| 1. |
- Gaziano, Liam, et al.
(författare)
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Mild-to-moderate kidney dysfunction and cardiovascular disease : Observational and mendelian randomization analyses
- 2022
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Ingår i: Circulation. - : Wolters Kluwer. - 0009-7322 .- 1524-4539. ; 146:20, s. 1507-1517
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: End-stage renal disease is associated with a high risk of cardiovascular events. It is unknown, however, whether mild-to-moderate kidney dysfunction is causally related to coronary heart disease (CHD) and stroke.METHODS: Observational analyses were conducted using individual-level data from 4 population data sources (Emerging Risk Factors Collaboration, EPIC-CVD [European Prospective Investigation into Cancer and Nutrition-Cardiovascular Disease Study], Million Veteran Program, and UK Biobank), comprising 648 135 participants with no history of cardiovascular disease or diabetes at baseline, yielding 42 858 and 15 693 incident CHD and stroke events, respectively, during 6.8 million person-years of follow-up. Using a genetic risk score of 218 variants for estimated glomerular filtration rate (eGFR), we conducted Mendelian randomization analyses involving 413 718 participants (25 917 CHD and 8622 strokes) in EPIC-CVD, Million Veteran Program, and UK Biobank.RESULTS: There were U-shaped observational associations of creatinine-based eGFR with CHD and stroke, with higher risk in participants with eGFR values <60 or >105 mL·min-1·1.73 m-2, compared with those with eGFR between 60 and 105 mL·min-1·1.73 m-2. Mendelian randomization analyses for CHD showed an association among participants with eGFR <60 mL·min-1·1.73 m-2, with a 14% (95% CI, 3%-27%) higher CHD risk per 5 mL·min-1·1.73 m-2 lower genetically predicted eGFR, but not for those with eGFR >105 mL·min-1·1.73 m-2. Results were not materially different after adjustment for factors associated with the eGFR genetic risk score, such as lipoprotein(a), triglycerides, hemoglobin A1c, and blood pressure. Mendelian randomization results for stroke were nonsignificant but broadly similar to those for CHD.CONCLUSIONS: In people without manifest cardiovascular disease or diabetes, mild-to-moderate kidney dysfunction is causally related to risk of CHD, highlighting the potential value of preventive approaches that preserve and modulate kidney function.
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| 2. |
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| 3. |
- Chen, H.Y., et al.
(författare)
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Dyslipidemia, inflammation, calcification, and adiposity in aortic stenosis: a genome-wide study
- 2023
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Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 44:21, s. 1927-1939
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Tidskriftsartikel (refereegranskat)abstract
- Aims Although highly heritable, the genetic etiology of calcific aortic stenosis (AS) remains incompletely understood. The aim of this study was to discover novel genetic contributors to AS and to integrate functional, expression, and cross-phenotype data to identify mechanisms of AS. Methods and results A genome-wide meta-analysis of 11.6 million variants in 10 cohorts involving 653 867 European ancestry participants (13 765 cases) was performed. Seventeen loci were associated with AS at P ≤ 5 × 10−8, of which 15 replicated in an independent cohort of 90 828 participants (7111 cases), including CELSR2–SORT1, NLRP6, and SMC2. A genetic risk score comprised of the index variants was associated with AS [odds ratio (OR) per standard deviation, 1.31; 95% confidence interval (CI), 1.26–1.35; P = 2.7 × 10−51] and aortic valve calcium (OR per standard deviation, 1.22; 95% CI, 1.08–1.37; P = 1.4 × 10−3), after adjustment for known risk factors. A phenome-wide association study indicated multiple associations with coronary artery disease, apolipoprotein B, and triglycerides. Mendelian randomization supported a causal role for apolipoprotein B-containing lipoprotein particles in AS (OR per g/L of apolipoprotein B, 3.85; 95% CI, 2.90–5.12; P = 2.1 × 10−20) and replicated previous findings of causality for lipoprotein(a) (OR per natural logarithm, 1.20; 95% CI, 1.17–1.23; P = 4.8 × 10−73) and body mass index (OR per kg/m2, 1.07; 95% CI, 1.05–1.9; P = 1.9 × 10−12). Colocalization analyses using the GTEx database identified a role for differential expression of the genes LPA, SORT1, ACTR2, NOTCH4, IL6R, and FADS. Conclusion Dyslipidemia, inflammation, calcification, and adiposity play important roles in the etiology of AS, implicating novel treatments and prevention strategies. © The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.
