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  • Oxford University Press (OUP)  (279)
  • 1
    In: Brain, Oxford University Press (OUP), Vol. 146, No. 9 ( 2023-09-01), p. 3719-3734
    Kurzfassung: Mechanisms of resilience against tau pathology in individuals across the Alzheimer’s disease spectrum are insufficiently understood. Longitudinal data are necessary to reveal which factors relate to preserved cognition (i.e. cognitive resilience) and brain structure (i.e. brain resilience) despite abundant tau pathology, and to clarify whether these associations are cross-sectional or longitudinal. We used a longitudinal study design to investigate the role of several demographic, biological and brain structural factors in yielding cognitive and brain resilience to tau pathology as measured with PET. In this multicentre study, we included 366 amyloid-β-positive individuals with mild cognitive impairment or Alzheimer’s disease dementia with baseline 18F-flortaucipir-PET and longitudinal cognitive assessments. A subset (n = 200) additionally underwent longitudinal structural MRI. We used linear mixed-effects models with global cognition and cortical thickness as dependent variables to investigate determinants of cognitive resilience and brain resilience, respectively. Models assessed whether age, sex, years of education, APOE-ε4 status, intracranial volume (and cortical thickness for cognitive resilience models) modified the association of tau pathology with cognitive decline or cortical thinning. We found that the association between higher baseline tau-PET levels (quantified in a temporal meta-region of interest) and rate of cognitive decline (measured with repeated Mini-Mental State Examination) was adversely modified by older age (Stβinteraction = −0.062, P = 0.032), higher education level (Stβinteraction = −0.072, P = 0.011) and higher intracranial volume (Stβinteraction = −0.07, P = 0.016). Younger age, higher education and greater cortical thickness were associated with better cognitive performance at baseline. Greater cortical thickness was furthermore associated with slower cognitive decline independent of tau burden. Higher education also modified the negative impact of tau-PET on cortical thinning, while older age was associated with higher baseline cortical thickness and slower rate of cortical thinning independent of tau. Our analyses revealed no (cross-sectional or longitudinal) associations for sex and APOE-ε4 status on cognition and cortical thickness. In this longitudinal study of clinically impaired individuals with underlying Alzheimer’s disease neuropathological changes, we identified education as the most robust determinant of both cognitive and brain resilience against tau pathology. The observed interaction with tau burden on cognitive decline suggests that education may be protective against cognitive decline and brain atrophy at lower levels of tau pathology, with a potential depletion of resilience resources with advancing pathology. Finally, we did not find major contributions of sex to brain nor cognitive resilience, suggesting that previous links between sex and resilience might be mainly driven by cross-sectional differences.
    Materialart: Online-Ressource
    ISSN: 0006-8950 , 1460-2156
    RVK:
    Sprache: Englisch
    Verlag: Oxford University Press (OUP)
    Publikationsdatum: 2023
    ZDB Id: 1474117-9
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 2
    In: Brain, Oxford University Press (OUP), ( 2023-06-07)
    Kurzfassung: A clinical diagnosis of Alzheimer’s disease dementia (ADD) encompasses considerable pathological and clinical heterogeneity. While Alzheimer’s disease patients typically show a characteristic temporo-parietal pattern of glucose hypometabolism on 18F-fluorodeoxyglucose (FDG)-PET imaging, previous studies have identified a subset of patients showing a distinct posterior-occipital hypometabolism pattern associated with Lewy body pathology. Here, we aimed to improve the understanding of the clinical relevance of these posterior-occipital FDG-PET patterns in patients with Alzheimer’s disease-like amnestic presentations. Our study included 1214 patients with clinical diagnoses of ADD (n = 305) or amnestic mild cognitive impairment (aMCI, n = 909) from the Alzheimer’s Disease Neuroimaging Initiative, who had FDG-PET scans available. Individual FDG-PET scans were classified as being suggestive of Alzheimer’s (AD-like) or Lewy body (LB-like) pathology by using a logistic regression classifier trained on a separate set of patients with autopsy-confirmed Alzheimer’s disease or Lewy body pathology. AD- and LB-like subgroups were compared on amyloid-β and tau-PET, domain-specific cognitive profiles (memory versus executive function performance), as well as the presence of hallucinations and their evolution over follow-up (≈6 years for aMCI, ≈3 years for ADD). Around 12% of the aMCI and ADD patients were classified as LB-like. For both aMCI and ADD patients, the LB-like group showed significantly lower regional tau-PET burden than the AD-like subgroup, but amyloid-β load was only significantly lower in the aMCI LB-like subgroup. LB- and AD-like subgroups did not significantly differ in global cognition (aMCI: d = 0.15, P = 0.16; ADD: d = 0.02, P = 0.90), but LB-like patients exhibited a more dysexecutive cognitive profile relative to the memory deficit (aMCI: d = 0.35, P = 0.01; ADD: d = 0.85 P & lt; 0.001), and had a significantly higher risk of developing hallucinations over follow-up [aMCI: hazard ratio = 1.8, 95% confidence interval = (1.29, 3.04), P = 0.02; ADD: hazard ratio = 2.2, 95% confidence interval = (1.53, 4.06) P = 0.01]. In summary, a sizeable group of clinically diagnosed ADD and aMCI patients exhibit posterior-occipital FDG-PET patterns typically associated with Lewy body pathology, and these also show less abnormal Alzheimer’s disease biomarkers as well as specific clinical features typically associated with dementia with Lewy bodies.
