: aHR, 1.49 [95% CI, 1.03-2.14] ; multiracial: aHR, 1.81 [95% CI, 1.21-2.69]; overall P  = .001), body mass index (aHR per 1-unit increase, 1.03 [95% CI, 1.01-1.04]; P  = .001), and diabetes (aHR, 1.85 [95% CI, 1.37-2.49]; P   & amp;lt; .001). Previous SARS-CoV-2 infection was associated with decreased severe COVID-19 rates (aHR, 0.04 [95% CI, 0.01-0.14]; P   & amp;lt; .001). Conclusions and Relevance In this secondary cross-protocol analysis of 4 randomized clinical trials, exposure and demographic factors had the strongest associations with outcomes; results could inform mitigation strategies for SARS-CoV-2 and viruses with comparable epidemiological characteristics.
    Type of Medium: Online Resource
    ISSN: 2574-3805
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2023
    detail.hit.zdb_id: 2931249-8
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  • 3
    In: JAMA Psychiatry, American Medical Association (AMA), Vol. 78, No. 11 ( 2021-11-01), p. 1258-
    Type of Medium: Online Resource
    ISSN: 2168-622X
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2021
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  • 4
    In: JAMA Internal Medicine, American Medical Association (AMA), Vol. 183, No. 10 ( 2023-10-01), p. 1111-
    Abstract: Despite growing evidence of persistent problems after acute COVID-19, how long the excess mortality risk associated with COVID-19 persists is unknown. Objective To measure the time course of differential mortality among Veterans who had a first-documented COVID-19 infection by separately assessing acute mortality from later mortality among matched groups with infected and uninfected individuals who survived and were uncensored at the start of each period. Design, Settings, and Participants This retrospective cohort study used prospectively collected health record data from Veterans Affairs hospitals across the US on Veterans who had COVID-19 between March 2020 and April 2021. Each individual was matched with up to 5 comparators who had not been infected with COVID-19 at the time of matching. This match balanced, on a month-by-month basis, the risk of developing COVID-19 using 37 variables measured in the 24 months before the date of the infection or match. A primary analysis censored comparators when they developed COVID-19 with inverse probability of censoring weighting in Cox regression. A secondary analysis did not censor. Data analyses were performed from April 2021 through June 2023. Exposure First-documented case of COVID-19 (SARS-CoV-2) infection. Main Outcome Measures Hazard ratios for all-cause mortality at clinically meaningful intervals after infection: 0 to 90, 91 to 180, 181 to 365, and 366 to 730 days. Results The study sample comprised 208 061 Veterans with first-documented COVID-19 infection (mean [SD] age, 60.5 (16.2) years; 21 936 (10.5) women; 47 645 [22.9] Black and 139 604 [67.1] White individuals) and 1 037 423 matched uninfected comparators with similar characteristics. Veterans with COVID-19 had an unadjusted mortality rate of 8.7% during the 2-year period after the initial infection compared with 4.1% among uninfected comparators, with censoring if the comparator later developed COVID-19—an adjusted hazard ratio (aHR) of 2.01 (95% CI, 1.98-2.04). The risk of excess death varied, being highest during days 0 to 90 after infection (aHR, 6.36; 95% CI, 6.20-6.51) and still elevated during days 91 to 180 (aHR, 1.18; 95% CI, 1.12-1.23). Those who survived COVID-19 had decreased mortality on days 181 to 365 (aHR, 0.92; 95% CI, 0.89-0.95) and 366 to 730 (aHR, 0.89; 95% CI, 0.85-0.92). These patterns were consistent across sensitivity analyses. Conclusion and Relevance The findings of this retrospective cohort study indicate that although overall 2-year mortality risk was worse among those infected with COVID-19, by day 180 after infection they had no excess mortality during the next 1.5 years.
