bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetics and safety of tobramycin nebulization with the I‐neb and PARI‐LC Plus in children with cystic fibrosis: A randomized, crossover study
Authors: van Velzen Annelies J. , Uges Joris W.F. , Heijerman Harry G.M. , Arets Bert G.M. , Nuijsink Marianne , van der Wiel‐Kooij Els C. , van Maarseveen Erik M. , van Zanten Gijsbert A. , Pullens Bas , Touw Daan J. , Janssens Hettie M. 
Published: May 2019

AimsWe aimed to compare the pharmacokinetics (PK) and safety profile of tobramycin inhalation solution (TIS) using the I‐neb device to the standard PARI‐LC Plus nebulizer in children with cystic fibrosis.MethodsA randomized, open‐label, crossover study was performed. In 2 separate study visits, blood samples from 22 children were collected following TIS nebulization with I‐neb (75 mg) and PARI‐LC Plus (300 mg). Study visits were separated by 1 month, in which 1 of the study nebulizers was used twice daily. Tobramycin PK for both nebulizers was established using measured tobramycin concentrations and Bayesian PK modelling software. Hearing and renal function tests were performed to test for aminoglycoside associated toxicity. In addition to standard estimated glomerular filtration rate values, biomarkers for tubular injury (KIM‐1 and NAG) were measured. Patient and nebulizer satisfaction were assessed.ResultsInhalations were well tolerated and serum trough concentrations below the predefined toxic limit were reached with no significant differences in PK parameters between nebulizers. Results of audiometry and estimated glomerular filtration rate revealed no abnormalities. However, increased urinary NAG/creatinine ratios at visit 2 for both nebulizers suggest TIS‐induced subclinical tubular kidney injury. Nebulization time was 50% shorter and patient satisfaction was significantly higher with the I‐neb.ConclusionsNebulization of 75 mg TIS with the I‐neb in children with cystic fibrosis resulted in comparable systemic exposure to 300 mg TIS with the PARI‐LC Plus and was well tolerated and preferred over the PARI‐LC Plus. Long‐term safety of TIS nebulization should be monitored clinically, especially regarding the effects on tubular kidney injury.
Optimizing the dose in patients treated with imatinib as first line treatment for gastrointestinal stromal tumours: A cost‐effectiveness study
Authors: Zuidema Sander , Desar Ingrid M.E. , van Erp Nielka P. , Kievit Wietske 
Published: May 2019

AimsPatients with metastatic gastrointestinal stromal tumours (GIST) are treated in first line with the oral tyrosine kinase inhibitor, imatinib, until progressive disease. With this fixed dosing regimen, only approximately 40% of patients reach adequate plasma levels within the therapeutic index. Therapeutic drug monitoring (TDM) is a solution to reach plasma levels within the therapeutic index. However, introducing TDM will also increase costs, due to prolonged imatinib use and laboratory costs. The aim of this study was to evaluate the cost‐effectiveness of TDM in patients with metastatic/unresectable GIST treated with imatinib as a first line treatment, compared with fixed dosing.MethodsA survival model was created to simulate progression, mortality and treatment costs over a 5‐year time horizon, comparing fixed dosing vs TDM‐guided dosing. The outcomes measured were treatments costs, life‐years and quality‐adjusted life‐years.ResultsTotal costs over the 5‐year time horizon were estimated to be €106 994.85 and €150 477.08 for fixed dosing vs TDM‐guided dosing, respectively. A quality‐adjusted life year gain of 0.74 (95% confidence interval 0.66–0.90) was estimated with TDM‐guided dosing compared to fixed dosing. An average incremental cost‐effectiveness ratio of €58 785.70 per quality‐adjusted life year gained was found, mainly caused by longer use and higher dosages of imatinib.ConclusionBased on the currently available data, this analysis suggests that TDM‐guided dosing may be a cost‐effective intervention for patients with metastatic/unresectable GIST treated with imatinib which will be improved when imatinib losses its patency.
Changes in body composition in male adolescents with childhood‐onset GH deficiency during transition
Authors: Binder Gerhard , Donner Julia , Becker Bettina , Bauer Jana Leonie , Schweizer Roland 
Published: May 2019

