| 1. |
- Andersson, Henrik, et al.
(författare)
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Using optimization to provide decision support for strategic emergency medical service planning - Three case studies
- 2020
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Ingår i: International Journal of Medical Informatics. - : ELSEVIER IRELAND LTD. - 1386-5056 .- 1872-8243. ; 133
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Tidskriftsartikel (refereegranskat)abstract
- To achieve high performing emergency medical services (EMS), planning is of vital importance. EMS planners face several challenges when managing ambulance stations and the fleet of ambulances. In this paper, three strategic cases for EMS planners are presented together with potential solutions. In the first case, the effects of closing down a local emergency room (ER) are analyzed together with how adding an ambulance station and an ambulance to the area affected by the closing of the ER can be used to mitigate the negative consequences from the closing. The second case investigates a change in the organization of EMS. Currently, many non-urgent transport assignments are performed by ambulances which make them unavailable for more urgent calls. The potential for a more effective utilization of the ambulances is explored through transferring these assignments to designated transport vehicles. The third case is more technical and challenges the common practice regarding how time dependent demand is handled. Looking at the busiest hour or the average daily demand, is compared with taking time varying demand into account. The cases and solutions are studied using a recently developed strategic ambulance station location and ambulance allocation model for the Maximum Expected Performance Location Problem with Heterogeneous Regions (MEPLP-HR). The model has been extended to also include multiple time periods. This article demonstrates an innovative use of the model and how it can be applied to find and evaluate solutions to real cases within the field of strategic planning of EMS. The model is found to be a useful decision support tool when analyzing the cases and the expected performance of potential solutions.
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| 2. |
- Bauden, Monika, et al.
(författare)
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Circulating nucleosomes as epigenetic biomarkers in pancreatic cancer.
- 2015
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Ingår i: Clinical Epigenetics. - : Springer Science and Business Media LLC. - 1868-7075 .- 1868-7083. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- To improve the prognosis of patients with pancreatic cancer, new biomarkers are required for earlier, pre-symptomatic diagnosis. Epigenetic mutations take place at the earliest stages of tumorigenesis and therefore offer new approaches for detecting and diagnosing disease. Nucleosomes are the repeating subunits of DNA and histone proteins that constitute human chromatin. Because of their release into the circulation, intact nucleosome levels in serum or plasma can serve as diagnostic disease biomarkers, and elevated levels have been reported in various cancers. However, quantifying nucleosomes in the circulation for cancer detection has been challenging due to nonspecific elevation in sera of patients with benign diseases. Here, we report for the first time differential, disease-associated epigenetic profiles of intact cell-free nucleosomes (cfnucleosomes) containing specific DNA and histone modifications as well as histone variants circulating in the blood. The study comprised serum samples from 59 individuals, including 25 patients with resectable pancreatic cancer, 10 patients with benign pancreatic disease, and 24 healthy individuals using Nucleosomics(®), a novel ELISA method.
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| 3. |
- Leknes, Hakon, et al.
(författare)
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Strategic ambulance location for heterogeneous regions
- 2017
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Ingår i: European Journal of Operational Research. - : ELSEVIER SCIENCE BV. - 0377-2217 .- 1872-6860. ; 260:1, s. 122-133
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Tidskriftsartikel (refereegranskat)abstract
- Providing Emergency Medical Services (EMS) is a key function of society. To achieve high quality EMS, planning is of vital importance. An important strategic and tactical problem is the location of ambulance stations and the allocation of ambulances to these stations. This paper presents a new mixed integer model for this problem especially suitable for regions with heterogeneous demand and multiple performance measures. The model decides on the location/allocation of stations/ambulances, calculates the service and arrival rates for each station and the probabilities that a call is served by a particular station. The model is tested on a combined urban and rural area in Norway with multiple performance measures. Compared with the current solution for the area, the best solution from the model has a higher expected performance on each of the performance measures used. (C) 2016 Elsevier B.V. All rights reserved.
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| 4. |
- Persson, Josefine, 1980, et al.
(författare)
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Stratification of COVID-19 patients based on quantitative immune-related gene expression in whole blood.
