| 1. |
- Vigorito, Elena, et al.
(författare)
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Fine-Scale Mapping at 9p22.2 Identifies Candidate Causal Variants That Modify Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers
- 2016
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:7
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Tidskriftsartikel (refereegranskat)abstract
- Population-based genome wide association studies have identified a locus at 9p22.2 associated with ovarian cancer risk, which also modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. We conducted fine-scale mapping at 9p22.2 to identify potential causal variants in BRCA1 and BRCA2 mutation carriers. Genotype data were available for 15,252 (2,462 ovarian cancer cases) BRCA1 and 8,211 (631 ovarian cancer cases) BRCA2 mutation carriers. Following genotype imputation, ovarian cancer associations were assessed for 4,873 and 5,020 SNPs in BRCA1 and BRCA2 mutation carriers respectively, within a retrospective cohort analytical framework. In BRCA1 mutation carriers one set of eight correlated candidate causal variants for ovarian cancer risk modification was identified (top SNP rs10124837, HR: 0.73, 95% CI: 0.68 to 0.79, p-value 2x 10-16). These variants were located up to 20 kb upstream of BNC2. In BRCA2 mutation carriers one region, up to 45 kb upstream of BNC2, and containing 100 correlated SNPs was identified as candidate causal (top SNP rs62543585, HR: 0.69, 95% CI: 0.59 to 0.80, p-value 1.0 x 10-6). The candidate causal in BRCA1 mutation carriers did not include the strongest associated variant at this locus in the general population. In sum, we identified a set of candidate causal variants in a region that encompasses the BNC2 transcription start site. The ovarian cancer association at 9p22.2 may be mediated by different variants in BRCA1 mutation carriers and in the general population. Thus, potentially different mechanisms may underlie ovarian cancer risk for mutation carriers and the general population.
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| 2. |
- Zeng, Chenjie, et al.
(författare)
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Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus
- 2016
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Ingår i: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 18
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Tidskriftsartikel (refereegranskat)abstract
- Background: Multiple recent genome-wide association studies (GWAS) have identified a single nucleotide polymorphism (SNP), rs10771399, at 12p11 that is associated with breast cancer risk. Method: We performed a fine-scale mapping study of a 700 kb region including 441 genotyped and more than 1300 imputed genetic variants in 48,155 cases and 43,612 controls of European descent, 6269 cases and 6624 controls of East Asian descent and 1116 cases and 932 controls of African descent in the Breast Cancer Association Consortium (BCAC; http://bcac.ccge.medschl.cam.ac.uk/), and in 15,252 BRCA1 mutation carriers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Stepwise regression analyses were performed to identify independent association signals. Data from the Encyclopedia of DNA Elements project (ENCODE) and the Cancer Genome Atlas (TCGA) were used for functional annotation. Results: Analysis of data from European descendants found evidence for four independent association signals at 12p11, represented by rs7297051 (odds ratio (OR) = 1.09, 95 % confidence interval (CI) = 1.06-1.12; P = 3 x 10(-9)), rs805510 (OR = 1.08, 95 % CI = 1.04-1.12, P = 2 x 10(-5)), and rs1871152 (OR = 1.04, 95 % CI = 1.02-1.06; P = 2 x 10(-4)) identified in the general populations, and rs113824616 (P = 7 x 10(-5)) identified in the meta-analysis of BCAC ER-negative cases and BRCA1 mutation carriers. SNPs rs7297051, rs805510 and rs113824616 were also associated with breast cancer risk at P < 0.05 in East Asians, but none of the associations were statistically significant in African descendants. Multiple candidate functional variants are located in putative enhancer sequences. Chromatin interaction data suggested that PTHLH was the likely target gene of these enhancers. Of the six variants with the strongest evidence of potential functionality, rs11049453 was statistically significantly associated with the expression of PTHLH and its nearby gene CCDC91 at P < 0.05. Conclusion: This study identified four independent association signals at 12p11 and revealed potentially functional variants, providing additional insights into the underlying biological mechanism(s) for the association observed between variants at 12p11 and breast cancer risk.
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| 3. |
- Zheng, Hou-Feng, et al.
(författare)
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WNT16 influences bone mineral density, Cortical bone thickness, bone strength, and Osteoporotic fracture risk
- 2012
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Ingår i: PLoS genetics. - SAN FRANCISCO, USA : PUBLIC LIBRARY SCIENCE. - 1553-7404. ; 8:7, s. e1002745-
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Tidskriftsartikel (refereegranskat)abstract
- We aimed to identify genetic variants associated with cortical bone thickness (CBT) and bone mineral density (BMD) by performing two separate genome-wide association study (GWAS) meta-analyses for CBT in 3 cohorts comprising 5,878 European subjects and for BMD in 5 cohorts comprising 5,672 individuals. We then assessed selected single-nucleotide polymorphisms (SNPs) for osteoporotic fracture in 2,023 cases and 3,740 controls. Association with CBT and forearm BMD was tested for ∼2.5 million SNPs in each cohort separately, and results were meta-analyzed using fixed effect meta-analysis. We identified a missense SNP (Thr>Ile; rs2707466) located in the WNT16 gene (7q31), associated with CBT (effect size of -0.11 standard deviations [SD] per C allele, P = 6.2×10(-9)). This SNP, as well as another nonsynonymous SNP rs2908004 (Gly>Arg), also had genome-wide significant association with forearm BMD (-0.14 SD per C allele, P = 2.3×10(-12), and -0.16 SD per G allele, P = 1.2×10(-15), respectively). Four genome-wide significant SNPs arising from BMD meta-analysis were tested for association with forearm fracture. SNP rs7776725 in FAM3C, a gene adjacent to WNT16, was associated with a genome-wide significant increased risk of forearm fracture (OR = 1.33, P = 7.3×10(-9)), with genome-wide suggestive signals from the two missense variants in WNT16 (rs2908004: OR = 1.22, P = 4.9×10(-6) and rs2707466: OR = 1.22, P = 7.2×10(-6)). We next generated a homozygous mouse with targeted disruption of Wnt16. Female Wnt16(-/-) mice had 27% (P<0.001) thinner cortical bones at the femur midshaft, and bone strength measures were reduced between 43%-61% (6.5×10(-13)
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| 4. |
- Karlsson, Christofer A.Q., et al.
