Effect of active temperature management on mortality in intensive care unit patients.

OBJECTIVE: To evaluate the effect of active temperature management on mortality, intensive care unit (ICU) and hospital length of stay, as well as the relative efficacy of antipyretic medications and physical cooling devices for achieving reductions in temperature in critically ill adults. DESIGN, SETTING AND PARTICIPANTS: Systematic review and meta-analysis of randomised controlled trials (RCTs) investigating treatments administered to febrile patients in order to reduce body temperature. Fifteen studies reporting results from 13 RCTs met our eligibility criteria. INTERVENTIONS: Treatments administered to reduce body temperature were defined as physical cooling, nonsteroidal anti-inflammatory drugs, paracetamol, or any combination of these. MAIN OUTCOME MEASURES: The primary outcome variable was all-cause mortality at the longest time point after randomisation. Secondary outcomes were ICU and hospital length of stay, and body temperature 12 hours after randomisation. RESULTS: Active temperature control had no statistically significant association with mortality (odds ratio, 1.01; 95% confidence interval [CI], 0.81-1.28; P = 0.95, for fixed effects). There was no statistically significant association between active temperature management and ICU or hospital length of stay. Active temperature management was associated with a statistically significant reduction in temperature. The fixed effects estimate for the active minus control treatment for pharmaceutical management was -0.62C (95% CI, -0.72C to -0.51C; P < 0.001) and for physical cooling was -1.59C (95% CI, -1.82C to -1.35C; P < 0.001). CONCLUSIONS: Active temperature management neither increased nor decreased mortality risk in critically ill adults. When the therapeutic goal is to reduce body temperature, physical cooling approaches may be more effective than pharmacological measures in critically ill adults.

An Improved Process for the Preparation of an α,α-Difluorosulfonylisoxazoline Herbicide.

An efficient synthesis of a difluorosulfone-containing herbicide has been achieved by selective reductive silylation of a symmetrical bis(trifluoromethyl)-1,2,3-triazole. Subsequently, a fluoride-induced reaction led to a difluoromethyl anion equivalent, which was reacted with a sulfur electrophile leading ultimately to the key difluorosulfide moiety.

Synthesis of pandamarilactone-1.

The first total synthesis of pandamarilactone-1, an alkaloid of Pandanus amaryllifolius, is reported. The nine-step synthesis features furan oxidation with singlet oxygen and then spiro-N,O-acetalization and elimination to generate the natural product and further Pandanus alkaloids, pandamarilactonines A-D.

Conformational preferences of oxy-substituents in butenolide-tetrahydropyran spiroacetals and butenolide-piperidine spiro-N,O-acetals.

We describe the synthesis of a series of oxy-substituted butenolide spiroacetals and spiro-N,O-acetals by oxidative spirocyclisation of 2-[(4-hydroxy or 4-sulfonamido)butyl]furans. The axial-equatorial preference of each oxy-substituent is investigated (NMR) by an acid-catalysed thermodynamic relay of configuration between the spiro- and oxy-centres. The axial site is preferred for most oxy-substituents at synthetically useful levels. The potential origins of this preference are discussed in terms of a stabilising gauche effect combined with the influence of solvation. These results have relevance to the synthesis of bis(acetylenic)enol ether spiroacetals including AL-1 and related compounds.

Iron(II) triflate as an efficient catalyst for the imination of sulfoxides.

The challenging imination of benzyl-, sterically demanding alkyl-, and heteroaryl-substituted sulfoxides has been studied. Iron(II) triflate was identified as a highly efficient and robust catalyst for sulfur imination reactions. A variety of sulfoxides and sulfides were efficiently iminated with sulfonyliminoiodinanes (PhI=NSO(2)R) at room temperature to give the corresponding sulfoximines and sulfilimines in good yields and with short reaction times.

Progress in the synthesis of the lituarines: stereocontrol in sequential C-C bond formation on a spirobutenolide template.

[structure: see text] We describe elaboration of a tricyclic spirobutenolide corresponding to the C(7-18) tricyclic substructure common to lituarines A-C. Conjugate addition, to install the C(16) methyl, is followed by construction of the crucial C(18-19) bond by silyl enol ether addition to the derived spiroacetal C(18)-O oxonium ion. Esterification with a C(1-6) acid, and selective ozonolysis to release the C(23) carbonyl, complete the assembly of all the carbons present in the lituarine macrocyclic core.

Syntheses of the C(1-6) and C(19-24) fragments of lituarines A, B, and C.

[structure: see text] Lituarines A-C are marine natural products comprising a tricyclic spiroacetal bridged at C(8) and C(18) by a functionalized ester linkage conceptually obtained from a C(19-24) alcohol and a C(1-6) carboxylic acid whose oxidation level varies at C(4) and C(5). Stereoselective routes are described to compounds 26 and 27, fully functionalized ester fragments of lituarine A and lituarines B and C, respectively.

Stereoselective synthesis of the lituarine tricyclic spiroacetal.

[reaction: see text] Oxidative cyclizations of 2-(4-hydroxybutyl)furan derivatives provide spirobutenolide acetals directly; on the basis of this methodology, we describe an asymmetric synthesis of a tricyclic spirobutenolide precursor to the C(7-18) fragment common to lituarines A-C.