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| 4. |
- Kälvemark Sporrong, Sofia, et al.
(författare)
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Challenges in qualitative social pharmacy research : Reflections based on a conference workshop
- 2022
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Ingår i: Research in Social and Administrative Pharmacy. - : Elsevier. - 1551-7411 .- 1934-8150. ; 18:1, s. 2254-2258
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Tidskriftsartikel (refereegranskat)abstract
- A methodological debate within social pharmacy is ongoing regarding how to apply a qualitative approach. This paper emanates from a workshop at the Nordic Social Pharmacy Conference in 2019, named 'How do we know it's good? A workshop on quality criteria in qualitative social and clinical pharmacy research', that addressed this debate. The aim of this paper is twofold (1) to present the main key points raised during the workshop and (2) based on these inputs to contribute to the ongoing discussion on qualitative methodology within social pharmacy research. This paper starts with what was discussed at the workshop and further elaborated are some of the challenges with conducting qualitative research within social pharmacy. These include methodological and disciplinary competence and insecurity, reflections on the consequences of that many social pharmacy researchers come from a natural science background and how this (possibly) shapes the practice of qualitative research within the field. For example, how concepts like transparency and saturation, together with checklists and quality criteria are understood and used. Finally, we make suggestions for the next step for qualitative research in social pharmacy.
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| 5. |
- Lindskog, Magnus, et al.
(författare)
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Ilixadencel, a Cell-based Immune Primer, plus Sunitinib Versus Sunitinib Alone in Metastatic Renal Cell Carcinoma: A Randomized Phase 2 Study
- 2022
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Ingår i: European Urology Open Science. - : Elsevier BV. - 2666-1691 .- 2666-1683. ; 40, s. 38-45
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Tidskriftsartikel (refereegranskat)abstract
- Background: The prognosis of patients with synchronous metastatic renal cell carcinoma (mRCC) is poor. Whereas single-agent tyrosine kinase inhibition (TKI) is clearly insufficient, the effects can be enhanced by combinations with immune checkpoint inhibitors. Innovative treatment options combining TKI and other immune-stimulating agents could prove beneficial. Objective: To evaluate the clinical effects on metastatic disease when two doses of allogeneic monocyte-derived dendritic cells (ilixadencel) are administrated intratumorally followed by nephrectomy and treatment with sunitinib compared with nephrectomy and sunitinib monotherapy, in patients with synchronous mRCC. Design, setting, and participants: A randomized (2:1) phase 2 multicenter trial enrolled 88 patients with newly diagnosed mRCC to treatment with the combination ilixadencel/sunitinib (ILIXA/SUN; 58 patients) or sunitinib alone (SUN; 30 patients).Outcome measurements and statistical analysis: The primary endpoints were 18mo survival rate and overall survival (OS). A secondary endpoint was objective response rate (ORR) assessed up to 18 mo after enrollment. Statistic evaluations included Kaplan-Meier estimates, log-rank tests, Cox regression, and stratified Cochran-Mantel-Haenszel tests.Results and limitations: The median OS was 35.6 mo in the ILIXA/SUN arm versus 25.3 mo in the SUN arm (hazard ratio 0.73, 95% confidence interval 0.42-1.27; p = 0.25), while the 18-mo OS rates were 63% and 66% in the ILIXA/SUN and SUN arms, respectively. The confirmed ORR in the ILIXA/SUN arm were 42.2% (19/45), including three patients with complete response, versus 24.0% (six/25) in the SUN arm (p = 0.13) without complete responses. The study was not adequately powered to detect modest differences in survival. Conclusions: The study failed to meet its primary endpoints. However, ilixadencel in combination with sunitinib was associated with a numerically higher, nonsignificant, confirmed response rate, including complete responses, compared with sunitinib monotherapy.Patient summary: We studied the effects of intratumoral vaccination with ilixadencel followed by sunitinib versus sunitinib only in a randomized phase 2 study. The combination treatment showed numerically higher numbers of confirmed responses, suggesting an immunologic effect.(c) 2022 The Author(s). Published by Elsevier B.V. on behalf of European Association of Urology. This is an open access article under the CC BY license (http://creativecommons. org/licenses/by/4.0/).