    Materialart: Online-Ressource
    ISSN: 0006-8950 , 1460-2156
    RVK:
    Sprache: Englisch
    Verlag: Oxford University Press (OUP)
    Publikationsdatum: 2023
    ZDB Id: 1474117-9
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 3
    In: Sleep, Oxford University Press (OUP), Vol. 45, No. 3 ( 2022-03-14)
    Kurzfassung: Astronauts are required to maintain optimal neurobehavioral functioning despite chronic exposure to the stressors and challenges of spaceflight. Sleep of adequate quality and duration is fundamental to neurobehavioral functioning, however astronauts commonly experience short sleep durations in spaceflight ( & lt;6 h). As humans embark on long-duration space exploration missions, there is an outstanding need to identify the consequences of sleep deficiency in spaceflight on neurobehavioral functions. Therefore, we conducted a longitudinal study that examined the sleep-wake behaviors, neurobehavioral functions, and ratings of stress and workload of N = 24 astronauts before, during, and after 6-month missions aboard the International Space Station (ISS). The computerized, Reaction SelfTest (RST), gathered astronaut report of sleep–wake behaviors, stress, workload, and somatic behavioral states; the RST also objectively assessed vigilant attention (i.e. Psychomotor Vigilance Test-Brief). Data collection began 180 days before launch, continued every 4 days in-flight aboard the ISS, and up to 90 days post-landing, which produced N = 2,856 RSTs. Consistent with previous ISS studies, astronauts reported sleeping ~6.5 h in-flight. The adverse consequences of short sleep were observed across neurobehavioral functions, where sleep durations  & lt;6 h were associated with significant reductions in psychomotor response speed, elevated stress, and higher workload. Sleep durations  & lt;5 h were associated with elevated negative somatic behavioral states. Furthermore, longer sleep durations had beneficial effects on astronaut neurobehavioral functions. Taken together, our findings highlight the importance of sleep for the maintenance of neurobehavioral functioning and as with humans on Earth, astronauts would likely benefit from interventions that promote sleep duration and quality.
    Materialart: Online-Ressource
    ISSN: 0161-8105 , 1550-9109
    Sprache: Englisch
    Verlag: Oxford University Press (OUP)
    Publikationsdatum: 2022
    ZDB Id: 2056761-3
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 4
    Online-Ressource
    Online-Ressource
    Oxford University Press (OUP) ; 2014
    In:  Monthly Notices of the Royal Astronomical Society Vol. 445, No. 3 ( 2014-12-11), p. 2677-2697
    In: Monthly Notices of the Royal Astronomical Society, Oxford University Press (OUP), Vol. 445, No. 3 ( 2014-12-11), p. 2677-2697
    Materialart: Online-Ressource
    ISSN: 1365-2966 , 0035-8711
    Sprache: Englisch
    Verlag: Oxford University Press (OUP)
    Publikationsdatum: 2014
    ZDB Id: 2016084-7
    SSG: 16,12
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 5
    In: Clinical Infectious Diseases, Oxford University Press (OUP), Vol. 70, No. 8 ( 2020-04-10), p. 1643-1651
    Kurzfassung: Shiga toxin–producing Escherichia coli (STEC) infections are leading causes of pediatric acute renal failure. Identifying hemolytic uremic syndrome (HUS) risk factors is needed to guide care. Methods We conducted a multicenter, historical cohort study to identify features associated with development of HUS (primary outcome) and need for renal replacement therapy (RRT) (secondary outcome) in STEC-infected children without HUS at initial presentation. Children aged & lt;18 years who submitted STEC-positive specimens between January 2011 and December 2015 at a participating study institution were eligible. Results Of 927 STEC-infected children, 41 (4.4%) had HUS at presentation; of the remaining 886, 126 (14.2%) developed HUS. Predictors (all shown as odds ratio [OR] with 95% confidence interval [CI] ) of HUS included younger age (0.77 [.69–.85] per year), leukocyte count ≥13.0 × 103/μL (2.54 [1.42–4.54] ), higher hematocrit (1.83 [1.21–2.77] per 5% increase) and serum creatinine (10.82 [1.49–78.69] per 1 mg/dL increase), platelet count & lt;250 × 103/μL (1.92 [1.02–3.60]), lower serum sodium (1.12 [1.02–1.23 per 1 mmol/L decrease), and intravenous fluid administration initiated ≥4 days following diarrhea onset (2.50 [1.14–5.46] ). A longer interval from diarrhea onset to index visit was associated with reduced HUS risk (OR, 0.70 [95% CI, .54–.90]). RRT predictors (all shown as OR [95% CI] ) included female sex (2.27 [1.14–4.50]), younger age (0.83 [.74–.92] per year), lower serum sodium (1.15 [1.04–1.27] per mmol/L decrease), higher leukocyte count ≥13.0 × 103/μL (2.35 [1.17–4.72] ) and creatinine (7.75 [1.20–50.16] per 1 mg/dL increase) concentrations, and initial intravenous fluid administration ≥4 days following diarrhea onset (2.71 [1.18–6.21] ). Conclusions The complex nature of STEC infection renders predicting its course a challenge. Risk factors we identified highlight the importance of avoiding dehydration and performing close clinical and laboratory monitoring.
