Severe episodic viral wheeze in preschool children: High risk of asthma at age 5–10 years

In population studies, most children with episodic viral wheeze (EVW) become symptom free by 6 years. We studied the outcome of children with severe EVW, treated and followed up in hospital. We followed up 78 children <4 years, managed by paediatricians for severe EVW, to the age of 5–10 years. We recorded respiratory symptoms, spirometry and exhaled nitric oxide (FeNO). At follow-up, 42 children (54%) had current wheeze or dyspnoea, and 52 (67%) had current asthma. There was no significant difference between children with and without current asthma in FEV1 (p = 0.420), but FeNO was higher in children with current asthma (median (interquartile range) 14.5 (11.25–21.50) ppb) than in those without (12.0 (10.0–13.8) ppb, p = 0.020). Positive family history of asthma was the only factor associated with current asthma (odds ratio 8.77, 95% CI 2.88–26.69, p < 0.001). This remained significant after adjustment for duration of follow-up, gender and parental smoking. Conclusion. Severe EVW at preschool age has a high risk of asthma at age 5–10 years, and this is reinforced by a positive family history of asthma and to elevated FeNO levels

Safety and Efficacy of Extended Interval Dosing for Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer During the COVID-19 Pandemic

INTRODUCTION: Extended interval (EI) dosing for immune checkpoint inhibitor (ICI) mono- or consolidation therapy initiated due to the COVID-19 pandemic led to a significant reduction in ICI-related site visits for patients with stage III and IV non-small cell lung cancer (NSCLC). Here we report the safety and efficacy compared to standard dose (SD) schedules. METHOD: In this retrospective analysis patients who received ICI mono- or consolidation therapy, or adjuvant ICI therapy were assessed. Safety and efficacy of EI dosing with data of SD schedules were compared. RESULTS: One hundred seventeen patients received EI dosing for ICI and 88 patients SD. Patient characteristics were comparable. We observed 237 adverse events in the EI dosing cohort versus 118 in the SD group (p = 0.02). Overall, there was no difference in the occurrence of grade ≥3 adverse events (EI dosing: 21/237 [8.9%]; SD group: 20/118 [17.0%], p = 0.42), except for the pembrolizumab EI dosing cohort. Of all patients who received an EI dosing schedule, however, only 8 (6.8%) were reduced to SD because of toxicity. In 5 (4.3%) patients ICI was permanently stopped because of severe toxicity compared to 11 (12.5%) discontinuations in the SD group. Short-term treatment interruption occurred with similar frequencies in both groups. PFS and OS were comparable in patients receiving pembrolizumab and in those receiving adjuvant durvalumab. Progression-free survival and OS were better in the EI dosing cohort of nivolumab. CONCLUSION: EI dosing for ICI did not lead to an increase of clinically relevant toxicities resulting in dose reduction and/or treatment discontinuation. Efficacy of EI dosing of pembrolizumab and durvalumab were comparable to SD. Based on our safety and efficacy data EI dosing for ICI seems a safe and effective strategy. MICRO ABSTRACT: Aim Retrospective analysis of the safety and efficacy of extended interval dosing (EI) ICI compared to standard dose (SD) schedules. Results 117 patients received EI dosing and 88 SD. In the EI dosing cohort was no increase in toxicity leading to dose reduction and/or discontinuation of treatment. Furthermore, efficacy of EI dosing of pembrolizumab and durvalumab were comparable to SD. Based on our safety and efficacy data EI dosing for ICI seem a safe and effective strategy and should be continued also beyond the COVID-19 pandemic

Жанрово-стильові модифікації прози Антона Крушельницького крізь виміри сецесії

Мета нашої статті - інтерпретація прози Антона Крушельницького як визначального представника сецесії через призму жанрово-стильових особливостей

Asymptotic expansions for the Laplace approximations for Itô functionals of Brownian rough paths

