| 1. |
- Dahlberg, Jacob, et al.
(författare)
-
Use of healthcare before and after sepsis in Sweden : a case-control study
- 2023
-
Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 13:2, s. 065967-065967
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The aim of this study was to compare readmissions and death between sepsis and non-sepsis hospitalisations the first year after discharge, and to investigate what diagnoses patients with sepsis present with at readmission. The aim was also to evaluate to what degree patients hospitalised for sepsis seek medical attention prior to hospitalisation. DESIGN: Retrospective case-control study with data validated through clinical chart review. A disproportionate stratified sampling model was used to include a relatively larger number of sepsis hospitalisations. SETTING: All eight public hospitals in region Scania, Sweden (1 January to 3 December 2019). PARTICIPANTS: There were 447 patients hospitalised for sepsis (cases), and 541 hospitalised for other causes (control) identified through clinical chart review. OUTCOME MEASURES: Cox regression was used to analyse readmission and death the year after discharge, and logistic regression was used to analyse healthcare the week prior to hospitalisation. Both analyses were made unadjusted, and adjusted for age, sex and comorbidities. RESULTS: Out of patients who survived a sepsis hospitalisation, 48% were readmitted the year after discharge, compared with 39% for patients without sepsis (HR 1.50, 95% CI 1.03 to 2.19), p=0.04. The majority (52%) of readmissions occurred within 90 days and 75% within 180 days. The readmissions were most often caused by infection (32%), and 18% by cardiovascular disease. Finally, 34% of patients with sepsis had sought prehospital contact with a physician the week before hospitalisation, compared with 22% for patients without sepsis (OR 1.80, 95% CI 1.06 to 3.04), p=0.03. CONCLUSION: Patients hospitalised for sepsis had a higher risk of readmission the year after discharge compared with patients without sepsis. The most common diagnoses at readmission were infection followed by cardiovascular disease. With better follow-up, some of these readmissions could potentially be prevented. Patients hospitalised for sepsis had sought prehospital contact the week prior to hospitalisation to a greater extent than patients without sepsis.
|
|
| 2. |
- Fisher, Jane, et al.
(författare)
-
The Dynamics of Circulating Heparin-Binding Protein : Implications for Its Use as a Biomarker
- 2022
-
Ingår i: Journal of Innate Immunity. - : S. Karger AG. - 1662-811X .- 1662-8128. ; 14:5, s. 447-460
-
Tidskriftsartikel (refereegranskat)abstract
- Heparin-binding protein (HBP) is a promising biomarker for the development and severity of sepsis. To guide its use, it is important to understand the factors that could lead to false-positive or negative results, such as inappropriate release and inadequate clearance of HBP. HBP is presumably released only by neutrophils, and the organs responsible for its elimination are unknown. In this study, we aimed to determine whether non-neutrophil cells can be a source of circulating HBP and which organs are responsible for its removal. We found that in two cohorts of neutropenic patients, 12% and 19% of patients in each cohort, respectively, had detectable plasma HBP levels. In vitro, three leukemia-derived monocytic cell lines and healthy CD14+ monocytes constitutively released detectable levels of HBP. When HBP was injected intravenously in rats, we found that plasma levels of HBP decreased rapidly, with a distribution half-life below 10 min and an elimination half-life of 1-2 h. We measured HBP levels in the liver, spleen, kidneys, lungs, and urine using both ELISA and immunofluorescence quantitation, and found that the majority of HBP was present in the liver, and a small amount was present in the spleen. Immunofluorescence imaging indicated that HBP is associated mainly with hepatocytes in the liver and monocytes/macrophages in the spleen. The impact of hematologic malignancies and liver diseases on plasma HBP levels should be explored further in clinical studies.
|
|
| 3. |
- Jönsson, Göran, et al.
