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  • 1
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    Methotrexate in Abdominal Pregnancy
    American Medical Association (AMA) ; 1969
    In:  JAMA: The Journal of the American Medical Association Vol. 208, No. 3 ( 1969-04-21), p. 529-
    Details
    In: JAMA: The Journal of the American Medical Association, American Medical Association (AMA), Vol. 208, No. 3 ( 1969-04-21), p. 529-
    Type of Medium: Online Resource
    ISSN: 0098-7484
    URL: Article
    DOI: 10.1001/jama.1969.03160030103019
    RVK:
    XA 10000
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 1969
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  • 2
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    Effect of Convalescent Plasma on Organ Support–Free Days in Critically Ill Patients With COVID-19 : A Randomized Clinical Trial
    American Medical Association (AMA) ; 2021
    In:  JAMA Vol. 326, No. 17 ( 2021-11-02), p. 1690-
    Details
    In: JAMA, American Medical Association (AMA), Vol. 326, No. 17 ( 2021-11-02), p. 1690-
    Type of Medium: Online Resource
    ISSN: 0098-7484
    URL: Article
    DOI: 10.1001/jama.2021.18178
    RVK:
    XA 10000
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2021
    detail.hit.zdb_id: 2958-0
    detail.hit.zdb_id: 2018410-4
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  • 3
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    Effect of Probiotics on Incident Ventilator-Associated Pneumonia in Critically Ill Patients : A Randomized Clinical Trial
    American Medical Association (AMA) ; 2021
    In:  JAMA Vol. 326, No. 11 ( 2021-09-21), p. 1024-
    Details
    In: JAMA, American Medical Association (AMA), Vol. 326, No. 11 ( 2021-09-21), p. 1024-
    Type of Medium: Online Resource
    ISSN: 0098-7484
    URL: Article
    DOI: 10.1001/jama.2021.13355
    RVK:
    XA 10000
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2021
    detail.hit.zdb_id: 2958-0
    detail.hit.zdb_id: 2018410-4
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  • 4
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    Spatial Extent of Amyloid-β Levels and Associations With Tau-PET and Cognition
    American Medical Association (AMA) ; 2022
    In:  JAMA Neurology Vol. 79, No. 10 ( 2022-10-01), p. 1025-
    Details
    In: JAMA Neurology, American Medical Association (AMA), Vol. 79, No. 10 ( 2022-10-01), p. 1025-
    Abstract: Preventive trials of anti-amyloid agents might preferably recruit persons showing earliest biologically relevant β-amyloid (Aβ) binding on positron emission tomography (PET). Objective To investigate the timing at which Aβ-PET binding starts showing associations with other markers of Alzheimer disease. Design, Setting, and Participants This longitudinal multicentric cohort study included 3 independent cohorts: Presymptomatic Evaluation of Experimental or Novel Treatments for Alzheimer Disease (PREVENT-AD) (data collected from 2012-2020), Alzheimer Disease Neuroimaging Initiative (ADNI) (data collected from 2005-2019), and Harvard Aging Brain Study (HABS) (data collected from 2011-2019). In a 3-tiered categorization of Aβ-PET binding spatial extent, individuals were assigned as having widespread Aβ deposition if they showed positive signal throughout a designated set of brain regions prone to early Aβ accumulation. Those with binding in some but not all were categorized as having regional deposition, while those who failed to show any criterion Aβ signal were considered Aβ-negative. All participants who were cognitively unimpaired at their first Aβ PET scan. Main Outcomes and Measures Differences in cerebrospinal fluid (CSF), genetics, tau-PET burden, and cognitive decline. Results A total of 817 participants were included, including 129 from the PREVENT-AD cohort (mean [SD] age, 63.5 [4.7] years; 33 [26%] male; 126 [98%] White), 400 from ADNI (mean [SD] age, 73.6 [5.8] years; 190 [47%] male; 10 [5%] Hispanic, 338 [91%] White), and 288 from HABS (mean [SD] age, 73.7 [6.2] years; 117 [40%] male; 234 [81%] White). Compared with Aβ-negative persons, those with regional Aβ binding showed proportionately more APOE ε4 carriers (18 [64%] vs 22 [27%] in PREVENT-AD and 34 [31%] vs 38 [19%] in ADNI), reduced CSF Aβ1-42 levels ( F  = 24 and 71), and greater longitudinal Aβ-PET accumulation (significant β = 0.019 to 0.056). Participants with widespread amyloid binding further exhibited notable cognitive decline (significant β = −0.014 to −0.08), greater CSF phosphorylated tau 181 ( F  = 5 and 27), and tau-PET binding (all F   & amp;gt; 7.55). Using each cohort’s specified dichotomous threshold for Aβ positivity or a visual read classification, most participants (56% to 100%, depending on classification method and cohort) with regional Aβ would have been classified Aβ-negative. Conclusions and Relevance Regional Aβ binding appears to be biologically relevant and participants at this stage remain relatively free from CSF phosphorylated tau 181 , tau-PET binding, and related cognitive decline, making them ideal targets for anti-amyloid agents. Most of these individuals would be classified as negative based on classical thresholds of Aβ positivity.
