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

О распространении кольцевых гомеоморфизмов на границу

Samenvatting Koekkoek PS, Rutten GEHM, Van den Berg E, Kappelle LJ, Biessels GJ. Test Your Memory-test: een alternatief voor de MMSE. Huisarts Wet 2014;57(1):618-21. De Mini-Mental State Examination (MMSE) is de meest gebruikte screeningstest om een indruk over het cognitieve functioneren te krijgen. Deze test kost relatief veel tijd en kan niet door patiënt zelfstandig uitgevoerd worden. De Test Your Memory-test (TYM) is een potentieel alternatief. In dit onderzoek worden uitkomsten van de TYM en de MMSE vergeleken met een neuropsychologisch onderzoek (NPO) in een populatie die niet met klinisch relevante cognitieve stoornissen bekend was. Mensen zonder bekende cognitieve stoornissen, ondergingen een NPO inclusief MMSE en een TYM. De relatie tussen de TYM, de MMSE en een NPO werd onderzocht met correlatieanalyses, ROC-curves voor discriminatie tussen ‘normale’ cognitie en ‘lichte cognitieve tekorten’ (≥ 1 SD onder het gemiddelde), en bland-altmanplots. 86 mensen vulden de TYM in (gemiddelde leeftijd 69 jaar; 59% man). De correlatie met een volledig NPO was significant sterker voor de TYM dan de MMSE (r = 0,78 versus r = 0,55; Steiger’s Z = 2,66, p < 0,01). De oppervlakte onder de ROC-curve was 0,88 (TYM) versus 0,71 (MMSE). Bland-altmanplots laten zien dat de TYM beter overeenkomt met het NPO dan de MMSE. De TYM komt beter overeen met een NPO dan de MMSE en maakt een beter onderscheid tussen ‘lichte cognitieve tekorten’ en normaal cognitief functioneren. Hiermee is de TYM een veelbelovende test voor gebruik in de huisartsenpraktijk

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]