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71.
Journal of Autism and Developmental Disorders - An employer-based work-experience program run by a multinational organization temporarily employs people with an autism spectrum disorder (ASD) to... 相似文献
72.
A. W. Postema T. M. De Reijke O. Ukimura W. Van den Bos A. R. Azzouzi E. Barret D. Baumunk A. Blana A. Bossi M. Brausi J. A. Coleman S. Crouzet J. Dominguez-Escrig S. Eggener R. Ganzer S. Ghai I. S. Gill R. T. Gupta T. O. Henkel M. Hohenfellner J. S. Jones F. Kahmann C. Kastner K. U. Köhrmann G. Kovacs R. Miano R. J. van Moorselaar N. Mottet L. Osorio B. R. Pieters T. J. Polascik A. R. Rastinehad G. Salomon R. Sanchez-Salas M. Schostak L. Sentker K. J. Tay I. M. Varkarakis A. Villers J. Walz J. J. De la Rosette 《World journal of urology》2016,34(10):1373-1382
Purpose
To reach standardized terminology in focal therapy (FT) for prostate cancer (PCa).Methods
A four-stage modified Delphi consensus project was undertaken among a panel of international experts in the field of FT for PCa. Data on terminology in FT was collected from the panel by three rounds of online questionnaires. During a face-to-face meeting on June 21, 2015, attended by 38 experts, all data from the online rounds were reviewed and recommendations for definitions were formulated.Results
Consensus was attained on 23 of 27 topics; Targeted FT was defined as a lesion-based treatment strategy, treating all identified significant cancer foci; FT was generically defined as an anatomy-based (zonal) treatment strategy. Treatment failure due to the ablative energy inadequately destroying treated tissue is defined as ablation failure. In targeting failure the energy is not adequately applied to the tumor spatially and selection failure occurs when a patient was wrongfully selected for FT. No definition of biochemical recurrence can be recommended based on the current data. Important definitions for outcome measures are potency (minimum IIEF-5 score of 21), incontinence (new need for pads or leakage) and deterioration in urinary function (increase in IPSS >5 points). No agreement on the best quality of life tool was established, but UCLA-EPIC and EORTC-QLQ-30 were most commonly supported by the experts. A complete overview of statements is presented in the text.Conclusion
Focal therapy is an emerging field of PCa therapeutics. Standardization of definitions helps to create comparable research results and facilitate clear communication in clinical practice.73.
W. van den Bos D. M. de Bruin R. R. Jurhill C. D. Savci-Heijink B. G. Muller I. M. Varkarakis A. Skolarikos P. J. Zondervan M. P. Laguna-Pes H. Wijkstra T. M. de Reijke J. J. M. C. H. de la Rosette 《World journal of urology》2016,34(5):657-664
Purpose
Irreversible electroporation (IRE) is a novel minimally invasive therapy for prostate cancer using short electric pulses to ablate prostate tissue. The purpose of this study is to determine the IRE effects in prostate tissue and correlate electrode configuration with the histology of radical prostatectomy (RP) specimens. We hypothesize that the area within the electrode configuration is completely ablated and that the area within the electrode configuration is predictive for the ablated area after treatment.Methods
A prospective phase I/II study was conducted in 16 consecutive patients with histopathologically confirmed prostate cancer scheduled for RP. Focal or extended IRE treatment of the prostate was performed 4 weeks prior to RP. The locations of the electrodes were used to calculate the planned ablation zone. Following RP, the specimens were processed into whole-mount sections, histopathology (PA) was assessed and ablation zones were delineated. The area of the tissue alteration was determined by measuring the surface. The planned and the histological ablation zones were compared, analysed per individual patient and per protocol (focal vs. extended).Results
All cells within the electrode configuration were completely ablated and consisted only of necrotic and fibrotic tissue without leaving any viable cells. The histological ablation zone was always larger than the electrodes configuration (2.9 times larger for the 3 electrodes configuration and 2.5 times larger for the ≥4 electrode configuration). These ablation effects extended beyond the prostatic capsule in the neurovascular bundle in 13 out of 15 cases.Conclusions
IRE in prostate cancer results in completely ablated, sharply demarcated lesions with a histological ablation zone beyond the electrode configuration. No skip lesions were observed within the electrode configuration.Clinical trials
ClinicalTrials.gov Identifier: NCT01790451 https://clinicaltrials.gov/ct2/show/NCT0179045174.