    Type of Medium: Online Resource
    ISSN: 2168-6149
    URL: Article
    DOI: 10.1001/jamaneurol.2022.2442
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2022
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  • 5
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    Incidence of and Neurodevelopmental Outcomes After Late-Onset Meningitis Among Children Born Extremely Preterm
    American Medical Association (AMA) ; 2022
    In:  JAMA Network Open Vol. 5, No. 12 ( 2022-12-08), p. e2245826-
    Details
    In: JAMA Network Open, American Medical Association (AMA), Vol. 5, No. 12 ( 2022-12-08), p. e2245826-
    Abstract: Late-onset meningitis (LOM) has been associated with adverse neurodevelopmental outcomes in children born extremely preterm. Objective To report the incidence of LOM during birth hospitalization and neurodevelopmental outcomes at 18 to 26 months’ corrected age. Design, Setting, and Participants This cohort study is a secondary analysis of a multicenter prospective cohort of children born at 22 to 26 weeks’ gestation between 2003 and 2017 with follow-up from 2004 to 2021. The study was conducted at 25 Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network centers. Exposures Culture-confirmed LOM. Main Outcomes and Measures Incidence and microbiology of LOM (2003-2017); lumbar puncture (LP) performance in late-onset sepsis (LOS) evaluations (2011-2017); composite outcome of death or neurodevelopmental impairment (NDI; 2004-2021). Results Among 13 372 infants (median [IQR] gestational age, 25.4 [24.4-26.1] weeks; 6864 [51%] boys), LOM was diagnosed in 167 (1%); LOS without LOM in 4564 (34%); and neither LOS nor LOM in 8641 (65%). The observed incidence of LOM decreased from 2% (95% CI, 1%-3%) in 2003 to 0.4% (95% CI, 0.7%-1.0%) in 2017 ( P   & amp;lt; .001). LP performance in LOS evaluations decreased from 36% (95% CI, 33%-40%) in 2011 to 24% (95% CI, 21%-27%) in 2017 ( P   & amp;lt; .001). Among infants with culture-confirmed LOS, LP performance decreased from 58% (95% CI, 51%-65%) to 45% (95% CI, 38%-51%; P  = .008). LP performance varied by center among all LOS evaluations (10%-59%, P   & amp;lt; .001) and among those with culture-confirmed LOS (23%-79%, P   & amp;lt; .001). LOM occurred in the absence of concurrent LOS in 27 of 167 cases (16%). The most common LOM isolates were coagulase-negative Staphylococcus (98 [59%]), Candida albicans (38 [23%]), and Escherichia coli (27 [16%]). Death or NDI occurred in 22 of 46 children (48%) with LOM due to coagulase-negative Staphylococcus , 43 of 67 (64%) due to all other bacterial pathogens, and 26 of 33 (79%) due to fungal pathogens. The adjusted relative risk of death or NDI was increased among children with LOM (aOR, 1.53; 95% CI, 1.04-2.25) and among those with LOS without LOM (aOR, 1.41; 95% CI, 1.29-1.54) compared with children with neither infection. Conclusions and Relevance In this cohort study, LP was performed with decreasing frequency, and the observed incidence of LOM also decreased. Both LOM and LOS were associated with increased risk of death or NDI; risk varied by LOM pathogen. The full association of LOM with outcomes of children born extremely preterm may be underestimated by current diagnostic practices.
