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  • 1
    Online Resource
    Online Resource
    Risk Factors for Progression and Toxic Effects After Preoperative Stereotactic Radiosurgery for Patients With Resected Brain Metastases
    American Medical Association (AMA) ; 2023
    In:  JAMA Oncology Vol. 9, No. 8 ( 2023-08-01), p. 1066-
    Details
    In: JAMA Oncology, American Medical Association (AMA), Vol. 9, No. 8 ( 2023-08-01), p. 1066-
    Abstract: Preoperative stereotactic radiosurgery (SRS) has been demonstrated as a feasible alternative to postoperative SRS for resectable brain metastases (BMs) with potential benefits in adverse radiation effects (AREs) and meningeal disease (MD). However, mature large-cohort multicenter data are lacking. Objective To evaluate preoperative SRS outcomes and prognostic factors from a large international multicenter cohort (Preoperative Radiosurgery for Brain Metastases–PROPS-BM). Design, Setting, and Participants This multicenter cohort study included patients with BMs from solid cancers, of which at least 1 lesion received preoperative SRS and a planned resection, from 8 institutions. Radiosurgery to synchronous intact BMs was allowed. Exclusion criteria included prior or planned whole-brain radiotherapy and no cranial imaging follow-up. Patients were treated between 2005 and 2021, with most treated between 2017 and 2021. Exposures Preoperative SRS to a median dose to 15 Gy in 1 fraction or 24 Gy in 3 fractions delivered at a median (IQR) of 2 (1-4) days before resection. Main Outcomes and Measures The primary end points were cavity local recurrence (LR), MD, ARE, overall survival (OS), and multivariable analysis of prognostic factors associated with these outcomes. Results The study cohort included 404 patients (214 women [53%]; median [IQR] age, 60.6 [54.0-69.6] years) with 416 resected index lesions. The 2-year cavity LR rate was 13.7%. Systemic disease status, extent of resection, SRS fractionation, type of surgery (piecemeal vs en bloc), and primary tumor type were associated with cavity LR risk. The 2-year MD rate was 5.8%, with extent of resection, primary tumor type, and posterior fossa location being associated with MD risk. The 2-year any-grade ARE rate was 7.4%, with target margin expansion greater than 1 mm and melanoma primary being associated with ARE risk. Median OS was 17.2 months (95% CI, 14.1-21.3 months), with systemic disease status, extent of resection, and primary tumor type being the strongest prognostic factors associated with OS. Conclusions and Relevance In this cohort study, the rates of cavity LR, ARE, and MD after preoperative SRS were found to be notably low. Several tumor and treatment factors were identified that are associated with risk of cavity LR, ARE, MD, and OS after treatment with preoperative SRS. A phase 3 randomized clinical trial of preoperative vs postoperative SRS (NRG BN012) has began enrolling (NCT05438212).
    Type of Medium: Online Resource
    ISSN: 2374-2437
    URL: Article
    DOI: 10.1001/jamaoncol.2023.1629
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2023
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  • 2
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    Online Resource
    Heterogeneity of Treatment Effects of Hydrocortisone by Risk of Bronchopulmonary Dysplasia or Death Among Extremely Preterm Infants in the National Institute of Child Health and Human Development Neonatal Research Network Trial : A Secondary Analysis of a Randomized Clinical Trial
    American Medical Association (AMA) ; 2023
    In:  JAMA Network Open Vol. 6, No. 5 ( 2023-05-31), p. e2315315-
    Details
    In: JAMA Network Open, American Medical Association (AMA), Vol. 6, No. 5 ( 2023-05-31), p. e2315315-
    Abstract: Extremely preterm infants who develop bronchopulmonary dysplasia (BPD) are at a higher risk for adverse pulmonary and neurodevelopmental outcomes. In the National Institute of Child Health and Human Development Neonatal Research Network (NICHD NRN) Hydrocortisone Trial, hydrocortisone neither reduced rates of BPD or death nor increased rates of neurodevelopmental impairment (NDI) or death. Objective To determine whether estimated risk for grades 2 to 3 BPD or death is associated with the effect of hydrocortisone on the composite outcomes of (1) grades 2 to 3 BPD or death and (2) moderate or severe NDI or death. Design, Setting, and Participants This secondary post hoc analysis used data from the NICHD NRN Hydrocortisone Trial, which was a double-masked, placebo-controlled, randomized clinical trial conducted in 19 US academic centers. The NICHD HRN Hydrocortisone Trial enrolled infants born at a gestational age of less than 30 weeks who received mechanical ventilation for at least 7 days, including at the time of enrollment, and who were aged 14 to 28 postnatal days. Infants were enrolled between August 22, 2011, and February 4, 2018, with follow-up between 22 and 26 months of corrected age completed on March 29, 2020. Data were analyzed from September 13, 2021, to March 25, 2023. Intervention Infants were randomized to 10 days of hydrocortisone or placebo treatment. Main Outcomes and Measures Infants’ baseline risk of grades 2 to 3 BPD or death was estimated using the NICHD Neonatal BPD Outcome Estimator. Differences in absolute and relative treatment effects by baseline risk were evaluated using interaction terms in models fitted to the