Journal of Neuro-Oncology - Understanding the molecular landscape of glioblastoma (GBM) is increasingly important in the age of targeted therapy. O-6-Methylguanine-DNA methyltransferase (MGMT)... 相似文献
Posaconazole is indicated for prophylaxis and treatment of invasive aspergillosis. Therapeutic drug monitoring (TDM) of posaconazole is used to optimise drug exposure. The aim of this study was to analyse and describe the TDM practices and exposure of posaconazole tablets. Patients who received posaconazole for treatment or prophylaxis of fungal infections were included in the study. The following therapeutic window was defined: if concentration was low (<0.7 mg/L for prophylaxis or < 1.5 mg/L for treatment) or high (>3.75 mg/L), the hospital pharmacist provided the physician with dosage advice, which implementation to patient care was analysed. A longitudinal analysis was performed to analyse if different confounding variables had an effect on posaconazole concentrations. Forty‐seven patients were enrolled resulting in 217 posaconazole trough concentrations. A median of 3 (IQR 1‐7) samples was measured per patient. The median concentration was 1.7 mg/L (IQR 0.8‐2.7) for prophylaxis and 1.76 mg/L (IQR 1.3‐2.3) for treatment. Overall, 78 posaconazole concentrations were out of the therapeutic window. For 45 (54%) of these concentrations, a dosage change was recommended. In the longitudinal analysis, the laboratory markers and patient baseline variables did not have an effect on posaconazole concentrations. Adequate posaconazole exposure was shown in 64% (affected 28 patients) of the measured concentrations. TDM practice of posaconazole can be improved by increasing the implementation rate of dose recommendation by a multidisciplinary antifungal stewardship team. 相似文献
We examined the association between three inflammatory markers (Interleukin (IL)-6, C-reactive protein (CRP), tumor necrosis factor (TNF)-α) and incident lung cancer using baseline, updated, and averaged inflammatory measures in older adults.
Methods
We fitted multivariable Cox models to assess whether circulating levels of inflammation markers were associated with incident lung cancers in the Health Aging, Body and Composition (HealthABC) prospective cohort of 3075 older adults aged 70–79?years at baseline. IL-6 and CRP were measured biennially, whereas TNF-α was measured at baseline.
Results
Baseline levels of IL-6 were significantly associated with incident lung cancer risk in a model that adjusted for age, gender, race, and site (Model 1) (Hazard RatioT3 vs. T1: 3.34, 95% Confidence Interval: 1.91, 5.85) and in a model adjusted for health factors linked to chronic inflammation (Model 2) (HR T3 vs. T1: 2.57, 95% CI: 1.41, 4.65). The associations observed in time-updated IL-6 (HR T3 vs. T1: 2.47, 95% CI: 1.43, 4.28), cumulatively averaged IL-6 (HR T3 vs. T1: 2.47, 95% CI: 1.43, 4.35), and baseline CRP levels (HR T3 vs. T1: 1.85, 95% CI: 1.11, 3.08) with incident lung cancer in Model 1 were not statistically significant in Model 2.
Conclusions
Baseline CRP and IL-6 levels were associated with increased risk of lung cancer in Model 1 and both models, respectively. Chronic IL-6 inflammation, as quantified by repeated measures was associated with incident lung cancer in Model 1, but not Model 2. Further research is needed to understand the role of CRP and IL-6 in lung carcinogenesis. 相似文献
Background: The practice of Norwegian occupational therapists (OTs) in municipal practice is a little explored area and with the Coordination Reform Act from 2012, Norwegian OTs in municipal practice have received responsibilities concerning clients with cognitive impairments. The aim of this study was to explore municipal OTs experiences with assessment of clients with cognitive impairments.
Method: Fourteen individual interviews with OTs who worked with clients with cognitive impairments, were conducted. An inductive thematic analysis, using text condensation and coding, was performed.
Results: The results revealed three themes; power of occupation, advantages and disadvantages of assessments used and the need for competencies within municipal services. The participants emphasized using observation in the assessment process and reflected on pros and cons of the standardized assessment tools they used. They expressed a need for competence development, although it was difficult to prioritize to do so.