AbstractIn this paper, we establish asymptotic expansions for the Laplace approximations for Itô functionals of Brownian rough paths under the condition that the phase function has finitely many non-degenerate minima. Our main tool is the Banach space-valued rough path theory of T. Lyons. We use a large deviation principle and the stochastic Taylor expansion with respect to the topology of the space of geometric rough paths. This is a continuation of a series of papers by Inahama [Y. Inahama, Laplace's method for the laws of heat processes on loop spaces, J. Funct. Anal. 232 (2006) 148–194] and by Inahama and Kawabi [Y. Inahama, H. Kawabi, Large deviations for heat kernel measures on loop spaces via rough paths, J. London Math. Soc. 73 (3) (2006) 797–816], [Y. Inahama, H. Kawabi, On asymptotics of certain Banach space-valued Itô functionals of Brownian rough paths, in: Proceedings of the Abel Symposium 2005, Stochastic Analysis and Applications, A Symposium in Honor of Kiyosi Itô, Springer, Berlin, in press. Available at: http://www.abelprisen.no/no/abelprisen/deltagere_2005.html]

Эффективная система охлаждения квантоскопов

Разработана каскадная компрессорная система охлаждения, реализующая цикл Линде с многокомпонентными рабочими телами, ресурс работы которой составляет 30 тыс. часов

В. Липинський про бюрократію ("Листи до братів-хліборобів"): до проблеми визначення теоретичного підґрунтя поглядів

Розглянуто формування поглядів В. Липинського на бюрократію під впливом ідей Ж. Сореля, Р. Міхельса, К. Маркса, А. де Токвіля. Стверджено, що основу його поглядів становлять ідеї про бюрократію, запозичені у Ж. Сореля та Р. Міхельса. Підкреслено, що під час розгляду проблеми бюрократії вітчизняний мислитель не звертався до ідей М. Вебера.Deals with the formation of attitudes of Viacheslav Lypynsky on bureaucracy under the influence of Georges Sorel, Robert Michels, Karl Marx, Alexis de Tocqueville. It is alleged that his views were based on ideas of the bureaucracy borrowed from Georges Sorel and Robert Michels. Emphasizing that, in considering the problem of bureaucracy Ukrainian thinker did not approach the ideas of Max Weber

Early time course of major bleeding on antiplatelet therapy after TIA or ischemic stroke

Objective: To study the early time course of major bleeding and its subtypes in patients with cerebral ischemia on dual and single antiplatelet therapy. Methods: We performed a post hoc analysis on individual patient data from 6 randomized clinical trials (Clopidogrel Versus Aspirin in Patients at Risk of Ischaemic Events [CAPRIE], Second European Stroke Prevention Study [ESPS-2], Management of Atherothrombosis With Clopidogrel in High Risk Patients [MATCH], Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance [CHARISMA], European/Australasian Stroke Prevention in Reversible Ischaemia Trial [ESPRIT], and Prevention Regimen for Effectively Avoiding Second Strokes [PRoFESS]) including 45,195 patients with a TIA or noncardioembolic ischemic stroke. We studied incidence rates of bleeding per antiplatelet regimen stratified by time from randomization (≤30, 31–90, 91–180, 181–365, >365 days). We calculated incidence rates per trial and pooled estimates with random-effects meta-analysis. We performed Poisson regression to assess differences between time periods with adjustment for age and sex. Results: The incidence of major bleeding on aspirin plus clopidogrel and aspirin plus -dipyridamole was highest in the first 30 days, 5.8 and 4.9 per 100 person-years, respectively, and was significantly higher than at 31 to 90 days (rate ratio 1.98, 95% confidence interval 1.16–3.40 for aspirin plus clopidogrel; rate ratio 1.94, 95% confidence interval 1.24–3.03 for aspirin plus dipyridamole). Incidence rates on aspirin and clopidogrel monotherapy were 2.8 and 2.5 per 100 person-years, respectively, in the first 30 days, with no significant change over time. The time course was similar for gastrointestinal bleeds. There was no early excess of intracranial hemorrhage in patients on either dual or single antiplatelet therapy. Conclusion: Dual antiplatelet therapy is associated with high early risks of major and gastrointestinal bleeding that decline after the first month in trial cohorts

Validity of an enhanced EQ-5D-5L measure with an added cognitive dimension in patients with stroke

