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  • 1
    In: Epidemiology, Ovid Technologies (Wolters Kluwer Health), Vol. 31, No. 2 ( 2020-03), p. 301-309
    Abstract: Assessing aspects of intersections that may affect the risk of pedestrian injury is critical to developing child pedestrian injury prevention strategies, but visiting intersections to inspect them is costly and time-consuming. Several research teams have validated the use of Google Street View to conduct virtual neighborhood audits that remove the need for field teams to conduct in-person audits. Methods: We developed a 38-item virtual audit instrument to assess intersections for pedestrian injury risk and tested it on intersections within 700 m of 26 schools in New York City using the Computer-assisted Neighborhood Visual Assessment System (CANVAS) with Google Street View imagery. Results: Six trained auditors tested this instrument for inter-rater reliability on 111 randomly selected intersections and for test–retest reliability on 264 other intersections. Inter-rater kappa scores ranged from −0.01 to 0.92, with nearly half falling above 0.41, the conventional threshold for moderate agreement. Test–retest kappa scores were slightly higher than but highly correlated with inter-rater scores (Spearman rho = 0.83). Items that were highly reliable included the presence of a pedestrian signal (K = 0.92), presence of an overhead structure such as an elevated train or a highway (K = 0.81), and intersection complexity (K = 0.76). Conclusions: Built environment features of intersections relevant to pedestrian safety can be reliably measured using a virtual audit protocol implemented via CANVAS and Google Street View.
    Type of Medium: Online Resource
    ISSN: 1044-3983
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
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  • 2
    In: Biological Psychiatry, Elsevier BV, Vol. 93, No. 4 ( 2023-02), p. 362-369
    Type of Medium: Online Resource
    ISSN: 0006-3223
    RVK:
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2023
    detail.hit.zdb_id: 1499907-9
    SSG: 12
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  • 3
    In: Biological Psychiatry, Elsevier BV, Vol. 91, No. 7 ( 2022-04), p. 626-636
    Type of Medium: Online Resource
    ISSN: 0006-3223
    RVK:
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2022
    detail.hit.zdb_id: 1499907-9
    SSG: 12
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  • 4
    In: Sleep, Oxford University Press (OUP), Vol. 43, No. 4 ( 2020-04-15)
    Abstract: Sleep problems are common, serving as both a predictor and symptom of posttraumatic stress disorder (PTSD), with these bidirectional relationships well established in the literature. While both sleep phenotypes and PTSD are moderately heritable, there has been a paucity of investigation into potential genetic overlap between sleep and PTSD. Here, we estimate genetic correlations between multiple sleep phenotypes (including insomnia symptoms, sleep duration, daytime sleepiness, and chronotype) and PTSD, using results from the largest genome-wide association study (GWAS) to date of PTSD, as well as publicly available GWAS results for sleep phenotypes within UK Biobank data (23 variations, encompassing four main phenotypes). Methods Genetic correlations were estimated utilizing linkage disequilibrium score regression (LDSC), an approach that uses GWAS summary statistics to compute genetic correlations across traits, and Mendelian randomization (MR) analyses were conducted to follow up on significant correlations. Results Significant, moderate genetic correlations were found between insomnia symptoms (rg range 0.36–0.49), oversleeping (rg range 0.32–0.44), undersleeping (rg range 0.48–0.49), and PTSD. In contrast, there were mixed results for continuous sleep duration and daytime sleepiness phenotypes, and chronotype was not correlated with PTSD. MR analyses did not provide evidence for casual effects of sleep phenotypes on PTSD. Conclusion Sleep phenotypes, particularly insomnia symptoms and extremes of sleep duration, have shared genetic etiology with PTSD, but causal relationships were not identified. This highlights the importance of further investigation into the overlapping influences on these phenotypes as sample sizes increase and new methods to investigate directionality and causality become available.