(författare)
-
Increased serum bactericidal activity of autologous serum in C2 deficiency after vaccination against Haemophilus influenzae type b, and further support for an MBL-dependent C2 bypass mechanism
- 2021
-
Ingår i: Vaccine. - : Elsevier BV. - 0264-410X. ; 39:8, s. 1297-1302
-
Tidskriftsartikel (refereegranskat)abstract
- Deficiencies of C2 and other components of the classical pathway of complement are associated with increased risk of infections with encapsulated bacteria, such as Haemophilus (H.) influenzae. Defense against H. influenzae is dependent on specific antibodies and complement, which mediate serum bactericidal activity (SBA) and opsonization. Due to lack of normal classical and lectin complement pathway function in C2 deficiency (C2D), SBA would have to depend either on the alternative pathway or on C2 bypass mechanisms. Here we studied SBA against H. influenzae type b (Hib) before and after vaccination in a group of C2-deficient persons, as the bactericidal capacity of antibodies in autologous complement in relation to vaccination has not been investigated at group level in C2D. Sera from 22 persons with C2D and 26 healthy controls were available. Out of these, 18 persons with C2D and all controls had been vaccinated with Act-HIB®. SBA against Hib bacteria was analyzed with autologous serum as the only complement source. Antibodies to Hib capsular polysaccharide had been analyzed previously. Concentrations of mannose-binding lectin (MBL) and other complement components were measured in serum. SBA of both C2-deficient persons and controls was significantly more efficient after vaccination (p = 0.002 and p < 0.0001, respectively). After vaccination, all but two C2-deficient sera and one control serum showed sufficient SBA (<50% surviving bacteria). Before vaccination, SBA of C2-deficient sera was negatively correlated to serum concentrations of MBL (lower proportion of surviving bacteria with higher MBL concentration; r = −0.55, p = 0.008). After vaccination, SBA of C2-deficient sera was negatively correlated to serum concentrations of IgG Hib antibodies (r = −0.56, p = 0.01). In conclusion, SBA against Hib in autologous serum is increased after vaccination in persons with C2D. In unvaccinated C2-deficient persons SBA was correlated to MBL concentration, providing further support for an MBL-dependent C2 bypass mechanism operating in C2D.
|
|
| 4. |
- Kahn, Fredrik, et al.
(författare)
-
Heparin-Binding Protein As A Prognostic Biomarker of Sepsis and Disease Severity at The Emergency Department
- 2019
-
Ingår i: Shock. - 1540-0514. ; 52:6, s. 135-135
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Rapid and early detection of patients at risk to develop sepsis remains demanding. Heparin-binding protein (HBP) has previously demonstrated good prognostic properties in detecting organ dysfunction among patients with suspected infections. This study aimed to evaluate the plasma-levels of HBP as a prognostic biomarker for infection-induced organ dysfunction among patients seeking medical attention at the emergency department.DESIGN: Prospective, international multicenter, convenience sample study SETTING:: Four general emergency departments at academic centers in Sweden, Switzerland and Canada.PATIENTS: All emergency encounters among adults where one of the following criteria were fulfilled: a) respiratory rate >25 breaths per minute; b) heart rate >120 beats per minute; c) altered mental status; d) systolic blood pressure <100 mm Hg; e) oxygen saturation <90% without oxygen; f) oxygen saturation <93% with oxygen; g) reported oxygen saturation <90%.INTERVENTION: None MEASUREMENTS AND MAIN RESULTS:: A total of 524 ED patients were prospectively enrolled, of these 236 (45%) were eventually adjudicated to have a non-infectious disease. Three hundred forty-seven patients (66%) had or developed organ dysfunction within 72 hours, 54 patients (10%) were admitted to an intensive care unit (ICU), and 23 patients (4%) died within 72 hours. For the primary outcome, detection of infected-related organ dysfunction within 72 hours, the AUC for HBP was 0.73 (95% C.I. 0.68-0.78) among all patients and 0.82 (95% C.I. 0.76-0.87) among patients confidently adjudicated to either infection or no infection. Against the secondary outcome, infection leading to admittance to the ICU, death or a persistent high SOFA-score due to an infection (SOFA-score ≥5 at 12-24 hours) HBP had an AUC of 0.87 (95% C.I. 0.79-0.95) among all patients and 0.88 (95% C.I. 0.77-0.99) among patients confidently adjudicated to either infection or non-infection.CONCLUSIONS: Among patients at the emergency department, HBP demonstrated good prognostic and discriminatory properties in detecting the most severely ill patients with infection.
|
|
| 5. |
- Karlsson Valik, John, et al.
