Background: Radiomic features may quantify characteristics present in medical imaging. However, the lack of standardized definitions and validated reference values have hampered clinical use... Show moreBackground: Radiomic features may quantify characteristics present in medical imaging. However, the lack of standardized definitions and validated reference values have hampered clinical use.Purpose: To standardize a set of 174 radiomic features.Materials and Methods: Radiomic features were assessed in three phases. In phase I, 487 features were derived from the basic set of 174 features. Twenty-five research teams with unique radiomics software implementations computed feature values directly from a digital phantom, without any additional image processing. In phase II, 15 teams computed values for 1347 derived features using a CT image of a patient with lung cancer and predefined image processing configurations. In both phases, consensus among the teams on the validity of tentative reference values was measured through the frequency of the modal value and classified as follows: less than three matches, weak; three to five matches, moderate; six to nine matches, strong; 10 or more matches, very strong. In the final phase (phase III), a public data set of multimodality images (CT, fluorine 18 fluorodeoxyglucose PET, and T1-weighted MRI) from 51 patients with soft-tissue sarcoma was used to prospectively assess reproducibility of standardized features.Results: Consensus on reference values was initially weak for 232 of 302 features (76.8%) at phase I and 703 of 1075 features (65.4%) at phase II. At the final iteration, weak consensus remained for only two of 487 features (0.4%) at phase I and 19 of 1347 features (1.4%) at phase II. Strong or better consensus was achieved for 463 of 487 features (95.1%) at phase I and 1220 of 1347 features (90.6%) at phase II. Overall, 169 of 174 features were standardized in the first two phases. In the final validation phase (phase III), most of the 169 standardized features could be excellently reproduced (166 with CT; 164 with PET; and 164 with MRI).Conclusion: A set of 169 radiomics features was standardized, which enabled verification and calibration of different radiomics software. (C) RSNA, 2020 Show less
This review article provides a systematic overview of the currently available evidence on the clinical effectiveness of particle therapy for the treatment of non-small cell lung cancer and... Show moreThis review article provides a systematic overview of the currently available evidence on the clinical effectiveness of particle therapy for the treatment of non-small cell lung cancer and summarizes findings of in silico comparative planning studies. Furthermore, technical issues and dosimetric uncertainties with respect to thoracic particle therapy are discussed. Show less
Background: We evaluated the effectiveness of eradication of methicillin-resistant Staphylococcus aureus (MRSA) carriage in the Netherlands after the introduction of a guideline in 2006. The... Show moreBackground: We evaluated the effectiveness of eradication of methicillin-resistant Staphylococcus aureus (MRSA) carriage in the Netherlands after the introduction of a guideline in 2006. The guideline distinguishes complicated (defined as the presence of MRSA infection, skin lesions, foreign-body material, mupirocin resistance and/or exclusive extranasal carriage) and uncomplicated carriage (not meeting criteria for complicated carriage). Mupirocin nasal ointment and chlorhexidine soap solution are recommended for uncomplicated carriers and the same treatment in combination with two oral antibiotics for complicated carriage. Methods: A prospective cohort study was performed in 18 Dutch centres from 1 October 2006 until 1 October 2008. Results: Six hundred and thirteen MRSA carriers underwent one or more decolonization treatments during the study period, mostly after hospital discharge. Decolonization was achieved in 367 (60%) patients with one eradication attempt and ultimately 493 (80%) patients were decolonized, with a median time until decolonization of 10 days (interquartile range 7-43 days). Three hundred and twenty-seven (62%) carriers were treated according to the guideline, which was associated with an absolute increase in treatment success of 20% [from 45% (91/203) to 65% (214/327)]. Conclusions: Sixty percent of MRSA carriers were successfully decolonized after the first eradication attempt and 62% were treated according to the guideline, which was associated with an increased treatment success. Show less
Background: Using data from an observational study in which the effectiveness of a guideline for eradication of methicillin-resistant Staphylococcus aureus (MRSA) carriage was evaluated, we... Show moreBackground: Using data from an observational study in which the effectiveness of a guideline for eradication of methicillin-resistant Staphylococcus aureus (MRSA) carriage was evaluated, we identified variables that were associated with treatment failure. Methods: A multivariate logistic regression model was performed with subgroup analyses for uncomplicated and complicated MRSA carriage (the latter including MRSA infection, skin lesions, foreign-body material, mupirocin resistance and/or exclusive extranasal carriage) and for those treated according to the guideline (i.e. mupirocin nasal ointment and chlorhexidine soap solution for uncomplicated carriage, in combination with two oral antibiotics for complicated carriage). Results: Six hundred and thirteen MRSA carriers were included, of whom 333 (54%) had complicated carriage; 327 of 530 patients (62%) with known complexity of carriage were treated according to the guideline with an absolute increase in treatment success of 20% (95% confidence interval 12%-28%). Among those with uncomplicated carriage, guideline adherence [adjusted odds ratio (OR alpha) 7.4 (1.7-31.7)], chronic pulmonary disease [OR alpha 44 (2.9-668)], throat carriage [OR alpha 2.9 (1.4-6.1)], perineal carriage [OR alpha 2.2 (1.1-4.4)] and carriage among household contacts [OR alpha 5.6 (1.2-26)] were associated with treatment failure. Among those with complicated carriage, guideline adherence was associated with treatment success [OR alpha 0.2 (0.1-0.3)], whereas throat carriage [OR alpha 4.4 (2.3-8.3)] and dependence in activities of daily living [OR alpha 3.6 (1.4-8.9)] were associated with failure. Conclusions: Guideline adherence, especially among those with complicated MRSA carriage, was associated with treatment success. Adding patients with extranasal carriage or dependence in daily self-care activities to the definition of complicated carriage, and treating them likewise, may further increase treatment success. Show less
