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Aims A third of non-valvular atrial fibrillation (NVAF) patients are non-adherent to direct oral anticoagulants (DOACs). Estimates of the economic value of full adherence and the cost of two types of adherence improving interventions are important to healthcare planners and decision-makers. Methods A cost-utility analysis estimated the impact of non-adherence over a 20-year horizon, for a patient cohort with a mean age of 77 years, based on data from the Stockholm Healthcare database of NVAF patients with incident stroke between 2011 and 2018. Adherence was defined using a medication possession ratio (MPR) cut-off of 90%; primary outcomes were the number of ischemic strokes and associated incremental cost-utility ratio. Results Hypothetical comparisons between cohorts of 1,000 patients with varying non-adherence levels and full adherence (MPR >90%) predicted an additional number of strokes ranging from 117 (MPR = 81-90%) to 866 (MPR

To compare cost offsets and contributing factors (false-negative rates and confirmatory imaging requirements, potentially leading to longer waiting times for diagnosis) as well as long-term cost effectiveness associated with the diagnostic and treatment pathways for colorectal cancer liver metastases (CRCLM) in the US, Japan, and China according to initial imaging modality used. Gadoxetate disodium (ethoxylbenzyl-diethylenetriaminepentaacetic acid)-enhanced magnetic resonance imaging (EOB-MRI) was compared to multidetector computed tomography (MDCT), extracellular contrast media enhanced-MRI (ECCM-MRI) (the US and China only) and contrast-enhanced ultrasound (CEUS). Decision tree models were developed to simulate the clinical pathway, from first diagnostic test to initial treatment decision, based on local clinical guidelines and validated by experts. Input data were derived from the literature (up to 31st December 2020) as well as from interviews with local experts. A Markov model extension was built to evaluate the number of false-negative patients and associated costs, over a lifetime horizon. The decision-tree models showed that, increasing proportionate use of initial EOB-MRI resulted in a cost-offset per patient (excluding false-negative patients) in all countries (USD 201 for the US, JPY 6,284 for Japan and CNY 446 for China) driven by reductions in follow-on diagnostic procedures and unnecessary treatment. The use of EOB-MRI was also associated with a shorter average waiting time to a final diagnosis and treatment decision compared to MDCT, ECCM-MRI and CEUS. The Markov model showed that with an increase in EOB-MRI use, there are fewer false-negative diagnoses over a lifetime horizon. In all three countries, the incremental cost-effectivenes ratio (ICER) was below standard willingness-to-pay thresholds. The findings of these models demonstrate that use of EOB-MRI early in the diagnostic pathway for CRCLM results in short-term cost savings, as well as being cost effective in the long term.

A direct and efficient approach for the trifluoromethylation and pentafluoroethylation of 1,1-diaryl-2,2-difluoroethenes with TMSCF3 and TMSCF2CF3 in the presence of TBAF was developed. The reactions proceeded smoothly under mild reaction conditions to give the corresponding monotrifluoromethylated, bistrifluoromethylated, monopentafluoroethylated and bispentafluoroethylated products in fair to good yields, respectively, without the addition of metal catalyst.

A mild and convenient method for the stereoselective synthesis of a series of conjugated β-fluoroenynes by the reaction of gem-difluoroalkenes with terminal alkynes with the assistance of n-butyllithium and K3PO4 is described.

A novel Kumada-Tamao-Corriu cross-coupling reaction of gem-di- or monofluoroalkenes with Grignard reagents, with or without β-hydrogen atoms, in the presence of a catalytic amount of palladium- or nickel-based catalysts has been developed. The reaction is performed under mild conditions (room temperature or reflux in diethyl ether for 1-2 h) and leads to di-cross- or mono-cross-coupled products in good to high yields.

A series of 1-aryl-5-trifluoromethyl (or difluoromethyl)–1,4,5-trisubstituted 1,2,3-triazoles were synthesized in high yield by a novel one-pot three-component reaction of arylboronic acids, sodium azide, and active methylene ketones, such as ethyl 4,4-difluoroacetoacetate or ethyl 4,4,4-trifluoroacetoacetate in the presence of Cu(OAc)2 and piperidine using a DMSO/H2O (10/1) mixture as solvent.

A novel, one-pot, three-component approach for the synthesis of 1,4,5-trisubstituted 1,2,3-triazoles through the cycloaddition of a wide range of primary alcohols with sodium azide and active methylene ketones in the presence of N-(p-toluenesulfonyl)imidazole, tetrabutylammonium iodide, and triethylamine in DMF/DMSO has been developed.

