| 1. |
- Blach, S., et al.
(författare)
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Global change in hepatitis C virus prevalence and cascade of care between 2015 and 2020: a modelling study
- 2022
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Ingår i: Lancet Gastroenterology & Hepatology. - : Elsevier BV. - 2468-1253. ; 7:5, s. 396-415
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Tidskriftsartikel (refereegranskat)abstract
- Background Since the release of the first global hepatitis elimination targets in 2016, and until the COVID-19 pandemic started in early 2020, many countries and territories were making progress toward hepatitis C virus (HCV) elimination. This study aims to evaluate HCV burden in 2020, and forecast HCV burden by 2030 given current trends. Methods This analysis includes a literature review, Delphi process, and mathematical modelling to estimate HCV prevalence (viraemic infection, defined as HCV RNA-positive cases) and the cascade of care among people of all ages (age =0 years from birth) for the period between Jan 1, 2015, and Dec 31, 2030. Epidemiological data were collected from published sources and grey literature (including government reports and personal communications) and were validated among country and territory experts. A Markov model was used to forecast disease burden and cascade of care from 1950 to 2050 for countries and territories with data. Model outcomes were extracted from 2015 to 2030 to calculate population-weighted regional averages, which were used for countries or territories without data. Regional and global estimates of HCV prevalence, cascade of care, and disease burden were calculated based on 235 countries and territories. Findings Models were built for 110 countries or territories: 83 were approved by local experts and 27 were based on published data alone. Using data from these models, plus population-weighted regional averages for countries and territories without models (n=125), we estimated a global prevalence of viraemic HCV infection of 0.7% (95% UI 0.7-0.9), corresponding to 56.8 million (95% UI 55.2-67.8) infections, on Jan 1, 2020. This number represents a decrease of 6.8 million viraemic infections from a 2015 (beginning of year) prevalence estimate of 63.6 million (61.8-75.8) infections (0.9% [0.8-1.0] prevalence). By the end of 2020, an estimated 12.9 million (12.5-15.4) people were living with a diagnosed viraemic infection. In 2020, an estimated 641 000 (623 000-765 000) patients initiated treatment. Interpretation At the beginning of 2020, there were an estimated 56.8 million viraemic HCV infections globally. Although this number represents a decrease from 2015, our forecasts suggest we are not currently on track to achieve global elimination targets by 2030. As countries recover from COVID-19, these findings can help refocus efforts aimed at HCV elimination. Copyright (C) 2022 Elsevier Ltd. All rights reserved.
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| 2. |
- Menden, MP, et al.
(författare)
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Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 2674-
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Tidskriftsartikel (refereegranskat)abstract
- The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca’s large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells.
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| 7. |
- Sartelli, Massimo, et al.
(författare)
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Ten golden rules for optimal antibiotic use in hospital settings: the WARNING call to action
- 2023
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Ingår i: WORLD JOURNAL OF EMERGENCY SURGERY. - 1749-7922. ; 18:1
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Forskningsöversikt (refereegranskat)abstract
- Antibiotics are recognized widely for their benefits when used appropriately. However, they are often used inappropriately despite the importance of responsible use within good clinical practice. Effective antibiotic treatment is an essential component of universal healthcare, and it is a global responsibility to ensure appropriate use. Currently, pharmaceutical companies have little incentive to develop new antibiotics due to scientific, regulatory, and financial barriers, further emphasizing the importance of appropriate antibiotic use. To address this issue, the Global Alliance for Infections in Surgery established an international multidisciplinary task force of 295 experts from 115 countries with different backgrounds. The task force developed a position statement called WARNING (Worldwide Antimicrobial Resistance National/International Network Group) aimed at raising awareness of antimicrobial resistance and improving antibiotic prescribing practices worldwide. The statement outlined is 10 axioms, or "golden rules," for the appropriate use of antibiotics that all healthcare workers should consistently adhere in clinical practice.
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| 8. |
- Pervjakova, Natalia, et al.