AbstractObjectiveRestarting rhGH in adolescents with childhood‐onset (CO‐) GHD is usually based on GH retest, IGF‐1, additional pituitary hormone deficiencies, pituitary morphology and history. Short‐term changes in body composition in adolescents with CO‐GHD when off rhGH may contribute to the identification of those in need of treatment continuation.DesignThis is a longitudinal single‐centre study.Patients and measurementsThe body composition of 90 male adolescents with low‐likelihood severe GHD of adolescence was measured by DXA at the time of rhGH discontinuation and 6 months thereafter. At diagnosis, mean age was 5.4 years, height was −2.68 SDS and stimulated GH peak was 5.1 ng/mL. RhGH treatment was stopped at 16.7 years at near‐final height of −0.44 SDS. The adolescents were re‐examined after 3 months off rhGH using both IGF‐1 and GHRH‐arginine tests. Severe GHD of adolescence was defined both by stimulated GH < 16 ng/mL and by IGF‐1 < −1.90 SDS.ResultsMales with severe GHD of adolescence (n = 8) gained more relative and absolute fat mass and lost significantly more relative lean body mass after 6 months off rhGH than healthy individuals (n = 82; P < 0.001). The sum of absolute fat mass gain and lean body mass loss (=body composition changes score; BCC score) correlated highly with the GH peak (R = 0.17; P < 0.001). A BCC score >7.0 kg was 88% sensitive and 94% specific for detecting severe GHD of adolescence (AUC = 0.975).ConclusionsShort‐term body composition changes when off rhGH are good clinical markers of severe GHD in male adolescents. The novel BBC score is an aggregate of these changes.
The radiological evaluation of posterior superior alveolar artery topography by using computed tomography
Authors: Duruel Onurcem , Ataman‐Duruel Emel T. , Tözüm Melek D. , Karabulut Erdem , Tözüm Tolga F. 
Published: May 2019

AbstractBackgroundPosterior superior alveolar artery (PSAA) is the most important limiting anatomic structure while lateral approach sinus surgeries. PSAA should be taken into consideration to avoid bleeding during preparation of bony window.PurposeThe aim of this article was to inform topography of PSAA and to evaluate measurements of this vital structure.Materials and MethodsThree hundred and fifty‐four cone‐beam computed tomography (CBCT) images of PSAA from 177 patients were evaluated retrospectively. Localization of PSAA, diameter of PSAA, classification of PSAA diameter, distance between PSAA and crest, buccal bone thickness, palatal bone thickness, crest height, and crest width were recorded for each posterior tooth separately.ResultsThe mean age of 177 patients was 54.05 ± 18.33 years. Although the most frequent localization of PSAA was intraosseous in premolar region, they were below Schneiderian membrane in molars. PSAA diameter was measured frequently less than 1 mm for all posterior teeth. Although palatal bone thickness was higher in premolar region than molars, no statistical relationship was found between tooth region and buccal bone thickness (P > 0.05). The width of residual ridge was measured both wider apically and posteriorly. Positive correlation was observed between buccal bone thickness and PSAA diameter in first molar and premolar regions (P < 0.05).ConclusionsDetailed evaluation of patients by CBCT provided us the opportunity to draw topography of PSAA and inform about overall measurements of PSAA in all posterior teeth region.
Youth weight status and family functioning in paediatric primary care
Authors: Pratt Keeley J. , Van Fossen Catherine A. , Berge Jerica M. , Murray Robert , Skelton Joseph A. 
Published: May 2019

SummaryThe purpose of this study is to examine the associations between family functioning and youth overweight and obesity in a sample of primary care paediatric patients. Specially, we hypothesize that caregivers of youth with an overweight/obese weight status will report more impaired family functioning. A cross‐sectional descriptive study was conducted with 329 caregivers of youth ages 2 to 18 seen in paediatric primary care. Caregivers completed the Family Assessment Device General Functioning Scale and clinical demographics, including parent‐reported youth height and weight to calculate body mass index (BMI). Family functioning was used as a continuous total variable, and as a dichotomous variable based on clinically impaired or healthy family functioning. Analyses included descriptive statistics, Pearson's correlations, and independent t tests. Caregivers who reported impaired family functioning based on the clinical cutoff score were more likely to report that their youth had a higher BMI and BMI z‐score. Caregivers with impaired family functioning and who identified as being in two‐parent families, with at least a Bachelor's degree, and a moderate to high family income were more likely to report their youth was a higher weight status. Further screening and assessment of family functioning in combination with youth weight status among a larger diverse sample of primary care paediatric patients over time will provide insight into what aspects of family functioning may contribute to maintaining a healthy lifestyle or adopting new health behaviours to prevent and/or treat obesity in youth.
Low‐fat and fat‐free spindle cell lipomas in the oral cavity: Immunohistochemical analysis and review of the literature
Authors: Rocha Audrey F. L. , Miotto Larissa N. , Ferrisse Túlio M. , Silveira Heitor A. , Almeida Luciana Y. , Bufalino Andreia , Navarro Cláudia M. , León Jorge E. 
Published: May 2019

