Background
Thromboembolism is more common in patients with critical COVID-19 than in other critically ill patients, and inflammation has been proposed as a possible mechanism. The aim of this study ...was to investigate if 12 mg vs. 6 mg dexamethasone daily reduced the composite outcome of death or thromboembolism in patients with critical COVID-19.
Methods
Using additional data on thromboembolism and bleeding we did a post hoc analysis of Swedish and Danish intensive care unit patients enrolled in the blinded randomized COVID STEROID 2 trial comparing 12 mg vs. 6 mg dexamethasone daily for up to 10 days. The primary outcome was a composite outcome of death or thromboembolism during intensive care. Secondary outcomes were thromboembolism, major bleeding, and any bleeding during intensive care.
Results
We included 357 patients. Whilst in intensive care, 53 patients (29%) in the 12 mg group and 53 patients (30%) in the 6 mg group met the primary outcome with an unadjusted absolute risk difference of − 0.5% (95% CI − 10 to 9.5%, p = 1.00) and an adjusted OR of 0.93 (CI 95% 0.58 to 1.49, p = 0.77). We found no firm evidence of differences in any of the secondary outcomes.
Conclusions
Among patients with critical COVID-19, 12 mg vs. 6 mg dexamethasone daily did not result in a statistically significant difference in the composite outcome of death or thromboembolism. However, uncertainty remains due to the limited number of patients.
Background
Critically ill patients in intensive care units (ICU) are frequently administered broad‐spectrum antibiotics (e.g., carbapenems or piperacillin/tazobactam) for suspected or confirmed ...infections. This retrospective cohort study aimed to describe the use of carbapenems and piperacillin/tazobactam in two international, prospectively collected datasets.
Methods
We conducted a post hoc analysis of data from the “Adjunctive Glucocorticoid Therapy in Patients with Septic Shock” (ADRENAL) trial (n = 3713) and the “Antimicrobial de‐escalation in the critically ill patient and assessment of clinical cure” (DIANA) study (n = 1488). The primary outcome was the proportion of patients receiving initial antibiotic treatment with carbapenems and piperacillin/tazobactam. Secondary outcomes included mortality, days alive and out of ICU and ICU length of stay at 28 days.
Results
In the ADRENAL trial, carbapenems were used in 648 out of 3713 (17%), whereas piperacillin/tazobactam was used in 1804 out of 3713 (49%) participants. In the DIANA study, carbapenems were used in 380 out of 1480 (26%), while piperacillin/tazobactam was used in 433 out of 1488 (29%) participants. Mortality at 28 days was 23% for patients receiving carbapenems and 24% for those receiving piperacillin/tazobactam in ADRENAL and 23% and 19%, respectively, in DIANA. We noted variations in secondary outcomes; in DIANA, patients receiving carbapenems had a median of 13 days alive and out of ICU compared with 18 days among those receiving piperacillin/tazobactam. In ADRENAL, the median hospital length of stay was 27 days for patients receiving carbapenems and 21 days for those receiving piperacillin/tazobactam.
Conclusions
In this post hoc analysis of ICU patients with infections, we found widespread initial use of carbapenems and piperacillin/tazobactam in international ICUs, with the latter being more frequently used. Randomized clinical trials are needed to assess if the observed variations in outcomes may be drug‐related effects or due to confounders.
Background
Health‐related quality of life (HRQoL) is frequently assessed in randomised clinical trials (RCTs) in the intensive care unit (ICU), but data are limited regarding the proportions of ...patients without responses or not surviving to HRQoL follow‐up and the handling of this. We aimed to describe the extent and pattern of missing HRQoL data in intensive care trials and describe how these data and deaths were handled statistically.
Methods
We conducted a systematic review and meta‐analysis following a published protocol. We searched PubMed, EMBASE, CINAHL and Cochrane Library for RCTs involving adult ICU patients reporting HRQoL as an outcome and excluded RCTs unobtainable in full text. We performed risk of bias assessment independently and in duplicate.
Results
We included 196 outcomes from 88 RCTs published in the years 2002–2022; the numbers of patients alive and eligible to respond HRQoL were reported in 76% of trials. At follow‐up, median 27% (interquartile range 14%–39%) of patients had died, and median 20% (9%–38%) of survivors did not respond across outcomes. Analyses of 80% of outcomes were restricted to complete cases only. The handling of non‐survivors in analyses were reported for 46% of outcomes, with 26% of all outcomes reported as including non‐survivors (using the value zero or the worst possible score).
Conclusion
For HRQoL outcomes in ICU trials, we found that mortality at time of follow‐up was high and non‐response among survivors frequent. The reporting and statistical handling of these issues were insufficient, which may have biased results.