    Type of Medium: Online Resource
    ISSN: 2574-3805
    URL: Article
    DOI: 10.1001/jamanetworkopen.2022.45826
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2022
    detail.hit.zdb_id: 2931249-8
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  • 6
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    Self-expanding Transcatheter vs Surgical Aortic Valve Replacement in Intermediate-Risk Patients : 5-Year Outcomes of the SURTAVI Randomized Clinical Trial
    American Medical Association (AMA) ; 2022
    In:  JAMA Cardiology Vol. 7, No. 10 ( 2022-10-01), p. 1000-
    Details
    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
    URL: Article
    DOI: 10.1001/jamacardio.2022.2695
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2022
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  • 7
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    Association of Elevated Amyloid and Tau Positron Emission Tomography Signal With Near-Term Development of Alzheimer Disease Symptoms in Older Adults Without Cognitive Impairment
    American Medical Association (AMA) ; 2022
    In:  JAMA Neurology Vol. 79, No. 10 ( 2022-10-01), p. 975-
    Details
    In: JAMA Neurology, American Medical Association (AMA), Vol. 79, No. 10 ( 2022-10-01), p. 975-
    Abstract: National Institute on Aging–Alzheimer’s Association (NIA-AA) workgroups have proposed biological research criteria intended to identify individuals with preclinical Alzheimer disease (AD). Objective To assess the clinical value of these biological criteria to identify older individuals without cognitive impairment who are at near-term risk of developing symptomatic AD. Design, Setting, and Participants This longitudinal cohort study used data from 4 independent population-based cohorts (PREVENT-AD, HABS, AIBL, and Knight ADRC) collected between 2003 and 2021. Participants were older adults without cognitive impairment with 1 year or more of clinical observation after amyloid β and tau positron emission tomography (PET). Median clinical follow-up after PET ranged from 1.94 to 3.66 years. Exposures Based on binary assessment of global amyloid burden (A) and a composite temporal region of tau PET uptake (T), participants were stratified into 4 groups (A+T+, A+T−, A−T+, A−T−). Presence (+) or absence (−) of neurodegeneration (N) was assessed using temporal cortical thickness. Main Outcomes and Measures Each cohort was analyzed separately. Primary outcome was clinical progression to mild cognitive impairment (MCI), identified by a Clinical Dementia Rating score of 0.5 or greater in Knight ADRC and by consensus committee review in the other cohorts. Clinical raters were blind to imaging, genetic, and fluid biomarker data. A secondary outcome was cognitive decline, based on a slope greater than 1.5 SD below the mean of an independent subsample of individuals without cognitive impairment. Outcomes were compared across the biomarker groups. Results Among 580 participants (PREVENT-AD, 128; HABS, 153; AIBL, 48; Knight ADRC, 251), mean (SD) age ranged from 67 (5) to 76 (6) years across cohorts, with between 55% (137/251) and 74% (95/128) female participants. Across cohorts, 33% to 83% of A+T+ participants progressed to MCI during follow-up (mean progression time, 2-2.72 years), compared with less than 20% of participants in other biomarker groups. Progression further increased to 43% to 100% when restricted to A+T+(N+) individuals. Cox proportional hazard ratios for progression to MCI in the A+T+ group vs other biomarker groups were all 5 or greater. Many A+T+ nonprogressors also showed longitudinal cognitive decline, while cognitive trajectories in other groups remained predominantly stable. Conclusions and Relevance The clinical prognostic value of NIA-AA research criteria was confirmed in 4 independent cohorts, with most A+T+(N+) older individuals without cognitive impairment developing AD symptoms within 2 to 3 years.
    Type of Medium: Online Resource
    ISSN: 2168-6149
    URL: Article
    DOI: 10.1001/jamaneurol.2022.2379
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2022
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  • 8
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    Interleukin 6 and Cardiovascular Outcomes in Patients With Chronic Kidney Disease and Chronic Coronary Syndrome
    American Medical Association (AMA) ; 2021
    In:  JAMA Cardiology Vol. 6, No. 12 ( 2021-12-01), p. 1440-
    Details
    In: JAMA Cardiology, American Medical Association (AMA), Vol. 6, No. 12 ( 2021-12-01), p. 1440-
    Type of Medium: Online Resource
    ISSN: 2380-6583
    URL: Article
    DOI: 10.1001/jamacardio.2021.3079
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2021
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  • 9
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    Associations of Sex, Race, and Apolipoprotein E Alleles With Multiple Domains of Cognition Among Older Adults
    American Medical Association (AMA) ; 2023
    In:  JAMA Neurology Vol. 80, No. 9 ( 2023-09-01), p. 929-
    Details
    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
    URL: Article
    DOI: 10.1001/jamaneurol.2023.2169
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2023
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  • 10
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    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
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