The influence of patient characteristics on the alarm rate in intensive care units: a retrospective cohort study

Intensive care units (ICU) are often overflooded with alarms from monitoring devices which constitutes a hazard to both staff and patients. To date, the suggested solutions to excessive monitoring alarms have remained on a research level. We aimed to identify patient characteristics that affect the ICU alarm rate with the goal of proposing a straightforward solution that can easily be implemented in ICUs. Alarm logs from eight adult ICUs of a tertiary care university-hospital in Berlin, Germany were retrospectively collected between September 2019 and March 2021. Adult patients admitted to the ICU with at least 24 h of continuous alarm logs were included in the study. The sum of alarms per patient per day was calculated. The median was 119. A total of 26,890 observations from 3205 patients were included. 23 variables were extracted from patients' electronic health records (EHR) and a multivariable logistic regression was performed to evaluate the association of patient characteristics and alarm rates. Invasive blood pressure monitoring (adjusted odds ratio (aOR) 4.68, 95%CI 4.15-5.29, p < 0.001), invasive mechanical ventilation (aOR 1.24, 95%CI 1.16-1.32, p < 0.001), heart failure (aOR 1.26, 95%CI 1.19-1.35, p < 0.001), chronic renal failure (aOR 1.18, 95%CI 1.10-1.27, p < 0.001), hypertension (aOR 1.19, 95%CI 1.13-1.26, p < 0.001), high RASS (aOR 1.22, 95%CI 1.18-1.25, p < 0.001) and scheduled surgical admission (aOR 1.22, 95%CI 1.13-1.32, p < 0.001) were significantly associated with a high alarm rate. Our study suggests that patient-specific alarm management should be integrated in the clinical routine of ICUs. To reduce the overall alarm load, particular attention regarding alarm management should be paid to patients with invasive blood pressure monitoring, invasive mechanical ventilation, heart failure, chronic renal failure, hypertension, high RASS or scheduled surgical admission since they are more likely to have a high contribution to noise pollution, alarm fatigue and hence compromised patient safety in ICUs

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Risk prediction based upon the expression of immunologic relevant genes