(författare)
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Streptococcus pyogenes Infection and the Human Proteome with a Special Focus on the Immunoglobulin G-cleaving Enzyme IdeS
- 2018
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Ingår i: Molecular and Cellular Proteomics. - 1535-9476. ; 17:6, s. 1097-1111
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Tidskriftsartikel (refereegranskat)abstract
- Infectious diseases are characterized by a complex interplay between host and pathogen, but how these interactions impact the host proteome is unclear. Here we applied a combined mass spectrometry-based proteomics strategy to investigate how the human proteome is transiently modified by the pathogen Streptococcus pyogenes, with a particular focus on bacterial cleavage of IgG in vivo. In invasive diseases, S. pyogenes evokes a massive host response in blood, whereas superficial diseases are characterized by a local leakage of several blood plasma proteins at the site of infection including IgG. S. pyogenes produces IdeS, a protease cleaving IgG in the lower hinge region and we find highly effective IdeS-cleavage of IgG in samples from local IgG poor microenvironments. The results show that IdeS contributes to the adaptation of S. pyogenes to its normal ecological niches. Additionally, the work identifies novel clinical opportunities for in vivo pathogen detection.
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| 5. |
- Moberg, Christina, et al.
(författare)
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De unga gör helt rätt när de stämmer staten
- 2022
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Ingår i: Aftonbladet. - 1103-9000.
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- 1 620 forskare och lärare i forskarvärlden: Vi ställer oss bakom Auroras klimatkrav
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| 6. |
- Andell, Pontus, et al.
(författare)
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Intravascular Ultrasound Guidance Is Associated With Better Outcome in Patients Undergoing Unprotected Left Main Coronary Artery Stenting Compared With Angiography Guidance Alone
- 2017
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Ingår i: Circulation. Cardiovascular Interventions. - : Lippincott Williams & Wilkins. - 1941-7640 .- 1941-7632. ; 10:5
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Tidskriftsartikel (refereegranskat)abstract
- Background: Small observational studies have indicated better outcome with intravascular ultrasound (IVUS) guidance when performing unprotected left main coronary artery (LMCA) percutaneous coronary intervention (PCI), but the overall picture remains inconclusive and warrants further investigation. We studied the impact of IVUS guidance on outcome in patients undergoing unprotected LMCA PCI in a Swedish nationwide observational study.Methods and Results: Patients who underwent unprotected LMCA PCI between 2005 and 2014 because of stable coronary artery disease or acute coronary syndrome were included from the nationwide SCAAR (Swedish Coronary Angiography and Angioplasty Registry). Of 2468 patients, IVUS guidance was used in 621 (25.2%). The IVUS group was younger (median age, 70 versus 75 years) and had fewer comorbidities but more complex lesions. IVUS was associated with larger stent diameters (median, 4 mm versus 3.5 mm). After adjusting for potential confounders, IVUS was associated with significantly lower occurrence of the primary composite end point of all-cause mortality, restenosis, or definite stent thrombosis (hazard ratio, 0.65; 95% confidence interval, 0.50-0.84) and all-cause mortality alone (hazard ratio, 0.62; 95% confidence interval, 0.47-0.82). In 340 propensity score-matched pairs, IVUS was also associated with significantly lower occurrence of the primary end point (hazard ratio, 0.54; 95% confidence interval, 0.37-0.80).Conclusions: IVUS was associated with an independent and significant outcome benefit when performing unprotected LMCA PCI. Potential mediators of this benefit include larger and more appropriately sized stents, perhaps translating into lower risk of subsequent stent thrombosis. Although residual confounding cannot be ruled out, our findings indicate a possible hazard when performing unprotected LMCA PCI without IVUS guidance.
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| 7. |
- Börjesson, Anna E, et al.
(författare)
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The role of estrogen receptor-alpha in growth plate cartilage for longitudinal bone growth.