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| 6. |
- Seruyange, Eric, et al.
(författare)
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Seroreactivity to Chikungunya and West Nile Viruses in Rwandan Blood Donors
- 2019
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Ingår i: Vector-Borne and Zoonotic Diseases. - : Mary Ann Liebert Inc. - 1530-3667 .- 1557-7759. ; 19:10, s. 731-740
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Chikungunya virus (CHIKV) and West Nile virus (WNV) have previously been reported from several African countries, including those bordering Rwanda where they may have originated. However, there have been no serosurveillance reports from Rwanda regarding these two viral pathogens. In this article, we present the first study of immunoglobulin G (IgG) seroreactivity of CHIKV and WNV in Rwandan blood donor samples. Methods: Blood donors from Rwanda (n = 874) and Sweden (n = 199) were tested for IgG reactivity against CHIKV, using an in-house enzyme-linked immunosorbent assay with the E1 envelope protein fused with p62 as antigen, and against WNV using a commercial kit. Data on mosquito distribution were obtained from the 2012 assessment of yellow fever virus circulation in Rwanda. Results: Seroreactivity to CHIKV was high in Rwanda (63.0%), when compared with Swedish donors, where only 8.5% were IgG positive. However, a cross-reactivity to O'nyong'nyong virus in neutralization test was noted in Rwandan donors. No significant difference in WNV seroreactivity was found (10.4% for Rwandan and 14.1% for Swedish donors). The relatively high seroreactivity to WNV among Swedish donors could partly be explained by cross-reactivity with tick-borne encephalitis virus prevalent in Sweden. Donors from the Eastern Province of Rwanda had the highest IgG reactivity to the two investigated viruses (86.7% for CHIKV and 33.3% for WNV). Five genera of mosquitoes were found in Rwanda where Culex was the most common (82.5%). The vector of CHIKV, Aedes, accounted for 9.6% of mosquitoes and this species was most commonly found in the Eastern Province. Conclusions: Our results showed high seroreactivity to CHIKV in Rwandan donors. The highest IgG reactivity to CHIKV, and to WNV, was found in the Eastern Province, the area reporting the highest number of mosquito vectors for these two viruses. Infection control by eliminating mosquito-breeding sites in population-dense areas is recommended, especially in eastern Rwanda.
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| 7. |
- Andersson, M., et al.
(författare)
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Evaluation of response in patients with hepatocellular carcinoma treated with intratumoral dendritic cell vaccination using intravoxel incoherent motion (IVIM) MRI and histogram analysis
- 2023
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Ingår i: Acta Radiologica. - : SAGE Publications. - 0284-1851 .- 1600-0455. ; 64:1, s. 32-41
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Tidskriftsartikel (refereegranskat)abstract
- Background Immunotherapy of hepatocellular carcinoma (HCC) is an emerging method with promising results. Immunotherapy can have an antitumor effect without affecting tumor size, calling for functional imaging methods for response evaluation. Purpose To evaluate the response to intratumoral injections with the immune primer ilixadencel in HCCs with diffusion-weighted magnetic resonance imaging (DW-MRI) using intravoxel incoherent motion (IVIM) and histogram analysis. Material and Methods A total of 17 patients with advanced HCC were treated with intratumoral injections with ilixadencel on three occasions 2-5 weeks apart. The patients were examined with IVIM before each injection as well as approximately three months after the first injection. Results The 10th percentile of perfusion-related parameter D* decreased significantly after the first and second intratumoral injections of ilixadencel compared to baseline (P < 0.05). There was a non-significant trend of lower median region of interest f (perfusion fraction) before injection 2 compared to baseline (P = 0.07). There were significant correlations between the 10th percentile and median of D at baseline and change in tumor size after three months (r = 0.79, P < 0.01 and r = 0.72, P < 0.05, respectively). Conclusion DW-MRI with IVIM and histogram analysis revealed significant reductions of D* early after treatment as well as an association between D at baseline and smaller tumor growth at three months. The lower percentiles (10th and 50th) were found more important. Further research is needed to confirm our preliminary findings of reduced perfusion after ilixadencel vaccinations, suggesting a treatment effect on HCC.
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| 8. |
- Eneman, Marie, 1969, et al.
