The predictive value of the modified early warning score for admission to the intensive care unit in patients with a hematologic malignancy – A multicenter observational study

Objectives: The modified early warning score (MEWS) is used to detect clinical deterioration of hospitalized patients. We aimed to investigate the predictive value of MEWS and derived quick Sequential Organ Failure Assessment (qSOFA) scores for intensive care unit admission in patients with a hematologic malignancy admitted to the ward. Design: Retrospective, observational study in two Dutch university hospitals. Setting: Data from adult patients with a hematologic malignancy, admitted to the ward over a 2-year period, were extracted from electronic patient files. Main outcome measures: Intensive care admission. Results: We included 395 patients with 736 hospital admissions; 2% (n = 15) of admissions resulted in admission to the intensive care unit. A higher MEWS (OR 1.5; 95 %CI 1.3–1.80) and qSOFA (OR 4.4; 95 %CI 2.1–9.3) were associated with admission. Using restricted cubic splines, a rise in the probability of admission for a MEWS ≥ 6 was observed. The AUC of MEWS for predicting admission was 0.830, the AUC of qSOFA was 0.752. MEWS was indicative for intensive care unit admission two days before admission. Conclusions: MEWS was a sensitive predictor of ICU admission in patients with a hematologic malignancy, superior to qSOFA. Future studies should confirm cut-off values and identify potential additional characteristics, to further enhance identification of critically ill hemato-oncology patients. Implications for Clinical Practice: The Modified Early Warning Score (MEWS) can be used as a tool for healthcare providers to monitor clinical deterioration and predict the need for intensive care unit admission in patients with a hematologic malignancy. Yet, consistent application and potential reevaluation of current thresholds is crucial. This will enable bedside nurses to more effectively identify patients needing adjunctive care, facilitating timely interventions and improved outcome.</p

Developing quality indicators for the care of HIV-infected pregnant women in the Dutch Caribbean

<p>Abstract</p> <p>Background</p> <p>Effective interventions to prevent mother-to-child HIV transmission (PMTCT) exist and when properly applied reduce the risk of vertical HIV transmission. As part of optimizing PMTCT in the Dutch Caribbean we developed a set of valid and applicable indicators in order to assess the quality of care in HIV-infected (pregnant) women and their newborns.</p> <p>Methods</p> <p>A multidisciplinary expert panel of 19 experts reviewed and prioritized recommendations extracted from locally used international PMTCT guidelines according to a 3-step-modified-Delphi procedure. Subsequently, the feasibility, sample size, inter-observer reliability, sensitivity to change and case mixed stability of the potential indicators were tested for a data set of 153 HIV-infected women, 108 pregnancies of HIV-infected women and 79 newborns of HIV-infected women in Aruba, Curaçao and St Maarten from 2000 to 2010.</p> <p>Results</p> <p>The panel selected and prioritized 13 potential indicators. Applicability could not be tested for 4 indicators regarding HIV-screening in pregnant women because of lack of data. Four indicators performed satisfactorily for Curaçao ('monitoring CD4-cell count', 'monitoring HIV-RNA levels', 'intrapartum antiretroviral therapy and infant prophylaxis if antepartum antiretroviral therapy was not received', 'scheduled caesarean delivery') and 3 for St Maarten ('monitoring CD4-cell count', 'monitoring HIV-RNA levels', 'discuss and provide combined antiretroviral therapy to all HIV-infected pregnant women') whilst none for Aruba.</p> <p>Conclusions</p> <p>A systemic evidence-and consensus-based approach was used to develop quality indicators in 3 Dutch Caribbean settings. The varying results of the applicability testing accentuate the necessity of applicability testing even in, at first, comparable settings.</p

Critically ill patients demonstrate large interpersonal variation in intestinal microbiota dysregulation : a pilot study

The intestinal microbiota has emerged as a virtual organ with essential functions in human physiology. Antibiotic-induced disruption of the microbiota in critically ill patients may have a negative influence on key energy resources and immunity. We set out to characterize the fecal microbiota composition in critically ill patients both with and without sepsis and to explore the use of microbiota-derived markers for clinical outcome measurements in this setting. In this prospective observational cohort study we analyzed the fecal microbiota of 34 patients admitted to the intensive care unit. Fifteen healthy subjects served as controls. The fecal microbiota was phylogenetically characterized by 16S rRNA gene sequencing, and associations with clinical outcome parameters were evaluated. A marked shift in fecal bacterial composition was seen in all septic and non-septic critically ill patients compared with controls, with extreme interindividual differences. In 13 of the 34 patients, a single bacterial genus made up > 50% of the gut microbiota; in 4 patients this was even > 75%. A significant decrease in bacterial diversity was observed in half of the patients. No associations were found between microbiota diversity, Firmicutes/Bacteroidetes ratio, or Gram-positive/Gram-negative ratio and outcome measurements such as complications and survival. We observed highly heterogeneous patterns of intestinal microbiota in both septic and non-septic critically ill patients. Nevertheless, some general patterns were observed, including disappearance of bacterial genera with important functions in host metabolism. More detailed knowledge of the short- and long-term health consequences of these major shifts in intestinal bacterial communities is needed.Peer reviewe