- 2010
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Ingår i: Journal of bone and mineral research. - : Wiley. - 1523-4681 .- 0884-0431. ; 25:12, s. 2414-24
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Tidskriftsartikel (refereegranskat)abstract
- Estrogens enhance skeletal growth during early sexual maturation while high estradiol levels during late puberty result in growth plate fusion in humans. Although the growth plates do not fuse directly after sexual maturation in rodents, a reduction in growth plate height is seen by treatment with a high dose of estradiol. It is unknown whether the effects of estrogens on skeletal growth are mediated directly via estrogen receptors (ERs) in growth plate cartilage and/or indirectly via other mechanisms such as the GH/IGF-I axis. To determine the role of ERalpha in growth plate cartilage for skeletal growth, we developed a mouse model with cartilage-specific inactivation of ERalpha. Although mice with total ERalpha inactivation displayed affected longitudinal bone growth associated with alterations in the GH/IGF-I axis, the skeletal growth was normal during sexual maturation in mice with cartilage-specific ERalpha inactivation. High dose estradiol treatment of adult mice reduced the growth plate height as a consequence of attenuated proliferation of growth plate chondrocytes in control mice but not in cartilage-specific ERalpha(-/-) mice. Adult cartilage-specific ERalpha(-/-) mice continued to grow after four months of age while growth was limited in control mice, resulting in increased femur length in one-year-old cartilage-specific ERalpha(-/-) mice compared with control mice. We conclude that during early sexual maturation ERalpha in growth plate cartilage is not important for skeletal growth. In contrast, it is essential for high dose estradiol to reduce the growth plate height in adult mice and for reduction of longitudinal bone growth in elderly mice. (c) 2010 American Society for Bone and Mineral Research.
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| 8. |
- Choong, Oi Kuan, 1985, et al.
(författare)
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SARS-CoV-2 replicates and displays oncolytic properties in clear cell and papillary renal cell carcinoma
- 2023
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- The SARS-CoV-2 virus is currently causing a global pandemic. Infection may result in a systemic disease called COVID-19, affecting primarily the respiratory tract. Often the gastrointestinal tract and kidneys also become involved. Angiotensin converting enzyme 2 (ACE2) serves as the receptor for SARS-CoV-2. The membrane proteins, Transmembrane serine protease 2 (TMPRSS2) and Neuropilin 1 (NRP1) are accessory proteins facilitating the virus entry. In this study we show that the human proximal kidney tubules, express these factors. We hypothesized that cancers derived from proximal tubules as clear cell (CCRCC) and papillary renal cell carcinoma (PRCC), retain the expression of the SARS-CoV-2 entry factors making these cancers susceptible to SARS-CoV-2 infection. We used bioinformatics, western blotting, and assessment of tissue micro arrays (TMA) including 263 cases of CCRCC, 139 cases of PRCC and 18 cases of chromophobe RCC to demonstrate that the majority of CCRCC and PRCC cases retained the RNA and protein expression of the entry factors for SARS-CoV-2. We furthermore show that SARS-CoV-2 virus propagated robustly in primary cultures of CCRCC and PRCC cells with a visible virus cytopathogenic effect correlating with viral RNA expression levels. We also noted that the delta-variant of SARS-CoV-2 causes cancer cells to form syncytia in-vitro. This phenomenon was also identified histologically in CCRCC tissue from a patient that had been hospitalized for COVID-19, twelve months prior to nephrectomy. Our data provide insights into SARS-CoV-2 infectivity in renal cell carcinoma and that the virus causes a distinct cytopathogenic effect.
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| 9. |
- Collinson, Glyn A., et al.
(författare)
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Shocklets and Short Large Amplitude Magnetic Structures (SLAMS) in the High Mach Foreshock of Venus
- 2023
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Ingår i: Geophysical Research Letters. - : American Geophysical Union (AGU). - 0094-8276 .- 1944-8007. ; 50:18
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Tidskriftsartikel (refereegranskat)abstract
- Shocklets and short large-amplitude magnetic structures (SLAMS) are steepened magnetic fluctuations commonly found in Earth's upstream foreshock. Here we present Venus Express observations from the 26th of February 2009 establishing their existence in the steady-state foreshock of Venus, building on a past study which found SLAMS during a substantial disturbance of the induced magnetosphere. The Venusian structures were comparable to those reported near Earth. The 2 Shocklets had magnetic compression ratios of 1.23 and 1.34 with linear polarization in the spacecraft frame. The 3 SLAMS had ratios between 3.22 and 4.03, two of which with elliptical polarization in the spacecraft frame. Statistical analysis suggests SLAMS coincide with unusually high solar wind Alfvén mach-number at Venus (12.5, this event). Thus, while we establish Shocklets and SLAMS can form in the stable Venusian foreshock, they may be rarer than at Earth. We estimate a lower limit of their occurrence rate of ≳14%.
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| 10. |
- Hero, Christel, et al.
