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  • Oxford University Press (OUP)  (13)
  • 1
    Online Resource
    Online Resource
    Neurological manifestations of COVID-19 in adults and children
    Oxford University Press (OUP) ; 2023
    In:  Brain Vol. 146, No. 4 ( 2023-04-19), p. 1648-1661
    Details
    In: Brain, Oxford University Press (OUP), Vol. 146, No. 4 ( 2023-04-19), p. 1648-1661
    Abstract: Different neurological manifestations of coronavirus disease 2019 (COVID-19) in adults and children and their impact have not been well characterized. We aimed to determine the prevalence of neurological manifestations and in-hospital complications among hospitalized COVID-19 patients and ascertain differences between adults and children. We conducted a prospective multicentre observational study using the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) cohort across 1507 sites worldwide from 30 January 2020 to 25 May 2021. Analyses of neurological manifestations and neurological complications considered unadjusted prevalence estimates for predefined patient subgroups, and adjusted estimates as a function of patient age and time of hospitalization using generalized linear models. Overall, 161 239 patients (158 267 adults; 2972 children) hospitalized with COVID-19 and assessed for neurological manifestations and complications were included. In adults and children, the most frequent neurological manifestations at admission were fatigue (adults: 37.4%; children: 20.4%), altered consciousness (20.9%; 6.8%), myalgia (16.9%; 7.6%), dysgeusia (7.4%; 1.9%), anosmia (6.0%; 2.2%) and seizure (1.1%; 5.2%). In adults, the most frequent in-hospital neurological complications were stroke (1.5%), seizure (1%) and CNS infection (0.2%). Each occurred more frequently in intensive care unit (ICU) than in non-ICU patients. In children, seizure was the only neurological complication to occur more frequently in ICU versus non-ICU (7.1% versus 2.3%, P & lt; 0.001). Stroke prevalence increased with increasing age, while CNS infection and seizure steadily decreased with age. There was a dramatic decrease in stroke over time during the pandemic. Hypertension, chronic neurological disease and the use of extracorporeal membrane oxygenation were associated with increased risk of stroke. Altered consciousness was associated with CNS infection, seizure and stroke. All in-hospital neurological complications were associated with increased odds of death. The likelihood of death rose with increasing age, especially after 25 years of age. In conclusion, adults and children have different neurological manifestations and in-hospital complications associated with COVID-19. Stroke risk increased with increasing age, while CNS infection and seizure risk decreased with age.
    Type of Medium: Online Resource
    ISSN: 0006-8950 , 1460-2156
    URL: Article
    DOI: 10.1093/brain/awac332
    RVK:
    XA 10000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 1474117-9
    SSG: 12
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  • 2
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    Characteristics and outcomes of an international cohort of 600 000 hospitalized patients with COVID-19
    Oxford University Press (OUP) ; 2023
    In:  International Journal of Epidemiology Vol. 52, No. 2 ( 2023-04-19), p. 355-376
    Details
    In: International Journal of Epidemiology, Oxford University Press (OUP), Vol. 52, No. 2 ( 2023-04-19), p. 355-376
    Abstract: We describe demographic features, treatments and clinical outcomes in the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) COVID-19 cohort, one of the world's largest international, standardized data sets concerning hospitalized patients. Methods The data set analysed includes COVID-19 patients hospitalized between January 2020 and January 2022 in 52 countries. We investigated how symptoms on admission, co-morbidities, risk factors and treatments varied by age, sex and other characteristics. We used Cox regression models to investigate associations between demographics, symptoms, co-morbidities and other factors with risk of death, admission to an intensive care unit (ICU) and invasive mechanical ventilation (IMV). Results Data were available for 689 572 patients with laboratory-confirmed (91.1%) or clinically diagnosed (8.9%) SARS-CoV-2 infection from 52 countries. Age [adjusted hazard ratio per 10 years 1.49 (95% CI 1.48, 1.49)] and male sex [1.23 (1.21, 1.24)] were associated with a higher risk of death. Rates of admission to an ICU and use of IMV increased with age up to age 60 years then dropped. Symptoms, co-morbidities and treatments varied by age and had varied associations with clinical outcomes. The case-fatality ratio varied by country partly due to differences in the clinical characteristics of recruited patients and was on average 21.5%. Conclusions Age was the strongest determinant of risk of death, with a ∼30-fold difference between the oldest and youngest groups; each of the co-morbidities included was associated with up to an almost 2-fold increase in risk. Smoking and obesity were also associated with a higher risk of death. The size of our international database and the standardized data collection method make this study a comprehensive international description of COVID-19 clinical features. Our findings may inform strategies that involve prioritization of patients hospitalized with COVID-19 who have a higher risk of death.