AbstractThe low‐fat and fat‐free spindle cell lipomas (SCLs) are rare and often mistaken for other benign and malignant morphological mimics, because of the fact that the diagnosis relies on its non‐lipogenic component analysis. Here, we report the clinicopathological features of two oral SCLs (low‐fat and fat‐free variants). Both lesions presented clinically as an asymptomatic nodule, which initially yielded diagnostic difficulties on the morphological analysis alone. One case was diagnosed as low‐fat SCL on the lower lip in a 29‐year‐old man, and the other as fat‐free SCL on the buccal mucosa in a 46‐year‐old man. In both cases, immunohistochemistry showed strong positivity for CD34 and, remarkably, retinoblastoma (Rb) protein was deficient. Mast cell (MC) tryptase and toluidine blue stain highlighted numerous MCs distributed throughout all tumor stroma. Alpha‐SMA and desmin were negative. S100 evidenced scarce adipocytes only in the low‐fat SCL case. Conservative surgical treatment was performed and no recurrence was noticed in about 2‐year of follow‐up in both cases. Because of the potential pitfalls, careful morphological analysis of the tumor stroma in the low‐fat/fat‐free SCL diagnosis, supported by immunohistochemistry (especially CD34, Rb and MC tryptase), is strongly recommended. To the best of our knowledge, these are the first and second cases reported of fat‐free and low‐fat SCL in the oral cavity.
Management der Dupilumab‐assoziierten Konjunktivitis beim atopischen Ekzem
Authors: Aszodi Nora , Thurau Stephan , Seegräber Marlene , de Bruin‐Weller Marjolein , Wollenberg Andreas 
Published: May 2019

ZusammenfassungDer monoklonale Antikörper Dupilumab (Dupixent®) ist seit September 2017 in der EU als neue systemische Therapie bei mittelschwerem bis schwerem atopischem Ekzem zugelassen. Eine Unterdrückung der IL‐4‐ und IL‐13‐Signalwege durch die Anwendung von Dupilumab führt zu einer Verbesserung objektiver und subjektiver Komponenten der Erkrankung. Die Blockade der IL‐4Rα‐Untereinheit führt zu einer Reduktion der Th2‐vermittelten Entzündung und zu einer Verbesserung der Hautbarriere. Die Nebenwirkungsrate unter Dupilumab ist gering. Allerdings entwickelten bis zu 28 % der Patienten unter Behandlung mit Dupilumab (gegenüber bis zu 11 % unter Placebo) eine bilaterale, milde bis moderate Konjunktivitis mit Rötung, Brennen und Fremdkörpergefühl der Augen. Mit topischen Steroiden und topischen Calcineurininhibitoren stehen verschiedene Therapieoptionen der Dupilumab‐assoziierten Konjunktivitis zur Verfügung. Dieser Artikel berichtet über die klinische Präsentation sowie die medikamentösen und nichtmedikamentösen Therapieoptionen der klinisch hochrelevanten Dupilumab‐assoziierten Konjunktivitis.
Drug Survival und Gründe für einen Therapieabbruch bei Pustulosis palmoplantaris: Eine retrospektive multizentrische Studie
Authors: Kromer Christian , Wilsmann‐Theis Dagmar , Gerdes Sascha , Philipp Sandra , Schaarschmidt Marthe‐Lisa , Schmieder Astrid , Dakna Mohammed , Arnold Tobias , Peitsch Wiebke Katharina , Mössner Rotraut 
Published: May 2019

