| 1. |
- Forsvall, Andreas, et al.
(författare)
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Evaluation of the Forsvall biopsy needle in an ex vivo model of transrectal prostate biopsy - a novel needle design with the objective to reduce the risk of post-biopsy infection
- 2021
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Ingår i: Scandinavian Journal of Urology. - : Medical Journals Sweden AB. - 2168-1805 .- 2168-1813. ; 55:3, s. 227-234
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Tidskriftsartikel (refereegranskat)abstract
- Background Transrectal prostate biopsy (TRbx) transfers colonic bacteria into prostatic tissue, potentially causing infectious complications, including sepsis. Our objective was to determine whether biopsy needle shape, surface properties and sampling mechanism affect the number of bacteria transferred through the colon wall, and evaluate a novel needle with improved properties. Methods The standard Tru-Cut biopsy needle used today was evaluated for mechanisms of bacterial transfer in a pilot study. A novel Tru-Cut needle (Forsvall needle prototype) was developed. TRbx was simulated using human colons ex-vivo. Four subtypes of the prototype needle were compared with a standard Tru-Cut needle (BARD 18 G). Prototype and standard needles were used to puncture 4 different colon specimens in 10 randomized sites per colon. Needles were submerged into culture media to capture translocated bacteria. The media was cultured on blood agar and then the total amount of transferred bacteria was calculated for each needle. The primary outcome measure was the percent reduction of bacteria translocated by the prototype needles relative to the standard needle. Secondary outcome measures were the effects of tip design and coating on the percent reduction of translocated bacteria. Results Prototype needles reduced the number of translocated bacteria by, on average, 96.0% (95% confidence interval 93.0-97.7%; p < 0.001) relative to the standard needle. This percent reduction was not significantly affected by prototype needle tip style or surface coating. Conclusions The Forsvall needle significantly reduces colonic bacterial translocation, suggesting that it could reduce infectious complications in prostate biopsy. A clinical trial has been initiated.
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| 2. |
- Ingefors, Erik, et al.
(författare)
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Low 30-day mortality and low carbapenem-resistance in a decade of Acinetobacter bacteraemia in South Sweden
- 2022
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Ingår i: Infection Ecology and Epidemiology. - : Informa UK Limited. - 2000-8686. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The aim of this study was to provide a descriptive account of carbapenem resistance and risk factors for mortality from invasive Acinetobacter infections in the south of Sweden.Methods: Blood isolates with growth of Acinetobacter species between 2010 and 2019 in Skåne county were subtyped using MALDI-TOF and subjected to susceptibility testing against clinically relevant antibiotics. Association between risk factors and 30-day mortality were analysed in univariate and multivariate logistic regression models.Results: There were 179 bacteraemia episodes in 176 patients included in the study. The 30-day all-cause mortality was 16%. In all, two percent of Acinetobacter strains were carbapenem resistant. Independent risk factors associated with 30-day mortality in the multivariate regression model were Acinetobacter growth in all blood cultures drawn at the day of bacteraemia onset (OR 5.0, 95% CI: 1.8 to 13.7, p= 0.002), baseline functional capacity (1-4 points, OR 2.0, 95% CI: 1.2 to 3.4, p= 0.010) and correct empiric antibiotics at time of culture (OR 3.5 95% CI: 1.0 to 11.8, p= 0.045).Conclusion: This study on Acinetobacter bacteraemia in South Sweden found low 30-day mortality and low carbapenem-resistance rates compared to previous international studies which may be due to a higher rate of contaminant findings.
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| 3. |
- Kahn, Fredrik, et al.
(författare)
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Heparin-Binding Protein As A Prognostic Biomarker of Sepsis and Disease Severity at The Emergency Department
- 2019
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Ingår i: Shock. - 1540-0514. ; 52:6, s. 135-135
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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.
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| 4. |
- Ljungquist, Oskar, et al.