Piperacillin/tazobactam may be associated with less favourable outcomes than carbapenems in patients with severe bacterial infections, but the certainty of evidence is low.
The Empirical Meropenem ...versus Piperacillin/Tazobactam for Adult Patients with Sepsis (EMPRESS) trial is an investigator-initiated, international, parallel-group, randomised, open-label, adaptive clinical trial with an integrated feasibility phase. We will randomise adult, critically ill patients with sepsis to empirical treatment with meropenem or piperacillin/tazobactam for up to 30 days. The primary outcome is 30-day all-cause mortality. The secondary outcomes are serious adverse reactions within 30 days; isolation precautions due to resistant bacteria within 30 days; days alive without life support and days alive and out of hospital within 30 and 90 days; 90- and 180-day all-cause mortality and 180-day health-related quality of life. EMPRESS will use Bayesian statistical models with weak to somewhat sceptical neutral priors. Adaptive analyses will be conducted after follow-up of the primary outcome for the first 400 participants concludes and after every 300 subsequent participants, with adaptive stopping for superiority/inferiority and practical equivalence (absolute risk difference <2.5%-points) and response-adaptive randomisation. The expected sample sizes in scenarios with no, small or large differences are 5189, 5859 and 2570 participants, with maximum 14,000 participants and ≥99% probability of conclusiveness across all scenarios.
EMPRESS will compare the effects of empirical meropenem against piperacillin/tazobactam in adult, critically ill patients with sepsis. Due to the pragmatic, adaptive design with high probability of conclusiveness, the trial results are expected to directly inform clinical practice.
Background
Characteristics and care of intensive care unit (ICU) patients with COVID‐19 may have changed during the pandemic, but longitudinal data assessing this are limited. We compared patients ...with COVID‐19 admitted to Danish ICUs in the first wave with those admitted later.
Methods
Among all Danish ICU patients with COVID‐19, we compared demographics, chronic comorbidities, use of organ support, length of stay and vital status of those admitted 10 March to 19 May 2020 (first wave) versus 20 May 2020 to 30 June 2021. We analysed risk factors for death by adjusted logistic regression analysis.
Results
Among all hospitalised patients with COVID‐19, a lower proportion was admitted to ICU after the first wave (13% vs. 8%). Among all 1374 ICU patients with COVID‐19, 326 were admitted during the first wave. There were no major differences in patient's characteristics or mortality between the two periods, but use of invasive mechanical ventilation (81% vs. 58% of patients), renal replacement therapy (26% vs. 13%) and ECMO (8% vs. 3%) and median length of stay in ICU (13 vs. 10 days) and in hospital (20 vs. 17 days) were all significantly lower after the first wave. Risk factors for death were higher age, larger burden of comorbidities (heart failure, pulmonary disease and kidney disease) and active cancer, but not admission during or after the first wave.
Conclusions
After the first wave of COVID‐19 in Denmark, a lower proportion of hospitalised patients with COVID‐19 were admitted to ICU. Among ICU patients, use of organ support was lower and length of stay was reduced, but mortality rates remained at a relatively high level.
Among ICU patients with COVID-19, it is largely unknown how the overall outcome and resource use have changed with time, different genetic variants, and vaccination status.
For all Danish ICU ...patients with COVID-19 from March 10, 2020 to March 31, 2022, we manually retrieved data on demographics, comorbidities, vaccination status, use of life support, length of stay, and vital status from medical records. We compared patients based on the period of admittance and vaccination status and described changes in epidemiology related to the Omicron variant.
Among all 2167 ICU patients with COVID-19, 327 were admitted during the first (March 10-19, 2020), 1053 during the second (May 20, 2020 to June 30, 2021) and 787 during the third wave (July 1, 2021 to March 31, 2022). We observed changes over the three waves in age (median 72 vs. 68 vs. 65 years), use of invasive mechanical ventilation (81% vs. 58% vs. 51%), renal replacement therapy (26% vs. 13% vs. 12%), extracorporeal membrane oxygenation (7% vs. 3% vs. 2%), duration of invasive mechanical ventilation (median 13 vs. 13 vs. 9 days) and ICU length of stay (median 13 vs. 10 vs. 7 days). Despite these changes, 90-day mortality remained constant (36% vs. 35% vs. 33%). Vaccination rates among ICU patients were 42% as compared to 80% in society. Unvaccinated versus vaccinated patients were younger (median 57 vs. 73 years), had less comorbidity (50% vs. 78%), and had lower 90-day mortality (29% vs. 51%). Patient characteristics changed significantly after the Omicron variant became dominant including a decrease in the use of COVID-specific pharmacological agents from 95% to 69%.