efficacy outcome of grades 2 to 3 BPD or death and the safety outcome of moderate or severe NDI or death by follow-up. Results Among the 799 infants included in the analysis (421 boys [52.7%]), the mean (SD) gestational age was 24.9 (1.5) weeks, and the mean (SD) birth weight was 715 (167) g. The mean estimated baseline risk for grades 2 to 3 BPD or death was 54% (range, 18%-84%) in the study population. The interaction between treatment group and baseline risk was not statistically significant on a relative or absolute scale for grades 2 to 3 BPD or death; the size of the effect ranged from a relative risk of 1.13 (95% CI, 0.82-1.55) in quartile 1 to 0.94 (95% CI, 0.81-1.09) in quartile 4. Similarly, the interaction between treatment group and baseline risk was not significant on a relative or absolute scale for moderate or severe NDI or death; the size of the effect ranged from a relative risk of 1.04 (95% CI, 0.80-1.36) in quartile 1 to 0.99 (95% CI, 0.80-1.22) in quartile 4. Conclusions and Relevance In this secondary analysis of a randomized clinical trial, the effect of hydrocortisone vs placebo was not appreciably modified by baseline risk for grades 2 to 3 BPD or death. Trial Registration ClinicalTrials.gov Identifier: NCT01353313
    Type of Medium: Online Resource
    ISSN: 2574-3805
    URL: Article
    DOI: 10.1001/jamanetworkopen.2023.15315
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2023
    detail.hit.zdb_id: 2931249-8
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  • 3
    Online Resource
    Online Resource
    Association Between False Memories and Delusions in Alzheimer Disease
    American Medical Association (AMA) ; 2023
    In:  JAMA Psychiatry Vol. 80, No. 7 ( 2023-07-01), p. 700-
    Details
    In: JAMA Psychiatry, American Medical Association (AMA), Vol. 80, No. 7 ( 2023-07-01), p. 700-
    Abstract: Understanding the mechanisms of delusion formation in Alzheimer disease (AD) could inform the development of therapeutic interventions. It has been suggested that delusions arise as a consequence of false memories. Objective To investigate whether delusions in AD are associated with false recognition, and whether higher rates of false recognition and the presence of delusions are associated with lower regional brain volumes in the same brain regions. Design, Setting, and Participants Since the Alzheimer’s Disease Neuroimaging Initiative (ADNI) launched in 2004, it has amassed an archive of longitudinal behavioral and biomarker data. This cross-sectional study used data downloaded in 2020 from ADNI participants with an AD diagnosis at baseline or follow-up. Data analysis was performed between June 24, 2020, and September 21, 2021. Exposure Enrollment in the ADNI. Main Outcomes and Measures The main outcomes included false recognition, measured with the 13-item Alzheimer’s Disease Assessment Scale–Cognitive Subscale (ADAS-Cog 13) and the Rey Auditory Verbal Learning Test (RAVLT) and volume of brain regions corrected for total intracranial volume. Behavioral data were compared for individuals with delusions in AD and those without using independent-samples t tests or Mann-Whitney nonparametric tests. Significant findings were further explored using binary logistic regression modeling. For neuroimaging data region of interest analyses using t tests, Poisson regression modeling or binary logistic regression modeling and further exploratory, whole-brain voxel-based morphometry analyses were carried out to explore the association between regional brain volume and false recognition or presence of delusions. Results Of the 2248 individuals in the ADNI database, 728 met the inclusion criteria and were included in this study. There were 317 (43.5%) women and 411 (56.5%) men. Their mean (SD) age was 74.8 (7.4) years. The 42 participants with delusions at baseline had higher rates of false recognition on the ADAS-Cog 13 (median score, 3; IQR, 1 to 6) compared with the 549 control participants (median score, 2; IQR, 0 to 4; U  = 9398.5; P  = .04). False recognition was not associated with the presence of delusions when confounding variables were included in binary logistic regression models. An ADAS-Cog 13 false recognition score was inversely associated with left hippocampal volume (odds ratio [OR], 0.91 [95% CI, 0.88-0.94] , P   & amp;lt; .001), right hippocampal volume (0.94 [0.92-0.97], P   & amp;lt; .001), left entorhinal cortex volume (0.94 [0.91-0.97], P   & amp;lt; .001), left parahippocampal gyrus volume (0.93 [0.91-0.96], P   & amp;lt; .001), and left fusiform gyrus volume (0.97 [0.96-0.99], P   & amp;lt; .001). There was no overlap between locations associated with false recognition and those associated with delusions. Conclusions and Relevance In this cross-sectional study, false memories were not associated with the presence of delusions after accounting for confounding variables, and no indication for overlap of neural networks for false memories and delusions was observed on volumetric neuroimaging. These findings suggest that delusions in AD do not arise as a direct consequence of misremembering, lending weight to ongoing attempts to delineate specific therapeutic targets for treatment of psychosis.
    Type of Medium: Online Resource
    ISSN: 2168-622X
    URL: Article
    DOI: 10.1001/jamapsychiatry.2023.1012
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2023
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