| 1. |
- Hálfdánarson, Óskar Ö., et al.
(författare)
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Proton pump inhibitor use and risk of breast cancer, prostate cancer, and malignant melanoma : An Icelandic population-based case-control study
- 2019
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Ingår i: Pharmacoepidemiology and Drug Safety. - : John Wiley & Sons. - 1053-8569 .- 1099-1557. ; 28:4, s. 471-478
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Increased expression of Vacuolar-type H+ ATPases (V-ATPases), in the plasma membrane of cancer cells has been suggested to contribute to the development of aggressive cancer phenotypes by promoting acidic tumor microenvironments. Accumulating data suggest that proton pump inhibitors (PPIs) may elicit a chemopreventive effect via V-ATPase inhibition in some cancers, but evidence is still limited. Therefore, we aimed to explore a potential preventive role of PPIs in this study.Methods: In this population-based case-control study, we identified incident cases of breast cancer (n=1739), prostate cancer (n=1897), and malignant melanoma (n=385) in Iceland between 2005 and 2014 from the Icelandic Cancer Registry. We assessed varying levels of PPI use through record linkages to the Icelandic Medicines Registry. For each case, we selected up to 10 age-matched, sex-matched, and calendar-matched population controls using risk-set sampling. Using conditional logistic regression, we calculated odds ratios (ORs) and 95% confidence intervals (CIs) controlling for NSAID use.Results: Adjusted ORs associated with ever use of PPIs were 1.03 (95% CI: 0.92-1.16) for breast cancer, 1.12 (95% CI: 1.00-1.25) for prostate cancer, and 0.84 (95% CI: 0.69-1.12) for malignant melanoma. Analyses of high use of PPIs (>= 1000 DDDs) yielded ORs of 0.97 (95% CI: 0.78-1.19), 1.20 (0.99-1.47), and 0.59 (0.40-1.13) for breast cancer, prostate cancer, and malignant melanoma, respectively. Analyses of cumulative exposure to PPIs did not support a dose-response relationship for any of the three cancer types.Conclusions: Our findings do not support a chemopreventive effect of PPI use on breast cancer, prostate cancer, or malignant melanoma.
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| 2. |
- Styrkarsdottir, Unnur, et al.
(författare)
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GWAS of bone size yields twelve loci that also affect height, BMD, osteoarthritis or fractures
- 2019
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Bone area is one measure of bone size that is easily derived from dual-energy X-ray absorptiometry (DXA) scans. In a GWA study of DXA bone area of the hip and lumbar spine (N ≥ 28,954), we find thirteen independent association signals at twelve loci that replicate in samples of European and East Asian descent (N = 13,608 – 21,277). Eight DXA area loci associate with osteoarthritis, including rs143384 in GDF5 and a missense variant in COL11A1 (rs3753841). The strongest DXA area association is with rs11614913[T] in the microRNA MIR196A2 gene that associates with lumbar spine area (P = 2.3 × 10 −42 , β = −0.090) and confers risk of hip fracture (P = 1.0 × 10 −8 , OR = 1.11). We demonstrate that the risk allele is less efficient in repressing miR-196a-5p target genes. We also show that the DXA area measure contributes to the risk of hip fracture independent of bone density.
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| 3. |
- Ingason, Arnar B., et al.
(författare)
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Comparison of medication adherence to different oral anticoagulants: population-based cohort study
- 2023
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Previous observational studies have yielded conflicting results on whether medication adherence differs between patients receiving warfarin and direct oral anticoagulants (DOACs). Importantly, no study has adequately accounted for warfarin dosing being continuously modified based on INR values while dosing of DOACs is fixed. We aimed to compare non-adherence between new users of apixaban, dabigatran, rivaroxaban and warfarin in a population-based cohort. METHODS: New users of apixaban, dabigatran, rivaroxaban and warfarin from 2014 to 2019 living in the Icelandic capital area were included. Non-adherence was defined as proportion of days covered below 80%. Inverse probability weighting was used to yield balanced study groups and non-adherence was compared using logistic regression. Factors associated with non-adherence were estimated using multivariable logistic regression. RESULTS: Overall, 1266 patients received apixaban, 247 dabigatran, 1566 rivaroxaban and 768 warfarin. The proportion of patients with non-adherence ranged from 10.5% to 16.7%. Dabigatran was associated with significantly higher odds of non-adherence compared with apixaban (OR 1.57, 95% CI 1.21 to 2.04, p<0.001), rivaroxaban (OR 1.45, 95% CI 1.12 to 1.89, p=0.005) and warfarin (OR 1.63, 95% CI 1.23 to 2.15, p<0.001). The odds of non-adherence were similar for apixaban, rivaroxaban and warfarin. Apart from the type of oral anticoagulants (OACs) used, female sex, hypertension, history of cerebrovascular accident and concomitant statin use were all independently associated with lower odds of non-adherence. CONCLUSION: Dabigatran was associated with higher odds of non-adherence compared with other OACs. Non-adherence was similar between apixaban, rivaroxaban and warfarin users. Female sex and higher comorbidity were associated with better medication adherence.