In Danish ICUs, the use of life support declined, while mortality seemed unchanged throughout the three waves of COVID-19. Vaccination rates were lower among ICU patients than in society, but the selected group of vaccinated patients admitted to the ICU still had very severe disease courses. When the Omicron variant became dominant a lower fraction of SARS-CoV-2 positive patients received COVID treatment indicating other causes for ICU admission.
Background
Intensive care unit (ICU) patients with Coronavirus disease 2019 (COVID‐19) have an increased risk of thromboembolic complications. We describe the occurrence of thromboembolic and ...bleeding events in all ICU patients with COVID‐19 in Denmark during the first and second waves of the pandemic.
Methods
This was a sub‐study of the Danish Intensive Care Covid database, in which all patients with SARS‐CoV‐2 admitted to Danish ICUs from 10th March 2020 to 30th June 2021 were included. We registered coagulation variables at admission, and all thromboembolic and bleeding events, and the use of heparins during ICU stay. Variables associated with thrombosis and bleeding and any association with 90‐day mortality were estimated using Cox regression analyses.
Results
We included 1369 patients in this sub‐study; 158 (12%, 95% confidence interval 10–13) had a thromboembolic event in ICU and 309 (23%, 20–25) had a bleeding event, among whom 81 patients (6%, 4.8–7.3) had major bleeding. We found that mechanical ventilation and increased D‐dimer were associated with thrombosis and mechanical ventilation, low platelet count and presence of haematological malignancy were associated with bleeding. Most patients (76%) received increased doses of thromboprophylaxis during their ICU stay. Thromboembolic events were not associated with mortality in adjusted analysis (hazard ratio 1.35 0.91–2.01, p = .14, whereas bleeding events were 1.55 1.18–2.05, p = .002).
Conclusions
Both thromboembolic and bleeding events frequently occurred in ICU patients with COVID‐19. Based on these data, it is not apparent that increased doses of thromboprophylaxis were beneficial.
DPR in high energy physics Gao, Wenxue; Kugel, Andreas; Männer, Reinhard ...
Proceedings of the Conference on Design, Automation and Test in Europe,
04/2009
Conference Proceeding
The Active Buffer project is part of the CBM (compressed baryonic matter) experiment and takes advantage of the DPR (dynamic partial reconfiguration) technology, in which a dynamic module can be ...reconfigured while the static part and other dynamic modules keep running untouched. Due to DPR, design flexibility and simplicity are achieved at the same time. The correctness and the performance have been verified by multiple tests.
Many of todaypsilas software-to-hardware compiler projects try to find dataflow parallelism in a sequential program description and use it to generate parallel running hardware components. In this ...paper we present a new possibility to do a parallel description based on the combination of object-oriented programming and dynamically partial reconfiguration. Our compiler translates software objects directly to hardware objects, which are running in parallel and can be instantiated and removed dynamically. Furthermore, we focus on parallel inter object communication which allows the hardware objects to communicate in parallel.
White matter hyperintensity (WMH) volume on MRI is increased among presymptomatic individuals with autosomal dominant mutations for Alzheimer's disease (AD). One potential explanation is that WMH, ...conventionally considered a marker of cerebrovascular disease, are a reflection of cerebral amyloid angiopathy (CAA) and that increased WMH in this population is a manifestation of this vascular form of primary AD pathology. We examined whether the presence of cerebral microbleeds, a marker of CAA, mediates the relationship between WMH and estimated symptom onset in individuals with and without autosomal dominant mutations for AD.
Participants (n = 175, mean age = 41.1 years) included 112 with an AD mutation and 63 first-degree non-carrier controls. We calculated the estimated years from expected symptom onset (EYO) and analyzed baseline MRI data for WMH volume and presence of cerebral microbleeds. Mixed effects regression and tests of mediation were used to examine microbleed and WMH differences between carriers and non-carriers and to test the whether the association between WMH and mutation status is dependent on the presence of microbleeds.
Mutation carriers were more likely to have microbleeds than non-carriers (p<0.05) and individuals with microbleeds had higher WMH volume than those without (p<0.05). Total WMH volume was increased in mutation carriers compared with non-carriers, up to 20 years prior to EYO, after controlling for microbleed status, as we demonstrated previously. Formal testing of mediation demonstrated that 21% of the association between mutation status and WMH was mediated by presence of microbleeds (p = 0.03) but a significant direct effect of WMH remained (p = 0.02) after controlling for presence of microbleeds.
Although there is some co-dependency between WMH and microbleeds, the observed increases in WMH among mutation carriers does not appear to be fully mediated by this marker of CAA. The findings highlight the possibility that WMH represent a core feature of AD independent of vascular forms of beta amyloid.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
PDF