Hypervalent alkylsilicates represent new and readily accessible precursors for the generation of alkyl radicals under photoredox conditions. Alkyl radicals generated from such silicates serve as ...effective hydrogen atom abstractors from thiols, furnishing thiyl radicals. The reactive sulfur species generated in this manner can be funneled into a nickel-mediated cross-coupling cycle employing aromatic bromides to furnish thioethers. The serendipitous discovery of this reaction and its utilization for the thioetherification of various aryl and heteroaryl bromides with a diverse array of thiols is described. The S–H selective H atom abstraction event enables a wide range of functional groups, including those bearing protic moieties, to be tolerated.
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In a prospective, randomized trial involving patients with resected pancreatic cancer, adjuvant combination chemotherapy with FOLFIRINOX resulted in a median disease-free survival of 21.6 months, as ...compared with 12.8 months with gemcitabine therapy. Overall survival was also longer with FOLFIRINOX.
A tale of mirrors: Bioisosteres are molecules resulting from the exchange of atoms or moieties with a functionally similar alternative to create a new molecule with similar biological properties to ...the parent compound. They could be described as an “imperfect” reflection in the mirror and are ubiquitous in medicinal chemistry. Though almost identical, their synthesis often implies very different routes and starting materials. In their Communication, F. H. Lutter and M. Jouffroy describe a mild and functional‐group‐tolerant synthesis of (hetero)aryl alkynes from the corresponding carboxylic acids toward the synthesis of triazole bioisosters. (DOI: 10.1002/chem. 202102130).
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Author’s response to letter “Implementation of earlier antibiotic administration in patients with severe sepsis and septic shock in Japan: antibiotic action needs time and tissue perfusion to reach ...target” Toshikazu Abe We appreciate the consideration and comments from the SAMU de Paris regarding our study. Management of time data is one of the most important processes in “time to intervention” studies. We studied multiple different time intervals as we recorded time as a continuous variable; however, results with these values were not different from what we ultimately described. The relationship between time to antibiotic administration and mortality is not linear; therefore, we dealt with time data as a categorical variable. Hourly categorization is the most acceptable time interval used by clinicians. Because the number of patients receiving antibiotics after 361 min was small, we grouped those patients together. Our study did not mention causal inference, and it is a descriptive analysis using implementation science. We did not show mean blood pressure, but we controlled tissue perfusion pressure by using the Sequential Organ Failure Assessment (SOFA), which includes a cardiovascular score. We also stratified patients by the presence or absence of shock. However, we did not find any association between time to antibiotic and outcomes with adjustment of those variables. As you noted, the effect of antibiotics would be related to the time to administration and antibiotic sensitivity, concentration, and tissue perfusion. These variables may be even more important than time to administration. The lack of association between time to antibiotic administration and outcomes in our study may have been because of the lack of information about the variables. Other aspects of treatment may have differed among institutions, although we controlled for that using generalized estimating equations (GEE). We believe that the effect of time to administration will be significant only when the overall quality of care is excellent. As with the differences for door to balloon time for acute coronary syndrome noted in the research by Menees and colleagues 6 and the research by Nallamothu and colleagues 7, the difference in quality may only be distinguished in highly standardized facilities. A more accurate diagnosis may allow for better antibiotic choices, which is related to the outcome of time to antibiotic administration 8, 9. Generally, antibiotics for meningitis should be administrated within 30 min, whereas antibiotics for infective endocarditis can wait for administration until culture results indicate the specific pathogen, as long as the patient’s vital signs are stable. Time recommendations for administration of antibiotics to patients with sepsis could be modified for different sites of infection as well as different clinical presentations, such as vague or apparent symptoms, and shock 10.
...sedation should be started as soon as possible in order to put the brain to rest. ...blood pressure should be optimized, avoiding both cerebral hypoperfusion due to post-resuscitation syndrome ...and, conversely, hyperperfusion, which could lead to cerebral edema. ...even if administration of adrenaline is a key aspect of ROSC, it is not sufficient alone to increase short- and especially long-term survival after cardiac arrest.
•In the “big five”.•Reporting about variable selection methods is insufficient.•Data-driven methods are not commonly used in causal explanatory models.•The addition of an adjustment variable is ...common in sensitivity analyses.
Objective This work presents a review of the literature on reporting, practice and misuse of knowledge-based and data-driven variable selection methods, in five highly cited medical journals, considering recoding and interaction unlike previous reviews.
Study Design and Setting Original observational studies with a predictive or explicative research question with multivariable analyses published in N. Engl. J. Med., Lancet, JAMA, Br. Med. J. and Ann. Intern. Med. between 2017 and 2019 were searched. Article screening was performed by a single reader, data extraction was performed by two readers and a third reader participated in case of disagreement. The use of data-driven variable selection methods in causal explicative questions was considered as misuse.
Results 488 articles were included. The variable selection method was unclear in 234 (48%) articles, data-driven in 78 (16%) articles and knowledge-based in 176 (36%) articles. The most common data-driven methods were: Univariate selection (n = 22, 4.5%) and model comparisons or testing for interaction (n = 17, 3.5%). Data-driven methods were misused in 51 (10.5%) of articles.
Conclusion Overall reporting of variable selection methods is insufficient. Data-driven methods seem to be used only in a minority of articles of the big five medical journals.
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Abstract Acetabular fractures can be challenging to treat, in part because the shape of the fixation plates needs to be adjusted during the surgical procedure. One possibility is to generate a model ...of the uninjured half of a fractured pelvis with 3D printing, and then pre-contour the fixation plates preoperatively on this model. The purpose of this technical note is to describe how we used 3D printing as an aid to treat acetabular fractures. The quality of the fracture reduction, fracture fixation and time savings were evaluated. Three-dimensional reconstructions of the preoperative CT scan of the pelvis were exported with OsiriX™ software, mirrored with Meshmixer™ software and then printed in polylactic acid (PLA). Two fracture fixation plates were pre-contoured on the printed hemipelvis and then sterilized. No additional intraoperative contouring was needed. Anatomical reduction was obtained with an estimated 30-minute time saving and € 6 consumables cost.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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