    Type of Medium: Online Resource
    ISSN: 0161-8105 , 1550-9109
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
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  • 5
    In: Nature Communications, Springer Science and Business Media LLC, Vol. 10, No. 1 ( 2019-10-08)
    Abstract: The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct a genome-wide association study of PTSD. We demonstrate SNP-based heritability estimates of 5–20%, varying by sex. Three genome-wide significant loci are identified, 2 in European and 1 in African-ancestry analyses. Analyses stratified by sex implicate 3 additional loci in men. Along with other novel genes and non-coding RNAs, a Parkinson’s disease gene involved in dopamine regulation, PARK2 , is associated with PTSD. Finally, we demonstrate that polygenic risk for PTSD is significantly predictive of re-experiencing symptoms in the Million Veteran Program dataset, although specific loci did not replicate. These results demonstrate the role of genetic variation in the biology of risk for PTSD and highlight the necessity of conducting sex-stratified analyses and expanding GWAS beyond European ancestry populations.
    Type of Medium: Online Resource
    ISSN: 2041-1723
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2019
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  • 6
    Online Resource
    Online Resource
    Elsevier BV ; 2023
    In:  Annals of Epidemiology Vol. 86 ( 2023-10), p. 49-56.e3
    In: Annals of Epidemiology, Elsevier BV, Vol. 86 ( 2023-10), p. 49-56.e3
    Type of Medium: Online Resource
    ISSN: 1047-2797
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2023
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  • 7
    In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 5702-5702
    Abstract: Introduction: Peri-transplant radiation (XRT) in Hodgkin Lymphoma (HL) patients undergoing autologous stem cell transplant (ASCT) has been associated with improved local control. However, this has not been well established with increased use of novel agents in peri-transplant setting. Methods: This was a retrospective analysis of HL patients who underwent their first ASCT between 2000 and 2018 at Karmanos Cancer Institute in Detroit, Michigan. Peri-transplant radiation was defined as XRT within 3-month window of autologous transplant. Novel agents included brentuximab, check-point inhibitors (CIs), and other targeted agents. The primary endpoint was to compare overall survival (OS) based on utilization of peri-transplant XRT and novel agents with standard salvage chemotherapy. Secondary endpoint was to assess the OS benefit of novel agent use in the post-transplant setting. Univariable and multivariable Cox proportional hazards regression models were fit to assess associations between OS and nine prior chosen predictors (bulky relapse, pulmonary or bone marrow relapse, extranodal disease, CT/PET response [CR vs less than CR] , novel salvage [anytime], peri-transplant XRT, site of relapse [local vs systemic] , maintenance brentuximab, relapse after initial diagnosis [ 〉 1 year vs ≤1 year]). Results: From 2000-2018, there were total of 220 patients who underwent ASCT for HL. Patients underwent ASCT median of 575 days after initial diagnosis. 65 (30%) patients had XRT during initial treatment and XRT was utilized less frequently in all patients (13% vs 35%) and stage I-II patients (29% vs 46%) who were diagnosed after 2010. Peri-transplant XRT was used in 30 (14%) patients and was utilized similarly in patients who had ASCT before or after 2010 (13% vs 14%) (Figure 1). There was no difference in baseline characteristics (bulky relapse, local vs systemic relapse, etc.) of patients who did or did not receive peri-transplant XRT (Table 1). Novel salvage was used in 32 (15%) patients at any time before transplant (Figure 1). Median OS of all the patients who had ASCT was 11 years [7.6-NR] and PFS was 4.3 years [2.3-7.4] . Median OS of patients who had peri-transplant XRT was not reached [9.4-NR] compared to 7.7 [5.3-NR] years for those without peri-transplant XRT [HR 0.38; 95% CI 0.15-0.96; p=0.033] (Figure 2); on the contrary, there was no difference in PFS between the two groups. Median OS of patients who had novel salvage at any time was not reached [4.3-NR] compared to 11 [7.6-NR] years for those without novel salvage [HR 1.08; 95% CI 0.43-2.72; p=0.877] . Median OS of patients who had either novel salvage (anytime) or peri-transplant XRT was not reached [9.4-NR] compared to 11 years [6.5-NR] for those who had chemotherapy salvage only [HR 0.64; 95% CI 0.32-1.26; p=0.193]. In the multivariable analysis, less than CR to salvage therapy and lack of peri-transplant XRT use were associated with worse OS. There were total of 85 (39%) patients who progressed after ASCT. Median OS for those patients was 3.5 years [2.3-8.8] and PFS was 1 year [0.8-1.5] after relapse from ASCT. The median OS for patients who received novel agents (brentuximab 61%, CI 14%) during first progression after ASCT was 6.9 years [2.3-NR] after relapse from ASCT compared to 2.9 years [2.3-NR] for those that did not [HR 1.47; 95% CI 0.72-3; p=. 