(författare)
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Agreement and reliability of hepatic transient elastography in patients with chronic hepatitis C : A cross-sectional test-retest study
- 2023
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Ingår i: Health Science Reports. - 2398-8835. ; 6:4, s. 1-8
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: Transient elastography (TE) has largely replaced liver biopsy to evaluate fibrosis stage and cirrhosis in chronic hepatitis C. Previous studies have reported excellent reliability of TE but agreement metrics have not been reported. This study aimed to assess interrater agreement and reliability of repeated TE measurements.METHODS: Two operators performed TE independently, directly after each other. The primary outcome was disagreement, defined as a difference in TE results between operators of ≥33%, as well as the smallest detectable change, SDC 95 (i.e., the difference between measurements needed to state with 95% certainty that there is a difference in underlying stiffness). Secondary outcomes included reliability, measured as intraclass correlation (ICC), and patient and examination characteristics associated with the agreement. RESULTS: In total, 65 patients were included, with a mean liver stiffness of 9.7 kPa. Of these, 21 (32%) had a disagreement in TE results of ≥33% between the two operators. The SDC 95 on the log scale was 1.97, indicating that an almost twofold increase or decrease in liver stiffness would be required to confidently represent a change in the underlying fibrosis. Reliability, estimated using the ICC, was acceptable at 0.86. In a post hoc analysis, fasting less than 5 h before TE was associated with a higher degree of disagreement (48% vs. 19%, p = 0.03). CONCLUSIONS: In our clinical setting, interrater agreement in directly repeated TE measurements was surprisingly low. It is essential to further investigate the reliability and agreement of TE to determine its validity and usefulness.
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| 5. |
- Mellhammar, Lisa, et al.
(författare)
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NEWS2 is Superior to qSOFA in Detecting Sepsis with Organ Dysfunction in the Emergency Department
- 2019
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Ingår i: Journal of Clinical Medicine. - : MDPI AG. - 2077-0383. ; 8:8
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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.
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| 6. |
- Mellhammar, Lisa, et al.
(författare)
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Scores for sepsis detection and risk stratification – construction of a novel score using a statistical approach and validation of RETTS
- 2020
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 15:2
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Tidskriftsartikel (refereegranskat)abstract
- Background To allow early identification of patients at risk of sepsis in the emergency department (ED), a variety of risk stratification scores and/or triage systems are used. The first aim of this study was to develop a risk stratification score for sepsis based upon vital signs and biomarkers using a statistical approach. Second, we aimed to validate the Rapid Emergency Triage and Treatment System (RETTS) for sepsis. RETTS combines vital signs with symptoms for risk stratification. Methods We retrospectively analysed data from two prospective, observational, multicentre cohorts of patients from studies of biomarkers in ED. A candidate risk stratification score called Sepsis Heparin-binding protein-based Early Warning Score (SHEWS) was constructed using the Least Absolute Shrinkage and Selector Operator (LASSO) method. SHEWS and RETTS were compared to National Early Warning Score 2 (NEWS2) for infection-related organ dysfunction, intensive care or death within the first 72h after admission (i.e. sepsis). Results 506 patients with a diagnosed infection constituted cohort A, in which SHEWS was derived and RETTS was validated. 435 patients constituted cohort B of whom 184 had a diagnosed infection where both scores were validated. In both cohorts (A and B), AUC for infection-related organ dysfunction, intensive care or death was higher for NEWS2, 0.80 (95% CI 0.76–0.84) and 0.69 (95% CI 0.63–0.74), than RETTS, 0.74 (95% CI 0.70–0.79) and 0.55 (95% CI 0.49–0.60), p = 0.05 and p <0.01, respectively. SHEWS had the highest AUC, 0.73 (95% CI 0.68–0.79) p = 0.32 in cohort B. Conclusions Even with a statistical approach, we could not construct better risk stratification scores for sepsis than NEWS2. RETTS was inferior to NEWS2 for screening for sepsis.
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| 7. |
- Tverring, Jonas, et al.
(författare)
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Helmet continuous positive airway pressure versus high-flow nasal cannula in COVID-19 : a pragmatic randomised clinical trial (COVID HELMET)
- 2020
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Ingår i: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Patients with COVID-19 and hypoxaemia despite conventional low-flow oxygen therapy are often treated with high-flow nasal cannula (HFNC) in line with international guidelines. Oxygen delivery by helmet continuous positive airway pressure (CPAP) is a feasible option that enables a higher positive end-expiratory pressure (PEEP) and may theoretically reduce the need for intubation compared to HFNC but direct comparative evidence is lacking. Methods: We plan to perform an investigator-initiated, pragmatic, randomised trial at an intermediate-level COVID-19 cohort ward in Helsingborg Hospital, southern Sweden. We have estimated a required sample size of 120 patients randomised 1:1 to HFNC or Helmet CPAP to achieve 90% power to detect superiority at a 0.05 significance level regarding the primary outcome of ventilator free days (VFD) within 28 days using a Mann-Whitney U test. Patient recruitment is planned to being June 2020 and be completed in the first half of 2021. Discussion: We hypothesise that the use of Helmet CPAP will reduce the need for invasive mechanical ventilation compared to the use of HFNC without having a negative effect on survival. This could have important implications during the current COVID-19 epidemic. Trial registration: ClinicalTrials.gov NCT04395807. Registered on 20 May 2020.