- 2022
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Ingår i: Molecular immunology. - : Elsevier BV. - 1872-9142 .- 0161-5890. ; 145, s. 17-26
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Tidskriftsartikel (refereegranskat)abstract
- The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes mild symptoms in the majority of infected individuals, yet in some cases it leads to a life-threatening condition. Determination of early predictive biomarkers enabling risk stratification for coronavirus disease 2019 (COVID-19) patients can inform treatment and intervention strategies. Herein, we analyzed whole blood samples obtained from individuals infected with SARS-CoV-2, varying from mild to critical symptoms, approximately one week after symptom onset. In order to identify blood-specific markers of disease severity status, a targeted expression analysis of 143 immune-related genes was carried out by dual-color reverse transcriptase multiplex ligation-dependent probe amplification (dcRT-MLPA). The clinically well-defined subgroups of COVID-19 patients were compared with healthy controls. The transcriptional profile of the critically ill patients clearly separated from that of healthy individuals. Moreover, the number of differentially expressed genes increased by severity of COVID-19. It was also found that critically ill patients can be distinguished by reduced peripheral blood expression of several genes, which most likely reflects the lower lymphocyte counts. There was a notable predominance of IFN-associated gene expression in all subgroups of COVID-19, which was most profound in critically ill patients. Interestingly, the gene encoding one of the main TNF-receptors, TNFRS1A, had selectively lower expression in mild COVID-19 cases. This report provides added value in understanding COVID-19 disease, and shows potential of determining early immune transcript signatures in the blood of patients with different disease severity. These results can guide further explorations to uncover mechanisms underlying immunity and immunopathology in COVID-19.
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| 5. |
- Vianello, Eleonora, et al.
(författare)
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Global blood miRNA profiling unravels early signatures of immunogenicity of Ebola vaccine rVSVΔG-ZEBOV-GP
- 2023
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Ingår i: iScience. - 2589-0042. ; 26:12
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Tidskriftsartikel (refereegranskat)abstract
- The vectored Ebola vaccine rVSVΔG-ZEBOV-GP elicits protection against Ebola Virus Disease (EVD). In a study of forty-eight healthy adult volunteers who received either the rVSVΔG-ZEBOV-GP vaccine or placebo, we profiled intracellular microRNAs (miRNAs) from whole blood cells (WB) and circulating miRNAs from serum-derived extracellular vesicles (EV) at baseline and longitudinally following vaccination. Further, we identified early miRNA signatures associated with ZEBOV-specific IgG antibody responses at baseline and up to one year post-vaccination, and pinpointed target mRNA transcripts and pathways correlated to miRNAs whose expression was altered after vaccination by using systems biology approaches. Several miRNAs were differentially expressed (DE) and miRNA signatures predicted high or low IgG ZEBOV-specific antibody levels with high classification performance. The top miRNA discriminators were WB-miR-6810, EV-miR-7151-3p, and EV-miR-4426. An eight-miRNA antibody predictive signature was associated with immune-related target mRNAs and pathways. These findings provide valuable insights into early blood biomarkers associated with rVSVΔG-ZEBOV-GP vaccine-induced IgG antibody responses.
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| 6. |
- Bhatt, Deepak L., et al.
(författare)
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Rationale, design and baseline characteristics of the effect of ticagrelor on health outcomes in diabetes mellitus patients Intervention study
- 2019
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Ingår i: Clinical Cardiology. - : Wiley. - 0160-9289 .- 1932-8737. ; 42:5, s. 498-505
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Tidskriftsartikel (refereegranskat)abstract
- In the setting of prior myocardial infarction, the oral antiplatelet ticagrelor added to aspirin reduced the risk of recurrent ischemic events, especially, in those with diabetes mellitus. Patients with stable coronary disease and diabetes are also at elevated risk and might benefit from dual antiplatelet therapy. The Effect of Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS, NCT01991795) is a Phase 3b randomized, double-blinded, placebo-controlled trial of ticagrelor vs placebo, on top of low dose aspirin. Patients >= 50 years with type 2 diabetes receiving anti-diabetic medications for at least 6 months with stable coronary artery disease as determined by a history of previous percutaneous coronary intervention, bypass grafting, or angiographic stenosis of >= 50% of at least one coronary artery were enrolled. Patients with known prior myocardial infarction (MI) or stroke were excluded. The primary efficacy endpoint is a composite of cardiovascular death, myocardial infarction, or stroke. The primary safety endpoint is Thrombolysis in Myocardial Infarction major bleeding. A total of 19 220 patients worldwide have been randomized and at least 1385 adjudicated primary efficacy endpoint events are expected to be available for analysis, with an expected average follow-up of 40 months (maximum 58 months). Most of the exposure is on a 60 mg twice daily dose, as the dose was lowered from 90 mg twice daily partway into the study. The results may revise the boundaries of efficacy for dual antiplatelet therapy and whether it has a role outside acute coronary syndromes, prior myocardial infarction, or percutaneous coronary intervention.
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| 7. |
- Bhatt, Deepak L., et al.
