11 research outputs found
Therapeutic drug monitoring of small molecule kinase inhibitors in oncology in a real-world cohort study: does age matter?
No full textAIM: Pharmacokinetics of small molecule kinase inhibitors (KIs) used in cancer treatment may alter with increasing age, but results are conflicting. This study aims to compare exposure to KIs between older and younger patients (≥70 and <70 years) in clinical practice. METHODS: KI plasma concentrations of routinely treated patients were measured using validated assays. Calculated trough concentrations were compared in both age groups. For KIs with a clinically meaningful target concentration (erlotinib, imatinib, pazopanib, sunitinib and vemurafenib), influence of older age on target attainment was assessed. RESULTS: We analysed 616 samples from 454 patients (median age: 61; range 20-93 years), treated with dabrafenib (n = 105), erlotinib (n = 49), imatinib (n = 165), pazopanib (n = 63), sunitinib (n = 87), trametinib (n = 95) and vemurafenib (n = 52). Older age did not significantly influence exposure to erlotinib, imatinib, pazopanib, sunitinib, trametinib and vemurafenib. Elderly patients had significantly higher dabrafenib trough concentrations than younger patients (P = 0.02; 62 ng ml-1 (coefficient of variation [CV] 41%), vs. 53 ng ml-1 (CV 46%), respectively). For KIs with a predefined target concentration, 68% of older and 61% of younger patients reached target. CONCLUSIONS: In this real-world study, exposure to most included KIs was comparable in older and younger patients, except for dabrafenib, which showed higher exposure in older patients. In the absence of an absolute target for this KI, clinical relevance remains unclear. For all other included KIs, our data suggest no clinically relevant influence of older age on KI exposure
Accurate Measurements of the Skin Surface Area of the Healthy Auricle and Skin Deficiency in Microtia Patients
No full textBACKGROUND: The limited cranial skin covering auricular implants is an important yet underrated factor in auricular reconstruction for both reconstruction surgery and tissue engineering strategies. We report exact measurements on skin deficiency in microtia patients and propose an accessible preoperative method for these measurements. METHODS: Plaster ear models (n = 11; male:female = 2:1) of lobular-type microtia patients admitted to the University Medical Center Utrecht in The Netherlands were scanned using a micro-computed tomographic scanner or a cone-beam computed tomographic scanner. The resulting images were converted into mesh models from which the surface area could be calculated. RESULTS: The mean total skin area of an adult-size healthy ear was 47.3 cm(2), with 49.0 cm(2) in men and 44.3 cm(2) in women. Microtia ears averaged 14.5 cm(2), with 15.6 cm(2) in men and 12.6 cm(2) in women. The amount of skin deficiency was 25.4 cm(2), with 26.7 cm(2) in men and 23.1 cm(2) in women. CONCLUSIONS: This study proposes a novel method to provide quantitative data on the skin surface area of the healthy adult auricle and the amount of skin deficiency in microtia patients. We demonstrate that the microtia ear has less than 50% of skin available compared with healthy ears. Limited skin availability in microtia patients can lead to healing problems after auricular reconstruction and poses a significant challenge in the development of tissue-engineered cartilage implants. The results of this study could be used to evaluate outcomes and investigate new techniques with regard to tissue-engineered auricular constructs
Age-Associated Hematological Toxicity in Patients with Metastatic Castration-Resistant Prostate Cancer Treated with Docetaxel in Clinical Practice
No full textBackground: Older patients with metastatic castration-resistant prostate cancer (mCRPC) may be more prone to chemotherapy-induced hematological toxicity, but tailored docetaxel dosing guidelines in older patients are lacking because of conflicting data. Objective: This study aims to evaluate the impact of older age on the incidence of hematological toxicity in patients with mCRPC treated with docetaxel in daily clinical practice. Methods: This study included patients with mCRPC treated with docetaxel between January 2006 and January 2016 at the Netherlands Cancer Institute and Medical Center Slotervaart for whom dosing and hematological toxicity data were available from electronic patient records. We evaluated the impact of age on the incidence of grade 3 and 4 hematological toxicity. Results: In total, 175 patients treated with docetaxel were included in the analysis, with a median age of 67 years (range 47–86). Baseline hematological laboratory values were not age related. After the first treatment cycle, hematological toxicity occurred significantly more frequently in the oldest age quartile (25%, p = 0.02) than in the younger age quartiles (9%, 11%, and 7%, respectively, for age quartiles 1, 2, and 3). Conclusion: The risk of hematological toxicity was significantly higher in the oldest age quartile than in younger patients with mCRPC treated with docetaxel in daily clinical practice
