Virtual Machining: Capabilities and Challenges of Process Simulations in the Aerospace Industry

AbstractMilling processes for the manufacturing of parts for aerospace applications can be influenced by various effects. When machining structural parts with high material removal rates, the stiffness of the machine tool can be a limiting factor because chatter vibrations. Additionally, vibrations of thin-walled structures, e. g., the blades of impellers or turbines, can lead to chatter vibrations and surface location errors. Thermo-mechanical deformations are another cause for violations of given shape tolerances. Geometric physically-based process simulations can be used to analyze milling processes with regard to these effects in order to optimize the process parameters. In this paper, an overview of several applications of a geometric physically-based simulation system for analyzing different effects during milling processes is presented. Depending on the relevant effects, process forces, the dynamic behaviour of the tool-spindle-machine system, vibrations of workpieces and fixture systems, as well as thermo-mechanical deformations are calculated

Use of cardiovascular registries in regulatory pathways:perspectives from the EU-MDR Cardiovascular Collaboratory

On May 26, 2021, the European Medical Device Regulation (EU-MDR) entered into effect resulting in a major shift in the requirements for assessment of medical devices in Europe. The EU-MDR Cardiovascular Collaboratory (EU-MCVC) was founded to contribute to the development of faster, more efficient, and more effective pathways for innovation of cardiac medical devices. A registry is an organized system that collects uniform data and evaluates specified outcomes in a population defined by a disease, condition, or exposure. Most registries have been created to improve the quality of care and provide feedback to physicians, hospitals, and health providers. Clinical registries represent an ideal construct for scientific, clinical, and policy-making collaboration. We describe diverse experiences from 5 European countries and address the traditional quality components in clinical trials. Continued collaboration is expected among academics, clinical trialists, patient representatives, regulatory experts, research organizations, registry platforms, regulatory bodies, and industry partners. Data quality is a primary concern and registry leaders need to optimize data quality to become regulatory compliant. A collaborative approach among medical device stakeholders may improve quality of care, reduce costs, and provide faster access to innovative technologies, with the common objective of improving cardiovascular care and outcomes

Colchicine for secondary prevention of ischaemic stroke and atherosclerotic events: a meta-analysis of randomised trials

\ua9 2024 The Authors. Background: Guidelines recommend low-dose colchicine for secondary prevention in cardiovascular disease, but uncertainty remains concerning its efficacy for stroke, efficacy in key subgroups and about uncommon but serious safety outcomes. Methods: In this trial-level meta-analysis, we searched bibliographic databases and trial registries form inception to May 16, 2024. We included randomised trials of colchicine for secondary prevention of ischaemic stroke and major adverse cardiovascular events (MACE: ischaemic stroke, myocardial infarction, coronary revascularisation, or cardiovascular death). Secondary outcomes were serious safety outcomes and mortality. A fixed-effect inverse-variance model was used to generate a pooled estimate of relative risk (RR) with 95% confidence intervals (CI). This study is registered with PROSPERO, CRD42024540320. Findings: Six trials involving 14,934 patients with prior stroke or coronary disease were included. In all patients, colchicine compared with placebo or no colchicine reduced the risk for ischaemic stroke by 27% (132 [1.8%] events versus 186 [2.5%] events, RR 0.73 [95% CI 0.58–0.90]) and MACE by 27% (505 [6.8%] events versus 693 [9.4%] events, with RR 0.73 [0.65–0.81]). Efficacy was consistent in key subgroups (females versus males, age below versus above 70, with versus without diabetes, statin versus non-statin users). Colchicine was not associated with an increase in serious safety outcomes: hospitalisation for pneumonia (109 [1.5%] versus 106 [1.5%], RR 0.99 [0.76–1.30]), cancer (247 [3.5%] versus 255 [3.6%], RR 0.97 [0.82–1.15]), and gastro-intestinal events (153 [2.1%] versus 135 [1.9%]), RR 1.15 [0.91–1.44]. There was no difference in all-cause death (201 [2.7%] versus 181 [2.4%], RR 1.09 [0.89–1.33]), cardiovascular death (70 [0.9%] versus 80 [1.1%], RR 0.89 [0.65–1.23]), or non-cardiovascular death (131 [1.8%] versus 101 [1.4%], RR 1.26 [0.98–1.64]). Interpretation: In patients with prior stroke or coronary disease, colchicine reduced ischaemic stroke and MACE, with consistent treatment effect in key subgroups, and did not increase serious safety events or death. Funding: There was no funding source for this study

Efficacy and Safety of Appropriate Shocks and Antitachycardia Pacing in Transvenous and Subcutaneous Implantable Defibrillators: Analysis of All Appropriate Therapy in the PRAETORIAN Trial.

