NS disease control rate was 90% (95% CI, 85%-93%; n = 246). Included studies reported complete intracranial response rates of 7% to 23%, median best decrease in intracranial lesion size of -40% to -64%, and Common Terminology Criteria for Adverse Events (version 3.0) grade 3 or higher adverse event rates of 19% to 39%. Subgroup analyses did not reveal additional sources of heterogeneity. Conclusions and Relevance Findings reported herein support a potential role for osimertinib in the treatment of patients with metastatic EGFR-variant NSCLC and IMD treated with osimertinib. Clinical decision makers would benefit from the inclusion of patients with IMD in future trials to identify factors that predict responses to targeted therapy.Importance Since 2011, immune checkpoint inhibitors (ICIs) have been effective treatment options for advanced melanoma. Little is known about how risks of immune-related adverse events (irAEs) vary by ICIs. Objective To compare the risk of irAEs across different treatment regimens for advanced melanoma using network meta-analysis. Data Sources PubMed/MEDLINE, Embase, Web of Science, and Scopus were searched for all randomized clinical trial (RCT) articles published from January 1, 2010, through June 30, 2019. Study Selection Studies included phases 2 and 3 RCTs in the treatment of advanced melanoma that compared ICIs (ipilimumab, nivolumab, and pembrolizumab) with chemotherapy drugs (eg, dacarbazine, carboplatin, and paclitaxel) or different ICI regimens. Data Extraction and Synthesis Different treatment regimens were compared using bayesian network meta-analysis with Markov chain Monte Carlo simulation with noninformative prior distribution and random-effects generalized linear models. Main Outcomes and Measvidence from head-to-head comparisons is lacking.Importance Suicide is a leading cause of mortality, with suicide-related deaths increasing in recent years.  https://www.selleckchem.com/products/h-1152-dihydrochloride.html  Automated methods for individualized risk prediction have great potential to address this growing public health threat. To facilitate their adoption, they must first be validated across diverse health care settings. Objective To evaluate the generalizability and cross-site performance of a risk prediction method using readily available structured data from electronic health records in predicting incident suicide attempts across multiple, independent, US health care systems. Design, Setting, and Participants For this prognostic study, data were extracted from longitudinal electronic health record data comprising International Classification of Diseases, Ninth Revision diagnoses, laboratory test results, procedures codes, and medications for more than 3.7 million patients from 5 independent health care systems participating in the Accessible Research Commons for Health network. Across sites, 6 to 17 yearsal health conditions (eg, borderline personality disorder, with odds ratios of 8.1-12.9, and bipolar disorder, with odds ratios of 0.9-9.1) and substance use disorders (eg, drug withdrawal syndrome, with odds ratios of 7.0-12.9). Despite variation in geographical location, demographic characteristics, and population health characteristics, model performance was similar across sites, with areas under the curve ranging from 0.71 (95% CI, 0.70-0.72) to 0.76 (95% CI, 0.75-0.77). Across sites, at a specificity of 90%, the models detected a mean of 38% of cases a mean of 2.1 years in advance. Conclusions and Relevance Across 5 diverse health care systems, a computationally efficient approach leveraging the full spectrum of structured electronic health record data was able to detect the risk of suicidal behavior in unselected patients. This approach could facilitate the development of clinical decision support tools that inform risk reduction interventions.Importance Opioid prescriptions for treatment of pain in emergency departments (EDs) are associated with long-term opioid use. The temporal pattern of opioid prescribing in the context of the opioid epidemic remains unknown. Objective To examine the temporal pattern of opioid prescribing within an ED for varying pain conditions between 2009 and 2018. Design, Setting, and Participants A population-based, cross-sectional study was conducted at the ED of an urban academic medical center. All patients treated within that ED between January 1, 2009, and December 31, 2018, were included. Main Outcomes and Measures The proportion of patients prescribed an opioid for treatment of pain in the ED temporally by condition, condition type, patient demographics, and physician prescriber. Results Between 2009 and 2018, 556 176 patient encounters took place in the ED, with 70 218 unique opioid prescriptions ordered. A total of 316 632 patients (55.9%) were female, 45 070 (42.6%) were of white race, and 43 412 (40.6%) were pran (aOR, 0.714; 95% CI, 0.665-0.764) had the lowest odds of receiving an opioid compared with other racial/ethnic groups. Conclusions and Relevance There was a substantial temporal decrease in the number of opioid prescriptions within this ED during the study period. This decrease was associated with substantial relative reductions in opioid prescribing for treatment of musculoskeletal pain compared with fractures and kidney stones.Rubber trees (Hevea brasiliensis) are the main source of natural rubber, extracted from latex, which exudes from the trunk after tapping. Tapped trees require large amounts of carbon (C) to regenerate the latex after its collection. Knowing the contribution of C sources involved in latex biosynthesis will help in understanding how rubber trees face this additional C demand. Whole crown 13CO2 pulse labelling was performed on 4-year-old rubber trees in June, when latex production was low, and in October, when it was high. 13C content was quantified in the foliage, phloem sap, wood, and latex. In both labelling periods, 13C was recovered in latex just after labelling, indicating that part of the carbohydrate was directly allocated to latex. However, significant amounts of 13C were still recovered in latex after 100 d and the peak was reached significantly later than in phloem sap, demonstrating the contribution of a reserve pool as a source of latex C. The contribution of new photosynthates to latex regeneration was faster and higher when latex metabolism was well established, in October, than in June.