Цифровизация, пандемия, экология языка, рынок информационных и образовательных услуг и библиотеки: курс на выживание и устойчивое развитие. Ежегодный доклад Шестого Международного профессионального форума «Крым–2021»
No full textAbstract: The author starts with two key topics, i. e. digitalization and COVID-19 pandemic that makes impact on every sphere of human life and activity worldwide. The digitalization explosive development to change information, educational and library infrastructure has been not equal to expectations due to the pandemic and turned out to be different. However, the pandemic has stimulated digitization systems, Open access and open science. The author considers stable interest to ward reading, and printed books especially, to be “adigital era paradox”. He also points to stabilizing market of printed and electronic books. The no-less important topic is language ecology, or ecology of language, which cannot be interpreted exclusively as the fight for languagepurity; the author provides several examples of borrowings (Anglicisms) in the Russian language, which is increasingly evident due to digitalization. The modern digitalization facilitates targeted transition toward “the libraries of the future”, drives mainstream trends and goals on this way. The library collections, premises and working conditions during the pandemic are characterized. The pandemic also has exacerbated the problem of copyright transformation in the digital era. The author provides examples of legislative solutions in copyright in several countries and characterizes the Russia’s trends in copyright transformation in the digital world. The author concludes that, in the conditions of expanding digitalization and sustainable development, the libraries find themselves in the avant-garde as they support and effectually implement many sustainable development goals within the nation.Аннотация: Прежде всего автор рассматривает две главные темы – цифровизация и пандемия COVID-19, обращая внимание на то, как пандемия повлияла на все сферы жизни и деятельности людей во всём мире. Ожидания от бурного развития цифровизации и её воздействия на информационную, образовательную и библиотечную инфраструктуру, столкнувшись с пандемией, не оправдались, в ернее, о казались и ными. В тоже в ремя пандемия я вилась с тимулом к более активному развитию систем оцифровки, Открытого доступа и Открытой науки. Одним из парадоксов «цифрового времени» назван устойчивый интерес к чтению, причём прежде всего печатных книг. Отмечена стабилизация рынка печатных и электронных книг. Автор обратился к ещё одной важной теме – к языковой экологии, или экологии языка, что не следует понимать как только борьбу за чистоту речи; на нескольких примерах рассмотрена проблема заимствований (англицизмов) в русском языке, которая становится всё более очевидной в связи с развитием цифровизации. Современная цифровизация содействует целенаправленному переходу к библиотеке будущего, обусловливает основные тенденции и задачи развития библиотек на этом пути. При этом обращено внимание на состояние библиотечных фондов, помещений библиотек и условий их работы в период пандемии. Вместе с тем пандемия обострила ещё одну проблему – трансформацию авторского права в цифровую эпоху. Приведены примеры решения отдельных вопросов законодательства в сфере авторского права в разных странах; рассмотрены российские тенденции преобразования авторского права в цифровом мире. В заключение автор подчёркивает, что сегодня – с позиций нарастающей цифровизации и целей устойчивого развития общества – библиотеки находятся на передовом фланге: они не только поддерживают, но и реально обеспечивают многие цели устойчивого развития государства
A 12-gene pharmacogenetic panel to prevent adverse drug reactions: an open-label, multicentre, controlled, cluster-randomised crossover implementation study.