Immune suppression is associated with enhanced systemic inflammatory, endothelial and procoagulant responses in critically ill patients

Objective: Patients admitted to the Intensive Care Unit (ICU) oftentimes show immunological signs of immune suppression. Consequently, immune stimulatory agents have been proposed as an adjunctive therapy approach in the ICU. The objective of this study was to determine the relationship between the degree of immune suppression and systemic inflammation in patients shortly after admission to the ICU. Design: An observational study in two ICUs in the Netherlands. Methods: The capacity of blood leukocytes to produce cytokines upon stimulation with lipopolysaccharide (LPS) was measured in 77 patients on the first morning after ICU admission. Patients were divided in four groups based on quartiles of LPS stimulated tumor necrosis factor (TNF)-α release, reflecting increasing extents of immune suppression. 15 host response biomarkers indicative of aberrations in inflammatory pathways implicated in sepsis pathogenesis were measured in plasma. Results: A diminished capacity of blood leukocytes to produce TNF-α upon stimulation with LPS was accompanied by a correspondingly reduced ability to release of IL-1β and IL-6. Concurrently measured plasma concentrations of host response biomarkers demonstrated that the degree of reduction in TNF-α release by blood leukocytes was associated with increasing systemic inflammation, stronger endothelial cell activation, loss of endothelial barrier integrity and enhanced procoagulant responses. Conclusions: In patients admitted to the ICU the strongest immune suppression occurs in those who simultaneously display signs of stronger systemic inflammation. These findings may have relevance for the selection of patients eligible for administration of immune enhancing agents.peer-reviewe

Особенности конфликтогенных зон у больных невротическими расстройствами женщин

Представлены данные о различии конфликтогенных зон у женщин и мужчин, страдающих невротическими расстройствами. Показано, что выявленные особенности необходимо учитывать в диагностике и психотерапии невротических расстройств.The authors report the data about the differences in conflectogenic zones among women and men with neurotic disorders. It was shown that the revealed peculiarities should be taken into consideration in diagnosis and psychotherapy of neurotic disorders

Association between age and the host response in critically ill patients with sepsis

Background: The association of ageing with increased sepsis mortality is well established. Nonetheless, current investigations on the influence of age on host response aberrations are largely limited to plasma cytokine levels while neglecting other pathophysiological sepsis domains like endothelial cell activation and function, and coagulation activation. The primary objective of this study was to gain insight into the association of ageing with aberrations in key host response pathways and blood transcriptomes in sepsis.Methods: We analysed the clinical outcome (n=1952), 16 plasma biomarkers providing insight in deregulation of specific pathophysiological domains (n=899), and blood leukocyte transcriptomes (n=488) of sepsis patients stratified according to age decades. Blood transcriptome results were validated in an independent sepsis cohort and compared with healthy individuals. se.Results: Older age was associated with increased mortality independent of comorbidities and disease severity. Ageing was associated with lower endothelial cell activation and dysfunction, and similar inflammation and coagulation activation, despite higher disease severity scores. Blood leukocytes of patients≥70 years, compared to patients<50 years, showed decreased expression of genes involved in cytokine signaling, and innate and adaptive immunity, and increased expression of genes involved in hemostasis and endothelial cell activation. The diminished expression of gene pathways related to innate immunity and cytokine signaling in subjects≥70 years was sepsis-induced, as healthy subjects≥70 years showed enhanced expression of these pathways compared to healthy individuals<50 years.Conclusions: This study provides novel evidence that older age is associated with relatively mitigated sepsis-induced endothelial cell activation and dysfunction, and a blood leukocyte transcriptome signature indicating impaired innate immune and cytokine signaling. These data suggest that age should be considered in patient selection in future sepsis trials targeting the immune system and/or the endothelial cell response.peer-reviewe

Integrating biology into clinical trial design

Purpose of review Critical care medicine revolves around syndromes, such as acute respiratory distress syndrome (ARDS), sepsis and acute kidney injury. Few interventions have shown to be effective in large clinical trials, likely because of between-patient heterogeneity. Translational evidence suggests that more homogeneous biological subgroups can be identified and that differential treatment effects exist. Integrating biological considerations into clinical trial design is therefore an important frontier of critical care research. Recent findings The pathophysiology of critical care syndromes involves a multiplicity of processes, which emphasizes the difficulty of integrating biology into clinical trial design. Biological assessment can be integrated into clinical trials using predictive enrichment at trial inclusion, time-dependent variation to better understand treatment effects and biological markers as surrogate outcomes. Summary Integrating our knowledge on biological heterogeneity into clinical trial design, which has revolutionized other medical fields, could serve as a solution to implement personalized treatment in critical care syndromes. Changing the trial design by using predictive enrichment, incorporation of the evaluation of time-dependent changes and biological markers as surrogate outcomes may improve the likelihood of detecting a beneficial effect from targeted therapeutic interventions and the opportunity to test multiple lines of treatment per patient