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| 4. |
- Jóhannesson, Gauti, et al.
(författare)
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Dorzolamide cyclodextrin nanoparticle suspension eye drops and trusopt in rabbit
- 2014
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Ingår i: Journal of Ocular Pharmacology and Therapeutics. - : Mary Ann Liebert. - 1080-7683 .- 1557-7732. ; 30:6, s. 464-467
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Purpose: Dorzolamide nanoparticle γ-cyclodextrin eye drops may prolong the effect of dorzolamide on intraocular pressure. We test whether the nanoparticle drops have an irritating or toxic effect on the eye in an in vivo rabbit model. Methods: Eighteen pigmented rabbits were divided into 4 groups receiving dorzolamide nanoparticle γ-cyclodextrin eye drops×1/day or×2/day, Trusopt(®) (dorzolamide HCl)×3/day, and untreated controls that received no drops. The rabbits received treatment for 1 month. After sacrifice, 33 eyes and 25 Harderian glands were evaluated for histopathology in a masked way. Results: Mild inflammation was seen in 19/31 eyes and 13/23 Harderian glands. The difference in inflammation (n=eyes/n=glands)between the γ-cyclodextrin nanoparticle eye drops×1/day (n=5/5),×2/day (n=5/3), Trusopt (n=7/4), or untreated control (n=2/0) groups was nonsignificant in both eyes and glands (P=0.87 and P=0.92) Acute inflammation was seen in 1 Harderian gland that received γ-cyclodextrin nanoparticle eye drops×2/day. The difference in conjunctival injection between the groups was nonsignificant (P=0.30). Conclusions: Dorzolamide γ-cyclodextrin nanoparticle eye drops are no more locally toxic or irritating to the eye than Trusopt.
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| 5. |
- Jóhannesson, Gauti, et al.
(författare)
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Kinetics of γ-cyclodextrin nanoparticle suspension eye drops in tear fluid
- 2014
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Ingår i: Acta Ophthalmologica. - : Wiley. - 1755-375X .- 1755-3768. ; 92:6, s. 550-556
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: We have developed nanoparticle γ-cyclodextrin dexamethasone (DexNP) and dorzolamide (DorzNP) eye drops that provide sustained high drug concentrations on the eye surface. To test these characteristics, we measured dexamethasone and dorzolamide levels in tear fluid in humans following eye drop administration.METHODS: Concentration of dexamethasone was measured by mass spectrometry. One drop of DexNP was instilled into one eye. Tear fluid was sampled with microcapillary pipettes at seven time-points after drop instillation. Control eyes received Maxidex(®) (dexamethasone). The same procedure was performed for dorzolamide with DorzNP and Trusopt(®) .RESULTS: Six subjects were included in each group. The peak concentration (μg/ml ± standard deviation) of dexamethasone for DexNP eye drops (636.6 ± 399.1) was up to 19-fold higher than with Maxidex(®) (39.3 ± 18.9) (p < 0.001). At 4 hr, DexNP was still 10 times higher than Maxidex(®) . In addition, DexNP resulted in about 30-fold higher concentration of dissolved dexamethasone in the tear fluid of extended time period allowing more drug to partition into the eye tissue. The overall concentration of dorzolamide was about 50% higher for DorzNP (59.5 ± 76.9) than Trusopt(®) (40.0 ± 76.7) (p < 0.05).CONCLUSION: The results indicate high and extended concentration of dissolved dexamethasone with DexNP, which can explain the greater and longer lasting effect of dexamethasone in the cyclodextrin nanoparticle drug delivery platform. Dexamethasone seems to fit the cyclodextrin nanoparticle suspension drug delivery platform with longer duration and higher concentrations in tear fluid than available commercial drops, while dorzolamide is less suitable.
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| 6. |
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| 7. |
- Ohira, Akihiro, et al.