(författare)
-
Peripheral Oxygen Saturation Facilitates Assessment of Respiratory Dysfunction in the Sequential Organ Failure Assessment Score With Implications for the Sepsis-3 Criteria
- 2022
-
Ingår i: Critical Care Medicine. - 0090-3493 .- 1530-0293. ; 50:3, s. e272-e283
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Sequential Organ Failure Assessment score is the basis of the Sepsis-3 criteria and requires arterial blood gas analysis to assess respiratory function. Peripheral oxygen saturation is a noninvasive alternative but is not included in neither Sequential Organ Failure Assessment score nor Sepsis-3. We aimed to assess the association between worst peripheral oxygen saturation during onset of suspected infection and mortality.DESIGN: Cohort study of hospital admissions from a main cohort and emergency department visits from four external validation cohorts between year 2011 and 2018. Data were collected from electronic health records and prospectively by study investigators.SETTING: Eight academic and community hospitals in Sweden and Canada.PATIENTS: Adult patients with suspected infection episodes.INTERVENTIONS: None.MEASUREMENTS AND MAIN RESULTS: The main cohort included 19,396 episodes (median age, 67.0 [53.0–77.0]; 9,007 [46.4%] women; 1,044 [5.4%] died). The validation cohorts included 10,586 episodes (range of median age, 61.0–76.0; women 42.1–50.2%; mortality 2.3–13.3%). Peripheral oxygen saturation levels 96–95% were not significantly associated with increased mortality in the main or pooled validation cohorts. At peripheral oxygen saturation 94%, the adjusted odds ratio of death was 1.56 (95% CI, 1.10–2.23) in the main cohort and 1.36 (95% CI, 1.00–1.85) in the pooled validation cohorts and increased gradually below this level. Respiratory assessment using peripheral oxygen saturation 94–91% and less than 91% to generate 1 and 2 Sequential Organ Failure Assessment points, respectively, improved the discrimination of the Sequential Organ Failure Assessment score from area under the receiver operating characteristics 0.75 (95% CI, 0.74–0.77) to 0.78 (95% CI, 0.77–0.80; p < 0.001). Peripheral oxygen saturation/Fio2 ratio had slightly better predictive performance compared with peripheral oxygen saturation alone, but the clinical impact was minor.CONCLUSIONS: These findings provide evidence for assessing respiratory function with peripheral oxygen saturation in the Sequential Organ Failure Assessment score and the Sepsis-3 criteria. Our data support using peripheral oxygen saturation thresholds 94% and 90% to get 1 and 2 Sequential Organ Failure Assessment respiratory points, respectively. This has important implications primarily for emergency practice, rapid response teams, surveillance, research, and resource-limited settings.
|
|
| 6. |
- Lengquist, Maria, et al.
(författare)
-
Sepsis mimics among presumed sepsis patients at intensive care admission: a retrospective observational study
-
Ingår i: Infection. - 1439-0973.
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundDiagnosing sepsis remains a challenge because of the lack of gold-standard diagnostics. Since there are no simple, broadly accepted criteria for infection, there is a risk of misclassifying sepsis patients (sepsis mimics) among patients with organ failure. The main objective of this study was to investigate the proportion of non-infected patients (sepsis mimics) in ICU patients with presumed sepsis at intensive care unit (ICU) admission.MethodsAdult patients were screened retrospectively during 3.5 years in four ICUs in Sweden for fulfilment of the sepsis-3 criteria at ICU admission (presumed sepsis). Proxy criteria for suspected infection were sampled blood culture(s) and concomitant antibiotic administration. Culture-negative presumed sepsis patients were screened for infection according to the Linder-Mellhammar Criteria of Infection (LMCI). Sepsis mimics were defined as without probable infection according to the LMCI. Confirmed sepsis was defined as presumed sepsis after the exclusion of sepsis mimics.ResultsIn the ICU presumed sepsis cohort (2664 patients), 25% were considered sepsis mimics. The most common reasons for ICU admission among sepsis mimics were acute heart failure and unspecific respiratory failure. Comparing sepsis mimics and confirmed sepsis showed that confirmed sepsis patients were slightly more severely ill but had similar mortality. C-reactive protein had modest discriminatory power (AUROC 0.71) with confirmed sepsis as the outcome.ConclusionsOne-fourth of a presumed ICU sepsis population identified with the sepsis-3 criteria could be considered sepsis mimics. The high proportion of sepsis mimics has a potential dilutional effect on the presumed sepsis population, which threatens the validity of results from sepsis studies using recommended sepsis criteria.
|
|
| 7. |
- Mellhammar, Lisa, et al.
