Long-term outcomes with haloperidol versus placebo in acutely admitted adult ICU patients with delirium.

Purpose: We assessed long-term outcomes in acutely admitted adult patients with delirium treated in intensive care unit (ICU) with haloperidol versus placebo.

Methods: We conducted pre-planned analyses of 1-year outcomes in the Agents Intervening against Delirium in the ICU (AID-ICU) trial, including mortality and health-related quality of life (HRQoL) assessed by Euroqol (EQ) 5-dimension 5-level questionnaire (EQ-5D-5L) index values and EQ visual analogue scale (EQ VAS) (deceased patients were assigned the numeric value zero). Outcomes were analysed using logistic and linear regressions with bootstrapping and G-computation, all with adjustment for the stratification variables (site and delirium motor subtype) and multiple imputations for missing HRQoL values.

Haloperidol vs. placebo for the treatment of delirium in ICU patients: a pre-planned, secondary Bayesian analysis of the AID-ICU trial.

Purpose: The AID-ICU trial was a randomised, blinded, placebo-controlled trial investigating effects of haloperidol versus placebo in acutely admitted, adult patients admitted in intensive care unit (ICU) with delirium. This pre-planned Bayesian analysis facilitates probabilistic interpretation of the AID-ICU trial results.

Methods: We used adjusted Bayesian linear and logistic regression models with weakly informative priors to analyse all primary and secondary outcomes reported up to day 90, and with sensitivity analyses using other priors.

Agents intervening against delirium in the intensive care unit trial-Protocol for a secondary Bayesian analysis.

Background: Delirium is highly prevalent in the intensive care unit (ICU) and is associated with high morbidity and mortality. The antipsychotic haloperidol is the most frequently used agent to treat delirium although this is not supported by solid evidence. The agents intervening against delirium in the intensive care unit (AID-ICU) trial investigates the effects of haloperidol versus placebo for the treatment of delirium in adult ICU patients.

The Agents Intervening against Delirium in the Intensive Care Unit Trial (AID-ICU trial): A detailed statistical analysis plan.

Background: The AID-ICU trial aims to assess the benefits and harms of haloperidol for the treatment of delirium in acutely admitted, adult intensive care unit (ICU) patients. This paper describes the detailed statistical analysis plan for the primary publication of results from the AID-ICU trial.

Methods: The AID-ICU trial is an investigator-initiated, pragmatic, international, multicentre, randomized, blinded, parallel-group trial allocating 1000 adult ICU patients with manifest delirium 1:1 to haloperidol or placebo.

Agents intervening against delirium in the intensive care unit (AID-ICU) - Protocol for a randomised placebo-controlled trial of haloperidol in patients with delirium in the ICU.

Background: Delirium among patients in the intensive care unit (ICU) is a common condition associated with increased morbidity and mortality. Haloperidol is the most frequently used pharmacologic intervention, but its use is not supported by firm evidence. Therefore, we are conducting Agents Intervening against Delirium in the Intensive Care Unit (AID-ICU) trial to assess the benefits and harms of haloperidol for the treatment of ICU-acquired delirium.

Anaesthetic Considerations in a Patient with Pycnodysostosis undergoing Caesarean Delivery.

Pycnodysostosis is a rare congenital disorder with several implications, which might complicate anesthesia. Patients are more prone to fractures and have an anticipated difficult airway. We report a case of a 34-year-old woman with pycnodysostosis who underwent elective caesarean delivery under epidural blockade.

Remote real-time supervision via tele-ultrasound in focused cardiac ultrasound: A single-blinded cluster randomized controlled trial.

Background: Supervision via tele-ultrasound presents a remedy for lacking on-site supervision in focused cardiac ultrasound, but knowledge of its impact is largely absent. We aimed to investigate tele-supervised physicians' cine-loop quality compared to that of non-supervised physicians and compared to that of experts.

Methods: We conducted a single-blinded cluster randomized controlled trial in an emergency department in western Denmark.

Constrictive pericarditis caused by Cutibacterium (Propionibacterium) acnes: A case report and review of literature.

