Search

Background: There is global concern regarding the public health impact of electronic cigarettes (ECs). ECs are commonly promoted as safer than conventional cigarettes (CCs), however there is limited knowledge of the long-term health effects. This scoping review examined the pulmonary health effects of ECs reported in the literature from 2009 to 2019. Method: PubMed, CINAHL, and Science Direct databases were used. Search terms included "vaping, electronic nicotine delivery systems, electronic cigarettes, lung diseases, respiratory diseases, and pulmonary." Original research articles in English that used human subjects between January 1, 2009 and January 31, 2020 and reported pulmonary outcomes were included. Results: Forty-five studies met the inclusion criteria. There were 14 (31.1%) randomized experimental, 7 (15.6%) nonrandomized experimental, 6 (13.3%) cohort, and 18 (40.0%) cross-sectional studies. Sixteen (35.6%) studies were conducted in the United States; the rest were conducted across 11 other countries. The total number of subjects was 1,465,292 and ages ranged from 12 to 99 years across studies. Eligible studies demonstrated an association between EC use and pulmonary symptoms, asthma and chronic obstructive pulmonary disease diagnosis and exacerbations. The degree of this association varied based on the use of additional tobacco products. EC use resulted in worse outcomes than nonsmoking, but resulted in improved outcomes when compared with CC use or dual use of CC and EC. Conclusion: Evidence indicates that EC use, especially dual use, leads to negative pulmonary effects and adverse outcomes. Education on the potential risks and publishing of EC ingredients on labels could help improve public health safety communication and reduce EC use. [ABSTRACT FROM AUTHOR]

What is known and objective: Metastatic renal cell carcinoma (mRCC) is the most common type of kidney cancers. Disease‐specific survival for mRCC has been significantly improved with the introduction of new targeted agents since 2005. However, there is a lack of head‐to‐head clinical trials comparing the efficacy between therapies. This study compared indirectly progression‐free survival (PFS) and overall survival (OS) among first‐line and second‐line therapies in patients with mRCC using network meta‐analysis (NMA). Methods: The PubMed, MEDLINE, Cochrane Library and Web of Science were searched to identify phase II or phase III randomized controlled trials (RCTs) of targeted and biological therapies in patients with mRCC published between January 2000 and June 2020. The Bayesian fixed‐effect NMA was performed to evaluate relative PFS and OS of first‐line and second‐line therapies of axitinib, bevacizumab, cabozantinib, everolimus, lenvatinib, nivolumab, ipilimumab, pazopanib, sorafenib, sunitinib, temsirolimus, tivozanib, avelumab and pembrolizumab, which were approved by the Food and Drug Administration or European Medicines Agency. End points were compared using hazard ratio (HR) and 95% credible interval (CrI). The surface under the cumulative ranking curve (SUCRA) was estimated to assess the probability of being the best treatment. Results and discussion: A total of 26 RCTs (first line: 19, second line: 9) with 13 893 patients were included in the NMA. For the first‐line therapy, cabozantinib was associated with the highest improved PFS (HR = 0.26, 95% CrI = 0.14‐0.44) followed by avelumab + axitinib and pembrolizumab + axitinib (HR = 0.27, SUCRA = 90%). Pembrolizumab + axitinib had a high likelihood of being the preferred treatment when using OS as the outcome measure (HR = 0.41, 95% CrI = 0.16‐0.85). Avelumab + axitinib had the lowest HR compared with placebo + interferon on discontinuations due to AE (HR = 1.04, 95% CrI = 0.54‐1.86). For second‐line therapy, cabozantinib was identified as the most effective treatment option when assessing PFS (HR = 0.17, 95% CrI = 0.12‐0.24). Axitinib had the lowest HR of OS and discontinuation due to AE (HR = 0.54, 95% CrI = 0.40‐0.71; HR = 0.98, 95% CrI = 0.42‐1.97, respectively). Pazopanib was the second choice in terms of OS (HR = 0.56, 95% CrI = 0.28‐1.00; SUCRA = 76%) compared with placebo. What is new and conclusion: With respect to PFS and OS improvement, cabozantinib, avelumab + axitinib and pembrolizumab + axitinib are likely to be the preferred options for the first‐line therapy and cabozantinib and axitinib for the second‐line therapy in the management of mRCC. Regarding safety, avelumab + axitinib and temsirolimus were considered preferred treatment options in first‐line and second‐line therapies. More future research is needed to establish subgroup analyses, allowing evaluation of the impact of some of the differences in patient characteristics, including treatment effect modifiers. [ABSTRACT FROM AUTHOR]

Alkylations of conformationally constrained acyclic nitriles containing vicinal dimethyl groups and an adjacent phenyl group or trisubstituted alkenes are shown to be highly diastereoselective. The analysis of metalated nitrile alkylations has identified the key structural features needed for high 1,2-asymmetric induction, has addressed the challenge of asymmetric alkylations with acyclic metalated nitriles and has provided a versatile method for installing hindered quaternary centers with excellent stereocontrol.