75.
Frederiek van den Bos M. H. Emmelot-Vonk H. J. Verhaar Y. T. van der Schouw 《The journal of nutrition, health & aging》2018,22(6):639-644
Background
Although the incidences of osteoporosis and atherosclerosis increase with age, there is growing evidence that the coincidental occurrence of both diseases may be independent of age. In general, studies in men are scarce and results are inconsistent.Objective
to investigate the relationship between atherosclerosis and bone mineral density, and the influence of insulin sensitivity and low grade inflammation on this relationship in 332 men without CVD.Methods
Aortic Pulse wave velocity (PWV), augmentation index (AIX) and measurements of carotid intima media thickness (CIMT) were assessed. BMD measurements were performed with dual-X-ray absorptiometry (DEXA), subcutaneous fat by ultrasonography. Serum concentrations of lipids, hsCRP, glucose and insulin were measured. Insulin sensitivity was calculated by use of the quantitative insulin sensitivity (QUICKI). We used multivariate linear regression models to examine the association of hsCRP, insulin sensitivity, PWV, Aix, CIMT with BMD.Results
A higher CIMT was significantly associated with higher BMD after multivariate adjustment (β 99.7; p=0.02). Further adjustment for weight attenuated the estimates towards non-significant. No association was found between PWV or AIX and BMD. Lower insulin sensitivity was associated with higher BMD (β -645.1; p<0.01). After adjustment for weight this association was no longer significant. A similar effect was seen for the association between hsCRP and BMD.Conclusion
In this population of healthy, non-obese, men without a history of cardiovascular disease the positively association between cardiovascular parameters and BMD was mainly explained by weight, suggesting that in this population weight plays a protective role in the development of osteoporosis76.
77.
Willemien van den Bos Berrend G. Muller Hashim Ahmed Chris H. Bangma Eric Barret Sebastien Crouzet Scott E. Eggener Inderbir S. Gill Steven Joniau Gyoergy Kovacs Sascha Pahernik Jean J. de la Rosette Olivier Rouvière Georg Salomon John F. Ward Peter T. Scardino 《European urology》2014
Background
Focal therapy has been introduced for the treatment of localised prostate cancer (PCa). To provide the necessary data for consistent assessment, all focal therapy trials should be performed according to uniform, systematic pre- and post-treatment evaluation with well-defined end points and strict inclusion and exclusion criteria.Objective
To obtain consensus on trial design for focal therapy in PCa.Design, setting, and participants
A four-staged consensus project based on a modified Delphi process was conducted in which 48 experts in focal therapy of PCa participated. According to this formal consensus-building method, participants were asked to fill out an iterative sequence of questionnaires to collect data on trial design. Subsequently, a consensus meeting was held in which 13 panellists discussed acquired data, clarified the results, and defined the conclusions.Outcome measurements and statistical analysis
A multidisciplinary board from oncologic centres worldwide reached consensus on patient selection, pretreatment assessment, evaluation of outcome, and follow-up.Results and limitations
Inclusion criteria for candidates in focal therapy trials are patients with prostate-specific antigen <15 ng/ml, clinical stage T1c–T2a, Gleason score 3 + 3 or 3 + 4, life expectancy of >10 yr, and any prostate volume. The optimal biopsy strategy includes transrectal ultrasound-guided biopsies to be taken between 6 mo and 12 mo after treatment. The primary objective should be focal ablation of clinically significant disease with negative biopsies at 12 mo after treatment as the primary end point.Conclusions
This consensus report provides a standard for designing a feasible focal therapy trial.Patient summary
A variety of ablative technologies have been introduced and applied in a focal manner for the treatment of prostate cancer (PCa). In this consensus report, an international panel of experts in the field of PCa determined pre- and post-treatment work-up for focal therapy research. 相似文献78.
