A Single Terminal [NiII-OH] Catalyst for Direct Julia-Type Olefination and α-Alkylation Involving Sulfones and Alcohols.

A terminal [NiII-OH] complex 1, supported by triflamide-functionalized NHC ligands, showed divergent reactivity for the reaction of sulfone with alcohol, contingent on base concentration, temperature, and time. Julia-type olefination of alcohols with sulfones was achieved using one equiv. of base, whereas lowering base loading to 0.5 equiv. afforded α-alkylated sulfones. Besides excellent substrate scope and selectivity, biologically active stilbene derivatives DMU-212, pinosylvin, resveratrol, and piceatannol were synthesized in high yield under Julia-type olefination conditions. An extensive array of controlled experiments and DFT calculations provide valuable insight on the reaction pathway.

A systematic review to summarize treatment patterns, guidelines, and characteristics of patients with renal cell carcinoma in the Asia-Pacific region.

INTRODUCTION: This systematic review evaluated treatment patterns and guidelines in advanced/metastatic and adjuvant renal cell carcinoma (RCC) in the Asia-Pacific region. AREAS COVERED: Embase, PubMed, and congresses were searched for observational studies and guidelines in accordance with PRISMA. Records published during 2016-2021 (2019-2021 for congresses) were included. EXPERT OPINION: Nine studies and three guidelines were identified overall. In advanced/metastatic RCC, the most common treatments were tyrosine kinase inhibitors (TKIs) (notably sunitinib: 33-100%) for first-line, and everolimus (13-85%) or axitinib (2-89%) for second-line therapy. In adjuvant RCC, sunitinib was most used (54%), followed by mammalian target of rapamycin inhibitors (mTORis, 27%) with immunotherapy being less common (16%). The guidelines provided varying recommendations for advanced/metastatic RCC. For first-line in advanced/metastatic clear cell RCC (the most common subtype), guidelines recommended mTORis (everolimus for poor-risk patients) (India, 2016); clinical study enrollment for high-risk patients or TKIs for low- to medium-risk patients (China, 2019); or immunotherapy based on survival benefits over sunitinib; dose adjustment was also recommended to manage TKI toxicities (Hong Kong, 2019). The landscape remained more static in the adjuvant setting, but best practice was uncertain. No clear trends were identified in patient characteristics.

Hydroarylation of alkynes via dual ortho-C-H functionalization of diaryl amines on a dicopper(I,I) platform.

A pyridine and morpholine-functionalized dicopper(I,I)-NHC complex (1) features both terminal and bridging coordination modes of NHC within the same molecule, and catalyzes dual ortho-C-H functionalization of diaryl amines for the hydroarylation of alkynes. A bimetallic construct in catalyst 1 allows sequential activation of ortho-C-H bonds of two aryl units to furnish a wide variety of 9,10-dihydroacridine derivatives without the explicit use of a directing group.

Cardiovascular safety of Glimepiride: An indirect comparison from CAROLINA and CARMELINA.

BACKGROUND: Despite having unquestionable glucose lowering efficacy, current guidelines no more favour the uses of sulphonylureas for CV safety concern, except when cost is an issue. However, formal cardiovascular outcome trial (CVOT) is not available. MATERIALS AND METHODS: We performed an indirect treatment comparison to find the hazard ratio for 3-point MACE, all-cause death, CV death and non-CV death between glimepiride and placebo based on two large CVOTs which established the CV safety of linagliptin (CARMELINA and CAROLINA). RESULTS: Glimepiride was shown to have a non-inferior risk compared to placebo for 3-point MACE (HR 1.04, 95% CI 0.850, 1.274), all-cause mortality (HR 1.08, 95% CI 0.880, 1.317), CV death (HR 0.96, 95% CI 0.732, 1.259), and non-CV death (HR 1.24, 95% CI 0.893, 1.733). CONCLUSION: Cardiovascular safety of glimepiride is re-assuring and may help patients with type 2 diabetes world-over to avail the benefit of this affordable efficacious medication.

Evaluation of Quality of Pharmacoeconomic Studies in Asia-Pacific Region and Identification of Influencing Variables.

OBJECTIVES: To assess the quality of pharmacoeconomic studies and identify different variables influencing the quality of these studies conducted in the Asia-Pacific (APAC) region. METHODS: A systematic literature search was performed with PubMed and Cochrane using different combinations of terms for cost-effectiveness, cost-utility, and cost-minimization analyses. The Quality of Health Economic Studies (QHES) instrument was used for quality assessment of included studies. Logistic regression was performed to determine the association of factors with high-quality studies (QHES score ≥75). RESULTS: Of 262 retrieved studies, 128 met the inclusion criteria. The mean QHES score was 67.4 ± 1.35. The distribution of studies in each quality quartile was as follows: high (n = 59 [46.09%]), fair (n = 50 [39.06%]), and poor (n = 19 [14.83%]). Most of the high-quality studies (n = 80 [62.5%]) were conducted in Japan and Australia. Only 11 high-quality studies (18.64%) were published in specialty journals and 4 (6.78%) in Asian journals. Primary authors who had advanced training in health economics were associated with a higher number of high-quality studies (n = 51 [86.44%]). Training of primary authors was significantly associated with high-quality studies (odds ratio 7.1; 95% confidence interval 2.9-19.23). Impact factor of journal, per-capita expenditure on health care, and out-of-pocket expense on health did not have a significant association with high-quality scores. CONCLUSIONS: High-quality pharmacoeconomic research is confined to a few countries of the APAC; it can be improved by advance training of authors in public health or health economics. Also, a greater interest of various stakeholders in funding the research and the introduction of specialty journals in the APAC are warranted.