ZusammenfassungHintergrundDie Pustulosis palmoplantaris (PPP) ist eine chronisch‐entzündliche Hauterkrankung, die mit Psoriasis verwandt ist. Ihre Therapie ist eine Herausforderung und es ist wenig über die Nachhaltigkeit der verschiedenen, therapeutisch eingesetzten Arzneimittel bekannt. Ziel dieser Studie war es die Anwendungsdauer von Medikamenten (Überlebensrate, „Drug Survival“) sowie deren Absetzen bei der Behandlung der PPP in einem Real‐World Setting zu untersuchen.Patienten und MethodenIn diese retrospektive Studie wurden Patienten mit PPP eingeschlossen, die zwischen 01/2005 und 08/2017 in den dermatologischen Abteilungen von fünf deutschen Universitätskliniken behandelt wurden. Das Drug Survival systemischer Therapien wurde mittels Kaplan‐Meier‐Analyse und multivariater Regression ermittelt.ErgebnisseInsgesamt wurden 347 Patienten mit 935 Behandlungen erfasst. Innerhalb der Gruppe nichtbiologischer systemischer Wirkstoffe zeigte Apremilast das beste mediane Drug Survival (15 Monate), gefolgt von Ciclosporin (12 Monate), der Kombination von Acitretin und topischer PUVA‐Behandlung (9 Monate), MTX (8 Monate), Acitretin‐Monotherapie (6 Monate), Alitretinoin (5 Monate) und Fumarsäureestern (3 Monate). Bei den Biologika hatte Certolizumab Pegol die höchste Erhaltungsrate (begrenzter Mittelwert 47,4 Monate), gefolgt von Infliximab (Median: 26 Monate), Golimumab (22 Monate), Ustekinumab (21 Monate), Adalimumab (18 Monate), Secukinumab (9 Monate) und Etanercept (8 Monate).SchlussfolgerungenBiologika und Apremilast sind mögliche Optionen für die Zweitlinientherapie der PPP und sollten weiter untersucht werden.
Comparison of prenatal ultrasound and postmortem findings in fetuses with common pulmonary vein atresia
Authors: Guo Yong , Gao Shuang , Kang Lei , Han Jiancheng , Zhang Ye , Weng Zongjie , Shang Jianfeng , Hao Xiaoyan , Zhao Ying , Ge Shuping , He Yihua 
Published: May 2019

AbstractBackgroundThe previous literature on common pulmonary vein atresia (CPVA) mainly consists of neonatal case reports. There is a lack of research on the prenatal diagnosis of CPVA.MethodsWe conducted a retrospective study of all fetuses with CPVA confirmed by autopsy between August 2010 and May 2018. Prenatal echocardiographic features, autopsy findings, and genetic test results were analyzed. We compared fetal CPVA with total anomalous pulmonary venous return (TAPVR) and neonatal CPVA.ResultsDuring the study period, fetal echocardiography was performed on 31 617 fetuses. Six cases of CPVA were identified by autopsies, including 1 case performed with a cardiovascular cast. All 6 cases (100%) had asplenia syndrome (AS) and bilateral superior vena cava (BSVC). In 1 case (16.7%), the prenatal ultrasound results were in complete agreement with the postmortem findings. Four cases (66.7%) were misdiagnosed as TAPVR by prenatal echocardiography. For the remaining case (16.7%), no pulmonary venous anomalies were detected on prenatal echocardiography. No aneuploidy was identified in any of the cases. There were no statistically significant differences among the proportions of associated complex anomalies and AS between the fetal CPVA and TAPVR groups. The proportion of associated complex anomalies and AS in the fetal CPVA group was higher than that in the neonatal group (P < 0.05).ConclusionsPrenatal diagnosis of fetal CPVA is difficult and challenging even for experts. Our study showed that fetal CPVA is often combined with AS, complex cardiac malformations, and BSVC. These findings may help in the diagnosis of fetal CPVA.
Seasonal and diurnal variation of downstream fish movement at four small‐scale hydropower plants
Authors: Knott Josef , Mueller Melanie , Pander Joachim , Geist Juergen 
Published: May 2019

AbstractHydropower structures hinder the movement and migration of fishes, impairing their life cycles. Additionally, downstream moving fish are often at risk of being injured during turbine passage. To improve hydropower production towards more fish‐friendly techniques and management, knowledge on timing and extent of natural patterns of fish downstream movement is necessary. So far, migration behaviour of long‐distance migrators such as eel or salmon has been well studied, but little is known about seasonal and diurnal movement patterns of nonmigratory species or medium‐distance migrators. In this study, movement patterns of 39 fish species captured by stownets while transiting hydropower facilities in four impounded rivers were assessed and compared with the fish community composition directly upstream of the hydropower plants assessed by electrofishing. Strong differences between the fish community composition inhabiting the upstream sides of the dams and the fish detected in downstream passage were evident. In each study river, the downstream moving fish community composition differed significantly between spring and autumn. On average, significantly more fish were caught during the night (2.9 fish/hr) than during the day (1.3 fish/hr). Topmouth gudgeon, European grayling and pike‐perch mostly moved downstream during the night, whereas roach, spirlin and bleak were the most frequent downstream moving fish during daytime. Downstream fish movement was positively related with turbidity, water temperature and discharge. The strong differences in seasonal and diurnal fish movement patterns suggest that fish damage can be strongly reduced by adaptive turbine and corridor management, for example by shutting down turbines at peak movements.
Hybrid job offer recommender system in a social network
Authors: Rivas Alberto , Chamoso Pablo , González‐Briones Alfonso , Casado‐Vara Roberto , Corchado Juan Manuel 
Published: May 2019