Background: Therapeutic drug monitoring (TDM) is recommended in several international HIV treatment guidelines. The adherence of clinicians to these recommendations is unknown. The authors... Show moreBackground: Therapeutic drug monitoring (TDM) is recommended in several international HIV treatment guidelines. The adherence of clinicians to these recommendations is unknown. The authors evaluated the adherence to the Dutch TDM guideline of 2005. Methods: From the ATHENA cohort study, three scenarios were selected for which the guideline recommended TDM: 1) start of a combination of lopinavir/ritonavir + efavirenz or nevirapine (drug-drug interaction); 2) start of efavirenz (routine TDM); and 3) use of nelfinavir during pregnancy. For each scenario, we determined the proportion of patients for whom TDM was performed. Multivariable logistic regression modeling was used to identify determinants for the use of TDM. Results: The adherence to the TDM guideline was 46.7% in patients who started lopinavir/ritonavir plus efavirenz or nevirapine; 9.5% for patients who started efavirenz; and 58.5% for patients who used nelfinavir during pregnancy. Patients treated in clinics that had a TDM assay available locally and patients treated in academic clinics were more likely to receive TDM. A higher baseline HIV viral load was another significant predictor for the performing TDM. Conclusion: The adherence of clinicians to the Dutch TDM guidelines varied from low to moderate for the three investigated TDM scenarios. This study identifies several determinants for the use of TDM, which may be useful information for those responsible for generating TDM guidelines. Show less
Luin, M. van; Ende, M.E. van der; Richter, C.; Visser, M.; Faraj, D.; Ven, A. van der; ... ; Burger, D.M. 2010
HIV-infected travellers frequently use atovaquone/ proguanil as malaria prophylaxis. We compared atovaquone/ proguanil pharmacokinetics between healthy volunteers and HIV-infected patients taking... Show moreHIV-infected travellers frequently use atovaquone/ proguanil as malaria prophylaxis. We compared atovaquone/ proguanil pharmacokinetics between healthy volunteers and HIV-infected patients taking efavirenz, lopinavir/ ritonavir or atazanavir/ritonavir. The geometric mean ratio (95% confidence interval) area under the curve (AUC)(0 -> t) for atovaquone relative to the healthy volunteers was 0.25 (0.16-0.38), 0.26 (0.17-0.41) and 0.54 (0.350.83) for patients on efavirenz, lopinavir/ ritonavir and atazanavir/ ritonavir, respectively. Proguanil plasma concentrations were also significantly lower (38-43%). Physicians should be alert for atovaquone/ proguanil prophylaxis failures in patients taking efavirenz, lopinavir/ ritonavir or atazanavir/ ritonavir. Show less
Water-soluble and particulate cadmium compounds are carcinogenic to humans. While direct interactions with DNA are unlikely to account for carcinogenicity, induction of oxidative DNA damage and... Show moreWater-soluble and particulate cadmium compounds are carcinogenic to humans. While direct interactions with DNA are unlikely to account for carcinogenicity, induction of oxidative DNA damage and interference with DNA repair processes might be more relevant underlying modes of action (recently summarized, for example, in Joseph, P. (2009) Tox. Appl. Pharmacol. 238, 271-279). The present study aimed to compare genotoxic effects of particulate CdO and soluble CdCl2 in cultured human cells (A549, VH10hTert). Both cadmium compounds increased the baseline level of oxidative DNA damage. Even more pronounced, both cadmium Compounds inhibited the nucleotide excision repair (NER) of BPDE-induced bulky DNA adducts and UVC-induced photolesions in a dose-dependent manner at noncytotoxic concentrations. Thereby, the uptake of cadmium in the nuclei strongly correlated with the repair inhibition of bulky DNA adducts, indicating that independent of the cadmium compound applied Cd2+ is the common species responsible for the observed repair inhibition. Regarding the underlying molecular mechanisms in human cells, CdCl2 (as shown before by Meplan, C., Mann, K., and Hainaut, P. (1999) J. Biol. Chem. 274, 3 1663-31670) and CdO altered the conformation of the zinc binding domain of the tumor Suppressor protein p53. In further Studies applying only CdCl2, cadmium decreased the total nuclear protein level of XPC, which is believed to be the principle initiator of global genome NER. This led to diminished association of XPC to sites of local UVC damage, resulting in decreased recruitment of further NER proteins. Additionally, CdCl2 strongly disturbed the disassembly of XPC and XPA. In Summary, our data indicate a general nucleotide excision repair inhibition by cadmium compounds, which is most likely caused by a diminished assembly and disassembly of the NER machinery. These data reveal new insights into the mechanisms involved in cadmium carcinogenesis and provide further evidence that DNA repair inhibition may be one predominant mechanism in cadmium induced carcinogenicity. Show less
