The Incidence of Perioperative Hypotension in Patients Undergoing Major Abdominal Surgery with the Use of Arterial Waveform Analysis and the Hypotension Prediction Index Hemodynamic Monitoring-A Retrospective Analysis.

Intraoperative hypotension (IH) is common in patients receiving general anesthesia and can lead to serious complications such as kidney failure, myocardial injury and increased mortality. The Hypotension Prediction Index (HPI) algorithm is a machine learning system that analyzes the arterial pressure waveform and alerts the clinician of an impending hypotension event. The purpose of the study was to compare the frequency of perioperative hypotension in patients undergoing major abdominal surgery with different types of hemodynamic monitoring. The study included 61 patients who were monitored with the arterial pressure-based cardiac output (APCO) technology (FloTrac group) and 62 patients with the Hypotension Prediction Index algorithm (HPI group). Our primary outcome was the time-weighted average (TWA) of hypotension below < 65 mmHg. The median TWA of hypotension in the FloTrac group was 0.31 mmHg versus 0.09 mmHg in the HPI group (p = 0.000009). In the FloTrac group, the average time of hypotension was 27.9 min vs. 8.1 min in the HPI group (p = 0.000023). By applying the HPI algorithm in addition to an arterial waveform analysis alone, we were able to significantly decrease the frequency and duration of perioperative hypotension events in patients who underwent major abdominal surgery.

Design, synthesis and spectroscopic properties of crown ether-capped dibenzotetraaza[14]annulenes.

The first crown ether-capped dibenzotetraaza[14]annulenes (DBTAAs), featuring two macrocyclic binding sites fixed in a face-to-face orientation, were synthesized in satisfactory 26-28% isolated yields. Direct N-alkylation of 1,4,10-trioxa-7,13-diazacyclopentadecane by symmetric DBTAA derivatives bearing bromoalkoxy pendants proceed smoothly at a reasonable level of dilution (1.25 mM). The structures were fully characterized by HR-ESIMS, FTIR-ATR, 1H and 13C NMR spectroscopy and elemental analysis.

Multichromophore arrays of dibenzotetraaza[14]annulene: a promising platform for bioorganic chemistry.

The first series of discrete multichromophore arrays of dibenzotetraaza[14]annulene (DBTAA), containing flexible bridges, have been synthesized in 40-46% isolated yields. The key asymmetrical intermediates, carrying two distinctly addressable functionalities (ROH vs. ROCH2-C[triple bond, length as m-dash]C-H and R(CH2)nBr vs. ROCH2-C[triple bond, length as m-dash]C-H) at the macrocycle periphery, were synthesized in moderate to high (30-78%) isolated yields. Facile synthetic protocols developed for the synthesis of discrete DBTAA arrays offer several advantages such as operational simplicity and easy post-synthetic workup that overcome the need for laborious chromatographic purification. All new compounds were characterized by microanalysis, mass spectrometry, UV-Vis, FTIR-ATR, and 1H and 13C NMR spectroscopy. Structural features were briefly discussed with emphasis on several potential applications.

Revealed preferences towards the appraisal of orphan drugs in Poland - multi criteria decision analysis.

BACKGROUND: A Multi Criteria Decision Analysis (MCDA) technique was adopted to reveal the preferences of the Appraisal Body of the Polish HTA agency towards orphan drugs (OMPs). RESULTS: There were 34 positive and 23 negative HTA recommendations out of 54 distinctive drug-indication pairs. The MCDA matrix consisted of 13 criteria, seven of which made the most impact on the HTA process. Appraisal of clinical evidence, cost of therapy, and safety considerations were the main contributors to the HTA guidance, whilst advancement of technology and manufacturing costs made the least impact. CONCLUSIONS: MCDA can be regarded as a valuable tool for revealing decision makers' preferences in the healthcare sector. Given that only roughly half of all criteria included in the MCDA matrix were deemed to make an impact on the HTA process, there is certainly some room for improvement with respect to the adaptation of a new approach towards the value assessment of OMPs in Poland.

Insight into lipophilicity of deoxyribonucleoside­boron cluster conjugates.

Lipophilicity was investigated for 20 2'-deoxyribonucleoside derivatives modified with electron-neutral 1,2-dicarba-closo-dodecaborane, 1,12-dicarba-closo-dodecaborane, 7,8-dicarba-nido-undecaborate anion, and metallacarborane containing Co, Fe, or Cr. The partition coefficient (P) for neutral conjugates and the distribution coefficient (D7.4) for ionic compounds were determined as a lipophilicity descriptor using a shake-flask method. All modified nucleosides had P/D7.4 values higher than those of an appropriate unmodified 2'-closo-dodecaborane and metallacarborane was found to be three orders of magnitude higher than that of its unmodified counterpart. The lowest impact on the P/D7.4 values of the conjugates was observed for the 7,8-dicarba-nido-undecaborate anion. A preliminary molecular modeling study of a thymidine-carborane conjugate with ß-cyclodextrin confirmed the ability of the components to form an inclusion complex.