No full textBackgroundThe benefit of pharmacogenetic testing before starting drug therapy has been well documented for several single gene-drug combinations. However, the clinical utility of a pre-emptive genotyping strategy using a pharmacogenetic panel has not been rigorously assessed.MethodsWe conducted an open-label, multicentre, controlled, cluster-randomised, crossover implementation study of a 12-gene pharmacogenetic panel in 18 hospitals, nine community health centres, and 28 community pharmacies in seven European countries (Austria, Greece, Italy, the Netherlands, Slovenia, Spain, and the UK). Patients aged 18 years or older receiving a first prescription for a drug clinically recommended in the guidelines of the Dutch Pharmacogenetics Working Group (ie, the index drug) as part of routine care were eligible for inclusion. Exclusion criteria included previous genetic testing for a gene relevant to the index drug, a planned duration of treatment of less than 7 consecutive days, and severe renal or liver insufficiency. All patients gave written informed consent before taking part in the study. Participants were genotyped for 50 germline variants in 12 genes, and those with an actionable variant (ie, a drug-gene interaction test result for which the Dutch Pharmacogenetics Working Group [DPWG] recommended a change to standard-of-care drug treatment) were treated according to DPWG recommendations. Patients in the control group received standard treatment. To prepare clinicians for pre-emptive pharmacogenetic testing, local teams were educated during a site-initiation visit and online educational material was made available. The primary outcome was the occurrence of clinically relevant adverse drug reactions within the 12-week follow-up period. Analyses were irrespective of patient adherence to the DPWG guidelines. The primary analysis was done using a gatekeeping analysis, in which outcomes in people with an actionable drug-gene interaction in the study group versus the control group were compared, and only if the difference was statistically significant was an analysis done that included all of the patients in the study. Outcomes were compared between the study and control groups, both for patients with an actionable drug-gene interaction test result (ie, a result for which the DPWG recommended a change to standard-of-care drug treatment) and for all patients who received at least one dose of index drug. The safety analysis included all participants who received at least one dose of a study drug. This study is registered with ClinicalTrials.gov, NCT03093818 and is closed to new participants.FindingsBetween March 7, 2017, and June 30, 2020, 41 696 patients were assessed for eligibility and 6944 (51·4 % female, 48·6% male; 97·7% self-reported European, Mediterranean, or Middle Eastern ethnicity) were enrolled and assigned to receive genotype-guided drug treatment (n=3342) or standard care (n=3602). 99 patients (52 [1·6%] of the study group and 47 [1·3%] of the control group) withdrew consent after group assignment. 652 participants (367 [11·0%] in the study group and 285 [7·9%] in the control group) were lost to follow-up. In patients with an actionable test result for the index drug (n=1558), a clinically relevant adverse drug reaction occurred in 152 (21·0%) of 725 patients in the study group and 231 (27·7%) of 833 patients in the control group (odds ratio [OR] 0·70 [95% CI 0·54-0·91]; p=0·0075), whereas for all patients, the incidence was 628 (21·5%) of 2923 patients in the study group and 934 (28·6%) of 3270 patients in the control group (OR 0·70 [95% CI 0·61-0·79]; p InterpretationGenotype-guided treatment using a 12-gene pharmacogenetic panel significantly reduced the incidence of clinically relevant adverse drug reactions and was feasible across diverse European health-care system organisations and settings. Large-scale implementation could help to make drug therapy increasingly safe.FundingEuropean Union Horizon 2020
Measuring (KSK +/-)-K-0 interactions using Pb-Pb collisions at root S-NN=2.76 TeV
No full textWe present the first ever measurements of femtoscopic correlations between the K-S(0) and K-+/- particles. The analysis was performed on the data from Pb-Pb collisions at root S-NN = 2.76 TeV measured by the ALICE experiment. The observed femtoscopic correlations are consistent with final-state interactions proceeding via the a(0)(980) resonance. The extracted kaon source radius and correlation strength parameters for (KSK-)-K-0 are found to be equal within the experimental uncertainties to those for (KSK+)-K-0. Comparing the results of the present study with those from published identical-kaon femtoscopic studies by ALICE, mass and coupling parameters for the a(0) resonance are tested. Our results are also compatible with the interpretation of the a(0) having a tetraquark structure instead of that of a diquark. (c) 2017 The Author. Published by Elsevier B.V