(författare)
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Multi-ancestry genome-wide association study of gestational diabetes mellitus highlights genetic links with type 2 diabetes
- 2022
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 31:19, s. 3377-3391
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Tidskriftsartikel (refereegranskat)abstract
- Gestational diabetes mellitus (GDM) is associated with increased risk of pregnancy complications and adverse perinatal outcomes. GDM often reoccurs and is associated with increased risk of subsequent diagnosis of type 2 diabetes (T2D). To improve our understanding of the aetiological factors and molecular processes driving the occurrence of GDM, including the extent to which these overlap with T2D pathophysiology, the GENetics of Diabetes In Pregnancy (GenDIP) Consortium assembled genome-wide association studies (GWAS) of diverse ancestry in a total of 5485 women with GDM and 347 856 without GDM. Through multi-ancestry meta-analysis, we identified five loci with genome-wide significant association (p < 5x10-8) with GDM, mapping to/near MTNR1B (p = 4.3x10-54), TCF7L2 (p = 4.0x10-16), CDKAL1 (p = 1.6 × 10-14), CDKN2A-CDKN2B (p = 4.1x10-9) and HKDC1 (p = 2.9x10-8). Multiple lines of evidence pointed to the shared pathophysiology of GDM and T2D: (i) four of the five GDM loci (not HKDC1) have been previously reported at genome-wide significance for T2D; (ii) significant enrichment for associations with GDM at previously reported T2D loci; (iii) strong genetic correlation between GDM and T2D; and (iv) enrichment of GDM associations mapping to genomic annotations in diabetes-relevant tissues and transcription factor binding sites. Mendelian randomisation analyses demonstrated significant causal association (5% false discovery rate) of higher body mass index on increased GDM risk. Our results provide support for the hypothesis that GDM and T2D are part of the same underlying pathology but that, as exemplified by the HKDC1 locus, there are genetic determinants of GDM that are specific to glucose regulation in pregnancy.
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| 10. |
- van den Berg, Victor J, et al.
(författare)
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IgM anti-malondialdehyde low density lipoprotein antibody levels indicate coronary heart disease and necrotic core characteristics in the Nordic Diltiazem (NORDIL) study and the Integrated Imaging and Biomarker Study 3 (IBIS-3)
- 2018
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Ingår i: EBioMedicine. - : Elsevier BV. - 2352-3964. ; 36, s. 63-72
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Tidskriftsartikel (refereegranskat)abstract
- Background: Certain immunoglobulins (Ig) are proposed to have protective functions in atherosclerosis.Objectives: We tested whether serum levels of IgG and IgM autoantibodies against malondialdehyde low density lipoprotein (MDA-LDL) are associated with clinical coronary heart disease (CHD) and unfavorable plaque characteristics.Methods: NORDIL was a prospective study investigating adverse cardiovascular outcomes in hypertensive patients. IBIS-3 analyzed lesions in a non-culprit coronary artery with <50% stenosis using radiofrequency intravascular ultrasound (RF-IVUS) and near-infrared spectroscopy (NIRS). Imaging was repeated after a median of 386?days on rosuvastatin. Associations of antibodies with incident CHD and imaging parameters were assessed in the two sub-studies respectively.Findings: From 10,881 NORDIL patients, 87 had serum sampled at baseline and developed CHD over 4.5 years, matched to 227 controls. Higher titers of IgM anti-MDA-LDL had a protective effect on adverse outcomes, with odds ratio 0.29 (0.11, 0.76; p=0.012; p=0.016 for trend). Therefore, the effect was explored at the lesional level in IBIS-3. 143 patients had blood samples and RF-IVUS measurements available, and NIRS was performed in 90 of these. At baseline, IgM anti-MDA-LDL levels had a strong independent inverse relationship with lesional necrotic core volume (p=0.027) and percentage of plaque occupied by necrotic core (p=0.011), as well as lipid core burden index (p=0.024) in the worst 4 mm segment.Interpretation: Our study supports the hypothesis that lower circulating levels of IgM anti-MDA-LDL are associated with clinical CHD development, and for the first time relates these findings to atherosclerotic plaque characteristics that are linked to vulnerability.
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| 13. |
- Siddiqi, S., et al.
(författare)
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Global strategies and local implementation of health and health-related SDGs: lessons from consultation in countries across five regions
- 2020
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Ingår i: Bmj Global Health. - : BMJ. - 2059-7908. ; 5:9
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Tidskriftsartikel (refereegranskat)abstract
- Evidence on early achievements, challenges and opportunities would help low-income and middle-income countries (LMICs) accelerate implementation of health and health-related sustainable development goals (HHSDGs). A series of country-specific and multicountry consultative meetings were conducted during 2018-2019 that involved 15 countries across five regions to determine the status of implementation of HHSDGs. Almost 120 representatives from health and non-health sectors participated. The assessment relied on a multidomain analytical framework drawing on existing public health policy frameworks. During the first 5 years of the sustainable development goals (SDGs) era, participating LMICs from South and Central Asia, East Africa and Latin America demonstrated growing political commitment to HHSDGs, with augmentation of multisectoral institutional arrangements, strengthening of monitoring systems and engagement of development partners. On the other hand, there has been limited involvement of civic society representatives and academia, relatively few capacity development initiatives were in place, a well-crafted communication strategy was missing, and there is limited evidence of additional domestic financing for implementing HHSDGs. While the momentum towards universal health coverage is notable, explicit linkages with non-health SDGs and integrated multisectoral implementation strategies are lacking. The study offers messages to LMICs that would allow for a full decade of accelerated implementation of HHSDGs, and points to the need for more implementation research in each domain and for testing interventions that are likely to work before scale-up.
