Prediction of mechanical fatigue caused by multiple random excitations

A simulation method is presented for the fatigue analysis of automotive and other products that are subjected to multiple random excitations. The method is denoted as frequency domain stress-life fatigue analysis and was implemented in the automotive industry at DAF Trucks N.V. in Eindhoven, The Netherlands. As an example case, a chassis part is analysed. The results of the analysis are consistent with fatigue cracks encountered during testing, which illustrates the effectiveness of the adopted method in the automotive industry

Atrial Fibrillation and Delayed Gastric Emptying

Background: Atrial fibrillation and delayed gastric emptying (DGE) are common after pancreaticoduodenectomy. Our aim was to investigate a potential relationship between atrial fibrillation and DGE, which we defined as failure to tolerate a regular diet by the 7 th postoperative day. Methods: We performed a retrospective chart review of 249 patients who underwent pancreaticoduodenectomy at our institution between 2000 and 2009. Data was analyzed with Fisher exact test for categorical variables and Mann-Whitney U or unpaired T-test for continuous variables. Results: Approximately 5 % of the 249 patients included in the analysis experienced at least one episode of postoperative atrial fibrillation. Median age of patients with atrial fibrillation was 74 years, compared with 66 years in patients without atrial fibrillation (p = 0.0005). Patients with atrial fibrillation were more likely to have a history of atrial fibrillation (p = 0.03). 92 % of the patients with atrial fibrillation suffered from DGE, compared to 46 % of patients without atrial fibrillation (p = 0.0007). This association held true when controlling for age. Conclusion: Patients with postoperative atrial fibrillation are more likely to experience delayed gastric emptying. Interventions to manage delayed gastric function might be prudent in patients at high risk for postoperative atrial fibrillation

Alcohol dose in septal ablation for hypertrophic obstructive cardiomyopathy

Background: The aim of this study was to evaluate short- and long-term outcomes related to dose of alcohol administered during alcohol septal ablation (ASA) in patients with hypertrophic obstructive cardiomyopathy (HOCM). Current guidelines recommend using 1–3 mL of alcohol administered in the target septal perforator artery, but this recommendation is based more on practical experience of interventionalists rather than on systematic evidence. Methods: We included 1448 patients and used propensity score to match patients who received a low-dose (1.0–1.9 mL) versus a high-dose (2.0–3.8 mL) of alcohol during ASA. Results: The matched cohort analysis comprised 770 patients (n = 385 in both groups). There was a similar occurrence of 30-day post-procedural adverse events (13% vs. 12%; p = 0.59), and similar all-cause mortality rates (0.8% vs. 0.5%; p = 1) in the low-dose group and the high-dose group, respectively. In the long-term follow-up (5.4 ± 4.5 years), a total of 110 (14%) patients died representing 2.58 deaths and 2.64 deaths per 100 patient-years in the low dose and the high dose group (logrank, p = 0.92), respectively. There were no significant differences in the long-term dyspnea and left ventricular outflow gradient between the two groups. Patients treated with a low-dose of alcohol underwent more subsequent septal reduction procedures (logrank, p = 0.04). Conclusions: Matched HOCM patients undergoing ASA with a low-dose (1.0–1.9 mL) or a high-dose (2.0–3.8 mL) of alcohol had similar short- and long-term outcomes. A higher rate of repeated septal reduction procedures was observed in the group treated with a low-dose of alcohol. © 2021 The Author

