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SIMPLICITY (NCT01244750) is an observational study exploring tyrosine kinase inhibitor (TKI) use and management patterns in patients with chronic phase-chronic myeloid leukemia in the US and Europe in routine clinical practice. Herein we describe interruptions, discontinuations and switching of TKI therapy during the initial 2 years of treatment among 1121 patients prospectively enrolled between October 1, 2010 and March 7, 2017. Patient characteristics were broadly similar between the imatinib (n = 370), dasatinib (n = 376), and nilotinib (n = 375) cohorts. Treatment interruptions occurred in 16.4% (year 1) and 4.0% (year 2) of patients, mainly attributed to hematologic intolerances. Treatment discontinuations occurred in 21.8% (year 1) and 10.2% (year 2) of patients, with the highest rate within the first 3 months for intolerance. Switching of TKI was seen in 17.8% (year 1) and 9.5% (year 2) of patients. Significant associations were found between TKI switching and female gender (year 1), age ≥65 years at diagnosis (year 2) and treatment with imatinib (year 2). Intolerance was the most common reason given for patients discontinuing and for switching TKI therapy; however resistance was also cited. Lack of response monitoring in routine clinical practice may have resulted in lower identification of resistance in this dataset. Data from SIMPLICITY suggest that, in routine clinical practice, intolerance and resistance to TKIs influence decisions to change treatment. Changes in TKI therapy are frequent, with nearly a third of patients discontinuing their first-line TKI.  相似文献   
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Objective To investigate whether depression, anxiety and stress increase the risk for delirium and poor quality of life (QOL) after coronary artery bypass (CABG) surgery. Methods A total of 180 CABG patients (mean age of 63.5 ± 10.1 years, 82.2% males) completed baseline and postoperative self-report questionnaires to assess distress and QOL. Incident delirium was diagnosed postoperatively with a structured clinical interview and patients were monitored every day post-operatively for confusion and disturbance in consciousness. Results Delirium developed in 63 persons (35% of sample). After adjustment for covariates, delirium was significantly associated with depression [odds ratio (OR): 1.08; 95% confidence interval (CI): 1.03–1.13, P = 0.003], anxiety (OR: 1.07; 95% CI: 1.02–1.13, P = 0.01) and stress (OR: 1.05; 95% CI: 1.00–1.09, P = 0.03). Preoperative depression scores were associated with poorer QOL including bodily pain (β = -0.39, P = 0.013), vitality (β=-0.32, P = 0.020), social functioning (β = -0.51, P ≤ 0.001), emotional role function (β = -0.44, P = 0.003) and general health (β = -0.33, P = 0.038). Among the covariates, harmful levels of alcohol use was consistently associated with poorer QOL. Conclusions Depression and harmful levels of alcohol use were consistently associated with poorer QOL whereas depression, anxiety and stress were associated with delirium risk. These findings point to further research examining depression and harmful levels of alcohol use in coronary heart disease populations undergoing coronary revascularization.  相似文献   
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Background: Critically ill children have low plasma zinc (pZn), correlating with organ failure. Since Zn influences inflammation, immune function, and glucose control, Zn supplementation is a plausible therapeutic modality. We sought to determine a safe dose of intravenous (IV) Zn to restore pZn in critically ill children. Methods: Stepwise dose escalation study of IV Zn supplementation at a tertiary children's hospital. All children (<10 years) admitted to the pediatric intensive care unit with a Pediatric Risk of Mortality III score >5, or ≥1 new organ failure were eligible. After consent, patients were sequentially enrolled into 4 dosing groups: (1) no zinc, (2) Zn250: 250 mcg/kg/d ZnSO4, (3) Zn500: 500 mcg/kg/d ZnSO4, or (4) Zn750: 750 mcg/kg/d ZnSO4. ZnSO4 was administered 3 times daily for 7 days. pZn was measured at baseline, end of first ZnSO4 infusion, 1 hour postinfusion, and 7 hours postinfusion on day 1, then daily through days 2–7. Interleukin‐6 (IL‐6), C‐reactive protein (CRP), and lymphocyte subsets were measured on days 1 and 3. Glucose was measured 3 times daily for 7 days. Results: Twenty‐four patients were enrolled. Baseline demographics were similar among groups. Baseline pZn was low in all patients (mean [SD], 41.8 [16.0] mcg/dL). pZn increased over the study period in supplemented groups; however, mean pZn in the Zn750 group exceeded the 50th percentile. pZn was not associated with IL‐6, CRP, or lymphocyte subsets among groups. Degree of hyperglycemia did not differ among groups. No patient had a study‐related adverse event. Conclusions: IV zinc supplementation at 500 mcg/kg/d restores pZn to near the 50th percentile and is well tolerated.  相似文献   
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