(författare)
-
Bacteremic sepsis leads to higher mortality when adjusting for confounders with propensity score matching
- 2021
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11
-
Tidskriftsartikel (refereegranskat)abstract
- One can falsely assume that it is well known that bacteremia is associated with higher mortality in sepsis. Only a handful of studies specifically focus on the comparison of culture-negative and culture-positive sepsis with different conclusions depending on study design. The aim of this study was to describe outcome for critically ill patients with either culture-positive or -negative sepsis in a clinical review. We also aimed to identify subphenotypes of sepsis with culture status included as candidate clinical variables. Out of 784 patients treated in intensive care with a sepsis diagnosis, blood cultures were missing in 140 excluded patients and 95 excluded patients did not fulfill a sepsis diagnosis. Of 549 included patients, 295 (54%) had bacteremia, 90 (16%) were non-bacteremic but with relevant pathogens detected and in 164 (30%) no relevant pathogen was detected. After adjusting for confounders, 90-day mortality was higher in bacteremic patients, 47%, than in non-bacteremic patients, 36%, p = 0.04. We identified 8 subphenotypes, with different mortality rates, where pathogen detection in microbial samples were important for subphenotype distinction and outcome. In conclusion, bacteremic patients had higher mortality than their non-bacteremic counter-parts and bacteremia is more common in sepsis when studied in a clinical review. For reducing population heterogeneity and improve the outcome of trials and treatment for sepsis, distinction of subphenotypes might be useful and pathogen detection an important factor.
|
|
| 8. |
- Mellhammar, Lisa, et al.
(författare)
-
Estimating Sepsis Incidence Using Administrative Data and Clinical Medical Record Review
- 2023
-
Ingår i: JAMA Network Open. - 2574-3805. ; 6:8, s. 2331168-2331168
-
Tidskriftsartikel (refereegranskat)abstract
- Importance: Despite the large health burden, reliable data on sepsis epidemiology are lacking; studies using International Statistical Classification of Diseases and Related Health Problems (ICD)-coded hospital discharge diagnosis for sepsis identification suffer from limited sensitivity. Also, ICD data do not allow investigation of underlying pathogens and antimicrobial resistance. Objectives: To generate reliable epidemiological estimates by linking data from a population-based database to a reference standard of clinical medical record review. Design, Setting, and Participants: This was a retrospective, observational cohort study using a population-based administrative database including all acute care hospitals of the Scania region in Sweden in 2019 and 2020 to identify hospital-treated sepsis cases by ICD codes. From this database, clinical medical records were also selected for review within 6 strata defined by ICD discharge diagnosis (both with and without sepsis diagnosis). Data were analyzed from April to October 2022. Main outcomes and measures: Hospital and population incidences of sepsis, case fatality, antimicrobial resistance, and temporal dynamics due to COVID-19 were assessed, as well as validity of ICD-10 case identification methods compared with the reference standard of clinical medical record review. Results: Out of 295 531 hospitalizations in 2019 in the Scania region of Sweden, 997 patient medical records were reviewed, among which 457 had sepsis according to clinical criteria. Of the patients with clinical sepsis, 232 (51%) were female, and 357 (78%) had at least 1 comorbidity. The median (IQR) age of the cohort was 76 (67-85) years. The incidence of sepsis in hospitalized patients according to the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) criteria in 2019 was 4.1% (95% CI, 3.6-4.5) by medical record review. This corresponds to an annual incidence rate of 747 (95% CI, 663-832) patients with sepsis per 100 000 population. No significant increase in sepsis during the COVID-19 pandemic nor a decrease in sepsis incidence when excluding COVID-19 sepsis was observed. Few sepsis cases caused by pathogens with antimicrobial resistance were found. The validity of ICD-10-based case identification in administrative data was low. Conclusions and Relevance: In this cohort study of sepsis epidemiology, sepsis was a considerable burden to public health in Sweden. Supplying administrative data with information from clinical medical records can help to generate reliable data on sepsis epidemiology.
|
|
| 9. |
- Mellhammar, Lisa, et al.