First measurement of Xi(0)(c) production in pp collisions at root s=7 TeV
No full textThe production of the charm-strange baryon Xi(0)(c) is measured for the first time at the LHC via its semileptonic decay into e(+) Xi(-) nu(e) in ppcollisions at root s = 7 TeV with the ALICE detector. The transverse momentum ( p(T)) differential cross section multiplied by the branching ratio is presented in the interval 1 < p(T)< 8 GeV/c at mid-rapidity, vertical bar y vertical bar < 0.5. The transverse momentum dependence of the Xi(0)(c) baryon production relative to the D-0 meson production is compared to predictions of event generators with various tunes of the hadronisation mechanism, which are found to underestimate the measured cross-section ratio. (C) 2018 The Author(s). Published by Elsevier B.V
First measurement of the vertical bar t vertical bar-dependence of coherent J/psi photonuclear production
No full textThe first measurement of the cross section for coherent J/Psi photoproduction as a function of vertical bar t vertical bar, the square of the momentum transferred between the incoming and outgoing target nucleus, is presented. The data were measured with the ALICE detector in ultra-peripheral Pb-Pbcollisions at a centre-of-mass energy per nucleon pair root s(NN) = 5.02 TeV with the J/Psi produced in the central rapidity region vertical bar y vertical bar < 0.8, which corresponds to the small Bjorken-xrange (0.3 - 1.4) x 10(-3). The measured vertical bar t vertical bar-dependence is not described by computations based only on the Pb nuclear form factor, while the photonuclear cross section is better reproduced by models including shadowing according to the leading-twist approximation, or gluon-saturation effects from the impact-parameter dependent Balitsky-Kovchegov equation. These new results are therefore a valid tool to constrain the relevant model parameters and to investigate the transverse gluonic structure at very low Bjorken- x. (C) 2021 The Author(s). Published by Elsevier B.V
Measurement of strange baryon–antibaryon interactions with femtoscopic correlations
No full textTwo-particle correlation functions were measured for p (p) over bar, p (Lambda) over bar, (p) over bar Lambda, and Lambda(Lambda) over bar pairs in Pb-Pb collisions at root sNN = 2.76 TeV and root sNN = 5.02 TeV recorded by the ALICE detector. From a simultaneous fit to all obtained correlation functions, real and imaginary components of the scattering lengths, as well as the effective ranges, were extracted for combined p (Lambda) over bar and (p) over bar Lambda pairs and, for the first time, for Lambda(Lambda) over bar pairs. Effective averaged scattering parameters for heavier baryon-antibaryon pairs, not measured directly, are also provided. The results reveal similarly strong interaction between measured baryon-antibaryon pairs, suggesting that they all annihilate in the same manner at the same pair relative momentum k*. Moreover, the reported significant non-zero imaginary part and negative real part of the scattering length provide motivation for future baryon-antibaryon bound state searches. (C) 2020 The Author(s). Published by Elsevier B.V
First measurement of quarkonium polarization in nuclear collisions at the LHC
No full textThe polarization of inclusive J/psi and Upsilon(1S) produced in Pb-Pb collisions at root s(NN) = 5.02 TeV at the LHC is measured with the ALICE detector. The study is carried out by reconstructing the quarkonium through its decay to muon pairs in the rapidity region 2.5 < y < 4 and measuring the polar and azimuthal angular distributions of the muons. The polarization parameters lambda(theta), lambda(phi) and lambda(theta phi) are measured in the helicity and Collins-Soper reference frames, in the transverse momentum interval 2 < p(T) < 10 GeV/c and p(T) < 15 GeV/c for the J/psi and Upsilon(1S), respectively. The polarization parameters for the J/psi are found to be compatible with zero, within a maximum of about two standard deviations at low p(T), for both reference frames and over the whole p(T) range. The values are compared with the corresponding results obtained for pp collisions at root s = 7 and 8 TeV in a similar kinematic region by the ALICE and LHCb experiments. Although with much larger uncertainties, the polarization parameters for Upsilon(1S) production in Pb-Pb collisions are also consistent with zero. (c) 2021 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