(författare)
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Topical dexamethasone -cyclodextrin nanoparticle eye drops increase visual acuity and decrease macular thickness in diabetic macular oedema
- 2015
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Ingår i: Acta Ophthalmologica. - : Wiley. - 1755-375X .- 1755-3768. ; 93:7, s. 610-615
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Tidskriftsartikel (refereegranskat)abstract
- PurposeTo compare in a randomized, controlled trial topical 1.5% dexamethasone -cyclodextrin nanoparticle eye drops (DexNP) with posterior subtenon injection of triamcinolone acetonide in diabetic macular oedema (DME). MethodsIn this prospective, randomized, controlled trial, 22 eyes of 22 consecutive patients with DME were randomized to (i) topical treatment with DexNP x3/day (4weeks), x2/day (4weeks) and x1/day (4weeks) or (ii) one posterior subtenon injection of 20mg triamcinolone acetonide. Study visits were at baseline and 4, 8, 12 and 16weeks. ResultsThe logMAR (Snellen) visual acuity (meanSD) improved significantly with DexNP from 0.41 +/- 0.3 (Snellen 0.39) to 0.32 +/- 0.25 (0.48) and 0.30 +/- 0.26 (0.50) at 4 and 8weeks, respectively. One-third of the DexNP group improved more than 0.3 logMAR units. For triamcinolone, logMAR changed significantly from 0.42 +/- 0.28 (0.38) at baseline to 0.32 +/- 0.29 (0.48) at 4w and 0.33 +/- 0.37 (0.47) at 12w. The central macular thickness (CMT) decreased significantly with DexNP from 483 +/- 141m to 384 +/- 142m at 4w and 342 +/- 114m at 8w. For triamcinolone, CMT decreased significantly at all time-points: 494 +/- 94m, 388 +/- 120, 388 +/- 145, 390 +/- 136 and 411 +/- 104m at 0, 4, 8, 12 and 16weeks, respectively. There was a modest increase in intraocular pressure (IOP) at all time-points with DexNP while no increase was seen with triamcinolone. Serum cortisol was affected by both treatments. ConclusionTopical DexNP significantly improve visual acuity and decrease macular thickness in patients with DME. The effect is similar to that from subtenon triamcinolone. A modest increase in IOP was seen with the nanoparticle eye drops, but IOP normalized after the discontinuation of treatment.
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| 8. |
- Ohira, Akihiro, et al.
(författare)
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Topical Dexamethasone gamma-Cyclodextrin Nanoparticle Eye Drops increase Visual Acuity and decrease Macular Thickness in Diabetic Macular Edema
- 2015
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Ingår i: Investigative Ophthalmology and Visual Science. - : The Association for Research in Vision and Ophthalmology. - 0146-0404 .- 1552-5783. ; 56:7
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Purpose: To test the efficacy and safety of topical 1.5% dexamethasone γ-cyclodextrin nanoparticle eye drops (dexNP) for diabetic macular edema (DME) and compare to posterior subtenon injection of triamcinolone acetonide.Methods: This was a prospective, randomized controlled trial with 22 eyes in 22 consecutive patients with DME, who were randomized to a) topical treatment with dexNP eye drops x3/day for one month, x2/day the next month and finally x1/day the third month or b) one posterior subtenon injection of 20mg triamcinolone acetonide.Results: The central macular thickness (CMT) decreased significantly with dexNP eye drops from 483±141mm to 384±142 mm at 4 weeks and 342±114 mm at 8 weeks. For triamcinolone, CMT decreased significantly at all time points. Visual acuity (logMAR) improved significantly with dexNP eye drops from 0.41±0.3 (mean±SD) to 0.32±0.25 and 0.30±0.26 at 4 and 8 weeks respectively. One third of the eye drop group improved more than 0.3 logMAR units. For triamcinolone, logMAR changed significantly from 0.42±0.28 at baseline to 0.32±0.29 at 4 weeks and 0.33±0.37 at 12 weeks. There was a modest increase in IOP at all time points with dexNP eye drops while no increase was seen with triamcinolone. Serum cortisol was affected by both treatments.Conclusions: Topical dexamethasone γ-cyclodextrin nanoparticle eye drops significantly improve visual acuity and decrease macular thickness in patients with DME. The effect is similar to that from subtenon triamcinolone as well as to reports on intravitreal steroid implants and triamcinolone intravitreal injections. A modest increase in IOP was seen with the nanoparticle eye drops but IOP normalized after discontinuation of treatment.
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| 9. |
- Valdimarsdóttir, Unnur A., et al.
(författare)
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The mother's risk of premature death after child loss across two centuries
- 2019
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Ingår i: eLIFE. - : eLife Sciences Publications Ltd.. - 2050-084X. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- While the rare occurrence of child loss is accompanied by reduced life expectancy of parents in contemporary affluent populations, its impact in developing societies with high child mortality rates is unclear. We identified all parents in Iceland born 1800-1996 and compared the mortality rates of 47,711 parents who lost a child to those of their siblings (N = 126,342) who did not. The proportion of parents who experienced child loss decreased from 61.1% of those born 1800-1880 to 5.2% of those born after 1930. Child loss was consistently associated with increased rate of maternal, but not paternal, death before the age of 50 across all parent birth cohorts; the relative increase in maternal mortality rate ranged from 35% among mothers born 1800-1930 to 64% among mothers born after 1930. The loss of a child poses a threat to the survival of young mothers, even during periods of high infant mortality rates.
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