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| 14. |
- Wilkie, F. L., et al.
(författare)
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Cognitive functioning in younger and older HIV-1 - Infected adults
- 2003
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Ingår i: Journal of Acquired Immune Deficiency Syndromes. - : Wolters Kluwer. - 1525-4135 .- 1944-7884. ; 33, s. S93-S105
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Tidskriftsartikel (refereegranskat)abstract
- In young adults, a major neurologic complication of HIV-1 infection is cognitive motor impairment. Epidemiologic findings suggest that increasing age is a significant risk factor for HIV-1-associated dementia as the AIDS-defining illness. Findings from the few studies that have directly measured cognition in younger and older HIV-1-infected adults, however, have been mixed, in pan, because of small sample sizes and other methodologic differences between studies. The authors present preliminary findings on cognitive functioning in symptomatic HIV-1-infected younger (aged 20-39 years) and older (aged 50 years or older) adults. Independent of age, HIV-1 infection was accompanied by learning and memory retrieval deficits, which were significantly associated with high plasma viral loads in the young adults. Relative to the younger and older HIV-1-negative (HIV-1-) groups, only the younger HIV-1-positive (HIV-1(+))group had significantly longer reaction times (RTs). Within the older HIV-1(+) group, however, longer simple and choice RTs were significantly correlated with higher viral loads and lower CD4 cell counts. Although HIV-1 infection affects cognition independent of age, longitudinal studies involving large numbers of older individuals are needed to determine whether there are age differences in the prevalence, nature, and severity of HIV-1-associated cognitive dysfunction.
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| 15. |
- Ali, Noor Adel Mohammed, et al.
(författare)
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Enamel demineralization around orthodontic brackets bonded with new bioactive composite (in-vitro study)
- 2024
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Ingår i: Journal of Baghdad College of Dentistry. - : Baghdad College of Dentistry. - 1817-1869 .- 2311-5270. ; 36:2, s. 54-62
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Tidskriftsartikel (refereegranskat)abstract
- Background: This study aimed to evaluate the effect of bioactive composite (ACTIVA) on enamel demineralisation when used as an orthodontic adhesive, compared to other adhesives.Materials and methods: Human upper premolars (n=64) were randomly divided into two equal groups; the first group stored the bonded teeth in deionised water for 30 days at 37°C, and the second group exposed the bonded teeth to acidic media. Each group was further subdivided into four subgroups, with eight premolars in each subgroup, based on the type of adhesive used to bond metal brackets: non-fluoride-releasing adhesive (Transbond XT), fluoride-releasing adhesive (Light Bond), light-cured, resin-reinforced glass ionomer (GC Fuji ortho LC), and bioactive restorative composite (ACTIVA BioACTIVE-RESTORATIVE). Enamel demineralisation was assessed at baseline and after 30 days with a laser fluorescence device (DIAGNOdent™ Pen).Results: There were significant differences in fluorescence variation values (ΔFV) among all four tested adhesive systems in both water and acid groups after 30 days. Light Bond adhesive showed the highest fluorescence variation value, while glass ionomer showed the lowest, indicating less enamel demineralisation around the bracket. ACTIVA had less enamel demineralisation in acidic media. However, there was no significant difference in enamel demineralisation between water storage and acidic media groups.Conclusion: ACTIVA (RMGIC + composite) exhibited less enamel demineralisation than Light Bond; however, Fuji ortho LC showed the lowest enamel demineralisation.
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| 16. |
- Goodkin, K., et al.
(författare)
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"Putting a face" on HIV infection/AIDS in older adults : A psychosocial context
- 2003
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Ingår i: Journal of Acquired Immune Deficiency Syndromes. - : Lippincott Williams & Wilkins. - 1525-4135 .- 1944-7884. ; 33, s. S171-S184
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Forskningsöversikt (refereegranskat)abstract
- Older HIV-1-seropositive individuals largely have not been investigated with respect to their psychosocial characteristics. In this article, the authors review research reported to date regarding the psychosocial context of this growing subgroup of HIV-1-infected individuals. Specifically, the authors consider the characteristics of mood state, life stressor burden, social support network, and coping strategies that individuals older than 50 years are more likely to adopt in adjusting to HIV-1 infection. The authors also separately consider issues of caregiving burden. Data supporting a theoretically based stressor-support-coping model are presented and related to targeting psychotherapeutic interventions for this age group.
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