(författare)
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Adherence to lipid-lowering therapy and risk for cardiovascular disease and death in type 1 diabetes mellitus: A population-based study from the Swedish National Diabetes Register
- 2020
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Ingår i: BMJ Open Diabetes Research and Care. - : BMJ. - 2052-4897. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis Dyslipidemia is an important modifiable risk factor and lipid-lowering treatment (LLT) is essential to reduce the risk of cardiovascular disease (CVD). Studies in type 2 diabetes indicate that low adherence to statin therapy is a barrier to reach full protective potential, and less is known in type 1 diabetes (T1D). The aim was to assessrisk of CVD by adherence and nonpersistence to LLT in T1D. Method A population-based study with a retrospective longitudinal design was conducted between 2006 and 2010, with follow-up until December 2013. In total, 6192 adult individuals withT1D, initiatingLLTbetween 2006 and 2010, were included.Information on LLT, socioeconomic characteristics, comorbidities and cardiovascular eventswere collected. After 18 months, refill adherence was estimated by calculating medication possession ratio (MPR). Nonpersistence was defined as being without medicines on hand for at least 180 days. Individuals were thereafterfollowed untilCVD, deathorend of follow-up in December 2013. Cox regression analyses were performed to assess adherence level and nonpersistence of LLT as predictor ofCVD. Analyses wereadjusted for cardiovascular risk factors andsocioeconomic status. Results Mean MPRwas 72%, 52% of the participants had an MPR above 80% and 27% discontinued LLT. There were 637nonfataland58 fatal CVDevents, mean follow-up 3.6 and 3.9 years, respectively. MPR above 80% was associated with reduced risk for nonfatal CVD compared with lower MPR, HR 0.78 (95% CI 0.65 to 0.93)). For fatal CVD, results indicated a negative effect of high adherence but the association did not reach statistical significance, HR 1.96 (0.96 to 4.01). Individuals discontinuing LLT had higher risk of nonfatal CVD, HR 1.43 (95% CI 1.18 to 1.73). Conclusions/Interpretation In T1D, the risk for nonfatal CVD was lower among individuals with high adherence and higher among those discontinuing LLT within 18 months. It is important to evaluate andemphasize adherence toprescribedLLTat clinical visits to achieve treatment goals and reduce the risk of CVD. © Author(s) (or their employer(s)) 2020.
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| 11. |
- Hero, Christel, et al.
(författare)
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Impact of Socioeconomic Factors and Gender on Refill Adherence and Persistence to Lipid-Lowering Therapy in Type 1 Diabetes
- 2021
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Ingår i: Diabetes Therapy. - : Springer Science and Business Media LLC. - 1869-6953 .- 1869-6961. ; 12:9, s. 2371-2386
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Lipid-lowering therapy (LLT) reduces the risk of cardiovascular disease (CVD) in patients with type 1 diabetes (T1D). However, socioeconomic factors and gender may have an impact on the adherence to and non-persistence with LLT. Methods This was a nationwide register-based cohort study that included 6192 individuals with T1D aged >= 18 years who were registered in the Swedish National Diabetes Register and had initiated novel use of LLT. Information on socioeconomic parameters (source: Statistics Sweden) and comorbidity (source: National Patient Register) was collected. The individuals were followed for 36 months, and adherence to LLT was analyzed according to age, socioeconomics and gender. The medication possession ratio (MPR; categorized into <= 80% and > 80%) and non-persistence (discontinuation) with medication was calculated after 18 and 36 months. Results Individuals older than 53 years were more adherent to LLT (MPR > 80%) than those younger than 36 years (odds ratio [(OR] 1.30, p < 0.0001) at 36 months. Women were more adherent and less prone to discontinue LLT at 18 months (OR 1.05, p = 0.0005 and OR 0.95, p = 0.0004, respectively), but not at 36 months. Divorced individuals were less adherent than married ones (OR 0.93, p = 0.0005) and discontinued LLT more often than the latter (OR 1.06, p = 0.003). Education had no impact on adherence, but individuals with higher incomes discontinued LLT less frequently than those with lower incomes. Individuals with a country of origin other than Sweden discontinued LLT more often. Conclusion Lower adherence to LLT in individuals with T1D was associated with male gender, younger age, marital status and country of birth. These factors should be considered when evaluating adherence to LLT in clinical practice, with the aim to help patients achieve full cardioprotective treatment.
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| 12. |
- Karlsson, Sofia A.
(författare)
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Adherence to lipid-lowering medications and cardiovascular disease prevention in type 2 diabetes mellitus
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background and aims: Globally, cardiovascular disease (CVD) is the major cause of death among patients with type 2 diabetes mellitus (T2DM). Improved control of LDL cholesterol with lipid-lowering medications and patients’ adherence to such medications have been shown associate with lower risk of CV events and mortality among T2DM patients. The impact of healthcare providers’ adherence to guidelines regarding prescription for lipid-lowering medications is unclear. This thesis aimed to assess and compare i) patients’ adherence to lipid-lowering medications, ii) healthcare providers’ adherence to lipid-lowering prescription guidelines, and iii) risk of CV events and mortality in relation to patients’ adherence to lipidlowering medication and healthcare providers’ guideline adherence among patients with T2DM. Patients and methods: This thesis is based on four observational studies where individualized data were linked between Swedish National Registers. All studies included data about patients with T2DM of at least 18 years of age. To assess patients’ adherence, our studies used information about new users of lipidlowering medications from pharmacy claims data in the Swedish Prescribed Drug Register. Using data from the Swedish National Diabetes Register, guideline adherence was assessed for healthcare providers who treated patients with T2DM and LDL cholesterol above the recommended target values. We used information about cause of death and completed admissions of in and out-patients care to analyze risk of CV events and mortality, adjusted for sex, age, socioeconomic status, and concurrent medications as well as health-related and clinical characteristics. Results: On average, patients’ adherence to lipid-lowering medications was higher among secondary prevention patients, smokers and those with concurrent cardioprotective medications, compared to lower adherence among patients born outside of Sweden. Healthcare providers’ adherence to lipid-lowering prescription guidelines was higher among patients attributed to secondary prevention and the odds of receiving a prescription associated with patients’ individual risk of CV events. Adjusted for potential confounders, risk of CV events was higher among patients with less than complete adherence to lipidlowering medications and that risk gradually increased as patient adherence declined, independent of prevention group. Healthcare providers’ adherence to guidelines had little or no impact on patients’ risk of CV events and mortality. Conclusions: Patients’ adherence to lipid-lowering medications among patients with T2DM had greater impact on risk of CV events and mortality compared to healthcare providers’ adherence to prescription guidelines for such medications. This thesis emphasizes the value of individualized diabetes care among T2DM patients.