Constrictive and effusive-constrictive pericarditis are rare cardiac disorders. Only rarely are the conditions caused by purulent infection, and even more infrequently by anaerobe bacteria. We describe a case of constrictive - and effusive-constrictive pericarditis due to formerly in a 75-year old, immunocompetent and previously healthy patient without any predisposition.

[Cardiac arrest due to torsades de pointes ventricular tachycardia in a patient with Lyme carditis].

A 45-year-old female presented with third degree atrioventricular block and was diagnosed with Lyme carditis. Despite appropriate antibiotic treatment and continuous ventricular pacing, she suffered sudden cardiac arrest due to torsades de pointes ventricular tachycardia. Although rare, severe and potentially fatal ventricular tachyarrhythmias can occur in patients with Lyme borreliosis.

Large scale synthesis of 2'-amino-LNA thymine and 5-methylcytosine nucleosides.

Thymine intermediate 17 has been synthesized on a multigram scale (50 g, 70 mmol) from starting sugar 1 in 15 steps in an overall yield of 73%, with only 5 purification steps. The key thymine intermediate 18 was obtained from 17 in a single step in 96% yield, whereas the key 5-methylcytosine intermediate 20 was obtained from 17 in 2 steps in 58% yield. This highly efficient large scale route necessitates only 2 and 3 novel steps to obtain N2'-functionalized thymine and 5-methylcytosine amino-LNA phosphoramidites from these key intermediates, respectively.

Pyrene-modified unlocked nucleic acids: synthesis, thermodynamic studies, and fluorescent properties.

Two pyrene-modified UNA monomers were synthesized and incorporated into 21-mer DNA oligonucleotides. Melting temperatures and thermodynamic properties of the modified duplexes were measured, and the fluorescence properties of single strands and duplexes containing one or more pyrene-UNA modifications were studied. It was found that incorporation of pyrene-UNA monomers increased duplex stability relative to UNA monomers, and thermodynamic studies revealed significant mismatch discriminative capabilities of the pyrene-UNA modified oligonucleotides.

High-affinity DNA targeting using readily accessible mimics of N2'-functionalized 2'-amino-α-L-LNA.

N2'-Pyrene-functionalized 2'-amino-α-L-LNAs (locked nucleic acids) display extraordinary affinity toward complementary DNA targets due to favorable preorganization of the pyrene moieties for hybridization-induced intercalation. Unfortunately, the synthesis of these monomers is challenging (~20 steps, <3% overall yield), which has precluded full characterization of DNA-targeting applications based on these materials. Access to more readily accessible functional mimics would be highly desirable.

Thermodynamic and biological evaluation of a thrombin binding aptamer modified with several unlocked nucleic acid (UNA) monomers and a 2'-C-piperazino-UNA monomer.

Thrombin binding aptamer is a DNA 15-mer which forms a G-quadruplex structure and possess promising anticoagulant properties due to specific interactions with thrombin. Herein we present the influence of a single 2'-C-piperazino-UNA residue and UNA residues incorporated in several positions on thermodynamics, kinetics and biological properties of the aptamer. 2'-C-Piperazino-UNA is characterized by more efficient stabilization of quadruplex structure in comparison to regular UNA and increases thermodynamic stability of TBA by 0.

Synthesis of an unlocked nucleic acid terpyridine monomer and binding of divalent metal ion in nucleic acid duplexes.

Herein we present the synthesis and thermal stability studies of modified oligonucleotides containing an unlocked nucleic acid (UNA) terpyridine monomer. Incorporation of this monomer into both strands of a DNA duplex allowed reversible thermal stability modulation upon addition or withdrawal of divalent metal ions. A likely explanation of this phenomenon is interstrand complexation between two terpyridine units and a metal ion.

Unlocked nucleic acid (UNA) and UNA derivatives: thermal denaturation studies.

A study on the thermal stability of duplexes formed between unlocked nucleic acid (UNA) modified DNA and RNA oligonucleotides and complementary DNA and RNA is presented. The acyclic UNA monomers are shown to induce a decrease in duplex thermal stability.