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| 8. |
- Tverring, Jonas, et al.
(författare)
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Heparin-binding protein (HBP) improves prediction of sepsis-related acute kidney injury
- 2017
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Ingår i: Annals of Intensive Care. - : Springer Science and Business Media LLC. - 2110-5820. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Sepsis-related acute kidney injury (AKI) accounts for major morbidity and mortality among the critically ill. Heparin-binding protein (HBP) is a promising biomarker in predicting development and prognosis of severe sepsis and septic shock that has recently been proposed to be involved in the pathophysiology of AKI. The objective of this study was to investigate the added predictive value of measuring plasma HBP on admission to the intensive care unit (ICU) regarding the development of septic AKI. Methods: We included 601 patients with severe sepsis or septic shock from the prospective, observational FINNAKI study conducted in seventeen Finnish ICUs during a 5-month period (1 September 2011–1 February 2012). The main outcome measure was the development of KDIGO AKI stages 2–3 from 12 h after admission up to 5 days. Statistical analysis for the primary endpoint included construction of a clinical risk model, area under the receiver operating curve (ROC area), category-free net reclassification index (cfNRI) and integrated discrimination improvement (IDI) with 95% confidence intervals (95% CI). Results: Out of 511 eligible patients, 101 (20%) reached the primary endpoint. The addition of plasma HBP to a clinical risk model significantly increased ROC area (0.82 vs. 0.78, p = 0.03) and risk classification scores: cfNRI 62.0% (95% CI 40.5–82.4%) and IDI 0.053 (95% CI 0.029–0.075). Conclusions: Plasma HBP adds predictive value to known clinical risk factors in septic AKI. Further studies are warranted to compare the predictive performance of plasma HBP to other novel AKI biomarkers.
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| 9. |
- Tverring, Jonas
(författare)
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On the prognostic value of Heparin-binding protein in Sepsis
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Sepsis causes major morbidity and mortality worldwide. There is wide consensus that biomarkers have an important role in sepsis research and patient care. Heparin-binding protein (HBP) is a neutrophil-derived, proinflammatory and vascular permeability-inducing protein and a promising novel sepsis biomarker. In this thesis, we investigate some aspects of the prognostic accuracy and added value of single and repeated HBP measurements in plasma at the emergency department (ED) and the intensive care unit (ICU) regarding infection-related organ dysfunction (OD) and sepsis survival. In Paper I, we conducted a prospective, observational, convenience sample study (NCT02366650) and recruited patients with affected vital signs regardless of infection suspicion at the ED of four centres in three countries in 2015 to 2016. Among 524 included patients, we found that plasma HBP on ED admission had an area under the receiver operating characteristics curve (AUC) of 0.73 (95% CI: 0.68-0.78) to discriminate the pre-specified primary endpoint of infection-induced OD within 72 hours compared to an AUC of 0.82 (0.78-0.86) for C-reactive protein and 0.69 (0.64-0.74) for procalcitonin. In Paper II, we did a post hoc study including patients with severe sepsis or septic shock and available plasma samples on ICU admission from the prospective, observational FINNAKI study conducted in 17 Finnish ICUs in 2011 to 2012. In a total of 511 patients, addition of plasma HBP to a prediction model including age, simplified acute physiology score II, and creatinine 48 hours pre-ICU increased the AUC from 0.78 (0.73–0.84) to 0.82 (95% CI: 0.77–0.87) regarding the primary endpoint of acute kidney injury (AKI) stage 2-3 from 12 hours up to 5 days. In Paper III, we conducted an observational, convenience sample study recruiting patients with suspected septic shock at two general mixed ICUs in Skåne, Sweden, and sampled patients for plasma from ICU admission and every 4 hours for 3 days. Among 24 included patients, we found that plasma HBP is highly variable in concentration between 4-hour measurements and that every 100 ng/mL increase in HBP (range 0 to 932 ng/mL) corresponded to 