BACKGROUND: The PRAETORIAN trial (A Prospective, Randomized Comparison of Subcutaneous and Transvenous Implantable Cardioverter Defibrillator Therapy) showed noninferiority of subcutaneous implantable cardioverter defibrillator (S-ICD) compared with transvenous implantable cardioverter defibrillator (TV-ICD) with regard to inappropriate shocks and complications. In contrast to TV-ICD, S-ICD cannot provide antitachycardia pacing for monomorphic ventricular tachycardia. This prespecified secondary analysis evaluates appropriate therapy and whether antitachycardia pacing reduces the number of appropriate shocks. METHODS: The PRAETORIAN trial was an international, investigator-initiated randomized trial that included patients with an indication for implantable cardioverter defibrillator (ICD) therapy. Patients with previous ventricular tachycardia <170 bpm or refractory recurrent monomorphic ventricular tachycardia were excluded. In 39 centers, 849 patients were randomized to receive an S-ICD (n=426) or TV-ICD (n=423) and were followed for a median of 49.1 months. ICD programming was mandated by protocol. Appropriate ICD therapy was defined as therapy for ventricular arrhythmias. Arrhythmias were classified as discrete episodes and storm episodes (≥3 episodes within 24 hours). Analyses were performed in the modified intention-to-treat population. RESULTS: In the S-ICD group, 86 of 426 patients received appropriate therapy, versus 78 of 423 patients in the TV-ICD group, during a median follow-up of 52 months (48-month Kaplan-Meier estimates 19.4% and 17.5%; P=0.45). In the S-ICD group, 83 patients received at least 1 shock, versus 57 patients in the TV-ICD group (48-month Kaplan-Meier estimates 19.2% and 11.5%; P=0.02). Patients in the S-ICD group had a total of 254 shocks, compared with 228 shocks in the TV-ICD group (P=0.68). First shock efficacy was 93.8% in the S-ICD group and 91.6% in the TV-ICD group (P=0.40). The first antitachycardia pacing attempt successfully terminated 46% of all monomorphic ventricular tachycardias, but accelerated the arrhythmia in 9.4%. Ten patients with S-ICD experienced 13 electrical storms, versus 18 patients with TV-ICD with 19 electrical storms. Patients with appropriate therapy had an almost 2-fold increased relative risk of electrical storms in the TV-ICD group compared with the S-ICD group (P=0.05). CONCLUSIONS: In this trial, no difference was observed in shock efficacy of S-ICD compared with TV-ICD. Although patients in the S-ICD group were more likely to receive an ICD shock, the total number of appropriate shocks was not different between the 2 groups. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01296022

Device-related complications in the subcutaneous and transvenous ICD: a secondary analysis of the PRAETORIAN trial.

BACKGROUND: The subcutaneous ICD (S-ICD) is developed to overcome lead-related complications and systemic infections, inherent to transvenous ICD (TV-ICD) therapy. The PRAETORIAN trial demonstrated that the S-ICD is non-inferior to the TV-ICD with regard to the combined primary endpoint of inappropriate shocks and complications. This prespecified secondary analysis evaluates all complications in the PRAETORIAN trial. METHODS: The PRAETORIAN trial is an international, multicenter, randomised trial in which 849 patients with an indication for ICD therapy were randomised to receive an SICD (N = 426) or TV-ICD (N = 423) and followed for a median of 49 months. Endpoints were device-related complications, lead-related complications, systemic infections and the need for invasive interventions. RESULTS: Thirty-six device-related complications occurred in 31 patients in the S-ICD group of which bleedings were the most frequent. In the TV-ICD group 49 complications occurred in 44 patients of which lead-dysfunction was most frequent (HR 0.69; P =0.11). In both groups half of all complications were within 30 days after implantation. Lead-related complications and systemic infections occurred significantly less in the S-ICD group compared to the TV-ICD group (P <0.001, P =0.03 respectively). Significantly more complications required invasive interventions in the TV-ICD group compared to the S-ICD group (8.3% vs. 4.3%, HR 0.59; P =0.047). CONCLUSIONS: This secondary analysis shows that, lead-related complications and systemic infections are more prevalent in the TV-ICD group compared to the S-ICD group. In addition, complications in the TV-ICD group were more severe as they required significantly more invasive interventions. This data contributes to shared decision making in clinical practice