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| 13. |
- Karlsson, Sofia A., et al.
(författare)
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Association between refill adherence to lipid-lowering medications and the risk of cardiovascular disease and mortality in Swedish patients with type 2 diabetes mellitus: a nationwide cohort study.
- 2018
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 8:3
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Tidskriftsartikel (refereegranskat)abstract
- To analyse the association between refill adherence to lipid-lowering medications, and the risk of cardiovascular disease (CVD) and mortality in patients with type 2 diabetes mellitus.Cohort study.National population-based cohort of Swedish patients with type 2 diabetes mellitus.86568 patients aged ≥18 years, registered with type 2 diabetes mellitus in the Swedish National Diabetes Register, who filled at least one prescription for lipid-lowering medication use during 2007-2010, 87% for primary prevention.Refill adherence of implementation was assessed using the medication possession ratio (MPR), representing the proportion of days with medications on hand during an 18-month exposure period. MPR was categorised by five levels (≤20%, 21%-40%, 41%-60%, 61%-80% and >80%). Patients without medications on hand for ≥180 days were defined as non-persistent. Risk of CVD (myocardial infarction, ischaemic heart disease, stroke and unstable angina) and mortality by level of MPR and persistence was analysed after the exposure period using Cox proportional hazards regression and Kaplan-Meier, adjusted for demographics, socioeconomic status, concurrent medications and clinical characteristics.The hazard ratios for CVD ranged 1.33-2.36 in primary prevention patients and 1.19-1.58 in secondary prevention patients, for those with MPR ≤80% (p<0.0001). The mortality risk was similar regardless of MPR level. The CVD risk was 74% higher in primary prevention patients and 33% higher in secondary prevention patients, for those who were non-persistent (p<0.0001). The mortality risk was 6% higher in primary prevention patients and 18% higher in secondary prevention patients, for non-persistent patients (p<0.0001).Higher refill adherence to lipid-lowering medications was associated with lower risk of CVD in primary and secondary prevention patients with type 2 diabetes mellitus.
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| 14. |
- Karlsson, Sofia A., et al.
(författare)
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Prescription of lipid-lowering medications for patients with type 2 diabetes mellitus and risk-associated LDL cholesterol: a nationwide study of guideline adherence from the Swedish National Diabetes Register.
- 2018
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Ingår i: BMC health services research. - : Springer Science and Business Media LLC. - 1472-6963. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- Management of type 2 diabetes mellitus (T2DM) encompasses intensive glycaemic control, along with treatment of comorbidities and complications to handle the increased risk of cardiovascular disease (CVD). Improved control of LDL-cholesterol (LDL-C) with lipid-lowering medications is associated with reduced CVD risk in T2DM patients. Thus, treatment guidelines recommend lipid-lowering medications for T2DM patients with LDL-C above risk-associated thresholds. This study aimed to assess healthcare provider adherence to guidelines regarding lipid-lowering medication prescription among T2DM patients and to analyse factors associated with lipid-lowering medication prescription.Observations in 2007-2014 for T2DM patients age≥18 were collected from the Swedish National Diabetes Register. Observations were excluded if they lacked information about LDL-C, lipid-lowering medication prescription or CVD. Observations with established CVD were attributed to secondary prevention; remaining observations were attributed to primary prevention. The analyses included primary and secondary prevention observations with LDL-C above risk-associated thresholds (LDL-C≥2.5mmol/l and LDL-C≥1.8mmol/l respectively). Guideline adherence was analysed as the probability of prescribing lipid-lowering medications using mixed-effect model regression adjusted for potential confounders. Factors associated with prescribing lipid-lowering medications were analysed for patient and healthcare provider characteristics using mixed-effect model regression and odds ratio.A total of 1,204,376 observations from 322,046 patients reported by 1352 healthcare providers were included. Primary prevention accounted for 63%; 52% were men, mean age was 64 and mean LDL-C was 3.4mmol/l. For secondary prevention, 60% were men, mean age was 72 and mean LDL-C was 2.7mmol/l. During 2007-2014, guideline adherence ranged from 36 to 47% for primary prevention and 59 to 69% for secondary prevention. In general, concomitant prescription of diabetes medications, antiplatelets and antihypertensives along with smoking and specialised care were associated with higher prescription of lipid-lowering medications. Patients age≥80 were associated with lower prescription of lipid-lowering medications. Higher prescription was associated with longer diabetes duration in primary prevention and men in secondary prevention.Adherence to treatment guidelines levelled off after an initial increase in both prevention groups. Lipid-lowering medication prescription was based on individualised CVD risk.