Conclusion: This study illustrated a conflicted practice related to choices OTs make in their practices. They valued the importance of working occupation based, however, they chose to use impairment based standardized assessments. They expressed a need to engage in professional development, but due to heavy workloads, the limited power they experienced and lack of knowledge, this was difficult. 相似文献
We explored levonorgestrel (LNG) concentrations, bleeding patterns and endometrial thickness in women with epilepsy (WWE) initiating an LNG-intrauterine device (IUD) co-administered with antiepileptic drugs (AEDs).
Study design
This pilot study included 20 WWE ages 18 to 45 years with well-controlled seizures and stable AED regimens initiating a 52-mg LNG-IUD (20 mcg/d initial release). We collected blood and measured endometrial thickness before IUD placement and 21 days, 3 months and 6 months thereafter. Participants recorded bleeding/spotting daily. We measured total LNG (radioimmunoassay), serum hormone binding globulin (SHBG, immunoassay) and calculated the free LNG index. We compared total LNG, free LNG index, SHBG and endometrial thickness over time using a linear mixed-effects model.
Results
Total LNG, free LNG index and SBHG levels remained stable from day 21 throughout. Endometrial thickness decreased from a median of 5.9 mm [interquartile range (IQR) 4.6–7.5] at day 21 to 3.3mm (2.8–4.9) by month 6 (p=0.02). Bleeding and spotting days decreased from a median of 16 (IQR 13–23) in month 1 to 6.5 (IQR 4–8.5) in month 6 regardless of AED regimen.
Conclusion
Like women without epilepsy, WWE initiating the LNG-IUD experience stable total LNG concentrations and decreasing endometrial thickness and bleeding over the first 6 months of use.
Implications
Like women without epilepsy, WWE using antiepileptic drugs can expect a stable LNG concentration and decreasing bleeding during the first 6 months of LNG-IUD use. Our data can be useful for guidance of WWE considering use the LNG-IUD. 相似文献
Obesity has been associated with upper gastrointestinal cancers; however, there are limited prospective data on associations by subtype/subsite. Obesity can impact hormonal factors, which have been hypothesized to play a role in these cancers. We investigated anthropometric and reproductive factors in relation to esophageal and gastric cancer by subtype and subsite for 476,160 participants from the European Prospective Investigation into Cancer and Nutrition cohort. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox models. During a mean follow-up of 14 years, 220 esophageal adenocarcinomas (EA), 195 esophageal squamous cell carcinomas, 243 gastric cardia (GC) and 373 gastric noncardia (GNC) cancers were diagnosed. Body mass index (BMI) was associated with EA in men (BMI ≥30 vs. 18.5–25 kg/m2: HR = 1.94, 95% CI: 1.25–3.03) and women (HR = 2.66, 95% CI: 1.15–6.19); however, adjustment for waist-to-hip ratio (WHR) attenuated these associations. After mutual adjustment for BMI and HC, respectively, WHR and waist circumference (WC) were associated with EA in men (HR = 3.47, 95% CI: 1.99–6.06 for WHR >0.96 vs. <0.91; HR = 2.67, 95% CI: 1.52–4.72 for WC >98 vs. <90 cm) and women (HR = 4.40, 95% CI: 1.35–14.33 for WHR >0.82 vs. <0.76; HR = 5.67, 95% CI: 1.76–18.26 for WC >84 vs. <74 cm). WHR was also positively associated with GC in women, and WC was positively associated with GC in men. Inverse associations were observed between parity and EA (HR = 0.38, 95% CI: 0.14–0.99; >2 vs. 0) and age at first pregnancy and GNC (HR = 0.54, 95% CI: 0.32–0.91; >26 vs. <22 years); whereas bilateral ovariectomy was positively associated with GNC (HR = 1.87, 95% CI: 1.04–3.36). These findings support a role for hormonal pathways in upper gastrointestinal cancers. 相似文献
Journal of Neurology - To investigate associations of social support to psychological well-being, cognition, and motor functioning in patients with multiple sclerosis (MS). Secondarily, we were... 相似文献