Numero XXXIII

<p><b>Cumulative Incidence of AUR (A) and UR (B) with FDC Soli 6 mg or 9 mg + TOCAS.</b> (A) Acute urinary retention. (B) Urinary retention. Black markers indicate 6 mg FDC dose at time of AUR/UR onset; orange markers indicate 9 mg FDC dose at time of AUR/UR onset. AUR cases were a subgroup of UR cases that required catheterization. Abbreviation: FDC, fixed-dose combination.</p

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

Tuolinjalan jyrsintäkiinnittimien suunnittelu

Opinnäytetyön tavoitteena oli suunnitella robotilla tehtävään kappaleenkäsittelyyn soveltuvat automaattiset jyrsintäkiinnikkeet epäsymmetrisen puusta valmistettavan tuolinjalan jyrsintään. Työ toteutettiin Savon ammatti- ja aikuisopiston puualan tiloihin rakennetussa RFID-tekniikan opetus- ja testausympäristössä. Suunnitteluvaiheessa pyrittiin hyödyntämään olemassa olevien laitteiden ja koneiden, kuten CNC-jyrsimen ja kappaleenkäsittelyrobotin ominaisuuksia jyrsintäkiinnittimien valmistuksessa. Opinnäytetyössä käytiin läpi työkappaleen, jyrsimen ja robotin asettamia vaatimuksia ja niiden huomiointia kiinnittimien suunnittelussa ja pohdittiin RFID-sirun integroinnin mahdollisuuksia työkappaleen työkierron ohjauksessa. Kiinnittimien suunnitteluun käytettiin Autodesk Inventor 3D -suunnitteluohjelmaa, jolla luotiin työn tuloksena syntyneet työkappaleen dimensioiden ja työstövaatimusten perusteella suunnitellut kiinnittimien tietokonemallit. Tietokonemallien pohjalta rakennettiin jyrsintään ja automaattiseen kappaleenvaihtoon soveltuvat jyrsintäkiinnittimet, joiden avulla tuolinjalkojen valmistus onnistuu miehittämättömään tuotantoon soveltuvassa solussa.The objective of this final year project was to design mechanical clamps which would be suitable for being used with a CNC milling machine. The clamps were designed according to the dimensions and design principles of a particular chair leg which is part of the Sakky-chair assembly. The project was commissioned by Savo Vocational Colleges and it is part of the RFID (Radio Frequency Identification) project. The design process was started by researching old manual clamps used for attaching the chair leg blank to the milling table. These manual clamps were used as design examples in the beginning of the process. The clamps were designed using Autodesk Inventor 3D CAD software. The clamps were designed to the testing phase and will be manufactured over the coming months. The new automatically controlled clamps were designed to be operated by using negative pressure that is available through the vacuum cups of the milling machines. Handling the blanks and the milled chair legs was designed to be carried out using the available material handling robot. The implementation of RFID tags for transferring milling and handling information in the blanks will be investigated. In order to get the clamp design to work, some minor tweaks to the final design might be necessary. These necessary design tweaks are mostly due to some small dimensional differences between different chair leg blanks used

Summary of patients on FDC Soli + TOCAS treatment with UR/AUR in NEPTUNE and NEPTUNE II, listed in chronological order of appearance.

<p>Summary of patients on FDC Soli + TOCAS treatment with UR/AUR in NEPTUNE and NEPTUNE II, listed in chronological order of appearance.</p

Numbers of patients on FDC Soli + TOCAS treatment with urinary retention or AUR in NEPTUNE and NEPTUNE II.

<p>Numbers of patients on FDC Soli + TOCAS treatment with urinary retention or AUR in NEPTUNE and NEPTUNE II.</p

Risk of developing AUR/UR by potential risk factors.

<p>Risk of developing AUR/UR by potential risk factors.</p

Study design of NEPTUNE and NEPTUNE II.

<p>Study design of NEPTUNE and NEPTUNE II.</p

The development of the ICIQ-UAB: A patient reported outcome measure for underactive bladder

Aims: To present the development of the International Consultation on Incontinence Questionnaire-underactive bladder (ICIQ-UAB) as the first patient reported outcome measure for the assessment of the symptoms and impact on the health-related quality of life of UAB developed in-line with the Food and Drug Administration Guidance for Industry.Methods: Draft items were developed following 44 semi-structured concept elicitation interviews in the UK and refined using 36 cognitive interviews. A pilot study was designed to assess the draft ICIQ-UAB's initial psychometric properties with 54 patients recruited from European hospitals. Further concept elicitation interviews were also carried out with 11 patients in the US and 10 patients in Japan. All participants had a prior urodynamic diagnosis of detrusor underactivity.Results: The cognitive interviews confirmed the initial items to be understood and interpreted as intended. Pilot testing showed that both internal consistency (Cronbach's α ≥ 0.85) and test-retest reliability (stable patients; intraclass correlation coefficient ≥ 0.88) werehigh. The interviews in the US and Japan elicited symptoms and impacts that support previous findings in the UK and provided further insight into the experiences of patients in those countries. The developmental ICIQ-UAB was refined using the evidence from all substudies.Conclusions: The validity and reliability of the ICIQ-UAB were supported in a pilot study settingand the wider cultural applicability by the additional interviews in the US and Japan. Following further validation in future clinical trials, the developmental ICIQ-UAB is envisaged as an important tool for the monitoring of future UAB treatment strategies