Alcohol dose in septal ablation for hypertrophic obstructive cardiomyopathy

Background: The aim of this study was to evaluate short- and long-term outcomes related to dose of alcohol administered during alcohol septal ablation (ASA) in patients with hypertrophic obstructive cardiomyopathy (HOCM). Current guidelines recommend using 1–3 mL of alcohol administered in the target septal perforator artery, but this recommendation is based more on practical experience of interventionalists rather than on systematic evidence. Methods: We included 1448 patients and used propensity score to match patients who received a low-dose (1.0–1.9 mL) versus a high-dose (2.0–3.8 mL) of alcohol during ASA. Results: The matched cohort analysis comprised 770 patients (n = 385 in both groups). There was a similar occurrence of 30-day post-procedural adverse events (13% vs. 12%; p = 0.59), and similar all-cause mortality rates (0.8% vs. 0.5%; p = 1) in the low-dose group and the high-dose group, respectively. In the long-term follow-up (5.4 ± 4.5 years), a total of 110 (14%) patients died representing 2.58 deaths and 2.64 deaths per 100 patient-years in the low dose and the high dose group (logrank, p = 0.92), respectively. There were no significant differences in the long-term dyspnea and left ventricular outflow gradient between the two groups. Patients treated with a low-dose of alcohol underwent more subsequent septal reduction procedures (logrank, p = 0.04). Conclusions: Matched HOCM patients undergoing ASA with a low-dose (1.0–1.9 mL) or a high-dose (2.0–3.8 mL) of alcohol had similar short- and long-term outcomes. A higher rate of repeated septal reduction procedures was observed in the group treated with a low-dose of alcohol

A randomized open label phase-II clinical trial with or without infusion of plasma from subjects after convalescence of SARS-CoV-2 infection in high-risk patients with confirmed severe SARS-CoV-2 disease (RECOVER): a structured summary of a study protocol for a randomised controlled trial

OBJECTIVES: Primary objectives • To assess the time from randomisation until an improvement within 84 days defined as two points on a seven point ordinal scale or live discharge from the hospital in high-risk patients (group 1 to group 4) with SARS-CoV-2 infection requiring hospital admission by infusion of plasma from subjects after convalescence of SARS-CoV-2 infection or standard of care. Secondary objectives • To assess overall survival, and the overall survival rate at 28 56 and 84 days. • To assess SARS-CoV-2 viral clearance and load as well as antibody titres. • To assess the percentage of patients that required mechanical ventilation. • To assess time from randomisation until discharge. TRIAL DESIGN: Randomised, open-label, multicenter phase II trial, designed to assess the clinical outcome of SARS-CoV-2 disease in high-risk patients (group 1 to group 4) following treatment with anti-SARS-CoV-2 convalescent plasma or standard of care. PARTICIPANTS: High-risk patients >18 years of age hospitalized with SARS-CoV-2 infection in 10-15 university medical centres will be included. High-risk is defined as SARS-CoV-2 positive infection with Oxygen saturation at ≤ 94% at ambient air with additional risk features as categorised in 4 groups: • Group 1, pre-existing or concurrent hematological malignancy and/or active cancer therapy (incl. chemotherapy, radiotherapy, surgery) within the last 24 months or less. • Group 2, chronic immunosuppression not meeting the criteria of group 1. • Group 3, age ≥ 50 - 75 years meeting neither the criteria of group 1 nor group 2 and at least one of these criteria: Lymphopenia 1μg/mL. • Group 4, age ≥ 75 years meeting neither the criteria of group 1 nor group 2. Observation time for all patients is expected to be at least 3 months after entry into the study. Patients receive convalescent plasma for two days (day 1 and day 2) or standard of care. For patients in the standard arm, cross over is allowed from day 10 in case of not improving or worsening clinical condition. Nose/throat swabs for determination of viral load are collected at day 0 and day 1 (before first CP administration) and subsequently at day 2, 3, 5, 7, 10, 14, 28 or until discharge. Serum for SARS-Cov-2 diagnostic is collected at baseline and subsequently at day 3, 7, 14 and once during the follow-up period (between day 35 and day 84). There is a regular follow-up of 3 months. All discharged patients are followed by regular phone calls. All visits, time points and study assessments are summarized in the Trial Schedule (see full protocol Table 1). All participating trial sites will be supplied with study specific visit worksheets that list all assessments and procedures to be completed at each visit. All findings including clinical and laboratory data are documented by the investigator or an authorized member of the study team in the patient's medical record and in the electronic case report forms (eCRFs). INTERVENTION AND COMPARATOR: This trial will analyze the effects of convalescent plasma from recovered subjects with SARS-CoV-2 antibodies in high-risk patients with SARS-CoV-2 infection. Patients at high risk for a poor outcome due to underlying disease, age or condition as listed above are eligible for enrollment. In addition, eligible patients have a confirmed SARS-CoV-2 infection and O2 saturation ≤ 94% while breathing ambient air. Patients are randomised to receive (experimental arm) or not receive (standard arm) convalescent plasma in two bags (238 - 337 ml plasma each) from different donors (day 1, day 2). A cross over from the standard arm into the experimental arm is possible after day 10 in case of not improving or worsening clinical condition. MAIN OUTCOMES: Primary endpoints: The main purpose of the study is to assess the time from randomisation until an improvement within 84 days defined as two points on a seven-point ordinal scale or live discharge from the hospital in high-risk patients (group 1 to group 4) with SARS-CoV-2 infection requiring hospital admission by infusion of plasma from subjects after convalescence of a SARS-CoV-2 infection or standard of care. Secondary endpoints: • Overall survival, defined as the time from randomisation until death from any cause 28-day, 56-day and 84-day overall survival rates. • SARS-CoV-2 viral clearance and load as well as antibody titres. • Requirement mechanical ventilation at any time during hospital stay (yes/no). • Time until discharge from randomisation. • Viral load, changes in antibody titers and cytokine profiles are analysed in an exploratory manner using paired non-parametric tests (before - after treatment). RANDOMISATION: Upon confirmation of eligibility (patients must meet all inclusion criteria and must not meet exclusion criteria described in section 5.3 and 5.4 of the full protocol), the clinical site must contact a centralized internet randomization system ( https://randomizer.at/ ). Patients are randomized using block randomisation to one of the two arms, experimental arm or standard arm, in a 1:1 ratio considering a stratification according to the 4 risk groups (see Participants). BLINDING (MASKING): The study is open-label, no blinding will be performed. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A total number of 174 patients is required for the entire trial, n=87 per group. TRIAL STATUS: Protocol version 1.2 dated 09/07/2020. A recruitment period of approximately 9 months and an overall study duration of approximately 12 months is anticipated. Recruitment of patients starts in the third quarter of 2020. The study duration of an individual patient is planned to be 3 months. After finishing all study-relevant procedures, therapy, and follow-up period, the patient is followed in terms of routine care and treated if necessary. Total trial duration: 18 months Duration of the clinical phase: 12 months First patient first visit (FPFV): 3rd Quarter 2020 Last patient first visit (LPFV): 2nd Quarter 2021 Last patient last visit (LPLV): 3rd Quarter 2021 Trial Report completed: 4th Quarter 2021 TRIAL REGISTRATION: EudraCT Number: 2020-001632-10, https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-001632-10/DE , registered on 04/04/2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2). The eCRF is attached (Additional file 3)