Objective: The 5-level EuroQoL (EQ-5D-5L) is a patient-reported outcome measure frequently used in stroke research. However, it does not assess the cognitive problems many patients with stroke experience. The aim of this article is to compare the content validity, internal consistency and discriminative ability of the EQ-5D-5L with and without an additional cognitive domain (EQ-5D-5L+C), administered three months post-stroke. Design: Cross-sectional study. Setting: Six general hospitals in the Netherlands. Subjects: In all, 360 individuals with stroke three months after the event. Interventions: Not applicable. Main measures: The modified Rankin Scale and EQ-5D-5L+C were administered in telephone interviews three months post-stroke. Results: A total of 360 patients with stroke were included. Mean age was 68.8 years (standard deviation (SD) = 11.7), 143 (40%) were female, 334 (93%) had had an ischemic stroke, 165 (46%) had a National Institutes of Health Stroke Scale (NIHSS) score ⩽ 4 at presentation and the Barthel Index was 17.2 (SD = 4) four days post-stroke. Cognitive problems were reported by 199 (55%) patients three months post-stroke. Internal consistencies of the EQ-5D-5L and EQ-5D-5L+C were 0.75 and 0.77, respectively. Adding a cognitive domain resulted in a decrease of the ceiling effect from 22% to 14%. Both EQ-5D-5L and EQ-5D-5L+C showed good discriminative ability, but differences between patients with different modified Rankin Scale scores and with/without reported decrease in health and daily activities were slightly larger with the EQ-5D-5L+C compared to the EQ-5D-5L. Conclusions: The EQ-5D-5L+C, which includes a cognitive domain that is highly significant for stroke patients, showed increased content validity and good discriminative ability, without losing internal consistency

Brain areas involved in spatial working memory

Spatial working memory entails the ability to keep spatial information active in working memory over a short period of time. To study the areas of the brain that are involved in spatial working memory, a group of stroke patients was tested with a spatial search task. Patients and healthy controls were asked to search through a number of boxes shown at different locations on a touch-sensitive computer screen in order to find a target object. In subsequent trials, new target objects were hidden in boxes that were previously empty. Within-search errors were made if a participant returned to an already searched box; between-search errors occurred if a participant returned to a box that was already known to contain a target item. The use of a strategy to remember the locations of the target objects was calculated as well. Damage to the right posterior parietal and right dorsolateral prefrontal cortex impaired the ability to keep spatial information [`]on-line', as was indicated by performance on the Corsi Block-Tapping task and the within-search errors. Moreover, patients with damage to the right posterior parietal cortex, the right dorsolateral prefrontal cortex and the hippocampal formation bilaterally made more between-search errors, indicating the importance of these areas in maintaining spatial information in working memory over an extended time period.http://www.sciencedirect.com/science/article/B6T0D-4HM7WH2-2/1/b6b13c7b404377bae2b8cf632eb61fe

В портфеле редакции

OBJECTIVE Our aim is to compare the effect of type 2 diabetes on recurrent major cardiovascular events (MCVE) for patients with symptomatic vascular disease at different locations. RESEARCH DESIGN AND METHODS A total of 6,841 patients from the single-center, prospective Second Manifestations of ARTerial disease (SMART) cohort study from Utrecht, the Netherlands, with clinically manifest vascular disease with (n = 1,155) and without (n = 5,686) type 2 diabetes were monitored between 1996 and 2013. The effect of type 2 diabetes on recurrent MCVE was analyzed with Cox proportional hazards models, stratified for disease location (cerebrovascular disease, peripheral artery disease, abdominal aortic aneurysm, coronary artery disease, or polyvascular disease, defined as >= 2 vascular locations). RESULTS Five-year risks for recurrent MCVE were 9% in cerebrovascular disease, 9% in peripheral artery disease, 20% in those with an abdominal aortic aneurysm, 7% in coronary artery disease, and 21% in polyvascular disease. Type 2 diabetes increased the risk of recurrent MCVE in coronary artery disease (hazard ratio [HR] 1.67; 95% CI 1.25-2.21) and seemed to increase the risk in cerebrovascular disease (HR 1.36; 95% CI 0.90-2.07), while being no risk factor in polyvascular disease (HR 1.12; 95% CI 0.83-1.50). Results for patients with peripheral artery disease (HR 1.42; 95% CI 0.79-2.56) or an abdominal aortic aneurysm (HR 0.93; 95% CI 0.23-3.68) were inconclusive. CONCLUSIONS Type 2 diabetes increased the risk of recurrent MCVE in patients with coronary artery disease, but there is no convincing evidence that it is a major risk factor for subsequent MCVE in all patients with symptomatic vascular disease