The application of capillary electrophoresis and liquid chromatography/mass spectrometry to the analysis of anaerobic and cyanoacrylate adhesives

This thesis details the application of separation techniques to the analysis of anaerobic and cyanoacrylate adhesives Chapter 1 is an introduction to adhesives, where the chemistry, composition and analysis of both types of adhesives are discussed. Chapter 2 represents the analytical study into the determination of the products of decomposition of two reducing agents in anaerobic adhesives. The decomposition of the reducing agents, 1,2,3,4 tetrahydroquinohne and dihydropyndine, in the presence of saccharin, maleic acid, cumene hydroperoxide and the metals, iron and copper, was investigated utilising Liquid Chromatography/Mass Spectrometry. A system was developed which was applied to the LC/MS determination of the products. This chapter also includes a brief discussion on LC/MS and the cure chemistry of the cyanoacrylate adhesives. In Chapter 3 the application of Capillary Electrophoresis to the separation of basic components found in cyanoacrylate adhesives is detailed. This chapter includes a literature survey on the analysis of basic compounds with Capillary Electrophoresis. An investigation into the optimum system for the separation of piperidine, dipipendinomethane and ethylpipendme carboxylate was carried out. The study includes an assessment of the suitability of a variety of electrolytes for the separation. In Chapter 4 suggestions for future research are made and conclusions are drawn from the work carried out in the thesis

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570