    Type of Medium: Online Resource
    ISSN: 2168-6106
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2023
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  • 5
    In: JAMA, American Medical Association (AMA), Vol. 326, No. 17 ( 2021-11-02), p. 1690-
    Type of Medium: Online Resource
    ISSN: 0098-7484
    RVK:
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2021
    detail.hit.zdb_id: 2958-0
    detail.hit.zdb_id: 2018410-4
    SSG: 5,21
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  • 6
    In: JAMA Cardiology, American Medical Association (AMA), Vol. 7, No. 10 ( 2022-10-01), p. 1000-
    Abstract: In patients with severe aortic valve stenosis at intermediate surgical risk, transcatheter aortic valve replacement (TAVR) with a self-expanding supra-annular valve was noninferior to surgery for all-cause mortality or disabling stroke at 2 years. Comparisons of longer-term clinical and hemodynamic outcomes in these patients are limited. Objective To report prespecified secondary 5-year outcomes from the Symptomatic Aortic Stenosis in Intermediate Risk Subjects Who Need Aortic Valve Replacement (SURTAVI) randomized clinical trial. Design, Setting, and Participants SURTAVI is a prospective randomized, unblinded clinical trial. Randomization was stratified by investigational site and need for revascularization determined by the local heart teams. Patients with severe aortic valve stenosis deemed to be at intermediate risk of 30-day surgical mortality were enrolled at 87 centers from June 19, 2012, to June 30, 2016, in Europe and North America. Analysis took place between August and October 2021. Intervention Patients were randomized to TAVR with a self-expanding, supra-annular transcatheter or a surgical bioprosthesis. Main Outcomes and Measures The prespecified secondary end points of death or disabling stroke and other adverse events and hemodynamic findings at 5 years. An independent clinical event committee adjudicated all serious adverse events and an independent echocardiographic core laboratory evaluated all echocardiograms at 5 years. Results A total of 1660 individuals underwent an attempted TAVR (n = 864) or surgical (n = 796) procedure. The mean (SD) age was 79.8 (6.2) years, 724 (43.6%) were female, and the mean (SD) Society of Thoracic Surgery Predicted Risk of Mortality score was 4.5% (1.6%). At 5 years, the rates of death or disabling stroke were similar (TAVR, 31.3% vs surgery, 30.8%; hazard ratio, 1.02 [95% CI, 0.85-1.22]; P  =   .85). Transprosthetic gradients remained lower (mean [SD], 8.6 [5.5] mm Hg vs 11.2 [6.0] mm Hg; P   & amp;lt; .001) and aortic valve areas were higher (mean [SD], 2.2 [0.7] cm 2 vs 1.8 [0.6] cm 2 ; P   & amp;lt; .001) with TAVR vs surgery. More patients had moderate/severe paravalvular leak with TAVR than surgery (11 [3.0%] vs 2 [0.7%] ; risk difference, 2.37% [95% CI, 0.17%- 4.85%]; P  = .05). New pacemaker implantation rates were higher for TAVR than surgery at 5 years (289 [39.1%] vs 94 [15.1%] ; hazard ratio, 3.30 [95% CI, 2.61-4.17]; log-rank P   & amp;lt; .001), as were valve reintervention rates (27 [3.5%] vs 11 [1.9%] ; hazard ratio, 2.21 [95% CI, 1.10-4.45]; log-rank P  = .02), although between 2 and 5 years only 6 patients who underwent TAVR and 7 who underwent surgery required a reintervention. Conclusions and Relevance Among intermediate-risk patients with symptomatic severe aortic stenosis, major clinical outcomes at 5 years were similar for TAVR and surgery. TAVR was associated with superior hemodynamic valve performance but also with more paravalvular leak and valve reinterventions.
    Type of Medium: Online Resource
    ISSN: 2380-6583
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2022
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  • 7
    In: JAMA Network Open, American Medical Association (AMA), Vol. 4, No. 12 ( 2021-12-22), p. e2140568-
    Type of Medium: Online Resource
    ISSN: 2574-3805
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2021
    detail.hit.zdb_id: 2931249-8
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  • 8
    In: JAMA Neurology, American Medical Association (AMA), Vol. 80, No. 9 ( 2023-09-01), p. 929-
    Abstract: Sex differences are established in associations between apolipoprotein E ( APOE ) ε4 and cognitive impairment in Alzheimer disease (AD). However, it is unclear whether sex-specific cognitive consequences of APOE are consistent across races and extend to the APOE ε2 allele. Objective To investigate whether sex and race modify APOE ε4 and ε2 associations with cognition. Design, Setting, and Participants This genetic association study included longitudinal cognitive data from 4 AD and cognitive aging cohorts. Participants were older than 60 years and self-identified as non-Hispanic White or non-Hispanic Black (hereafter, White and Black). Data were previously collected across multiple US locations from 1994 to 2018. Secondary analyses began December 2021 and ended September 2022. Main Outcomes and Measures Harmonized composite scores for memory, executive function, and language were generated using psychometric approaches. Linear regression assessed interactions between APOE ε4 or APOE ε2 and sex on baseline cognitive