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| 15. |
- Karlsson, Sofia A., et al.
(författare)
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Refill adherence and persistence to lipid-lowering medicines in patients with type 2 diabetes: A nation-wide register-based study.
- 2017
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Ingår i: Pharmacoepidemiology and drug safety. - : Wiley. - 1099-1557 .- 1053-8569. ; 26:10, s. 1220-1232
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Tidskriftsartikel (refereegranskat)abstract
- This study aimed to describe and compare refill adherence and persistence to lipid-lowering medicines in patients with type 2 diabetes by previous cardiovascular disease (CVD).We followed 97595 patients (58% men; 23% with previous CVD) who were 18years of age or older when initiating lipid-lowering medicines in 2007-2010 until first fill of multi-dose dispensed medicines, death, or 3years. Using personal identity numbers, we linked individuals' data from the Swedish Prescribed Drug Register, the Swedish National Diabetes Register, the National Patient Register, the Cause of Death Register, and the Longitudinal Integration Database for Health Insurance and Labour Market Studies. We assessed refill adherence using the medication possession ratio (MPR) and the maximum gap method, and measured persistence from initiation to discontinuation of treatment or until 3years after initiation. We analyzed differences in refill adherence and persistence by previous CVD in multiple regression models, adjusted for socioeconomic status, concurrent medicines, and clinical characteristics.The mean age of the study population was 64years, 80% were born in Sweden, and 56% filled prescriptions for diabetes medicines. Mean MPR was 71%, 39% were adherent according to the maximum gap method, and mean persistence was 758days. Patients with previous CVD showed higher MPR (3%) and lower risk for discontinuing treatment (12%) compared with patients without previous CVD (P<0.0001).Patients with previous CVD were more likely to be adherent to treatment and had lower risk for discontinuation compared with patients without previous CVD.
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| 16. |
- Karlsson, Sofia A., et al.
(författare)
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Risk of cardiovascular event and mortality in relation to refill and guideline adherence to lipid-lowering medications among patients with type 2 diabetes mellitus in Sweden
- 2019
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Ingår i: BMJ Open Diabetes Research and Care. - : BMJ. - 2052-4897. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Objective To analyze the risk of cardiovascular (CV) events and mortality in relation to adherence to lipid-lowering medications by healthcare centers and patients with type 2 diabetes mellitus (T2DM). Research design and methods We included 121914 patients (12% secondary prevention) with T2DM reported by 1363 healthcare centers. Patients initiated lipid-lowering medications between July 2006 and December 2012 and were followed from cessation of the first filled supply until multidose dispensed medications, migration, CV events, death or December 2016. The study period was divided into 4-month intervals through 2014, followed by annual intervals through 2016. Adherence measures were assessed for each interval. Patients’ (refill) adherence was measured using the medication possession ratio (MPR). Healthcare centers’ (guideline) adherence represented the prescription prevalence of lipid-lowering medications according to guidelines. The risk of CV events and mortality was analyzed for each interval using Cox proportional hazard regression and Kaplan-Meier. Results Compared with high-adherent patients (MPR >80%), low-adherent primary prevention patients (MPR ≤80%) showed higher risk of all outcomes: 44%–51 % for CV events, doubled for all-cause mortality and 79%–90% for CV mortality. Corresponding risks for low-adherent secondary prevention patients were 17%–19% for CV events, 88%–97% for all-cause and 66%–79% for CV mortality. Primary prevention patients treated by low-adherent healthcare centers (guideline adherence <48%) had a higher risk of CV events and CV mortality. Otherwise, no difference in the risk of CV events or mortality was observed by guideline adherence level. Conclusions Our results demonstrate the importance of high refill adherence and thus the value of individualized care among patients with T2DM.
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| 17. |
- Karlsson, Sofia A., et al.
(författare)
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The impact of a changed legislation on reporting of adverse drug reactions in Sweden, with focus on nurses' reporting
- 2015
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Ingår i: European Journal of Clinical Pharmacology. - : Springer Science and Business Media LLC. - 0031-6970 .- 1432-1041. ; 71:5, s. 631-636
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: In March 2007, a legislative amendment was issued in Sweden compelling nurses to report all suspected adverse drug reactions (ADRs) to the national pharmacovigilance system. The aims of this study were to describe the status of ADR reporting, before and after the implementation of the legislative changes, and to describe the general characteristics of suspected ADRs reported by nurses. Methods: The Swedish pharmacovigilance system during the study period constituted six regional centres responsible for the handling of all spontaneous ADR reports within their region. In this study, we identified all individual ADR reports from 2005 and 2010, analysed in depth the ADR reports from two regional centres and collated information about the reporter and the nature of the reported ADR. Results: From the two regional centres, a total of 898 and 1074 reports were submitted in 2005 and 2010 respectively. Nurses submitted 31% (275 reports) of the reports in 2005 and 24% (260 reports) in 2010. Nurses' reporting of serious ADRs was 3% (seven reports) in 2005 and 7% (17 reports) in 2010 with reporting of unlabelled ADRs at 4% (11 reports) in 2005 and 17% (45 reports) in 2010. Most of the serious and/or unlabelled reactions were related to vaccine administration (14 reports in 2005 and 36 reports in 2010). Conclusions: The overall ADR reporting by nurses did not appear to increase after the change in reporting legislation. The proportion of serious and/or unlabelled ADRs reported by nurses did however appear to increase during the same period. Taken together, our data suggests that further pro-active measures should be considered in order to involve nurses in the reporting of suspected ADRs.