1.4 mmHg decrease in mean arterial pressure in a linear mixed-effects model adjusted for time, noradrenaline dose and vasopressin use (95% CI: -1 to -2.3 mmHg, p=0.04). In Paper IV, we performed another post hoc investigation of the FINNAKI study, this time including longitudinal sampling for plasma HBP up to seven times during the first five days (hour 0, 12, 24, 36, 48 and day 3 and 5). We pre-published a statistical analysis plan (ISRCTN15560762). In a total of 652 patients, we found that longitudinal HBP adds a small but statistically significant prognostic value to a prediction model (including age, sex, functional performance pre-ICU, sequential organ failure assessment score, lactate and pre-existing chronic health conditions) regarding the primary endpoint of 90-day survival in a complete case analysis (HR 1.06, 95% CI: 1.01 to 1.12, n=576, p=0.019) and in a post-hoc analysis using multiple imputation and nonlinear HBP over time (HR 1.26, 95% CI: 1.11 to 1.43, p<0.001) but not in the pre-specified analysis using multiple imputation and linear HBP over time (HR 1.11, 95% CI: 0.93 to 1.31, p=0.245).In summary, the findings from this thesis indicate that plasma HBP does not outperform current biomarkers to prognosticate infection-induced OD within 72 hours in patients in the ED with and without suspected infection, that plasma HBP can add prognostic value to known risk factors regarding development of sepsis-related AKI in the ICU, that repeatedly measured plasma HBP concentrations can be highly variable over time during sepsis and that longitundinal HBP adds little prognostic value to known risk factors regarding 90-day survival in ICU patients with sepsis.
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| 10. |
- Tverring, Jonas, et al.
(författare)
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Pivmecillinam with Amoxicillin/Clavulanic acid as step down oral therapy in febrile Urinary Tract Infections caused by ESBL-producing Enterobacterales (PACUTI)
- 2023
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Ingår i: Trials. - 1745-6215. ; 24, s. 1-14
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundOral treatment alternatives for febrile urinary tract infections are limited in the era of increasing antimicrobial resistance. We aim to evaluate if the combination of pivmecillinam and amoxicillin/clavulanic acid is non-inferior to current alternatives for step-down therapy in adult patients with febrile urinary tract infection.MethodsWe plan to perform an investigator-initiated non-inferiority trial. Adult hospitalised patients treated with 1–5 days of intravenous antibiotics for acute febrile urinary tract infection caused by extended spectrum beta-lactamase (ESBL) producing Enterobacterales will be randomised 1:1 to either control (7–10 days of either oral ciprofloxacin 500 mg twice daily or oral trimethoprim–sulfamethoxazole 800 mg/160 mg twice daily or intravenous ertapenem 1 g once daily, depending on sex, drug allergy, glomerular filtration rate and susceptibility testing) or intervention (10 days of pivmecillinam 400 mg three times daily and amoxicillin/clavulanic acid 500/125 mg three times daily). The primary outcome will be clinical cure 10 days (+/− 2 days) after antibiotic treatment completion. Clinical cure is defined as being alive with absence of fever and return to non-infected baseline of urinary tract symptoms without additional antibiotic treatment or re-hospitalisation (for urinary tract infection) based on a centralised allocation-blinded structured telephone interview. We plan to recruit 330 patients to achieve 90% power based on a sample size simulation analysis using a two-group comparison, one-sided alpha of 2.5%, an absolute non-inferiority margin of 10% and expecting 93% clinical cure rate and 10% loss to follow-up. The primary endpoint will be analysed using generalised estimated equations and reported as risk difference for both intention-to-treat and per protocol populations. Patients are planned to be recruited from at least 10 centres in Sweden from 2023 to 2026.DiscussionIf the combination of pivmecillinam and amoxicillin/clavulanic acid is found to be non-inferior to the control drugs there are potential benefits in terms of tolerability, frequency of interactions, outpatient treatment, side effects, nosocomial infections and drive for further antimicrobial resistance compared to existing drugs.
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