H. Muijser J.J. van Triel E. Duistermaat P.M.J. Bos 《Regulatory toxicology and pharmacology : RTP》2014
Subterranean storage of carbon dioxide (CO2) has been proposed to diminish atmospheric increases of this greenhouse gas. To contribute to risk assessment of accidental release associated with handling, transport and storage, rats were exposed to high concentrations (targets 40, 43 and 50 volume %) of CO2. The oxygen concentrations dropped as a result, but were not supplemented. For each concentration, pairs of animals were exposed for different exposure durations to derive an exposure concentration–duration relation in which mortality is described as a function of Cn × t (probit relation). A very high “n” value for the probit function could be derived from the data obtained at 40% and 43% CO2, which indicates that for exposure durations longer than 30 min the LC50 decreases hardly with increasing exposure duration. Below 30 min the LC50 seemed to increase with decreasing exposure durations. The variability in the data of 43% and 50% CO2, however, did not allow to derive a meaningful value of “n”. 相似文献
79.
Simone M C Spoorenberg Vera H M Deneer Jan C Grutters Astrid E Pulles G P Voorn Ger T Rijkers Willem Jan W Bos Ewoudt M W van de Garde 《British journal of clinical pharmacology》2014,78(1):78-83
Aim
The use of corticosteroids as adjunctive therapy might be effective in patients with community-acquired pneumonia (CAP). Oral administration of dexamethasone is a practical and safer alternative to the intravenous route. Since patients hospitalized with pneumonia might have delayed gastric emptying, this study explored systemic exposure in terms of area under the concentration–time curve (AUC) of oral dexamethasone in patients hospitalized with CAP.Methods
In this randomized, open label study, 30 patients admitted with CAP were randomized to receive either 4 mg intravenous or 6 mg oral dexamethasone for 4 consecutive days. Serial blood samples were obtained before and after drug administration.Results
Median AUC to infinity was 626 μg l−1 h (IQR 401–1161) for the intravenous group and 774 μg l−1 h (IQR 618–1146) for the oral group. The AUC ratio of 6 mg oral and 4 mg intravenous dexamethasone was 1.22 (95% confidence interval (CI) 0.81, 1.82), which represents a bioavailability of 81% (95% CI 54, 121) after correction for differences in dexamethasone dose.Conclusions
Bioavailability of oral dexamethasone in patients hospitalized with pneumonia is sufficient. This makes oral dexamethasone an appropriate alternative for intravenous administration in these patients. 相似文献80.
Joel Jakobsson Maria Bjerke Carl Johan Ekman Carl Sellgren Anette GM Johansson Henrik Zetterberg Kaj Blennow Mikael Landén 《Neuropsychopharmacology》2014,39(10):2349-2356
Bipolar disorder (BD) is characterized by mood swings between manic and depressive states. The etiology and pathogenesis of BD is unclear, but many of the affected cognitive domains, as well as neuroanatomical abnormalities, resemble symptoms and signs of small vessel disease. In small vessel disease, cerebrospinal fluid (CSF) markers reflecting damages in different cell types and subcellular structures of the brain have been established. Hence, we hypothesized that CSF markers related to small vessel disease may also be applicable as biomarkers for BD. To investigate this hypothesis, we sampled CSF from 133 patients with BD and 86 healthy controls. The concentrations of neurofilament light chain (NF-L), myelin basic protein (MBP), S100B, and heart-type fatty acid binding protein (H-FABP) were measured in CSF and analyzed in relation to diagnosis, clinical characteristics, and ongoing medications. Hereby we found an elevation of the marker of subcortical axonal damage, NF-L, in bipolar subjects. We also identified positive associations between NF-L and treatment with atypical antipsychotics, MBP and lamotrigine, and H-FABP and lithium. These findings indicate axonal damage as an underlying neuropathological component of bipolar disorder, although the clinical value of elevated NF-L remains to be validated in follow-up studies. The associations between current medications and CSF brain injury markers might aid in the understanding of both therapeutic and adverse effects of these drugs. 相似文献