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| 18. |
- Karlsson, Sofia, et al.
(författare)
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Heparin pre-treatment in patients with ST-segment elevation myocardial infarction and the risk of intracoronary thrombus and total vessel occlusion : Insights from the TASTE trial
- 2019
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Ingår i: European Heart Journal. - : Sage Publications. - 2048-8726 .- 2048-8734. ; 8:1, s. 15-23
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Pre-treatment with unfractionated heparin is common in ST-segment elevation myocardial infarction (STEMI) protocols, but the effect on intracoronary thrombus burden is unknown. We studied the effect of heparin pre-treatment on intracoronary thrombus burden and Thrombolysis in Myocardial Infarction (TIMI) flow prior to percutaneous coronary intervention in patients with STEMI.METHODS: The Thrombus Aspiration in ST-Elevation Myocardial Infarction in Scandinavia (TASTE) trial angiographically assessed intracoronary thrombus burden and TIMI flow, prior to percutaneous coronary intervention, in patients with STEMI. In this observational sub-study, patients pre-treated with heparin were compared with patients not pre-treated with heparin. Primary end points were a visible intracoronary thrombus and total vessel occlusion prior to percutaneous coronary intervention. Secondary end points were in-hospital bleeding, in-hospital stroke and 30-day all-cause mortality.RESULTS: Heparin pre-treatment was administered in 2898 out of 7144 patients (41.0%). Patients pre-treated with heparin less often presented with an intracoronary thrombus (61.3% vs. 66.0%, p<0.001) and total vessel occlusion (62.9% vs. 71.6%, p<0.001). After adjustments, heparin pre-treatment was independently associated with a reduced risk of intracoronary thrombus (odds ratio (OR) 0.73, 95% confidence interval (CI)=0.65-0.83) and total vessel occlusion (OR 0.64, 95% CI=0.56-0.73), prior to percutaneous coronary intervention. There were no significant differences in secondary end points of in-hospital bleeding (OR 0.84, 95% CI=0.55-1.27), in-hospital stroke (OR 1.17, 95% CI=0.48-2.82) or 30-day all-cause mortality (hazard ratio 0.88, 95% CI=0.60-1.30).CONCLUSIONS: Heparin pre-treatment was independently associated with a lower risk of intracoronary thrombus and total vessel occlusion before percutaneous coronary intervention in patients with STEMI, without evident safety concerns, in this large multi-centre observational study.
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| 19. |
- Lundell, Anna-Carin, 1976, et al.
(författare)
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Increased levels of circulating soluble CD14 but not CD83 in infants are associated with early intestinal colonization with Staphylococcus aureus
- 2007
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Ingår i: Clin Exp Allergy. ; 37:1, s. 62-71
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Soluble forms of the monocyte marker CD14 and the mature dendritic cell marker CD83 are plasma proteins with immunoregulatory functions. The physiological stimulus for their production is unclear and their possible role in allergy development is unknown. METHODS: We measured the plasma levels of soluble CD14 (sCD14) and soluble CD83 (sCD83) in 64 Swedish children in relation to intestinal bacterial colonization pattern in a prospective birth cohort. Soluble CD14 and sCD83 levels were quantified by enzyme linked immunosorbent assay in plasma obtained at birth and at 4, 18 and 36 months of age. All major aerobic and anaerobic bacteria were quantified in faecal samples obtained regularly over the first 8 weeks of life. Clinical allergy and IgE levels were evaluated at 18 months of age. RESULTS: Soluble CD14 in plasma increased during the first 18 months of life while sCD83 peaked at 4 months of age. Children who were perinatally colonized with Staphylococcus aureus had significantly higher levels of sCD14 in plasma at 4 months of age relative to non-colonized children. The levels of sCD14 were unrelated to colonization with Escherichia coli, other enterobacteria, enterococci, clostridia, Bacteroides, bifidobacteria or lactobacilli. Further, children with food allergy by 18 months tended to have lower levels of sCD14 than healthy children. Plasma levels of sCD83 were not related to either bacterial colonization pattern or allergy development. CONCLUSIONS: Perinatal colonization with S. aureus may trigger the occurrence of sCD14 in plasma, which may influence development of the infantile immune system and risk of allergy development.
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| 20. |
- Mohammad, Moman A., et al.