    Materialart: Online-Ressource
    ISSN: 1058-4838 , 1537-6591
    RVK:
    Sprache: Englisch
    Verlag: Oxford University Press (OUP)
    Publikationsdatum: 2020
    ZDB Id: 2002229-3
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 6
    In: Open Forum Infectious Diseases, Oxford University Press (OUP)
    Kurzfassung: Keeping abreast of the antimicrobial stewardship-related articles published each year is challenging. The Southeastern Research Group Endeavor (SERGE-45) identified antimicrobial stewardship-related, peer-reviewed literature that detailed an actionable intervention during 2022. The top 13 publications were selected using a modified Delphi technique. These manuscripts were reviewed to highlight actionable interventions used by antimicrobial stewardship programs to capture potentially effective strategies for local implementation.
    Materialart: Online-Ressource
    ISSN: 2328-8957
    Sprache: Englisch
    Verlag: Oxford University Press (OUP)
    Publikationsdatum: 2024
    ZDB Id: 2757767-3
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 7
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 5, No. 11 ( 2018-11-01)
    Kurzfassung: Multidrug-resistant Pseudomonas aeruginosa infections remain common in hospitals worldwide. We investigated the outcomes associated with the use of ceftolozane-tazobactam for the treatment of these infections. Methods Data were collected retrospectively from 20 hospitals across the United States about adults who received ceftolozane-tazobactam for the treatment of multidrug-resistant P aeruginosa infections of any source for at least 24 hours. The primary outcome was a composite of 30-day and inpatient mortality, and secondary outcomes were clinical success and microbiological cure. Multivariable regression analysis was conducted to determine factors associated with outcomes. Results Two-hundred five patients were included in the study. Severe illness and high degrees of comorbidity were common, with median Acute Physiology and Chronic Health Evaluation (APACHE) II scores of 19 (interquartile range [IQR], 11–24) and median Charlson Comorbidity Indexes of 4 (IQR, 3–6). Delayed initiation of ceftolozane-tazobactam was common with therapy started a median of 9 days after culture collection. Fifty-nine percent of patients had pneumonia. On susceptibility testing, 125 of 139 (89.9%) isolates were susceptible to ceftolozane-tazobactam. Mortality occurred in 39 patients (19%); clinical success and microbiological cure were 151 (73.7%) and 145 (70.7%), respectively. On multivariable regression analysis, starting ceftolozane-tazobactam within 4 days of culture collection was associated with survival (adjusted odds ratio [OR] , 5.55; 95% confidence interval [CI], 2.14–14.40), clinical success (adjusted OR, 2.93; 95% CI, 1.40–6.10), and microbiological cure (adjusted OR, 2.59; 95% CI, 1.24–5.38). Conclusions Ceftolozane-tazobactam appeared to be effective in the treatment of multidrug-resistant P aeruginosa infections, particularly when initiated early after the onset of infection.