(författare)
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Ticagrelor in patients with diabetes and stable coronary artery disease with a history of previous percutaneous coronary intervention (THEMIS-PCI) : a phase 3, placebo-controlled, randomised trial
- 2019
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 394:10204, s. 1169-1180
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Tidskriftsartikel (refereegranskat)abstract
- Background Patients with stable coronary artery disease and diabetes with previous percutaneous coronary intervention (PCI), particularly those with previous stenting, are at high risk of ischaemic events. These patients are generally treated with aspirin. In this trial, we aimed to investigate if these patients would benefit from treatment with aspirin plus ticagrelor.Methods The Effect of Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS) was a phase 3 randomised, double-blinded, placebo-controlled trial, done in 1315 sites in 42 countries. Patients were eligible if 50 years or older, with type 2 diabetes, receiving anti-hyperglycaemic drugs for at least 6 months, with stable coronary artery disease, and one of three other mutually non-exclusive criteria:a history of previous PCI or of coronary artery bypass grafting, or documentation of angiographic stenosis of 50% or more in at least one coronary artery. Eligible patients were randomly assigned (1:1) to either ticagrelor or placebo, by use of an interactive voice-response or web-response system. The THEMIS-PCI trial comprised a prespecified subgroup of patients with previous PCI. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, or stroke (measured in the intention-to-treat population).Findings Between Feb 17, 2014, and May 24, 2016, 11 154 patients (58% of the overall THEMIS trial) with a history of previous PCI were enrolled in the THEMIS-PCI trial. Median follow-up was 3.3 years (IQR 2.8-3.8). In the previous PCI group, fewer patients receiving ticagrelor had a primary efficacy outcome event than in the placebo group (404 [7.3%] of 5558 vs 480 [8.6%] of 5596; HR 0.85 [95% CI 0.74-0.97], p=0.013). The same effect was not observed in patients without PCI (p=0.76, p(interaction)=0.16). The proportion of patients with cardiovascular death was similar in both treatment groups (174 [3.1%] with ticagrelor vs 183 (3.3%) with placebo; HR 0.96 [95% CI 0.78-1.18], p=0.68), as well as all-cause death (282 [5.1%] vs 323 [5.8%]; 0.88 [0.75-1.03], p=0.11). TIMI major bleeding occurred in 111 (2.0%) of 5536 patients receiving ticagrelor and 62 (1.1%) of 5564 patients receiving placebo (HR 2.03 [95% CI 1.48-2.76], p<0.0001), and fatal bleeding in 6 (0.1%) of 5536 patients with ticagrelor and 6 (0.1%) of 5564 with placebo (1.13 [0.36-3.50], p=0.83). Intracranial haemorrhage occurred in 33 (0.6%) and 31 (0.6%) patients (1.21 [0.74-1.97], p=0.45). Ticagrelor improved net clinical benefit:519/5558 (9.3%) versus 617/5596 (11.0%), HR=0.85, 95% CI 0.75-0.95, p=0.005, in contrast to patients without PCI where it did not, p(interaction)=0.012. Benefit was present irrespective of time from most recent PCI.Interpretation In patients with diabetes, stable coronary artery disease, and previous PCI, ticagrelor added to aspirin reduced cardiovascular death, myocardial infarction, and stroke, although with increased major bleeding. In that large, easily identified population, ticagrelor provided a favourable net clinical benefit (more than in patients without history of PCI). This effect shows that long-term therapy with ticagrelor in addition to aspirin should be considered in patients with diabetes and a history of PCI who have tolerated antiplatelet therapy, have high ischaemic risk, and low bleeding risk.
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| 8. |
- Bonaca, Marc P., et al.