Thrombocytopenia and platelet transfusions in ICU patients: an international inception cohort study (PLOT-ICU)

Purpose Thrombocytopenia (platelet count < 150 × 109/L) is common in intensive care unit (ICU) patients and is likely associated with worse outcomes. In this study we present international contemporary data on thrombocytopenia in ICU patients. Methods We conducted a prospective cohort study in adult ICU patients in 52 ICUs across 10 countries. We assessed frequencies of thrombocytopenia, use of platelet transfusions and clinical outcomes including mortality. We evaluated pre-selected potential risk factors for the development of thrombocytopenia during ICU stay and associations between thrombocytopenia at ICU admission and 90-day mortality using pre-specified logistic regression analyses. Results We analysed 1166 ICU patients; the median age was 63 years and 39.5% were female. Overall, 43.2% (95% confidence interval (CI) 40.4–46.1) had thrombocytopenia; 23.4% (20–26) had thrombocytopenia at ICU admission, and 19.8% (17.6–22.2) developed thrombocytopenia during their ICU stay. Non-AIDS-, non-cancer-related immune deficiency, liver failure, male sex, septic shock, and bleeding at ICU admission were associated with the development of thrombocytopenia during ICU stay. Among patients with thrombocytopenia, 22.6% received platelet transfusion(s), and 64.3% of in-ICU transfusions were prophylactic. Patients with thrombocytopenia had higher occurrences of bleeding and death, fewer days alive without the use of life-support, and fewer days alive and out of hospital. Thrombocytopenia at ICU admission was associated with 90-day mortality (adjusted odds ratio 1.7; 95% CI 1.19–2.42). Conclusion Thrombocytopenia occurred in 43% of critically ill patients and was associated with worse outcomes including increased mortality. Platelet transfusions were given to 23% of patients with thrombocytopenia and most were prophylactic.publishedVersio