288]. In addition, the median OS for patients who received novel agent at any time after transplant was 6.9 years [2.6-NR] after relapse from ASCT compared to 2.5 years [2.2-7] for those who did not [HR 1.96; 95% CI 1-3.86; p=0.048] (Figure 3). Lastly, OS after relapse from ASCT was better if patients progressing on novel agent post-transplant received another novel agent for their successive therapy rather than any other treatment [HR 4.87; 95% CI 1.14-20.8; p=0.018]. Conclusions: We show that there was a lack of standardized patient selection for utilization of peri-transplant XRT and its use was similar before and after the novel agent era. Peri-transplant XRT was possibly used in patients who had residual disease or other high -risk features that could not be identified due to retrospective nature of this study and, despite this, use of peri-transplant XRT was associated with modest survival benefit. Surprisingly, use of novel agent at any time during salvage was not associated with survival benefit. Utilization of novel agents at any time after post-transplant progression was associated with OS benefit. Disclosures Deol: Kite: Other: Advisory board; Novartis: Other: Advisory board; Agios: Other: Advisory board.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2019
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  • 8
    Online Resource
    Online Resource
    American Society of Hematology ; 2021
    In:  Blood Vol. 138, No. Supplement 1 ( 2021-11-05), p. 4828-4828
    In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 4828-4828
    Abstract: Background Chimeric Antigen Receptor (CAR) T cell therapy has emerged as a promising therapeutic option for relapsed/refractory non-Hodgkin lymphoma. However, access to CAR T cell therapy remains limited as CAR T cells are routinely administered in the hospital setting. Hence, there's a growing interest in standardizing outpatient administration of CAR T cells to increase patient access and minimize costs. Here, we describe our institution's experience with outpatient administration of CAR T cells. Methods In this retrospective study, we reviewed who received CAR T cell therapy in the outpatient setting at Karmanos Cancer Center between June 2019 and June 2021.Charts were reviewed for age, disease pathology, prior lines of therapy, need for hospitalization within 30 days, development of CRS and/or neurotoxicity, need for ICU admission, need for steroids and/or tocilizumab, length of admission, and disease state at last follow up. All patients received fludarabine and cyclophosphamide as lymphodepletion (LD) therapy day -5 to -3. CAR T cells were infused on day 0. Patients subsequently followed up in clinic daily for 2 weeks and were started on allopurinol, ciprofloxacin, fluconazole, acyclovir and levetiracetam. First response was assessed by FDG PET scan 4 weeks after CAR T cell . Results A total of 12 patients received CAR T cells during the study period. All patients had a diagnosis of DLBCL and received Tisagenlecleucel. Median age at CAR T cell therapy was 69.5 years (40-78 years). Median number of prior lines of therapy was (2-3) while 2 patients had received prior stem cell transplantation. Table 1 describes patient characteristics and lines of therapy. Two patients received bridging therapy prior to LD. Overall response rate was 58.3% (complete response-3, partial response-4). Median duration of follow up was 6.7 (0.6-13.8 months). Four patients required subsequent therapy after CAR T cell for disease progression while 9 patients were alive at the time of data cut off. Figure 1 summarizes disease response and follow . Table 2 summarizes complications during follow up. Nine (75%) patients developed anemia (grade 3-4 n=4, 33.3%), 8 (66.7%) developed thrombocytopenia (grade 3-4 n= 3, 37.5%), and 8 (66.7%) developed neutropenia (grade 3-4 n=8, 66.7%). Median time to platelet recovery to & gt;,000 and neutrophil recovery to & gt;500 was 66 days (44-81 days) and 11.5 days (6-65 days), respectively. Three (25%) patients required platelet and red blood cell transfusion support. Six (50%) patients developed cytokine release syndrome (CRS) with median grade 2 (range 1-3, grade 3-4 n=1). Five (5/6) patients required hospitalization, five (5/6) required tocilizumab, and one (1/6) required steroids. One (8.3%) patient developed