    Type of Medium: Online Resource
    ISSN: 0300-5771 , 1464-3685
    URL: Article
    DOI: 10.1093/ije/dyad012
    RVK:
    XF 4100
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 1494592-7
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  • 3
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    New data and an old puzzle: the negative association between schizophrenia and rheumatoid arthritis
    Oxford University Press (OUP) ; 2015
    In:  International Journal of Epidemiology Vol. 44, No. 5 ( 2015-10), p. 1706-1721
    Details
    In: International Journal of Epidemiology, Oxford University Press (OUP), Vol. 44, No. 5 ( 2015-10), p. 1706-1721
    Type of Medium: Online Resource
    ISSN: 0300-5771 , 1464-3685
    URL: Article
    DOI: 10.1093/ije/dyv136
    RVK:
    XF 4100
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2015
    detail.hit.zdb_id: 1494592-7
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  • 4
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    CTNI-04. RECURRENT GLIOBLASTOMA LONG-TERM SURVIVORS TREATED WITH CUSP9v3
    Oxford University Press (OUP) ; 2021
    In:  Neuro-Oncology Vol. 23, No. Supplement_6 ( 2021-11-12), p. vi59-vi59
    Details
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 23, No. Supplement_6 ( 2021-11-12), p. vi59-vi59
    Abstract: CUSP9v3 is a new treatment regimen for glioblastoma. It consists of continuous daily use of 9 drugs repurposed from general medicine. Their primary non-oncology uses are given in parentheses: aprepitant (nausea), auranofin (rheumatoid arthritis), celecoxib (pain), captopril (hypertension), disulfiram (alcohol abuse), itraconazole (fungal infection), minocycline (bacterial infection), ritonavir (viral infection) and sertraline (depression). All drugs have preclinical or clinical data indicating that they can retard glioblastoma growth, as reviewed in the published background papers. In CUSP9v3 all 9 medicines are given daily with added metronomic, low-dose (20 mg/m2 BSA twice daily) temozolomide. After 3 years of daily, uninterrupted use of CUSP9v3, of an initial cohort of 10 recurrent glioblastoma patients, as of May 2021, 3 are alive, functioning well, progression-free at 44, 44, and 57 months after recurrence and CUSP9v3 started. We report now that there were no unexpected toxicities from this combination of 10 daily drugs, although all patients required dose reduction of one or more of the drugs. CUSP9v3 was reasonably well-tolerated. Ritonavir, temozolomide, captopril and itraconazole were the drugs most frequently requiring dose reduction or pausing. The most common adverse events were nausea, headache, fatigue, diarrhea and ataxia. There were no treatment-related deaths. In the 3 long-term survivors, the median neutrophil-to-lymphocyte ratio decreased from 2.5 to 1.5 during CUSP9v3 treatment. In the group of the 3 shortest-term survivors that ratio increased from 4.7 to 14.3. CUSP9v3 follows the injunction of Palmer et al. that cancer therapy can be constructed using drug combinations that are independently effective, with non-overlapping mechanisms of action, and non-overlapping resistance pathways. We interpret the data accrued over the last few decades on the ever-shifting spatial and temporal growth drives active at any given moment in glioblastoma as requiring a complex pharmacological approach like CUSP9v3.
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    URL: Article
    DOI: 10.1093/neuonc/noab196.229
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 2094060-9
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  • 5
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    A phase Ib/IIa trial of 9 repurposed drugs combined with temozolomide for the treatment of recurrent glioblastoma: CUSP9v3
    Oxford University Press (OUP) ; 2021
    In:  Neuro-Oncology Advances Vol. 3, No. 1 ( 2021-01-01)
    Details
    In: Neuro-Oncology Advances, Oxford University Press (OUP), Vol. 3, No. 1 ( 2021-01-01)
    Abstract: The dismal prognosis of glioblastoma (GBM) may be related to the ability of GBM cells to develop mechanisms of treatment resistance. We designed a protocol called Coordinated Undermining of Survival Paths combining 9 repurposed non-oncological drugs with metronomic temozolomide—version 3—(CUSP9v3) to address this issue. The aim of this phase Ib/IIa trial was to assess the safety of CUSP9v3. Methods Ten adults with histologically confirmed GBM and recurrent or progressive disease were included. Treatment consisted of aprepitant, auranofin, celecoxib, captopril, disulfiram, itraconazole, minocycline, ritonavir, and sertraline added to metronomic low-dose temozolomide. Treatment was continued until toxicity or progression. Primary endpoint was dose-limiting toxicity defined as either any unmanageable grade 3–4 toxicity or inability to receive at least 7 of the 10 drugs at ≥ 50% of the per-protocol doses at the end of the second treatment cycle. Results One patient was not evaluable for the primary endpoint (safety). All 9 evaluable patients met the primary endpoint. Ritonavir, temozolomide, captopril, and itraconazole were the drugs most frequently requiring dose modification or pausing. The most common adverse events were nausea, headache, fatigue, diarrhea, and ataxia. Progression-free survival at 12 months was 50%. Conclusions CUSP9v3 can be safely administered in patients with recurrent GBM under careful monitoring. A randomized phase II trial is in preparation to assess the efficacy of the CUSP9v3 regimen in GBM.