    Materialart: Online-Ressource
    ISSN: 2328-8957
    Sprache: Englisch
    Verlag: Oxford University Press (OUP)
    Publikationsdatum: 2018
    ZDB Id: 2757767-3
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 8
    Online-Ressource
    Online-Ressource
    Oxford University Press (OUP) ; 2021
    In:  American Journal of Health-System Pharmacy Vol. 78, No. 14 ( 2021-07-09), p. 1270-1272
    In: American Journal of Health-System Pharmacy, Oxford University Press (OUP), Vol. 78, No. 14 ( 2021-07-09), p. 1270-1272
    Materialart: Online-Ressource
    ISSN: 1079-2082 , 1535-2900
    Sprache: Englisch
    Verlag: Oxford University Press (OUP)
    Publikationsdatum: 2021
    SSG: 15,3
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 9
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 8, No. 3 ( 2021-03-01)
    Kurzfassung: Real-world data assessing outcomes of immunocompromised patients treated with ceftolozane/tazobactam (C/T) are limited. This study evaluated treatment and clinical outcomes of immunocompromised patients receiving C/T for multidrug-resistant (MDR) Pseudomonas aeruginosa. Methods This was a 14-center retrospective cohort study of adult immunocompromised inpatients treated for ≥24 hours with C/T for MDR P. aeruginosa infections. Patients were defined as immunocompromised if they had a history of previous solid organ transplant (SOT), disease that increased susceptibility to infection, or received immunosuppressive therapies. The primary outcomes were all-cause 30-day mortality and clinical cure. Results Sixty-nine patients were included; 84% received immunosuppressive agents, 68% had a history of SOT, and 29% had diseases increasing susceptibility to infection. The mean patient age was 57 ± 14 years, and the median (interquartile range) patient Acute Physiology and Chronic Health Evaluation II and Charlson Comorbidity Index scores were 18 (13) and 5 (4), respectively, with 46% receiving intensive care unit care at C/T initiation. The most frequent infection sources were respiratory (56%) and wound (11%). All-cause 30-day mortality was 19% (n = 13), with clinical cure achieved in 47 (68%) patients. Clinical cure was numerically higher (75% vs 30%) in pneumonia patients who received 3-g pneumonia regimens vs 1.5-g regimens. Conclusions Of 69 immunocompromised patients treated with C/T for MDR P. aeruginosa, clinical cure was achieved in 68% and mortality was 19%, consistent with other reports on a cross-section of patient populations. C/T represents a promising agent for treatment of P. aeruginosa resistant to traditional antipseudomonal agents in this high-risk population.
    Materialart: Online-Ressource
    ISSN: 2328-8957
    Sprache: Englisch
    Verlag: Oxford University Press (OUP)
    Publikationsdatum: 2021
    ZDB Id: 2757767-3
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 10
    Online-Ressource
    Online-Ressource
    Oxford University Press (OUP) ; 2019
    In:  Open Forum Infectious Diseases Vol. 6, No. Supplement_2 ( 2019-10-23), p. S351-S351
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 6, No. Supplement_2 ( 2019-10-23), p. S351-S351
    Kurzfassung: Antimicrobial stewardship programs (ASP) play an important role in the assessment of patients with a reported history of penicillin allergy. Full-time pharmacists performing antimicrobial stewardship face many time barriers and limited resources to interviewing and investigating self-reported allergies. Pharmacy students on Advanced Pharmacy Practice Experience (APPE) rotations during their fourth year can potentially play an important role in this evaluation if properly trained, but data are limited. This study evaluated APPE student interventions on hospital inpatients self-reporting a penicillin allergy. Methods This quasi-experimental study assessed patients with a self-reported penicillin allergy who were interviewed by APPE students from October 2018 through March 2019. Students on a 5-week infectious diseases rotation were trained in allergy assessment and interview skills by their preceptor and given a daily list of all inpatients with a self-reported penicillin allergy. After reviewing patients with the preceptor, the electronic health record was updated with specifics of the allergy, including the range, reaction, and any β-lactams tolerated since. Interventions included penicillin re-challenge, graded challenge, penicillin skin testing, desensitization, or removal or the allergy. The primary outcome was interventions attributed to APPE student patient interviews. Results A total of 12 APPE students participated in the study. Reported reactions ranged from mild allergies (itching, rash) or adverse reactions (nausea, vomiting) to intermediate or severe allergies (hives, anaphylaxis). For the primary outcome there were 162 interventions performed, with 154 verbal, 2 re-challenges, and 6 skin tests. For the verbal interventions, 95 had their allergy updated, 34 removed, and 33 confirmed. None of the 8 patients who were skin tested or re-challenged had a subsequent reaction. Conclusion Pharmacy students can expand ASP allergy reconciliation services for patients with penicillin allergies in settings with limited resources. After proper training, students were effective in multiple aspects of allergy reconciliation with a significant number able to have their penicillin allergy removed. Disclosures All authors: No reported disclosures.
    Materialart: Online-Ressource
    ISSN: 2328-8957
    Sprache: Englisch
    Verlag: Oxford University Press (OUP)
    Publikationsdatum: 2019
    ZDB Id: 2757767-3
    Standort Signatur Einschränkungen Verfügbarkeit
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