AbstractRecommender systems (RSs) play a very important role in web navigation, ensuring that the users easily find the information they are looking for. Today's social networks contain a large amount of information and it is necessary that they employ a mechanism that will guide users to the information they are interested in. However, to be able to recommend content according to user preferences, it is necessary to analyse their profiles and determine their preferences. The present work proposes a job offer RS for a career‐oriented social network. The recommendation system is a hybrid, it consists of a case‐based reasoning (CBR) system and an argumentation framework, based on a multi‐agent system (MAS) architecture. The CBR system uses a series of metrics and similar cases to decide whether a job offer is likely to be recommended to a user. Besides, the argumentation framework extends the system with an argumentation CBR, through which old and similar cases can be obtained from the CBR system. Finally, a discussion process is established amongst the agents who debate using their experience from past cases to take a final decision.
Factor VIII prophylaxis effects outweigh other hemostasis contributors in predicting severe haemophilia A joint outcomes
Authors: Warren Beth Boulden , Jacobson Linda , Kempton Christine , Buchanan George R. , Recht Michael , Brown Deborah , Leissinger Cindy , Shapiro Amy D. , Abshire Thomas C. , Manco‐Johnson Marilyn J. ,   for the Joint Outcome Study Group Investigators
Published: May 2019

AbstractIntroductionThe Joint Outcome Study (JOS) demonstrated that previously untreated children with severe haemophilia A treated with prophylactic factor VIII (FVIII) concentrate had superior joint outcomes at age 6 years compared to those children treated episodically for bleeding. However, variation in joint outcome within each treatment arm was not well explained.AimIn this study, we sought to better understand variation in joint outcomes at age 6 years in participants of the JOS.MethodsWe evaluated the influence of FVIII half‐life, treatment adherence, constitutional coagulant and anticoagulant proteins, and global assays on joint outcomes (number of joint bleeds, total number of bleeds, total MRI score and joint physical exam score). Logistic regression was used to evaluate the association of variables with joint failure status on MRI, defined as presence of subchondral cyst, surface erosion or joint‐space narrowing. Each parameter was also correlated with each joint outcome using Spearman correlations.ResultsProphylaxis treatment arm and FVIII trough were each found to reduce risk of joint failure on univariate logistic regression analysis. When controlling for treatment arm, FVIII trough was no longer significant, likely because of the high level of covariation between these variables. We found no consistent correlation between any laboratory assay performed and any joint outcome parameter measured.ConclusionIn the JOS, the effect of prescribed prophylactic FVIII infusions on joint outcome overshadowed the contribution of treatment adherence, FVIII half‐life, global assays of coagulation and constitutional coagulation proteins. (ClinicalTrials.gov number, NCT00207597).
Discrepancy between volume and functional recovery in early phase liver regeneration following extended hepatectomy with extrahepatic bile duct resection
Authors: Maeda Takashi , Yokoyama Yukihiro , Ebata Tomoki , Igami Tsuyoshi , Mizuno Takashi , Yamaguchi Junpei , Onoe Shunsuke , Ando Masahiko , Nagino Masato 
Published: May 2019

AimTo elucidate the clinical factors having an impact on liver regeneration rate following preoperative portal vein embolization (PVE) and subsequent extended hepatectomy. The correlation between liver volume and functional recovery after extended hepatectomy was also investigated.MethodsRecords of patients who underwent extended hepatectomy with extrahepatic bile duct resection following PVE for perihilar cholangiocarcinoma were reviewed retrospectively with attention to liver regeneration. All patients underwent computed tomography before PVE, after PVE (immediately before surgery), and on postoperative day (POD) 7. The kinetic growth rate (KGR) was calculated as the percent increase in liver volume relative to the future liver remnant volume per day after PVE (KGRPVE) and after POD 7 (KGRPOD7) using the computed tomography images before PVE, after PVE, and on POD 7.ResultsIn the 289 study patients, the median of KGRPVE was 1.35%/day whereas that of KGRPOD7 was 5.56%/day. The extent of liver resection had the greatest impact on both KGRPVE and KGRPOD7 and the impacts of other factors were less. There was a significant negative correlation between KGRPVE and KGRPOD7 (P = 0.002). No correlations were observed between KGRPVE or KGRPOD7 and serum total bilirubin and prothrombin time – international normalized ratio on POD 7, nor in the incidence of liver failure after surgery.ConclusionsEarly phase liver regeneration after extended hepatectomy was largely influenced by the extent of liver resection and showed no correlation with the indices of liver failure. There was a discrepancy between volume and functional recovery in early phase liver regeneration.