    Type of Medium: Online Resource
    ISSN: 2632-2498
    URL: Article
    DOI: 10.1093/noajnl/vdab075
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 3009682-0
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  • 6
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    Maximum norm error bounds for the full discretization of nonautonomous wave equations
    Oxford University Press (OUP) ; 2023
    In:  IMA Journal of Numerical Analysis ( 2023-09-09)
    Details
    In: IMA Journal of Numerical Analysis, Oxford University Press (OUP), ( 2023-09-09)
    Abstract: In the present paper, we consider a specific class of nonautonomous wave equations on a smooth, bounded domain and their discretization in space by isoparametric finite elements and in time by the implicit Euler method. Building upon the work of Baker and Dougalis (1980, On the ${L}^{\infty }$-convergence of Galerkin approximations for second-order hyperbolic equations. Math. Comp., 34, 401–424), we prove optimal error bounds in the $W^{1,\infty } \times L^\infty $-norm for the semidiscretization in space and the full discretization. The key tool is the gain of integrability coming from the inverse of the discretized differential operator. For this, we have to pay with (discrete) time derivatives on the error in the $H^{1} \times L^2$-norm, which are reduced to estimates of the differentiated initial errors. To confirm our theoretical findings, we also present numerical experiments.
    Type of Medium: Online Resource
    ISSN: 0272-4979 , 1464-3642
    URL: Article
    DOI: 10.1093/imanum/drad065
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 796681-7
    detail.hit.zdb_id: 1466710-1
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  • 7
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    Factors influencing the efficacy of nutritional interventions on muscle mass in older adults: a systematic review and meta-analysis
    Oxford University Press (OUP) ; 2021
    In:  Nutrition Reviews Vol. 79, No. 3 ( 2021-02-11), p. 315-330
    Details
    In: Nutrition Reviews, Oxford University Press (OUP), Vol. 79, No. 3 ( 2021-02-11), p. 315-330
    Abstract: Nutritional interventions stimulate muscle protein synthesis in older adults. To optimize muscle mass preservation and gains, several factors, including type, dose, frequency, timing, duration, and adherence have to be considered. Objective This systematic review and meta-analysis aimed to summarize these factors influencing the efficacy of nutritional interventions on muscle mass in older adults. Data Sources A systematic search was performed using the electronic databases MEDLINE, Embase, CINAHL, Cochrane Central Register of Controlled Trials, and SPORTDiscus from inception date to November 22, 2017, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Inclusion criteria included randomized controlled trials, mean or median age ≥65 years, and reporting muscle mass at baseline and postintervention. Exclusion criteria included genetically inherited diseases, anabolic drugs or hormone therapies, neuromuscular electrical stimulation, chronic kidney disease, kidney failure, neuromuscular disorders, and cancer. Data Extraction Extracted data included study characteristics (ie, population, sample size, age, sex), muscle mass measurements (ie, method, measure, unit), effect of the intervention vs the control group, and nutritional intervention factors (ie, type, composition, dose, duration, frequency, timing, and adherence). Data Analysis Standardized mean differences and 95%CIs were calculated from baseline to postintervention. A meta-analysis was performed using a random-effects model and grouped by the type of intervention. Conclusions Twenty-nine studies were included, encompassing 2255 participants (mean age, 78.1 years; SD, 2.22). Amino acids, creatine, β-hydroxy-β-methylbutyrate, and protein with amino acids supplementation significantly improved muscle mass. No effect was found for protein supplementation alone, protein and other components, and polyunsaturated fatty acids. High interstudy variability was observed regarding the dose, duration, and frequency, coupled with inconsistency in reporting timing and adherence. Overall, several nutritional interventions could be effective to improve muscle mass measures in older adults. Because of the substantial variability of the intervention factors among studies, the optimum profile is yet to be established. Systematic Review Registration PROSPERO registration no. CRD42018111306.