scores, while linear mixed-effect models assessed interactions on cognitive trajectories. The intersectional effect of race was modeled using an APOE  × sex × race interaction term, assessing whether APOE  × sex interactions differed by race. Models were adjusted for age at baseline and corrected for multiple comparisons. Results Of 32 427 participants who met inclusion criteria, there were 19 007 females (59%), 4453 Black individuals (14%), and 27 974 White individuals (86%); the mean (SD) age at baseline was 74 years (7.9). At baseline, 6048 individuals (19%) had AD, 4398 (14%) were APOE ε2 carriers, and 12 538 (38%) were APOE ε4 carriers. Participants missing APOE status were excluded (n = 9266). For APOE ε4, a robust sex interaction was observed on baseline memory (β = −0.071, SE = 0.014; P  = 9.6 × 10 −7 ), whereby the APOE ε4 negative effect was stronger in females compared with males and did not significantly differ among races. Contrastingly, despite the large sample size, no APOE ε2 × sex interactions on cognition were observed among all participants. When testing for intersectional effects of sex, APOE ε2, and race, an interaction was revealed on baseline executive function among individuals who were cognitively unimpaired (β = −0.165, SE = 0.066; P  = .01), whereby the APOE ε2 protective effect was female-specific among White individuals but male-specific among Black individuals. Conclusions and Relevance In this study, while race did not modify sex differences in APOE ε4, the APOE ε2 protective effect could vary by race and sex. Although female sex enhanced ε4-associated risk, there was no comparable sex difference in ε2, suggesting biological pathways underlying ε4-associated risk are distinct from ε2 and likely intersect with age-related changes in sex biology.
    Type of Medium: Online Resource
    ISSN: 2168-6149
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2023
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  • 9
    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
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2022
    detail.hit.zdb_id: 2931249-8
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  • 10
    In: JAMA Ophthalmology, American Medical Association (AMA), Vol. 141, No. 8 ( 2023-08-01), p. 705-
    Abstract: Lensectomy with primary intraocular lens (IOL) implantation is often used in the management of nontraumatic pediatric cataract, but long-term data evaluating the association of age and IOL location with the incidence of complications are limited. Objective To describe the incidence of complications and additional eye surgeries through 5 years following pediatric lensectomy with primary IOL implantation and association with age at surgery and IOL location. Design, Setting, and Participants This prospective cohort study used Pediatric Eye Disease Investigator Group cataract registry data from 61 institution- and community-based practices over 3 years (June 2012 to July 2015). Participants were children younger than 13 years without baseline glaucoma who had primary IOL implantation (345 bilateral and 264 unilateral) for nontraumatic cataract. Data analysis was performed between September 2021 and January 2023. Exposures Lensectomy with primary IOL implantation. Main Outcome and Measures Five-year cumulative incidence of complications by age at surgery ( & amp;lt;2 years, 2 to & amp;lt;4 years, 4 to & amp;lt;7 years, and 7 to & amp;lt;13 years) and by IOL location (sulcus vs capsular bag) were estimated using Cox proportional hazards models. Results The cohort included 609 eyes from 491 children (mean [SD] age, 5.6 [3.3] years; 261 [53%] male and 230 [47%] female). Following cataract extraction with primary IOL implantation, a frequent complication was surgery for visual axis opacification (VAO) (cumulative incidence, 32%; 95% CI, 27%-36%). Cumulative incidence was lower with anterior vitrectomy at the time of IOL placement (12%; 95% CI, 8%-16%) vs without (58%; 95% CI, 50%-65%), and the risk of undergoing surgery for VAO was associated with not performing anterior vitrectomy (hazard ratio [HR], 6.19; 95% CI, 3.70-10.34; P   & amp;lt; .001). After adjusting for anterior vitrectomy at lens surgery, there were no differences in incidence of surgery for VAO by age at surgery ( & amp;lt;2 years, HR, 1.35 [95% CI, 0.63-2.87], 2 to & amp;lt;4 years, HR, 0.86 [95% CI, 0.44-1.68], 4 to & amp;lt;7 years, HR, 1.06 [95% CI, 0.72-1.56]; P  = .74) or by capsular bag vs sulcus IOL fixation (HR, 1.22; 95% CI, 0.36-4.17; P  = .75). Cumulative incidence of glaucoma plus glaucoma suspect by 5 years was 7% (95% CI, 4%-9%), which did not differ by age after controlling for IOL location and laterality. Conclusions and Relevance In this cohort study, a frequent complication following pediatric lensectomy with primary IOL was surgery for VAO, which was associated with primary anterior vitrectomy not being performed but was not associated with age at surgery or IOL location. The risk of glaucoma development across all ages at surgery suggests a need for long-term monitoring.
    Type of Medium: Online Resource
    ISSN: 2168-6165
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2023
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