Efficacy of haloperidol to decrease the burden of delirium in adult critically ill patients:the EuRIDICE randomized clinical trial

Background:The role of haloperidol as treatment for ICU delirium and related symptoms remains controversial despite two recent large controlled trials evaluating its efficacy and safety. We sought to determine whether haloperidol when compared to placebo in critically ill adults with delirium reduces days with delirium and coma and improves delirium-related sequelae.Methods:This multi-center double-blind, placebo-controlled randomized trial at eight mixed medical-surgical Dutch ICUs included critically ill adults with delirium (Intensive Care Delirium Screening Checklist ≥ 4 or a positive Confusion Assessment Method for the ICU) admitted between February 2018 and January 2020. Patients were randomized to intravenous haloperidol 2.5 mg or placebo every 8 h, titrated up to 5 mg every 8 h if delirium persisted until ICU discharge or up to 14 days. The primary outcome was ICU delirium- and coma-free days (DCFDs) within 14 days after randomization. Predefined secondary outcomes included the protocolized use of sedatives for agitation and related behaviors, patient-initiated extubation and invasive device removal, adverse drug associated events, mechanical ventilation, ICU length of stay, 28-day mortality, and long-term outcomes up to 1-year after randomization.Results:The trial was terminated prematurely for primary endpoint futility on DSMB advice after enrolment of 132 (65 haloperidol; 67 placebo) patients [mean age 64 (15) years, APACHE IV score 73.1 (33.9), male 68%]. Haloperidol did not increase DCFDs (adjusted RR 0.98 [95% CI 0.73–1.31], p = 0.87). Patients treated with haloperidol (vs. placebo) were less likely to receive benzodiazepines (adjusted OR 0.41 [95% CI 0.18–0.89], p = 0.02). Effect measures of other secondary outcomes related to agitation (use of open label haloperidol [OR 0.43 (95% CI 0.12–1.56)] and other antipsychotics [OR 0.63 (95% CI 0.29–1.32)], self-extubation or invasive device removal [OR 0.70 (95% CI 0.22–2.18)]) appeared consistently more favorable with haloperidol, but the confidence interval also included harm. Adverse drug events were not different. Long-term secondary outcomes (e.g., ICU recall and quality of life) warrant further study.Conclusions:Haloperidol does not reduce delirium in critically ill delirious adults. However, it may reduce rescue medication requirements and agitation-related events in delirious ICU patients warranting further evaluation.Trial registration: ClinicalTrials.gov (#NCT03628391), October 9, 2017

Two Legionnaires' disease cases associated with industrial waste water treatment plants: a case report

<p>Abstract</p> <p>Background</p> <p>Finnish and Swedish waste water systems used by the forest industry were found to be exceptionally heavily contaminated with legionellae in 2005.</p> <p>Case presentation</p> <p>We report two cases of severe pneumonia in employees working at two separate mills in Finland in 2006. <it>Legionella </it>serological and urinary antigen tests were used to diagnose Legionnaires' disease in the symptomatic employees, who had worked at, or close to, waste water treatment plants. Since the findings indicated a <it>Legionella </it>infection, the waste water and home water systems were studied in more detail. The antibody response and <it>Legionella </it>urinary antigen finding of Case A indicated that the infection had been caused by <it>Legionella pneumophila </it>serogroup 1. Case A had been exposed to legionellae while installing a pump into a post-clarification basin at the waste water treatment plant of mill A. Both the water and sludge in the basin contained high concentrations of <it>Legionella pneumophila </it>serogroup 1, in addition to serogroups 3 and 13. Case B was working 200 meters downwind from a waste water treatment plant, which had an active sludge basin and cooling towers. The antibody response indicated that his disease was due to <it>Legionella pneumophila </it>serogroup 2. The cooling tower was the only site at the waste water treatment plant yielding that serogroup, though water in the active sludge basin yielded abundant growth of <it>Legionella pneumophila </it>serogroup 5 and <it>Legionella rubrilucens</it>. Both workers recovered from the disease.</p> <p>Conclusion</p> <p>These are the first reported cases of Legionnaires' disease in Finland associated with industrial waste water systems.</p

Effectiveness of an Interactive Website Aimed at Empowerment of Disability Benefit Claimants: Results of a Pragmatic Randomized Controlled Trial

Introduction The aim of this study was to investigate the effectiveness of an interactive website aimed at empowerment of disability claimants, prior to the assessment of disability by an insurance physician. Methods A randomized controlled trial was conducted. Claimants applying for a work disability pension after being sick-listed for 104 weeks, were randomized into either an intervention group or control group. Participants who were randomized into the intervention group were able to logon to the website www.wiagesprek.nl, which mainly consisted of five interactive modules aimed at increasing knowledge, self-awareness, expectations, self-efficacy, and active participation. Participants from the control group were directed to a ‘sham’ website with commonly available information only. The primary outcome was empowerment. Secondary outcomes included coping, knowledge, claimant satisfaction, perceived justice, and physician satisfaction. Outcomes were assessed at baseline, 2 days before the disability assessment, as well as 1 day after, 6 weeks, and 4 months after the disability assessment. Results Claimants were randomly assigned to the intervention group (n = 123) or a control group (n = 119). The intervention had no significant short- and long-term effects on empowerment, but the intervention increased claimants’ knowledge significantly compared to the control group. Claimant satisfaction with the disability assessment interview and claimant perceived justice on the outcome of the assessment were lower in the intervention group (statistically not significant). Furthermore, the intervention had a significant negative effect on claimants perceived procedural justice. Conclusion Although knowledge increased significantly, the intervention www.wiagesprek.nl was not successful in reaching its primary target, that is, to increase levels of empowerment among disability claimants, prior to the assessment of disability

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD

Pediatric interventional radiography equipment: safety considerations

This paper discusses pediatric image quality and radiation dose considerations in state-of-the-art fluoroscopic imaging equipment. Although most fluoroscopes are capable of automatically providing good image quality on infants, toddlers, and small children, excessive radiation dose levels can result from design deficiencies of the imaging device or inappropriate configuration of the equipment’s capabilities when imaging small body parts. Important design features and setup choices at installation and during the clinical use of the imaging device can improve image quality and reduce radiation exposure levels in pediatric patients. Pediatric radiologists and cardiologists, with the help of medical physicists, need to understand the issues involved in creating good image quality at reasonable pediatric patient doses. The control of radiographic technique factors by the generator of the imaging device must provide a large dynamic range of mAs values per exposure pulse during both fluoroscopy and image recording as a function of patient girth, which is the thickness of the patient in the posterior–anterior projection at the umbilicus (less than 10 cm to greater than 30 cm). The range of pulse widths must be limited to less than 10 ms in children to properly freeze patient motion. Variable rate pulsed fluoroscopy can be leveraged to reduce radiation dose to the patient and improve image quality. Three focal spots with nominal sizes of 0.3 mm to 1 mm are necessary on the pediatric unit. A second, lateral imaging plane might be necessary because of the child’s limited tolerance of contrast medium. Spectral and spatial beam shaping can improve image quality while reducing the radiation dose. Finally, the level of entrance exposure to the image receptor of the fluoroscope as a function of operator choices, of added filter thickness, of selected pulse rate, of the selected field-of-view and of the patient girth all must be addressed at installation