(författare)
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Christmas, national holidays, sport events, and time factors as triggers of acute myocardial infarction : SWEDEHEART observational study 1998-2013
- 2018
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Ingår i: The BMJ. - : BMJ Publishing Group Ltd. - 1756-1833 .- 0959-8138. ; 363
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To study circadian rhythm aspects, national holidays, and major sports events as triggers of myocardial infarction.DESIGN: Retrospective observational study using the nationwide coronary care unit registry, SWEDEHEART.SETTING: Sweden.PARTICIPANTS: 283 014 cases of myocardial infarction reported to SWEDEHEART between 1998 and 2013. Symptom onset date was documented for all cases, and time to the nearest minute for 88%.INTERVENTIONS: Myocardial infarctions with symptom onset on Christmas/New Year, Easter, and Midsummer holiday were identified. Similarly, myocardial infarctions that occurred during a FIFA World Cup, UEFA European Championship, and winter and summer Olympic Games were identified. The two weeks before and after a holiday were set as a control period, and for sports events the control period was set to the same time one year before and after the tournament. Circadian and circaseptan analyses were performed with Sunday and 24:00 as the reference day and hour with which all other days and hours were compared. Incidence rate ratios were calculated using a count regression model.MAIN OUTCOME MEASURES: Daily count of myocardial infarction.RESULTS: Christmas and Midsummer holidays were associated with a higher risk of myocardial infarction (incidence rate ratio 1.15, 95% confidence interval 1.12 to 1.19, P<0.001, and 1.12, 1.07 to 1.18, P<0.001, respectively). The highest associated risk was observed for Christmas Eve (1.37, 1.29 to 1.46, P<0.001). No increased risk was observed during Easter holiday or sports events. A circaseptan and circadian variation in the risk of myocardial infarction was observed, with higher risk during early mornings and on Mondays. Results were more pronounced in patients aged over 75 and those with diabetes and a history of coronary artery disease.CONCLUSIONS: In this nationwide real world study covering 16 years of hospital admissions for myocardial infarction with symptom onset documented to the nearest minute, Christmas, and Midsummer holidays were associated with higher risk of myocardial infarction, particularly in older and sicker patients, suggesting a role of external triggers in vulnerable individuals.
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| 21. |
- Skibniewski, Mikolaj, et al.
(författare)
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Long-term antithrombotic therapy after coronary artery bypass grafting in patients with preoperative atrial fibrillation. A nationwide observational study from the SWEDEHEART registry
- 2023
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Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 257, s. 69-77
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Tidskriftsartikel (refereegranskat)abstract
- Aims To provide data guiding long-term antithrombotic therapy after coronar y arter y by-pass grafting (CABG) in patients with preoperative atrial fibrillation (AF). Methods and results From the SWEDEHEART registry, we included all patients, between January 2006 and September 2016, with preoperative AF and CHA2DS2-VASC score >2, undergoing CABG. Based on dispensed prescriptions 12 to 18 months after CABG, patients were divided in 3 groups: use of platelet inhibitors (PI) only, oral anticoagulant (OAC) only or a combination of OAC + PI. Outcomes were: Major adverse cardiac and cerebrovascular events (MACCE, [all-cause death, myocardial infarction, or stroke]), net adverse clinical events (NACE, [MACCE or bleeding]) and the individual components of NACE. Inverse probability of treatment weighting was used to adjust for the non-randomized study design. Among 2,564 patients, 1,040 (41%) were treated with PI alone, 1,064 (41%) with OAC alone, and 460 (18%) with PI + OAC. Treatment with PI alone was associated with higher risk for MACCE (adjusted HR 1.43, 95% CI 1.09-1.88), driven by higher risk for stroke and MI, compared with OAC alone. Treatment with PI + OAC, was associated with higher risk for NACE (adjusted HR 1.40, 95% CI 1.06-1.85), driven by higher risk for bleeds, compared with OAC alone. Conclusion In this real-world observational study, a high proportion of patients with AF, undergoing CABG, did not receive a long-term OAC therapy. Treatment with OAC alone was associated with a net clinical benefit, compared with PI alone or PI + OAC. (Am Heart J 2023;257:69-77.)
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| 22. |
- Åberg, Anna-Maja, et al.
(författare)
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High monocyte count and expression of s100a9 and s100a12 in peripheral blood mononuclear cells are associated with poor outcome in patients with metastatic prostate cancer
- 2021
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Ingår i: Cancers. - : MDPI. - 2072-6694. ; 13:10
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Tidskriftsartikel (refereegranskat)abstract
- Increasing evidence indicates calcium-binding S100 protein involvement in inflammation and tumor progression. In this prospective study, we evaluated the mRNA levels of two members of this family, S100A9 and S100A12, in peripheral blood mononuclear cells (PBMCs) in a cohort of 121 prostate cancer patients using RT-PCR. Furthermore, monocyte count was determined by flow cytometry. By stratifying patients into different risk groups, according to TNM stage, Gleason score and PSA concentration at diagnosis, expression of S100A9 and S100A12 was found to be significantly higher in patients with metastases compared to patients without clinically detectable metastases. In line with this, we observed that the protein levels of S100A9 and S100A12 in plasma were higher in patients with advanced disease. Importantly, in patients with metastases at diagnosis, high monocyte count and high levels of S100A9 and S100A12 were significantly associated with short progression free survival (PFS) after androgen deprivation therapy (ADT). High monocyte count and S100A9 levels were also associated with short cancer-specific survival, with monocyte count providing independent prognostic information. These findings indicate that circulating levels of monocytes, as well as S100A9 and S100A12, could be biomarkers for metastatic prostate cancer associated with particularly poor prognosis.
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