Biomedical subjects

Steffen Christensen

Publications and source records attributed to Steffen Christensen.

4 recordsLinked to original sources

PubMed2026

Empirical Meropenem Versus Piperacillin/Tazobactam for Critically Ill Adults With Sepsis: Feasibility of a Randomised Trial.

BACKGROUND: Meropenem and piperacillin/tazobactam are commonly used empirical antibiotics in critically ill adults with sepsis, but whether one is superior to the other is uncertain. METHODS: The Empirical Meropenem versus Piperacillin/Tazobactam for Adult Patients with Sepsis (EMPRESS) trial is an ongoing investigator-initiated, randomised, open-label, adaptive clinical trial with an integrated feasibility phase comparing empirical treatment with meropenem versus piperacillin/tazobactam in critically ill adults with sepsis. The integrated feasibility phase enrolled 200 participants across 10 intensive care units (ICUs) in Denmark between 28 June and 12 December 2025. Five pre-specified feasibility criteria were evaluated; if all feasibility criteria were met, the trial would proceed unaltered, whereas failure to meet one or more criteria would require intervention and re-evaluation. RESULTS: We randomised 200 of 284 screened patients (70.4%). The median age was 70 years (interquartile range (IQR): 60-77), 65.5% were males. At randomisation, 80.0% received vasopressors or inotropes, and 43.5% were on invasive mechanical ventilation. Four of five pre-specified feasibility criteria were met: time to completion of the feasibility phase (5.5 months vs. threshold < 12.0 months), recruitment proportion (70.4% vs. threshold ≥ 50.0%), proportion of participants without consent to the continued collection of data (2.5% vs. threshold < 5.0%) and protocol adherence (81.0% vs. threshold ≥ 75.0%). The proportion of participants with timely primary outcome data availability (30-day mortality) within 45 days was 85.5% and below the pre-specified threshold of ≥ 95.0%. The proportions were low in the first 3 months (33.3%, 22.2% and 30.8%, respectively), increasing to 95.8% in the last month of the feasibility phase. All-cause mortality at 30 days was 30.5%, and specific serious adverse reactions occurred in 4.0% of participants. CONCLUSIONS: In this integrated feasibility evaluation of the EMPRESS trial comparing empirical meropenem versus piperacillin/tazobactam in critically ill adults with sepsis, four of five pre-specified feasibility criteria were met. The unmet criterion, timely primary outcome data availability, improved substantially during the feasibility phase. We consider the trial feasible and will proceed without modifications. EDITORIAL COMMENT: This feasibility study assessed recruitment, randomised allocation and data collection for the multicentre EMPRESS trial. For adaptive trials on trial platforms, careful interim checking of trial design functions is an important and necessary process. TRIAL REGISTRATION: Clinical Trials Information System EUCT number: 2023-509703-33-00; ClinicalTrials.gov identifier: NCT06184659; Universal Trial Number: U1111-1301-6379.

Humans↗

PubMed2006

30-day mortality after peptic ulcer perforation among users of newer selective COX-2 inhibitors and traditional NSAIDs: a population-based study.

OBJECTIVES: Nonsteroidal anti-inflammatory drug (NSAID) use is a strong risk factor for peptic ulcer perforation, yet little is known about the outcome of this condition among NSAID users. We examined 30-day mortality after peptic ulcer perforation associated with the use of traditional NSAIDs and newer selective cyclo-oxygenase-2 (COX-2) inhibitors. METHODS: We conducted a cohort study of patients with the first hospitalization for peptic ulcer perforation, identified in discharge registries of three Danish counties between 1991 and 2003. Data on preadmission NSAID use, other ulcer-related drugs, and comorbidity were likewise from population-based registries. Mortality was ascertained from the Civil Registration System. We compared 30-day mortality in NSAID users and nonusers while adjusting for age, gender, comorbidity, previous uncomplicated peptic ulcer, and ulcer medication use. RESULTS: Of the 2,061 patients hospitalized with peptic ulcer perforation, 38% were current NSAID users. The 30-day mortality was 25% overall, and 35% among current NSAID users. Compared with never-use, the adjusted 30-day mortality rate ratios (MRRs) were 1.8 (95% CI 1.4-2.3) for current use of NSAIDs alone and 1.6 (95% CI 1.2-2.2) for current use combined with other ulcer-associated drugs. The mortality increase associated with the use of COX-2 inhibitors was similar to that of traditional NSAIDs: adjusted MRR for users of COX-2 inhibitors alone and in combination, 2.0 (1.3-3.1) and 1.4 (0.8-2.5), and for users of traditional NSAIDs alone or in combination, 1.7 (1.3-2.3) and 1.6 (1.2-2.3). CONCLUSION: Current use of NSAIDs, including COX-2 inhibitors, is associated with a poor prognosis for patients hospitalized with peptic ulcer perforation.

Aged↗

PubMed2006

Guidelines: From artificial evolution to computational evolution: a research agenda.

Computational scientists have developed algorithms inspired by natural evolution for at least 50 years. These algorithms solve optimization and design problems by building solutions that are 'more fit' relative to desired properties. However, the basic assumptions of this approach are outdated. We propose a research programme to develop a new field: computational evolution. This approach will produce algorithms that are based on current understanding of molecular and evolutionary biology and could solve previously unimaginable or intractable computational and biological problems.

Algorithms↗

PubMed2006

Diabetes and 30-day mortality from peptic ulcer bleeding and perforation: a Danish population-based cohort study.

OBJECTIVE: Diabetes may influence the outcome of complicated peptic ulcer disease, due to angiopathy, blurring of symptoms, and increased risk of sepsis. We examined whether diabetes increased 30-day mortality among Danish patients hospitalized with bleeding or perforated peptic ulcers. RESEARCH DESIGN AND METHODS: This population-based cohort study took place in the three Danish counties of North Jutland, Viborg, and Aarhus between 1991 and 2003. Patients hospitalized with a first-time diagnosis of peptic ulcer bleeding or perforation were identified using the counties' hospital discharge registries. Data on diabetes, other comorbidities, and use of ulcer-associated drugs were obtained from discharge registries and prescription databases. The Danish Civil Registry System allowed complete follow-up for mortality. The outcome under study was 30-day mortality in diabetic versus nondiabetic patients, adjusted for potential confounders. RESULTS: We identified 7,232 patients hospitalized for bleeding ulcers, of whom 731 (10.1%) had diabetes. The 30-day mortality among diabetic patients was 16.6 vs. 10.1% for other patients with bleeding ulcers. The adjusted 30-day mortality rate ratio (MRR) for diabetic patients was 1.40 (95% CI 1.15-1.70). We also identified 2,061 patients with perforated ulcers, of whom 140 (6.8%) had diabetes. The 30-day mortality among diabetic patients was 42.9 vs. 24.0% in other patients with perforated ulcers, corresponding to an adjusted 30-day MRR of 1.51 (1.15-1.98). CONCLUSIONS: Among patients with peptic ulcer bleeding and perforation, diabetes appears to be associated with substantially increased short-term mortality.

Aged↗