neurotoxicity of grade 1 severity improved without systemic therapy. Six patients required hospitalization within 30 days of CAR T cell infusion. Median day of admission from CAR T cell infusion was 4 days (range 2-12 days (range 2-12 days, admission within 3 days n=2, admission under observation n=1). Patient characteristics at admission are summarized in table 3. Of these, 5 patients were diagnosed with CRS,1 patient with colitis and none with blood stream infection. Two patients required ICU admission. Median length of hospital admission was 5.5 days (2-9 days). All patients were alive at discharge while 1 patient required subsequent admission within 30 . Conclusion Outpatient administration of Tisagenlecleucel is feasible with low risk of hospital admission within 3 days of infusion. Adoption of outpatient CAR T cell therapy may increase patient access for treatment of DLBCL and diseases such as multiple myeloma while reducing administration costs for this novel therapy. Figure 1 Figure 1. Disclosures Modi: Genentech: Research Funding; Seagen: Membership on an entity's Board of Directors or advisory committees; MorphoSys: Membership on an entity's Board of Directors or advisory committees. Deol: Kite, a Gilead Company: Consultancy.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2021
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  • 9
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2021
    In:  Innovation in Aging Vol. 5, No. Supplement_1 ( 2021-12-17), p. 409-410
    In: Innovation in Aging, Oxford University Press (OUP), Vol. 5, No. Supplement_1 ( 2021-12-17), p. 409-410
    Abstract: Posttraumatic stress disorder (PTSD) is twice as prevalent in women as in men, and is an established risk factor for chronic disease, but few studies have comprehensively assessed lifetime PTSD in middle-aged and older civilian women. We surveyed 33,328 women aged 54-74 from the Nurses’ Health Study II from August 2018 to January 2020 to understand trauma exposure, PTSD based on the Diagnostic and Statistical Manual of Mental Disorders Version 5, and trauma-related treatment use. The majority (82.2%) of women reported one or more lifetime traumas. 10.5% of those with trauma had lifetime PTSD and 1.5% had past-month PTSD. The most common trauma types were sudden or unexpected death of a loved one (44.9%) and interpersonal or sexual violence (43.5%). Almost 30% experienced occupational (nursing-related) trauma. Interpersonal or sexual violence event types explained the largest proportion of PTSD cases (33.6%) out of seven categories of events assessed. Only 25% of women with trauma ever accessed trauma-related treatment, but this proportion was higher (66.4%) among those with diagnosable PTSD, and among those with current depression (35.9%). Treatment was most common among women who experienced interpersonal/sexual violence and lowest among those with occupational trauma, but treatment satisfaction did not vary by worst trauma type. Psychotherapy was the most common type of treatment. These results demonstrate that trauma is nearly universal in middle-aged to older women, which has important implications for their long-term health and well-being—particularly in the era of COVID-19 which is likely to produce additional trauma in this population.
    Type of Medium: Online Resource
    ISSN: 2399-5300
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 2905697-4
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  • 10
    In: Nature Communications, Springer Science and Business Media LLC, Vol. 11, No. 1 ( 2020-11-24)
    Abstract: Epigenetic differences may help to distinguish between PTSD cases and trauma-exposed controls. Here, we describe the results of the largest DNA methylation meta-analysis of PTSD to date. Ten cohorts, military and civilian, contribute blood-derived DNA methylation data from 1,896 PTSD cases and trauma-exposed controls. Four CpG sites within the aryl-hydrocarbon receptor repressor ( AHRR) associate with PTSD after adjustment for multiple comparisons, with lower DNA methylation in PTSD cases relative to controls. Although AHRR methylation is known to associate with smoking, the AHRR association with PTSD is most pronounced in non-smokers, suggesting the result was independent of smoking status. Evaluation of metabolomics data reveals that AHRR methylation associated with kynurenine levels, which are lower among subjects with PTSD. This study supports epigenetic differences in those with PTSD and suggests a role for decreased kynurenine as a contributor to immune dysregulation in PTSD.
    Type of Medium: Online Resource
    ISSN: 2041-1723
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2553671-0
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