TEMPO-Appended Metal-Organic Frameworks as Highly Active, Selective, and Reusable Catalysts for Mild Aerobic Oxidation of Alcohols.

Metal-organic frameworks (MOFs) decorated with stable organic radicals are highly promising materials for redox catalysis. Unfortunately however, the synthesis of chemically robust MOFs typically requires harsh solvothermal conditions, which are not compatible with organic radicals. Here, we describe the synthesis of two isoreticular families of stable, mixed component, zirconium MOFs with UiO-66 and UiO-67 structures and controlled amounts of covalently attached TEMPO radicals. The materials were obtained using a relatively low-temperature, HCl-modulated de novo method developed by Hupp and Farha and shown to contain large amounts of missing cluster defects, forming nanodomains of the reo phase with 8-connected clusters. In the extreme case of homoleptic UiO-67-TEMPO(100%), the material exists as an almost pure reo phase. Large voids due to missing clusters and linkers allowed these materials to accommodate up to 2 times more of bulky TEMPO substituents than theoretically predicted for the idealized structures and proved to be beneficial for catalytic activity. The TEMPO-appended MOFs were shown to be highly active and recyclable catalysts for selective aerobic oxidation of a broad range of primary and secondary alcohols under exceptionally mild conditions (room temperature, atmospheric pressure of air). The influence of various parameters, including the pore size and TEMPO content, on the catalytic activity was also comprehensively investigated.

Potential impact of the implementation of multiple-criteria decision analysis (MCDA) on the Polish pricing and reimbursement process of orphan drugs.

BACKGROUND: The objective of this study was to assess the potential impact of the implementation of multiple-criteria decision analysis (MCDA) on the Polish pricing and reimbursement (P&R) process with regard to orphan drugs. METHODS: A four step approach was designed. Firstly, a systematic literature review was conducted to select the MCDA criteria. Secondly, a database of orphan drugs was established. Thirdly, health technology appraisals (HTA recommendations) were categorized and an MCDA appraisal was conducted. Finally, a comparison of HTA and MCDA outcomes was carried out. An MCDA outcome was considered positive if more than 50% of the maximum number of points was reached (base case). In the sensitivity analysis, 25% and 75% thresholds were tested as well. RESULTS: Out of 2242 publications, 23 full-text articles were included. The final MCDA tool consisted of ten criteria. In total, 27 distinctive drug-indication pairs regarding 21 drugs were used for the study. Six negative and 21 positive HTA recommendations were issued. In the base case, there were 19 positive MCDA outcomes. Of the 27 cases, there were 12 disagreements between the HTA and MCDA outcomes, the majority of which related to positive HTA guidance for negative MCDA outcomes. All drug-indication pairs with negative HTA recommendations were appraised positively in the MCDA framework. Economic details were available for 12 cases, of which there were 9 positive MCDA outcomes. Amongst the 12 drug-indication pairs, two were negatively appraised in the HTA process, with positive MCDA guidance, and two were appraised in the opposite direction. CONCLUSIONS: An MCDA approach may lead to different P&R outcomes compared to a standard HTA process. On the one hand, enrichment of the list of decision making criteria means further scrutiny of a given health technology and as such increases the odds of a negative P&R outcome. On the other hand, it may uncover additional values and as such increase the odds of positive P&R outcomes.

Oseltamivir analog with boron cluster modulator.

Synthesis of novel neuraminidase inhibitor -- carborane ester of oseltamivir carboxylic acid is described, and its physicochemical and spectral characteristics is provided. Surprisingly, carborane analog of oseltamivir is of an order of magnitude less active than its precursor, the corresponding ethyl ester, which is the active principle of pharmaceutical preparations used in influenza prophylactics and therapy.

[Bone turnover markers in patients with leg ischemia before and after revascularization]. / Markery obrotu kostnego u pacjentów z niedokrwieniem konczyn przed i po rewaskularyzacji.

In patients with leg ischemia bone metabolism impairment has been observed. The aim of this study was to investigate the biochemical bone metabolism markers. Elevated level of osteolysis markers was observed before and 7 days after revascularization the level of markers was unchanged.