1 EINLEITUNG 5 1.1 Klinische Definition der Sepsis und sepsisverwandter Erkrankungen 5 1.2 Entzündungsreaktion und Sepsis 8 1.3 Postoperative Immundepression als Risikofaktor für die Entstehung einer Sepsis 15 1.4 Immunomonitoring in septischen und postoperativen Patienten 16 1.5 Immunmodulatorische Strategien in der Sepsistherapie 18 1.6 Epidemiologie und Gesundheitsökonomische Bedeutung der Sepsis 19 2 FRAGESTELLUNG 21 3 MATERIALIEN UND METHODEN 23 3.1 Arbeitsmaterialien 23 3.2 Patienten 25 3.3 RNA-Präparation 26 3.4 Die cDNA (copyDNA)-Synthese 28 3.5 Die Polymerase- Ketten-Reaktion (PCR) 28 3.6 Statistische Auswertung 39 4 ERGEBNISSE 41 4.1 Patienten 41 4.2 Die Genexpression der proinflammatorischen Zytokine IL-1β , TNFa und IL-18 46 4.3 Die Expression von T-Zell- und Natürlichen-Killerzell- Genen 49 4.4 Die Expression der Chemokine IL-8, MIP-1a, IP-10, PF4 und GRO-1 52 4.5 Die Expression des antiinflammatorischen Zytokins TGFβ 56 4.6 Die Expression von Calgranulin A (S100A8) 57 4.7 Risikoprädiktion anhand der Genexpression einzelner Gene 58 4.8 Der kombinierte Genexpressionstest zur Risikoprädiktion 61 5 DISKUSSION 64 5.1 Expression von proinflammatorischen Zytokinen 65 5.2 Expression von T-Zell- und NK-Zell-Genen 68 5.3 Expression von Chemokinen 71 5.4 Expression des antiinflammatorischen Zytokins TGFβ 73 5.5 Expression von Calgranulin A (S100A8) 74 5.6 Vergleich des Kombinierten Genexpressionstests mit anderen Verfahren zum Immunomonitoring 75 5.7 Klinische Relevanz und Aussagekraft der gewonnenen Daten 77 5.8 Zusammenfassung und Ausblick 80 ZUSAMMENFASSUNG 83 ABKÜRZUNGSVERZEICHNIS 85 REFERENZEN 87 LEBENSLAUF 99 DANKSAGUNG 100Mit einer Inzidenz von über 200/100 000 Einwohner und Jahr ist die Sepsis eine der häufigsten schwerwiegenden Erkrankungen in Deutschland. Die Letalität ist dabei trotz verbesserter Behandlungsstrategien nach wie vor hoch. Bei der Entwicklung einer Sepsis kommt es infolge von eindringenden Mikroorganismen zu einem Ungleichgewicht von pro- und antiinflammatorischen Mechanismen. Aufgrund dieser Fehlregulation des Immunsystems ist die Abwehr von Krankheitserregern häufig eingeschränkt. Ähnliche immunologische Veränderungen wie bei der Sepsis nicht nur durch eindringende Mikroorganismen ausgelöst werden, sondern auch durch sterile Traumata, Verbrennungen oder eine akute Pankreatitis, weshalb diese Krankheitsbilder mit einer erhöhten Infektanfälligkeit einhergehen. Trotz des erweiterten Verständnisses pathophysiologischer Vorgänge sind bisherige Ansätze einer immunmodulatorischen Therapie weitgehend erfolglos geblieben. Eine wichtige Ursache dafür liegt in dem Mangel an validierten Instrumenten um die aktuelle Immunfunktion eines Patienten zu überwachen und eine mögliche Therapie zu steuern. Mit dem Ziel, Risikopatienten für eine Sepsis zu identifizieren wurde in der hier vorgestellten retrospektiven Untersuchung die perioperative Expression von 24 immunologisch relevanten Genen in Vollblutproben untersucht. 20 Patienten, die infolge eines operativen Eingriffs eine Sepsis entwickelten wurden dabei mit 20 Patienten mit ähnlicher Anamnese verglichen (sog. matched-pairs). Postoperativ zeigte sich eine signifikant niedrigere Expression der Botenstoffe IL-8, MIP1-a und IP-10 in beiden Patientengruppen. Zudem waren auch T-Zell- und NK-Zellspezifische Gene postoperativ geringer exprimiert. Die Gruppe von Patienten mit Sepsis im Verlauf zeigte am ersten postoperativen Tag eine signifikant geringere mRNA- Menge von TNFa, IL-1β, Perforin und CD3 im Vergleich zu den Kontrollpatienten. Basierend auf der Genexpression und einer logistischen Regression wurde ein klinisches Testverfahren entwickelt, welches Risikopatienten mit einer Spezifität und Sensitivität von 85% identifizierte. Eine prospektive Validierung der erhobenen Daten vorausgesetzt, stellt das vorgestellte Verfahren eine aussichtsreiche Erweiterung des bisher bestehenden diagnostischen Spektrums dar.With an incidence of about 200/100 000 citizens per year is sepsis one of the most frequent diseases in Germany. Despite of progress in the treatment of sepsis, lethality still remains high. The development of sepsis is characterized by a dysbalance of pro- and antiinflammatory mechanisms due to invading microorganisms. Resulting from this dysregulation of the immune sytem, the host defense against pathogens often is impaired. Similar immunologic changes can be found not only after infection but after sterile traumata, burns or acute pancreatitis as well, leading to a increased susceptibility for infection in these diseases. Despite of a growing comprehension of the pathophysiologic processes, most attempts for immunomodulatory therapies have failed so far. An important cause is the lack of validated tools for monitoring of the immune function and guidance of possible therapies in the individual patient. With the objective of identification of patients at risk for sepsis, the perioperative expression of 24 immunologic relevant genes in whole blood samples was evaluated in the here presented retrospective study. 20 patients who developed sepsis after major surgery were compared to 20 matched control patients. Postoperatively, a significant lower expression was found in the mediators IL-8, MIP1-a and IP10 in both groups of patients. Additionally, T cell and NK cell related genes were declined postoperatively. The group of patients prone to sepsis showed a significantly reduced amount of mRNA of TNFa, IL-1ß, perforin and CD3 in comparison to control patients. Based upon the gene expression and a logistic regression, a diagnostic test was developed that identified high-risk patients with a specificity and sensitivity of 85%. Under the condition of a prospective validation of this data, the presented method provides a promising extension of existing diagnostic tools

Gelfand numbers and metric entropy of convex hulls in Hilbert spaces

International audienc