(författare)
-
Heparin binding protein in severe COVID-19- A prospective observational cohort study
- 2021
-
Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 16:4 April
-
Forskningsöversikt (refereegranskat)abstract
- Background and aims Neutrophil-derived heparin binding protein (HBP; also known as azurocidin or CAP-37) is a key player in bacterial sepsis and a promising biomarker in severe infections. The aims of this study were to assess whether HBP is involved in the pathophysiology of COVID-19 and, if so, whether it can be used to predict severe disease preferably using a point-of-care test. Methods This was a prospective convenience sample study of biomarkers in patients admitted to Skåne University hospital in Sweden with a confirmed COVID-19 diagnosis. Plasma samples and clinical data were collected within 72h after admission, during hospital stay and at discharge. Plasma HBP concentrations samples were measured both with enzyme-linked immunosorbent assay (ELISA) and with a novel dry immunofluorescence analyzer (Joinstar) point-of-care test. Results Thirty-five COVID-19 patients were enrolled in the study. Twenty-nine patients had blood samples taken within 72h after admission. We compared the highest HBP value taken within 72h after admission in patients who eventually developed organ dysfunction (n = 23) compared to those who did not (n = 6), and found that HBP was significantly elevated in those who developed organ dysfunction (25.0 ng/mL (interquartile range (IQR) 16.6-48.5) vs 10.6 ng/mL (IQR 4.8-21.7 ng/mL), p = 0.03). Point-of-care test measurements correlated well with ELISA measurements (R = 0.83). HBP measured by the POC device predicted development of COVID-induced organ dysfunction with an AUC of 0.88 (95% confidence interval (CI) 0.70-1.0). Conclusions HBP is elevated prior to onset of organ dysfunction in patients with severe COVID-19 using a newly developed point-of-care test and hence HBP could be used in a clinical setting as a prognostic marker in COVID-19.
|
|
| 10. |
- Mellhammar, Lisa, et al.
(författare)
-
NEWS2 is Superior to qSOFA in Detecting Sepsis with Organ Dysfunction in the Emergency Department
- 2019
-
Ingår i: Journal of Clinical Medicine. - : MDPI AG. - 2077-0383. ; 8:8
-
Tidskriftsartikel (refereegranskat)abstract
- Early administration of antibiotics is associated with better survival in sepsis, thus screening and early detection for sepsis is of clinical importance. Current risk stratification scores used for bedside detection of sepsis, for example Quick Sequential Organ Failure Assessment (qSOFA) and National Early Warning Score 2 (NEWS2), are primarily validated for death and intensive care. The primary aim of this study was to compare the diagnostic accuracy of qSOFA and NEWS2 for a composite outcome of sepsis with organ dysfunction, infection-related mortality within <72 h, or intensive care due to an infection. Retrospective analysis of data from two prospective, observational, multicentre, convenience trials of sepsis biomarkers at emergency departments were performed. Cohort A consisted of 526 patients with a diagnosed infection, 288 with the composite outcome. Cohort B consisted of 645 patients, of whom 269 had a diagnosed infection and 191 experienced the composite outcome. In Cohort A and B, NEWS2 had significantly higher area under receiver operating characteristic curve (AUC), 0.80 (95% CI 0.75-0.83) and 0.70 (95% CI 0.65-0.74), than qSOFA, AUC 0.70 (95% CI 0.66-0.75) and 0.62 (95% CI 0.57-0.67) p < 0.01 and, p = 0.02, respectively for the composite outcome. NEWS2 was superior to qSOFA for screening for sepsis with organ dysfunction, infection-related mortality or intensive care due to an infection both among infected patients and among undifferentiated patients at emergency departments.
|
|