(författare)
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Regulating Police Body-Worn Camera Practice - A Four Modality Perspective
- 2019
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Ingår i: Proceedings of the 10th Scandinavian Conference on Information Systems (SCIS), Finland, 2019. - : Association for Information Systems.
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Konferensbidrag (refereegranskat)abstract
- Police authorities in a number of countries have recently introduced body-worn cameras (BWC). With the use of body-worn cameras, the police have gained access to new forms of wearable and powerful law enforcing technologies. The cameras enable collection of large volume of personal information and in some cases even sensitive information that must be managed and stored within the organisation in line with rules of law. As is often the case when technology develops faster than societal norms and values, a range of questions concerning issues related to regulation of these practises are still uninvestigated. Therefore, this paper will analyse what actually regulates individual police officers’ body-worn camera practice. Empirically, we use the Swedish police as a case and our study is based on qualitative interviews. Theoretically we draw upon Lawrence Les-sig’s four modality model - law, norms, market, and architecture - and we conclude that i) law is considered important although law regarding BWC is still in its infancy, ii) while law and official directives have a more macro applicability, norms are developed and maintained more locally, iii) market regulate indirectly via availability and cost, and iv) architecture is not necessarily as self-executed as often stated.
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| 9. |
- Hessulf, Fredrik, 1986, et al.
(författare)
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Campylobacter jejuni-associated perimyocarditis: two case reports and review of the literature
- 2016
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Ingår i: Bmc Infectious Diseases. - : Springer Science and Business Media LLC. - 1471-2334. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- Background: Campylobacter spp. are among the most common bacterial causes of gastroenteritis world-wide and mostly follow a benign course. We report two cases of Campylobacter jejuni-associated perimyocarditis, the first two simultaneous cases published to date and the third and fourth cases over all in Sweden, and a review of the literature. Case presentation: A previously healthy 24-yo male (A) presented at the Emergency Department(ED) with recent onset of chest pain and a 3-day history of abdominal pain, fever and diarrhoea. The symptoms began within a few hours of returning from a tourist visit to a central European capital. Vital signs were stable, the Electrocardiogram(ECG) showed generalized ST-elevation, laboratory testing showed increased levels of C-reactive protein(CRP) and high-sensitive Troponin T(hsTnT). Transthoracic echocardiogram (TTE) was normal, stool cultures were positive for C Jejuni and blood cultures were negative. Two days after patient A was admitted to the ED his travel companion (B), also a previously healthy male (23-yo), presented at the same ED with almost identical symptoms: chest pain precipitated by a few days of abdominal pain, fever and diarrhoea. Patient B declared that he and patient A had ingested chicken prior to returning from their tourist trip. Laboratory tests showed elevated CRP and hsTnT but the ECG and TTE were normal. In both cases, the diagnosis of C jejuni-associated perimyocarditis was set based on the typical presentation and positive stool cultures with identical strains. Both patients were given antibiotics, rapidly improved and were fully recovered at 6-week follow up. Conclusion: Perimyocarditis is a rare complication of C jejuni infections but should not be overlooked considering the risk of heart failure. With treatment, the prognosis of full recovery is good but several questions remain to be answered regarding the pathophysiology and the male preponderance of the condition.
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| 10. |
- Kano, M., et al.
(författare)
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Resting state functional connectivity of the pain matrix and default mode network in irritable bowel syndrome: a graph theoretical analysis
- 2020
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Irritable bowel syndrome (IBS) is a functional disorder of brain-gut interactions. Differential brain responses to rectal distention between IBS and healthy controls (HCs) have been demonstrated, particularly in the pain matrix and the default mode network. This study aims to compare resting-state functional properties of these networks between IBS patients and HCs using graph analysis in two independent cohorts. We used a weighted graph analysis of the adjacency matrix based on partial correlations between time series in the different regions in each subject to determine subject specific graph measures. These graph measures were normalized by values obtained in equivalent random networks. We did not find any significant differences between IBS patients and controls in global normalized graph measures, hubs, or modularity structure of the pain matrix and the DMN in any of our two independent cohorts. Furthermore, we did not find consistent associations between these global network measures and IBS symptom severity or GI-specific anxiety but we found a significant difference in the relationship between measures of psychological distress (anxiety and/or depressive symptoms) and normalized characteristic path length. The responses of these networks to visceral stimulation rather than their organisation at rest may be primarily disturbed in IBS.
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