    Type of Medium: Online Resource
    ISSN: 0029-6643 , 1753-4887
    URL: Article
    DOI: 10.1093/nutrit/nuaa064
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 2066844-2
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  • 8
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    Modular hierarchical and power-law small-world networks bear structural optima for minimal first passage times and cover time
    Oxford University Press (OUP) ; 2019
    In:  Journal of Complex Networks Vol. 7, No. 6 ( 2019-12-01), p. 865-895
    Details
    In: Journal of Complex Networks, Oxford University Press (OUP), Vol. 7, No. 6 ( 2019-12-01), p. 865-895
    Abstract: Networks that are organized as a hierarchy of modules have been the subject of much research, mainly focusing on algorithms that can extract this community structure from data. The question of why modular hierarchical (MH) organizations are so ubiquitous in nature, however, has received less attention. One hypothesis is that MH topologies may provide an optimal structure for certain dynamical processes. We revisit a MH network model that interpolates, using a single parameter, between two known network topologies: from strong hierarchical modularity to an Erdős–Rényi random connectivity structure. We show that this model displays a similar small-world effect as the Kleinberg model, where the connection probability between nodes decays algebraically with distance. We find that there is an optimal structure, in both models, for which the pair-averaged first passage time (FPT) and mean cover time of a discrete-time random walk are minimal, and provide a heuristic explanation for this effect. Finally, we show that analytic predictions for the pair-averaged FPT based on an effective medium approximation fail to reproduce these minima, which implies that their presence is due to a network structure effect.
    Type of Medium: Online Resource
    ISSN: 2051-1329
    URL: Article
    DOI: 10.1093/comnet/cnz010
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
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  • 9
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    Human cerebrospinal fluid monoclonal N -methyl-D-aspartate receptor autoantibodies are sufficient for encephalitis pathogenesis
    Oxford University Press (OUP) ; 2016
    In:  Brain Vol. 139, No. 10 ( 2016-10), p. 2641-2652
    Details
    In: Brain, Oxford University Press (OUP), Vol. 139, No. 10 ( 2016-10), p. 2641-2652
    Type of Medium: Online Resource
    ISSN: 0006-8950 , 1460-2156
    URL: Article
    DOI: 10.1093/brain/aww208
    RVK:
    XA 10000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2016
    detail.hit.zdb_id: 1474117-9
    SSG: 12
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  • 10
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    Modeling the impact of the Omicron infection wave in Germany
    Oxford University Press (OUP) ; 2023
    In:  Biology Methods and Protocols Vol. 8, No. 1 ( 2023-01-10)
    Details
    In: Biology Methods and Protocols, Oxford University Press (OUP), Vol. 8, No. 1 ( 2023-01-10)
    Abstract: In November 2021, the first infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant of concern (VOC) B.1.1.529 (‘Omicron’) was reported in Germany, alongside global reports of reduced vaccine efficacy (VE) against infections with this variant. The potential threat posed by its rapid spread in Germany was, at the time, difficult to predict. We developed a variant-dependent population-averaged susceptible-exposed-infected-recovered infectious-disease model that included information about variant-specific and waning VEs based on empirical data available at the time. Compared to other approaches, our method aimed for minimal structural and computational complexity and therefore enabled us to respond to changes in the situation in a more agile manner while still being able to analyze the potential influence of (non-)pharmaceutical interventions (NPIs) on the emerging crisis. Thus, the model allowed us to estimate potential courses of upcoming infection waves in Germany, focusing on the corresponding burden on intensive care units (ICUs), the efficacy of contact reduction strategies, and the success of the booster vaccine rollout campaign. We expected a large cumulative number of infections with the VOC Omicron in Germany with ICU occupancy likely remaining below capacity, nevertheless, even without additional NPIs. The projected figures were in line with the actual Omicron waves that were subsequently observed in Germany with respective peaks occurring in mid-February and mid-March. Most surprisingly, our model showed that early, strict, and short contact reductions could have led to a strong ‘rebound’ effect with high incidences after the end of the respective NPIs, despite a potentially successful booster campaign. The results presented here informed legislation in Germany. The methodology developed in this study might be used to estimate the impact of future waves of COVID-19 or other infectious diseases.
    Type of Medium: Online Resource
    ISSN: 2396-8923
    URL: Article
    DOI: 10.1093/biomethods/bpad005
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 2879161-7
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