Ten novel analogues of flubendiamide containing a hexafluoroisopropanol moiety were designed and synthesized. Their insecticidal activities against armyworm (Pseudaletia separata Walker) were examined and compared with the commercial product flubendiamide. Compound 7b showed nearly the same insecticidal activity as flubendiamide against armyworm.

Fourteen difluoromethyl-containing 1,4-disubstituted 1,2,3-triazoles were synthesized via a novel copper-catalyzed click-multicomponent reaction of 2,2-difluoro-2-phenylsulfanylethanol, sodium azide and terminal alkynes in the presence of N- (p-toluenesulfonyl)imidazole, tetrabutylammonium iodide and triethylamine, followed by reductive cleavage of the phenylsulfanyl group using tributyltin hydride and azobisisobutyronitrile.

A direct and efficient approach for the trifluoromethylation and pentafluoroethylation of 1,1-diaryl-2,2-difluoroethenes with TMSCF3 and TMSCF2CF3 in the presence of TBAF is developed.

A novel Kumada–Tamao–Corriu cross-coupling reaction of gem-di- or monofluoroalkenes with Grignard reagents, with or without β-hydrogen atoms, in the presence of a catalytic amount of palladium- or nickel-based catalysts has been developed. The reaction is performed under mild conditions (room temperature or reflux in diethyl ether for 1–2 h) and leads to di-cross- or mono-cross-coupled products in good to high yields.

A novel, inexpensive, and efficient palladium-, copper-, ligand-, and amine-free Sonogashira-type cross-coupling reaction of terminal alkynes with unreactive aryl fluorides in the presence of sodium, sodium methoxide, and calcium hydroxide under the assistance of a Grignard reagent was developed. A plausible mechanism was also suggested.

A series of 1-aryl-5-trifluoromethyl (or difluoromethyl)–1,4,5-trisubstituted 1,2,3-triazoles were synthesized in high yield by a novel one-pot three-component reaction of arylboronic acids, sodium azide, and active methylene ketones, such as ethyl 4,4-difluoroacetoacetate or ethyl 4,4,4-trifluoroacetoacetate in the presence of Cu(OAc)2 and piperidine using a DMSO/H2O (10/1) mixture as solvent.

A novel, inexpensive, and efficient palladium-, copper-, ligand-, and amine-free Sonogashira-type cross-coupling reaction of terminal alkynes with unreactive aryl fluorides in the presence of sodium, sodium methoxide, and calcium hydroxide under the assistance of a Grignard reagent was developed. A plausible mechanism was also suggested.

This method uses mild reaction conditions to give the 1,2,3-triazoles (III) in good yields.

Fourteen difluoromethyl-containing 1,4-disubstituted 1,2,3-triazoles were synthesized via a novel copper-catalyzed click-multicomponent reaction of 2,2-difluoro-2-phenylsulfanylethanol, sodium azide and terminal alkynes in the presence of N- (p-toluenesulfonyl)imidazole, tetrabutylammonium iodide and triethylamine, followed by reductive cleavage of the phenylsulfanyl group using tributyltin hydride and azobisisobutyronitrile.

For understanding the effects of rising temperature and alternate drying-wetting on soil respiration rate,the soil respiration rate(Rr),5 cm soil temperature(θ) and 5 cm soil volume water content(φ) were measured during the alternate drying-wetting period in a Pinus tabulaeformis plantation in the Taiyue Mountain of Shanxi Province,China.It was observed that three rainfall events caused significant alterations of φ in that period,meanwhile,θ increased due to the monsoon climate.The Li-8150 automated soil CO2flux system was used to monitor Rr in situ every hour from May 13th to June 19th,and the environmental factors were also measured simultaneously.In three different scales that include the raw data(Rr1,θ1,φ1),the hourly average data(Rr2,θ2,φ2) and the daily average data(Rr3,θ3,φ3),θ dependent models of soil respiration,φ dependent models of soil respiration and double predictor models of soil respiration based on both θ and φ were used to fit the data respectively.The results showed that:(1) During the alternate drying-wetting period,Rr was promoted as a whole by rainfalls;the dynamic changes of Rr and φ were very similar;while there was a negative correlation between φ and θ.(2) In different scales,the fitting effects of models based on the daily average data were the best,and those based on the raw data were the worst.(3) In the same scale,the double predictor models were superior to the single predictor ones;the non-linear models were superior to the linear ones.In conclusion,the dynamic response of soil respiration to the alternate drying-wetting was obvious in P.tabulaeformis plantation of the Taiyue Mountain.In all the models,the non-linear double predictor model based on the daily average data had the most explanatory power.