(författare)
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Limb Outcomes With Ticagrelor Plus Aspirin in Patients With Diabetes Mellitus and Atherosclerosis
- 2024
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Ingår i: Journal of the American College of Cardiology. - : Elsevier. - 0735-1097 .- 1558-3597. ; 83:17, s. 1627-1636
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Tidskriftsartikel (refereegranskat)abstract
- Background Ticagrelor reduced major adverse cardiovascular events (MACE) and increased bleeding in patients with type 2 diabetes mellitus (T2DM) and coronary artery disease. Limb events including revascularization, acute limb ischemia (ALI), and amputation are major morbidities in patients with T2DM and atherosclerosis.Objectives This study sought to determine the effect of ticagrelor on limb events.Methods Patients were randomized to ticagrelor or placebo on top of aspirin and followed for a median of 3 years. MACE (cardiovascular death, myocardial infarction, or stroke), limb events (ALI, amputation, revascularization), and bleeding were adjudicated by an independent and blinded clinical events committee. The presence of peripheral artery disease (PAD) was reported at baseline.Results Of 19,220 patients randomized, 1,687 (8.8%) had PAD at baseline. In patients receiving placebo, PAD was associated with higher MACE (10.7% vs 7.3%; HR: 1.48; P < 0.001) and limb (9.5% vs 0.8%; HR: 10.67; P < 0.001) risk. Ticagrelor reduced limb events (1.6% vs 1.3%; HR: 0.77; 95% CI: 0.61-0.96; P = 0.022) with significant reductions for revascularization (HR: 0.79; 95% CI: 0.62-0.99; P = 0.044) and ALI (HR: 0.24; 95% CI: 0.08-0.70; P = 0.009). The benefit was consistent with or without PAD (HR: 0.80; 95% CI: 0.58-1.11; and HR: 0.76; 95% CI: 0.55-1.05, respectively; P-interaction = 0.81). There was no effect modification of ticagrelor vs placebo based on PAD for MACE (P-interaction = 0.40) or TIMI major bleeding (P-interaction = 0.3239).Conclusions Patients with T2DM and atherosclerosis are at high risk of limb events. Ticagrelor decreased this risk, but increased bleeding. Future trials evaluating the combination of ticagrelor and aspirin would further elucidate the benefit/risk of such therapy in patients with PAD, including those without coronary artery disease. (A Study Comparing Cardiovascular Effects of Ticagrelor Versus Placebo in Patients With Type 2 Diabetes Mellitus [THEMIS]: NCT01991795)
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| 9. |
- Dahlin, Mats, et al.
(författare)
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Internet-delivered acceptance-based behavior therapy for generalized anxiety disorder : A pilot study
- 2016
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Ingår i: Internet Interventions. - : Elsevier. - 2214-7829. ; 6, s. 16-21
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Internet-delivered cognitive behavior therapy (ICBT) has been developed and tested for treating persons with generalized anxiety disorder (GAD). A new form of CBT focuses on acceptance (of internal experiences or difficult psychological content), mindfulness and valued actions. To date this form of CBT has not been delivered via the internet for persons with GAD. The aim of this study was to describe the functionality of a new internet-delivered acceptance-based behavior therapy for GAD, and to test the effect of the intervention in an open pilot trial. Methods: Following exclusion of two patients we included 14 patients diagnosed with GAD from two primary care clinics. At 2–3 months follow-up after treatment 10 patients completed the outcome measures. The treatment lasted for an average of 15 weeks and consisted of acceptance-based techniques, behavior therapy components and homework assignments. Results: A majority of participants completed all modules during the treatment. Findings on the Penn State Worry Questionnaire showed a within-group improvement of Cohen's d = 2.14 at posttreatment. At the follow-up results were maintained. Client satisfaction ratings were high. Conclusions: We conclude that internet-delivered acceptance-based behavior therapy potentially can be a promising new treatment for GAD. A controlled trial of the program has already been completed.
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| 10. |
- Ducrocq, Gregory, et al.
(författare)
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Balance of benefit and risk of ticagrelor in patients with diabetes and stable coronary artery disease according to bleeding risk assessment with the CRUSADE score : Data from THEMIS and THEMIS PCI
- 2022
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Ingår i: American Heart Journal. - : Elsevier. - 0002-8703 .- 1097-6744. ; 249, s. 23-33
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Tidskriftsartikel (refereegranskat)abstract
- Background The THEMIS trial demonstrated that in high-risk patients with stable coronary artery disease and diabetes without previous myocardial infarction or stroke, ticagrelor, in addition to aspirin, reduced the incidence of ischemic events but increased major bleeding. Identification of patients who could derive the greatest net benefit from the addition of ticagrelor appears important. We used the CRUSADE bleeding risk score to risk stratify the THEMIS population. Methods The population was divided into tertiles: score <= 22, 23 to 33, and >= 34. In each tertile, primary efficacy (composite of cardiovascular death, myocardial infarction, or stroke) and safety (TIMI major bleeding) outcomes were analyzed. NACE (net adverse clinical events) was defined as the irreversible harm composite, in which all-cause death, myocardial infarction, stroke, amputations, fatal bleeds, and intracranial hemorrhage were counted. Results Patients in the lower risk tertile experienced fewer ischemic events with ticagrelor than placebo, whereas there was no significant benefit from ticagrelor in the other tertiles (P-interaction = .008). Bleeding rates were consistently increased with ticagrelor across all tertiles (P-interaction = .79). Ticagrelor reduced NACE in the first tertile (HR = 0.74, 95% CI = 0.61-0.90) but not in the others (HR = 1.03, 95% CI = 0.86-1.23 and HR = 1.05, 95% CI = 0.91-1.22, respectively; P-interaction = .012). Conclusions In patients with stable coronary artery disease and diabetes without a history of myocardial infarction or stroke, only those at the lower end of the bleeding risk spectrum according to the CRUSADE score derived net benefit from ticagrelor.
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