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Factors identified could be grouped into four themes-therapy-related, patient-related, healthcare provider-related, and health system-related. Key barriers to optimal OAC management were mostly patient-related, whereas interventions focused on education or implementing protocols were shown through RCTs to be effective at improving knowledge scores of OAC patients. While multiple barriers and some facilitators were identified in this review, none was proven to be associated with clinical outcomes. With this in mind, individual physicians may wish to address the key barriers in their practice as a quality improvement initiative but system-wide or policy changes should await high-quality evidence. Future trials should address these factors.Systematic review registration PROSPERO CRD42017069043.PURPOSE Severe hepatotoxicity induced by the standard dose of gefitinib (250 mg daily) often becomes manageable by dose reduction to 250 mg every other day. Thus, we hypothesized that systemic exposure of standard-dose gefitinib in patients with experience of severe hepatotoxicity might be higher than that in patients without severe hepatotoxicity. METHODS Patients with advanced epidermal growth factor receptor-mutated non-small cell lung cancer who were receiving gefitinib either at a reduced dose (250 mg every other day) because of intolerable severe toxicity or at a standard dose (250 mg daily) were enrolled. A series of blood samples were collected to estimate pharmacokinetic parameters and calculate systemic exposure of standard-dose gefitinib (area under the concentration-time curve from 0 to 24 h at steady state, AUC0-24,ss). Systemic exposure of unbound gefitinib (fu·AUC0-24,ss) was also assessed, because gefitinib is extensively bound to serum proteins. RESULTS Of the 38 enrolled patients, 34 (23 patients without experience of severe hepatotoxicity, 11 patients with experience of severe hepatotoxicity) were evaluable. There was no significant differences in total AUC0-24,ss or unbound fu·AUC0-24,ss between patients with and without experience of severe hepatotoxicity. Analysis of the time to severe hepatotoxicity indicated no difference between patients with a high AUC0-24,ss and those with a low AUC0-24,ss of either total or unbound gefitinib. CONCLUSION This study suggests that reversible severe hepatotoxicity is not caused by high systemic exposure of gefitinib.Classical approaches to estimate mesophyll conductance ignore differences in resistance components for CO2 from intercellular air spaces (IAS) and CO2 from photorespiration (F) and respiration (Rd). Consequently, mesophyll conductance apparently becomes sensitive to (photo)respiration relative to net photosynthesis, (F + Rd)/A. This sensitivity depends on several hard-to-measure anatomical properties of mesophyll cells. We developed a method to estimate the parameter m (0 ≤ m ≤ 1) that lumps these anatomical properties, using gas exchange and chlorophyll fluorescence measurements where (F + Rd)/A ratios vary. This method was applied to tomato and rice leaves measured at five O2 levels. The estimated m was 0.3 for tomato but 0.0 for rice, suggesting that classical approaches implying m = 0 work well for rice. The mesophyll conductance taking the m factor into account still responded to irradiance, CO2, and O2 levels, similar to response patterns of stomatal conductance to these variables. Largely due to different m values, the fraction of (photo)respired CO2 being refixed within mesophyll cells was lower in tomato than in rice. But that was compensated for by the higher fraction via IAS, making the total re-fixation similar for both species. These results, agreeing with CO2 compensation point estimates, support our method of effectively analysing mesophyll resistance.BACKGROUND This meta-analysis aimed to investigate the value of preoperative sarcopenia in predicting complications after esophagectomy. Clinicopathologic characteristics of sarcopenia patients, which may support sarcopenia management, also were studied. read more METHODS This study searched for articles describing an association between sarcopenia and short-term outcomes after esophagectomy using PubMed, EMBASE, and the Cochrane Library. Mantel-Haenszel and inverse variance models were used for the meta-analyses of end points. RESULTS The meta-analysis included 14 studies comprising a total of 2387 patients. Sarcopenia was significantly associated with advanced age (weighted mean difference [WMD], 3.48; 95% confidence interval [CI], 2.22-4.74), lower body mass index (WMD - 2.22; 95% CI - 2.65 to - 1.79), squamous cell carcinoma (odds ratio [OR], 2.78; 95% CI 1.72-4.47), advanced clinical tumor stage (OR 1.65; 95% CI 1.28-2.15), and neoadjuvant therapy (OR 1.87; 95% CI 1.38-2.53). The sarcopenia patients showed lower preoperative albumin levels (WMD - 0.11; 95% CI - 0.19 to - 0.04) than the nonsarcopenia patients. Sarcopenia was significantly predictive of pneumonia (OR 2.58; 95% CI 1.75-3.81) and overall complications (OR 1.52; 95% CI 1.07-2.15) after esophagectomy. The sarcopenia patients also showed nonsignificant increases in the risks of anastomotic leakage (OR 1.29; 95% CI 0.99-1.67), vocal cord palsy (OR 2.03; 95% CI 0.89-4.64), and major complications (≥ Clavien-Dindo grade III; OR 1.30; 95% CI 0.95-1.79) but not increased operation time, blood loss, or mortality. CONCLUSIONS Preoperative sarcopenia assessment showed considerable potential for predicting postoperative complications for esophageal cancer patients. To realize this potential, more effective diagnostic criteria and severity classifications for sarcopenia are warranted.BACKGROUND Most previous risk-prediction models for gastrointestinal stromal tumors (GISTs) were based on Western populations. In the current study, we collected data from 23 hospitals in Shandong Province, China, and used the data to examine prognostic factors in Chinese patients and establish a new recurrence-free survival (RFS) prediction model. METHODS Records were analyzed for 5285 GIST patients. Independent prognostic factors were identified using Cox models. Receiver operating characteristic curve analysis was used to compare a novel RFS prediction model with current risk-prediction models. RESULTS Overall, 4216 patients met the inclusion criteria and 3363 completed follow-up. One-, 3-, and 5-year RFS was 94.6% (95% confidence interval [CI] 93.8-95.4), 85.9% (95% CI 84.7-87.1), and 78.8% (95% CI 77.0-80.6), respectively. Sex, tumor location, size, mitotic count, and rupture were independent prognostic factors. A new prognostic index (PI) was developed PI = 0.000 (if female) + 0.270 (if male) + 0.000 (if gastric GIST) + 0.
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